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Adherence to Guidelines for Inpatient Pharmacologic Management of Type 2 Diabetes in Adults and Glycemic Outcomes. | Diabetes is often poorly managed in hospitals. This study assessed the level of adherence to current Canadian practice guidelines for inpatient pharmacologic management of type 2 diabetes and whether it affected the frequency of hyperglycemia or hypoglycemia. Retrospectively, we assessed the first 3 days of routine inpatient capillary blood glucose measurement (CBGM) records for hyperglycemia (>8 mmol/L fasting, >10 mmol/L nonfasting) and hypoglycemia (<4 mmol/L) in adults with drug-treated type 2 diabetes admitted to internal medicine without metabolic decompensation or nil per os (NPO) status at 2 hospitals during October through December 2014. Patients, divided according to their admission orders into guideline-adherent versus guideline-nonadherent groups were compared for frequency of hyperglycemia and hypoglycemia. Factors predicting guideline adherence were assessed. Of 150 patients with diabetes who were admitted, 108 met entry criteria. A total of 89 patients received guideline-based care (82%), whereas 19 patients did not (18%). Charlson index and preadmission medications did not predict guideline-based care, but admitting physicians' seniority did (junior, senior resident, attending physician; p=0.05). In the adherent group, 43% of CBGMs were hyperglycemic, versus 64% in the nonadherent group (p=0.01). For hypoglycemia, proportions were 2% versus 1%, respectively (p=0.21). Adherence to guidelines for inpatient type 2 diabetes management is good and may be greater with more training. Hyperglycemia was more common in patients who did not receive guideline-based care. Hypoglycemia was uncommon and did not appear to be more common in the guideline-adherent group, although numbers were small. These results may alleviate physicians' fear that providing adequate insulin to hospitalized patients may cause hypoglycemia. | adherence;diabetes;diabète;guidelines;inpatient;lignes directrices;outcomes;patients hospitalisés;respect;résultats | pubmed |
Dual-Programmable Shape-Morphing and Self-Healing Organohydrogels Through Orthogonal Supramolecular Heteronetworks. | Programmable materials that can change their inherent shapes or properties are highly desirable due to their promising applications. However, among various programmable shape-morphing materials, the single control route allows temporary states to recover the unchangeable former state, thus lacking the sophisticated programmability for their shape-encoding behaviors and mechanics. Herein, dual-programmable shape-morphing organohydrogels featuring supramolecular heteronetworks are developed. In the system, the metallo-supramolecular hydrogel framework and micro-organogels featuring semicrystalline comb-type networks independently respond to different stimuli, thereby providing orthogonal dual-switching mechanics and ultrahigh mechanical strength. The supramolecular heteronetworks also possess excellent self-healing properties. More notably, such orthogonal supramolecular heteronetworks demonstrate hierarchical shape morphing performance that far exceeds conventional shape-morphing materials. Utilizing this dual programming strategy of the orthogonal supramolecular heteronetworks, the material's permanent shape can be manipulated in a step-wise shape morphing process, thereby realizing sophisticated shape changes with a high degree of freedom. The organohydrogels can act as a biomimetic smart device for the on-demand control of unidirectional liquid transport. Based on these characteristics, it is anticipated that the supramolecular organohydrogels may serve as adaptive programmable materials for a variety of applications. | dual-programmable shape morphing;gel materials;orthogonal supramolecular heteronetworks;programmable materials;self-healing | pubmed |
Inhibition of PDGF-BB-induced proliferation and migration in VSMCs by proanthocyanidin A2: Involvement of KDR and Jak-2/STAT-3/cPLA<sub>2</sub> signaling pathways. | Proanthocyanidin A2 (PA2), one of A-type proanthocyanidins, has been shown to harbor a broad spectrum of pharmacological activities, including anti-inflammatory, antioxidant, anti-HIV, anti-CDV and anti-?-glucosidase activities. However, little is known about the role for PA2 in regulating PDGF-induced VSMC proliferation and migration. In the present study, we investigated the possible effects of PA2 on PDGF-BB-induced proliferation, migration and inflammation in VSMCs in vitro to mimic a postangioplasty PDGF shedding condition. Herein, the data clearly show that PA2 markedly inhibited proliferation, migration and inflammatory responses at 0-30??g/ml concentration in VSMCs in vitro. 10-30??g/ml PA2 inhibited PDGF-mediated NAD(P)H oxidase activation and intracellular ROS formation in VSMCs. Furthermore, the effects exerted by PA2 involve the participation of KDR and Jak-2/STAT-3/cPLA<sub>2</sub> signaling pathways. These data also highlight the possible therapeutic use of PA2 in vascular proliferative diseases, where abnormal proliferation and migration play important pathological roles. | Jak2;KDR;Migration;PDGF;Procyanidin A2;Proliferation | pubmed |
Feasibility and outcomes of percutaneous thermal ablation of hepatocellular carcinoma in a transplanted allograft. | To examine the safety, feasibility, and oncologic control following percutaneous image-guided thermal ablation of hepatocellular carcinoma (HCC) in a transplanted allograft. Retrospective review was performed to identify patients who underwent liver transplantation for HCC and subsequently underwent percutaneous hepatic thermal ablation for recurrent HCC within the allograft between January 1st, 2000-September 1st, 2016. Eleven patients with hepatic allograft HCC underwent twelve percutaneous thermal ablation procedures to treat 16 lesions. Patient, procedural characteristics, and local oncologic efficacy were reviewed. Complications were characterized via the Common Terminology for Clinically Adverse Events nomenclature [CTCAE] v4.03). Eleven transplant recipients underwent treatment of 16 HCC tumors in their allografts during 12 ablation sessions. Mean follow-up time was 25 months (range 2-96 months). Local oncologic control was achieved in 10 of 11 tumors (91%) with imaging follow-up. One patient (8%) with Roux-en-Y biliary reconstruction developed a major complication with hepatic abscess. Thermal ablation of recurrent HCC in transplanted allografts can be accomplished safely with acceptable rates of local control for patients with duct-to-duct biliary reconstruction. Due to the high number of patients deemed surgically unresectable, the morbidity of surgical resection, the side effects of targeted therapies, and significant mortality associated with recurrences in the transplanted allograft, patients may benefit from percutaneous thermal ablative treatments. Further study is needed to assess the role of thermal ablation in allograft HCC recurrences as primary therapy or in a multimodality approach with emerging systemic therapies. | Hepatic allograft;Hepatocellular carcinoma;Percutaneous ablation;Thermal ablation | pubmed |
Clinical follow-up evaluation of Dalbo®-Rotex® retention elements in the private practice | The aim of this retrospective study was to investigate the clinical outcome of Dalbo®-Rotex® retention elements in a private practice. The majority of the retention elements was fixed with self-adhesive composite cement, and in almost 40% the exposed root surface was additionally covered with composite. The success rate of 96.3% after 24 months in a total of 50 included patients (response rate 48.5%) demonstrated that a simple and cost-effective fixation of removable dentures using prefabricated, chair-side inserted retention elements is feasible. Maintenance care comprised single or repeated replacement and activation of the female part in 12.3% and 39.4% of the cases, respectively. Fractures were rare, occurring in 3.4% of the cases and more likely in patients with parafunctional habits. Frequent oral hygiene correlated with probing depths up to 3 mm at the maxi- mum, while the risk of greater probing depths associated with less frequent oral hygiene increased by a factor of 2.4. Patients’ assessment of the parameters handling and wearing comfort, chewing ability and prosthesis retention was predominantly positive. Based on the findings of the study, covering of exposed dentin areas with composite resin and regular recall comprising professional cleaning, fluoride application and oral hygiene instruction are recommended. | Retention element;Dalbo®-Rotex®;Removable denture;Efficacy;Private practice | pubmed |
Deterioration of Deceleration Capacity of Heart Rate is Associated with Left Ventricular Hypertrophy in End-Stage Renal Disease Population. | Left ventricular hypertrophy (LVH) is prevalent in patients with end-stage renal disease (ESRD), and may be secondary to arterial stiffness and volume overload. It is unclear whether LVH is caused by autonomic nerve dysregulation (AND), a frequent condition in patients with ESRD that is characterized by sympathetic hyperactivity and vagal withdrawal. We hypothesized that AND estimated by heart rate variability (HRV) may be associated with LVH in patients with ESRD. We prospectively enrolled patients with ESRD undergoing hemodialysis. Cardiac function and LVH were assessed using echocardiography according to the recommendations of the American Society of Echocardiography. Holter recordings were used to quantify HRV and deceleration capacity (DC). Dataon comorbidities and medications, and serum markers were obtained. Logistic regression analysis was performed. Among the 281 included patients, 63% had LVH. The patients with LVH were older, had more comorbidities and advanced diastolic dysfunction than those without LVH. The root mean square of successive differences (rMSSD) (9.10 ± 5.44 versus 13.25 ± 8.61; p = 0.004) and DC (2.08 ± 1.90 versus 3.89 ± 1.45; p = 0.021) were lower in the patients with LVH than that in those without LVH. Multivariate regression analysis showed that hypertension, asymmetrical dimethylarginine (ADMA), advanced diastolic dysfunction grade, rMSSD, and DC were independently associated with LVH. Among these variables, DC and ADMA showed the highest diagnostic value for LVH with areas under curves of 0.701 and 0.751, respectively. AND is independently associated with LVH in patients with ESRD. | Deceleration capacity;ESRD;Left ventricle hypertrophy;Vagal withdrawal | pubmed |
Evaluation of an immunochromatographic strip test for alpha-thalassaemia screening. | Hb H inclusion test (HbH-i) commonly used for α-thalassaemia screening is not standardised and is labour-intensive. This study evaluated a strip test based on immunochromatographic detection of Hb Bart's (ICT) for use as a routine screening test for α-thalassaemia screening in the clinical laboratory setting. The performance characteristics of the ICT was determined by comparing the results of ICT and HbH-i on 67 patients, and the α-globin genotype on 47 of these patients who also had the molecular analysis. Specimen stability was tested on 16 specimens with the ICT repeated after 7 days of storage. The age of babies from which the ICT result becomes valid was determined on 49 samples with patient age ranged from 4 weeks to 12 months. The ICT had higher overall sensitivity of 76% compared to 24% for HbH-i in detecting carriers of α-thalassaemia mutations, and this is seen in all α-thalassaemia genotypes. The test could be carried out on specimens stored at 4°C for 7 days and gave valid results with no false positive from the age of 6 months onwards. It required no special technical expertise or equipment and gave the result in less than 5 minutes. The ICT is simple to perform, with higher sensitivity than HbH-i, and gives the result in a short time and at a lower cost. This can be used by clinical laboratories to replace HbH-i for α-thalassaemia detection. | Hb Bart's;HbH inclusion;ICT screen;alpha-thalassaemia | pubmed |
Importance of the knowledge of pathological processes for risk-based inspection in pig slaughterhouses (Study of 2002 to 2016). | The objective of this work was to determine the prevalence of the pathologies that caused the condemnation of pig carcasses in an area of intensive pig farming and Mediterranean climatology and to evaluate their influence in a risk-based inspection procedure for slaughterhouses. A retrospective observational investigation was carried out from 2002 to 2016 into the pathological processes that caused the condemnation of pig carcasses in a slaughterhouse from South-eastern Spain. The seasonal effect on the causes of condemnation carcass was reported. Negative binomial model was used to evaluate the effect of season on the rate of antemortem rejections and post-mortem condemnations. Histopathological examinations were performed to confirm the diagnosis. The risk of antemortem rejections (0.0564%) was significantly greater in summer (risk ratio [RR] = 1.57). Autumn was associated with higher rate (RR = 1.69) of the total postmortem condemnations (0.1046%). Significantly higher rates of pronounced anaemia (0.0111%) were observed in summer (RR = 3.20). The main causes of anaemia were observed gastroesophageal ulcers and haemorrhagic enteropathies. Significantly highest risk of erysipelas (0.0074%) were observed in autumn (RR = 5.485). About other zoonosis, only eight cases (0.0013%) of carcasses were declared unfit due to tuberculosis lesions. Porcine muscular cysticercosis was not detected. Nevertheless, nonspecific causes such as generalized infections and emaciation represented the half of the condemned carcasses (50.90%). The pathologies leading to the condemnation of carcasses in this study can be considered representative of the pathologies that affect the pig population from a region with a high intensive production and Mediterranean climatology because this slaughterhouse receives a lot of animals from many farms of different size in a high intensive pig production zone (Mediterranean region). Increased knowledge of environmental factors that may foment the appearance of the diseases is essential for implementing inspection programs based on risk assessment in pig's slaughterhouses. | Pathological Processes;Pigs;Risk-based Inspections;Slaughterhouse;South-Eastern Spain | pubmed |
BCL2 and BCL(X)L selective inhibitors decrease mitochondrial ATP production in breast cancer cells and are synthetically lethal when combined with 2-deoxy-D-glucose. | Cancer cells display differences regarding their engagement of glycolytic vs. mitochondrial oxidative phosphorylation (OXPHOS) pathway. Triple negative breast cancer, an aggressive form of breast cancer, is characterized by elevated glycolysis, while estrogen receptor positive breast cancer cells rely predominantly on OXPHOS. BCL2 proteins control the process of mitochondrial outer membrane permeabilization during apoptosis, but also regulate cellular bioenergetics. Because BCL2 proteins are overexpressed in breast cancer and targetable by selective antagonists, we here analysed the effect of BCL2 and BCL(X)L selective inhibitors, Venetoclax and WEHI-539, on mitochondrial bioenergetics and cell death. Employing single cell imaging using a FRET-based mitochondrial ATP sensor, we found that MCF7 breast cancer cells supplied with mitochondrial substrates reduced their mitochondrial ATP production when treated with Venetoclax or WEHI-539 at concentrations that <i>per se</i> did not induce cell death. Treatments with lower concentrations of both inhibitors also reduced the length of the mitochondrial network and the dynamics, as evaluated by quantitative confocal microscopy. We next tested the hypothesis that mitochondrial ATP production inhibition with BCL2 or BCL(X)L antagonists was synthetically lethal when combined with glycolysis inhibition. Treatment with 2-deoxy-D-glucose in combination with Venetoclax or WEHI-539 synergistically reduced the cellular bioenergetics of ER+ and TNBC breast cancer cells and abolished their clonogenic potential. Synthetic lethality was also observed when cultures were grown in 3D spheres. Our findings demonstrate that BCL2 antagonists exert potent effects on cancer metabolism independent of cell death-inducing effects, and demonstrate a synthetic lethality when these are applied in combination with glycolysis inhibitors. | BCL2 inhibitors;OXPHOS;bioenergetics;breast cancer;cell death | pubmed |
Colloidal Quantum Nanostructures: Emerging Materials for Display Applications. | Colloidal semiconductor nanocrystals (SCNCs) or, more broadly, colloidal quantum nanostructures constitute outstanding model systems for investigating size and dimensionality effects. Their nanoscale dimensions lead to quantum confinement effects that enable tuning of their optical and electronic properties. Thus, emission color control with narrow photoluminescence spectra, wide absorbance spectra, and outstanding photostability, combined with their chemical processability through control of their surface chemistry leads to the emergence of SCNCs as outstanding materials for present and next-generation displays. In this Review, we present the fundamental chemical and physical properties of SCNCs, followed by a description of the advantages of different colloidal quantum nanostructures for display applications. The open challenges with respect to their optical activity are addressed. Both photoluminescent and electroluminescent display scenarios utilizing SCNCs are described. | displays;electroluminescence;photoluminescence;quantum confinement;quantum dots | pubmed |
Reversible and Tunable Photoswitching of Protein Function through Genetic Encoding of Azobenzene Amino Acids in Mammalian Cells. | The genetic encoding of three different azobenzene phenylalanines with different photochemical properties was achieved in human cells by using an engineered pyrrolysyl tRNA/tRNA synthetase pair. In order to demonstrate reversible light control of protein function, azobenzenes were site-specifically introduced into firefly luciferase. Computational strategies were applied to guide the selection of potential photoswitchable sites that lead to a reversibly controlled luciferase enzyme. In addition, the new azobenzene analogues provide enhanced thermal stability, high photoconversion, and responsiveness to visible light. These small-molecule photoswitches can reversibly photocontrol protein function with excellent spatiotemporal resolution, and preferred sites for incorporation can be computationally determined, thus providing a new tool for investigating biological processes. | azobenzene;optochemical biology;photoswitching;unnatural amino acid | pubmed |
Use of semiquantitative analysis in local recurrence of colorectal carcinoma with <sup>18</sup>F-FDG PET/CT: A myth or a truth? | Recurrence of colorectal cancer is mostly seen within the first 2 years after surgery. The most frequent site of recurrence is the postsurgical areas and its surroundings. The purpose of this study was to evaluate the usefulness of semiquantitative analysis of <sup>18</sup>Fluorine fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in determining recurrence of colorectal carcinoma in the operation site. Files of 35 patients with colorectal carcinoma (25 men, 10 women, mean age: 59.25±2.82 years, range: 27-80 years) who were treated with surgery and underwent FDG PET/CT scanning for restaging of colorectal carcinoma and showing increased FDG uptake in the postsurgical area, were retrospectively analysed. Besides calculating SUVmax of the areas showing FDG uptake, SUVmax of physiological colonic activity was also obtained and SUVmax of lesion/SUVmax of colonic wall (RSUVmax), was calculated. Characteristics of FDG uptake were classified according to histological analysis or clinical and imaging follow-up. In 17 of 35 patients (49%) the standard of reference for the final diagnosis was histologic analysis and in 18 (51%), final diagnosis was based on imaging and clinical follow-up. In 15 of 35 patients (43%) the etiology of increased FDG uptake was recurrence and in 20 (57%), FDG accumulation was observed due to benign etiology. The difference between the mean of the results of SUVmax in patients with recurrent disease and with no evidence of recurrence was statistically significant (P=.030). For SUVmax, a cut-off value for recurrence was calculated as 9.51 with a sensitivity of 80% and a specificity of 70%. In terms of RSUVmax results, a statistically significant difference was also observed between mean values in patients with recurrent disease and in those without (P=.002). ROC analysis demonstrated that the best predictive value of RSUVmax for recurrence was 1.75 with a sensitivity of 67% and specificity of 95%. Semiquantitative analysis of FDG PET/CT may be used in detecting recurrent disease of patients with colorectal carcinoma. Eliminating interfering physiological colonic activity in analysis may have an incremental effect on the success of this technique, by means of increasing the specificity. | Actividad fisiológica;Carcinoma colorrectal;Colorectal carcinoma;FDG PET/CT;FDG PET/TC;Physiological activity;Recurrence;Recurrencia;Semicuantitativo;Semiquantitative | pubmed |
Deciphering the degradation/chlorination mechanisms of maleic acid in the Fe(II)/peroxymonosulfate process: An often overlooked effect of chloride. | In recent years, a significant effort has been devoted into investigating the effects of chloride on the degradation kinetics of aromatic pollutants. The impact of chloride on the decomposition of short-chain carboxylic acid intermediates from aromatics degradation has often been overlooked. In this study the roles of chloride in the oxidation of maleic acid (MA) in the Fe(II)/peroxymonosulfate (PMS) process was investigated. Degradation efficiency, reaction intermediates, adsorbable organic halogen (AOX) accumulation and mineralization were examined. The chloride ion (Cl<sup>-</sup>) was found to have an overall negative impact on MA degradation and mineralization in the Fe(II)/PMS system. The presence of Cl<sup>-</sup> led to the formation of chlorinated by-products and a high production of AOX. The mineralization of MA was decreased with increasing Cl<sup>-</sup> concentrations. Kinetic modeling demonstrated the impact of various radicals largely depended on the concentration of Cl<sup>-</sup>. The significance of Cl<sub>2</sub><sup>•-</sup> or Cl<sub>2</sub> for MA destruction was enhanced with increasing Cl<sup>-</sup> content, and overwhelmed that of SO<sub>4</sub><sup>•-</sup> when the Cl<sup>-</sup> concentration was over 5 mM. In the absence of Cl<sup>-</sup>, SO<sub>4</sub><sup>•-</sup> was the primary radical responsible for MA oxidation. A possible degradation pathway is proposed (cis-trans isomerization, decarboxylation and halogenations processes). These results may help to understand the full oxidation pathways of refractory aromatic compounds and the mechanism of chlorinated by-products formation in industrial saline wastewater treatment. | Advanced oxidation processes;Chloride;Chlorinated by-products;Kinetic modeling;Sulfate radical | pubmed |
TRIB3 Interacts With β-Catenin and TCF4 to Increase Stem Cell Features of Colorectal Cancer Stem Cells and Tumorigenesis. | Activation of Wnt signaling to β-catenin contributes to the development of colorectal cancer (CRC). Expression of tribbles pseudo-kinase 3 (TRIB3) is increased in some colorectal tumors and associated with poor outcome. We investigated whether increased TRIB3 expression promotes stem cell features of CRC cells and tumor progression by interacting with the Wnt signaling pathway. We performed studies with C57BL/6J-Apc<sup>Min</sup>/J mice injected with an adeno-associated virus vector that expresses a small hairpin RNA against Trib3 mRNA (Apc<sup>Min</sup>/J-Trib3<sup>KD</sup>) or a control vector (Apc<sup>Min</sup>/J-Ctrl). We created BALB/c mice that overexpress TRIB3 from an adeno-associated virus vector and mice with small hairpin RNA-mediated knockdown of β-catenin. The mice were given azoxymethane followed by dextran sodium sulfate to induce colitis-associated cancer. Intestinal tissues were collected and analyzed by histology, gene expression profiling, immunohistochemistry, and immunofluorescence. Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5)-positive (LGR5<sup>Pos</sup>) and LGR5-negative (LGR5<sup>Neg</sup>) HCT-8 CRC cells, with or without knockdown or transgenic expression of TRIB3, were sorted and analyzed in sphere-formation assays. We derived organoids from human and mouse colorectal tumors to analyze the function of TRIB3 and test the effect of a peptide inhibitor. Wnt signaling to β-catenin was analyzed in dual luciferase reporter, chromatin precipitation, immunofluorescence, and immunoblot assays. Proteins that interact with TRIB3 were identified by immunoprecipitation. CRC cell lines were grown in nude mice as xenograft tumors. At 10 weeks of age, more than half the Apc<sup>Min</sup>/J-Ctrl mice developed intestinal high-grade epithelial neoplasia, whereas Apc<sup>Min</sup>/J-Trib3<sup>KD</sup> mice had no intestinal polyps and normal histology. Colon tissues from Apc<sup>Min</sup>/J-Trib3<sup>KD</sup> mice expressed lower levels of genes regulated by β-catenin and genes associated with cancer stem cells. Mice with overexpression of Trib3 developed more tumors after administration of azoxymethane and dextran sodium sulfate than BALB/c mice. Mice with knockdown of β-catenin had a lower tumor burden after administration of azoxymethane and dextran sodium sulfate, regardless of Trib3 overexpression. Intestinal tissues from mice with overexpression of Trib3 and knockdown of β-catenin did not have activation of Wnt signaling or expression of genes regulated by β-catenin. LGR5<sup>Pos</sup> cells sorted from HCT-8 cells expressed higher levels of TRIB3 than LGR5<sup>Neg</sup> cells. CRC cells that overexpressed TRIB3 had higher levels of transcription by β-catenin and formed larger spheroids than control CRC cells; knockdown of β-catenin prevented the larger organoid size caused by TRIB3 overexpression. TRIB3 interacted physically with β-catenin and transcription factor 4 (TCF4). TRIB3 overexpression increased, and TRIB3 knockdown decreased, recruitment of TCF4 and β-catenin to the promoter region of genes regulated by Wnt. Activated β-catenin increased expression of TRIB3, indicating a positive-feedback loop. A peptide (P2-T3A6) that bound β-catenin disrupted its interaction with TRIB3 and TCF4. In primary CRC cells and HCT-8 cells, P2-T3A6 decreased expression of genes regulated by β-catenin and genes associated with cancer stem cells and decreased cell viability and migration. Injection of C57BL/6J-Apc<sup>Min</sup>/J mice with P2-T3A6 decreased the number and size of tumor nodules and colon expression of genes regulated by β-catenin. P2-T3A6 increased 5-fluorouracil-induced death of CRC cells and survival times of mice with xenograft tumors. TRIB3 interacts with β-catenin and TCF4 in intestine cells to increase expression of genes associated with cancer stem cells. Knockdown of TRIB3 decreases colon neoplasia in mice, migration of CRC cells, and their growth as xenograft tumors in mice. Strategies to block TRIB3 activity might be developed for treatment of CRC. | Carcinogenesis;Colon Cancer;Mouse Model;Tumor Development | pubmed |
Pulsatile flow through a constricted tube: effect of stenosis morphology on hemodynamic parameters. | In this paper, we investigate pulsatile flow through a constricted tube with the aim of assessing the effect of stenosis morphology on hemodynamic parameters. The fluid-solid interaction of pulsatile flow through a compliant tube with elastic walls was simulated using an arbitrary Lagrangian-Eulerian (ALE) finite-element method. We consider blood flow through various mild stenoses of 25.8% severity in diameter with trapezoidal and bell-like morphologies at a fixed Womersley number of 7.75. The results show that the distribution of the time-averaged wall shear stress (TAWSS), which is the main factor affecting the hemodynamic parameters, strongly depends on the axial stretch of the stenosis; elongation of the stenotic region increases by 41.1% the maximum TAWSS for stenoses of trapezoidal morphology whereas the maximum TAWSS decreases by 14.8% for the corresponding stenoses of bell-like morphology. The present findings indicate that risk factors due to atherosclerosis may vary in a complicated manner as an atheromatous plaque gradually builds up and morphs with time. | Atherosclerosis;atheromatous plaque;blood flow;hemodynamics;shear stress | pubmed |
Is the association of deliberate self-harm with emotional relief stable or dependent on emotional context? | Despite strong support for the role of emotional relief in deliberate self-harm (DSH), no research has examined the impact of emotional distress on the strength of the DSH-relief association. Thus, it remains unclear whether the association of DSH with emotional relief is stable across emotional contexts or context-dependent. This study aimed to examine if the implicit DSH-relief association is stronger in the context of emotional distress (relative to a neutral emotional context). Young adult women with (n = 60) and without (n = 60) a history of recent recurrent DSH were randomly assigned to complete a novel version of the Implicit Association Test (IAT) assessing the DSH-relief association at baseline (following an initial neutral emotion induction) and again following either a neutral or negative (i.e., social rejection) emotion induction. Consistent with hypotheses, the DSH-relief association was stronger among women with recent recurrent DSH (vs. those without DSH) at baseline. Contrary to hypotheses, however, whereas the DSH-relief association remained stable following both the neutral and negative emotion inductions among participants with DSH, it became stronger across both conditions for participants without DSH. The use of a community sample of young adult women may limit generalizability to other relevant populations (e.g., clinical populations, young men, adolescents). Additionally, the negative emotion induction may not have been powerful enough to affect the strength of the learned DSH-relief association among individuals with a repeated history of DSH. Findings suggest that the repeated use of DSH to bring about emotional relief may engender associations of DSH with relief that are relatively insensitive to emotional context. | Cognitive task;Emotion manipulation;Emotion regulation;Experiment;Nonsuicidal self-injury | pubmed |
Use of nonsteroidal antiinflammatory drugs during pregnancy and the risk of miscarriage. | Nonsteroidal antiinflammatory drugs are among the medications most widely used by pregnant women, and previous studies have reported an increased risk of miscarriage that is associated with nonsteroidal antiinflammatory drug use during pregnancy. Although the findings have not always been consistent, there is a well-established mechanism for the association: nonsteroidal antiinflammatory drugs inhibit the production of prostaglandin, which is essential for successful embryonic implantation. Abnormal implantation increases the risk of miscarriage. The purpose of this study was to examine the impact of nonsteroidal antiinflammatory drug use in early pregnancy on the risk of miscarriage, especially regarding the timing and duration of use. We conducted a cohort study among pregnant members of Kaiser Permanente Northern California, an integrated healthcare delivery system. Pregnant Kaiser Permanente Northern California members (N=1097) were recruited very early in pregnancy (median gestational age at enrollment, 39 days) to achieve optimal ascertainment of miscarriage, including early miscarriages, which are often missed in studies of miscarriages. Based on the use of nonsteroidal antiinflammatory drugs and acetaminophen, which has similar indication as nonsteroidal antiinflammatory drugs, 3 cohorts were formed: (1) women who used nonsteroidal antiinflammatory drugs only, (2) women who used acetaminophen only (to control for indication), and (3) women who used neither nonsteroidal antiinflammatory drugs nor acetaminophen (unexposed control subjects). Among all eligible women contacted, 63% participated in the study. Miscarriages were ascertained from both electronic medical record data and directly from interviews with participants. The Cox proportional hazards model with accommodation for left truncation was used to examine the risk of miscarriage associated with the use of nonsteroidal antiinflammatory drugs and acetaminophen during pregnancy; we controlled for potential confounders. After an adjustment for multiple confounders that included maternal age, previous miscarriage, multivitamin use, caffeine drinking, and smoking during pregnancy, we found that nonsteroidal antiinflammatory drug use during pregnancy was associated with a statistically significant increased risk of miscarriage compared with both unexposed control subjects (adjusted hazard ratio, 1.59; 95% confidence interval, 1.13-2.24) and acetaminophen users (indication control subjects; adjusted hazard ratio, 1.45; 95% confidence interval, 1.01-2.08). The risk was largely due to nonsteroidal antiinflammatory drug use around conception (adjusted hazard ratio, 1.89; 95% confidence interval, 1.31-2.71) with a statistically significant dose-response relationship: adjusted hazard ratio, 1.37 (95% confidence interval, 0.70-2.71) for nonsteroidal antiinflammatory drug use of ≤14 days; adjusted hazard ratio, 1.85 (95% confidence interval, 1.24-2.78) for nonsteroidal antiinflammatory drug use of ≥15 days. The association was stronger for early miscarriage (<8 weeks gestational age): adjusted hazard ratio, 4.08 (95% confidence interval, 2.25-7.41). Women with lower body mass index (<25 kg/m<sup>2</sup>) appeared to be more susceptible to the effect of nonsteroidal antiinflammatory drug use around conception (adjusted hazard ratio, 3.78; 95% confidence interval, 2.04-6.99) than women with high body mass index (≥25 kg/m<sup>2</sup>; adjusted hazard ratio, 1.03; 95% confidence interval, 0.61-1.72). After we controlled for confounding by indication, nonsteroidal antiinflammatory drug use around conception was associated with an increased risk of miscarriage with a dose-response relationship. In addition, women with lower body mass index could be especially vulnerable to the effects of nonsteroidal antiinflammatory drug use around the time of embryonic implantation, although this new observation must be confirmed in future studies. | NSAID;miscarriage;pregnancy | pubmed |
The emotional and professional wellbeing of Australian midwives: A comparison between those providing continuity of midwifery care and those not providing continuity. | Continuity of midwifery care contributes to significant positive outcomes for women and babies. There is a perception that providing continuity of care may negatively impact on the wellbeing and professional lives of midwives. To compare the emotional and professional wellbeing as well as satisfaction with time off and work-life balance of midwives providing continuity of care with midwives not providing continuity. Online survey. Measures included; Copenhagen Burnout Inventory (CBI); Depression, Anxiety and Stress Scale-21; and Perceptions of Empowerment in Midwifery Scale (PEMS-Revised). The sample (n=862) was divided into two groups; midwives working in continuity (n=214) and those not working in continuity (n=648). Mann Whitney U tests were used to compare the groups. The continuity group had significantly lower scores on each of the burnout subscales (CBI Personal p=.002; CBI Work p<.001; CBI Client p<.001) and Anxiety (p=.007) and Depression (p=.004) sub-scales. Midwives providing continuity reported significantly higher scores on the PEMs Autonomy/Empowerment subscale (p<.001) and the Skills and Resources subscale (p=.002). There was no difference between the groups in terms of satisfaction with time off and work-life balance. Our results indicate that providing continuity of midwifery care is also beneficial for midwives. Conversely, midwives working in shift-based models providing fragmented care are at greater risk of psychological distress. Maternity service managers should feel confident that re-orientating care to align with the evidence is likely to improve workforce wellbeing and is a sustainable way forward. | Anxiety;Burnout;Continuity;Empowerment;Midwives | pubmed |
Negative video capsule enteroscopy - what's the next step? | Video capsule endoscopy (VCE) is a reliable noninvasive method for examination of small-bowel mucosa. However, it has some limitations. The aim of this article was to review the approach in patients with negative VCE. It is clear that a negative VCE should be interpreted based on the indication. In suspected small bowel bleeding (SSBB), patients with ongoing/recurrent overt bleeding, or occult bleeders who experience significant declines in hemoglobin after a negative VCE should proceed small bowel study; on the other hand, patients with occult SSBB and only mild-moderate anemia should be managed with supportive care. In inflammatory bowel disease, a normal VCE has a very high sensitivity and negative predictive value. In small bowel tumor suspicion there is a high risk of false negative results, so another imaging modality should be considered. In polyposis syndromes, if VCE is negative, patients should continue screening within 2-3 years. | Capsule endoscopy;Cápsula endoscópica;Enfermedad inflamatoria intestinal;Enteroscopia;Enteroscopy;Hemorragia del intestino delgado;Inflammatory bowel disease;Intestino delgado;Small bowel bleeding;Small bowel tumors;Small-bowel;Tumores intestinales pequeños | pubmed |
DKey software for editing and browsing dichotomous keys. | Despite advances in computer technology and the increasing availability of multiple-access taxonomic keys, traditional dichotomous keys remain the most often used taxonomic identification tools. On the other hand, there seems to be a lack of an editor of dichotomous keys, which is both freely available and easy to use. The DKey software was developed in order to alleviate this problem. A taxonomic key in text format can be imported to the software in order to edit it. Various editing options are possible, including: moving couplets, removing couplets, combining keys and renumbering keys. The software can output the key either in the traditional text format, ready for publication in a scientific journal, or in hypertext linked format, which makes identification faster and easier, due to the fact that pointers can be clicked in order to move to the next couplet. The DKey software should be useful for both taxonomic experts creating keys and those who use them for identification. The DKey software is freely available and open source. | key;single-access key;software;taxonomic identification of species | pubmed |
Expression and characterization of a novel truncated rotavirus VP4 for the development of a recombinant rotavirus vaccine. | The outer capsid protein VP4 is an important target for the development of a recombinant rotavirus vaccine because it mediates the attachment and penetration of rotavirus. Due to the poor solubility of full-length VP4, VP8 was explored as candidate rotavirus vaccines in the past years. In previous studies, it has been found that the N-terminal truncated VP8 protein, VP8-1 (aa26-231), could be expressed in soluble form with improved immunogenicity compared to the core of VP8 (aa65-223). However, this protein stimulated only a weak immune response when aluminum hydroxide was used as an adjuvant. In addition, it should be noted that the protective efficacy of VP4 was higher than that of VP8 and VP5. In this study, it was found that when the N-terminal 25 amino acids were deleted, the truncated VP4<sup>∗</sup> (aa26-476) containing VP8 and the stalk domain of VP5 could be expressed in soluble form in E. coli and purified to homogeneous trimers. Furthermore, the truncated VP4 could induce high titers of neutralizing antibodies when aluminum adjuvant was used and conferred high protective efficacy in reducing the severity of diarrhea and rotavirus shedding in stools in animal models. The immunogenicity of the truncated VP4 was significantly higher than that of VP8<sup>∗</sup> and VP5<sup>∗</sup> alone. Taken together, the truncated VP4<sup>∗</sup> (aa26-476), with enhanced immunogenicity and immunoprotectivity, could be considered as a viable candidate for further development and has the potential to become a parenterally administered rotavirus vaccine. | Diarrhea score;Maternal antibody model;Neutralizing activity;Recombinant rotavirus vaccine;VP4;Virus shedding | pubmed |
PVDF-Based Piezoelectric Microphone for Sound Detection Inside the Cochlea: Toward Totally Implantable Cochlear Implants. | We report the fabrication and characterization of a prototype polyvinylidene fluoride polymer-based implantable microphone for detecting sound inside gerbil and human cochleae. With the current configuration and amplification, the signal-to-noise ratios were sufficiently high for normally occurring sound pressures and frequencies (ear canal pressures >50-60 dB SPL and 0.1-10 kHz), though 10 to 20 dB poorer than for some hearing aid microphones. These results demonstrate the feasibility of the prototype devices as implantable microphones for the development of totally implantable cochlear implants. For patients, this will improve sound reception by utilizing the outer ear and will improve the use of cochlear implants. | PVDF;cochlear implant;microphone;piezoelectric | pubmed |
The nonsense-mediated mRNA decay (NMD) pathway differentially regulates COX17, COX19 and COX23 mRNAs. | The differential regulation of COX17, COX19 and COX23 mRNAs by the nonsense-mediated mRNA decay (NMD) pathway was investigated. The NMD pathway regulates mRNAs that aberrantly terminate translation. This includes mRNAs harboring premature translation termination codons and natural mRNAs. Most natural mRNAs regulated by NMD encode fully functional proteins involved in various cellular processes. However, the cause and targeting of most of these mRNAs by the pathway is not understood. Analysis of a set of mRNAs involved in copper homeostasis showed that a subset of these mRNAs function in mitochondrial copper homeostasis. Here, we examined the regulation of COX17, COX19 and COX23 mRNAs by NMD. These mRNAs encode homologous mitochondrial proteins involved in metallation of cytochrome c oxidase. We found that COX17, COX19 and COX23 mRNAs are differentially regulated by NMD depending on environmental copper levels. A long 3'-UTR contributes to the direct regulation of COX19 mRNA by the pathway. Alternatively, COX23 mRNA contains a long 3'-UTR, but is indirectly regulated by the pathway under two conditions tested here. Analysis of the functionality of the NMD targeting features in COX23 mRNA showed that the COX23 3'-UTR is sufficient to trigger NMD. The regulation of mRNAs involved in mitochondrial copper metabolism by NMD is physiologically significant because excess copper enhances growth of NMD mutants on a non-fermentable carbon source. These findings suggest that regulation of mRNAs encoding homologous proteins by NMD can be differential depending on environmental copper levels. Furthermore, these findings suggest copper ion homeostatic mechanisms in the mitochondria occur at the mRNA level via the NMD pathway. | Mitochondrial copper homeostasis;Nonsense-mediated mRNA decay;Saccharomyces cerevisiae;mRNA;mRNA decay | pubmed |
Symptom control in chronic rhinosinusitis is an independent predictor of productivity loss. | Sinonasal symptoms cause significant productivity losses in patients with chronic rhinosinusitis (CRS). Patient-perceived CRS symptom control is a longitudinal measure of CRS symptomatology and is directly associated with general health-related quality of life (QOL) in patients with CRS. The aim of this study was to better understand the relationship between symptom control and productivity loss in CRS. Prospective cross-sectional cohort study of 200 patients with CRS. Patients categorized their CRS symptom control as "Not at all", "A little", "Somewhat", "Very", and "Completely". Lost productivity was assessed by determining the number of work and/or school days missed in the last 3 months due to CRS symptoms. Sinonasal symptom severity was measured using the 22-item Sinonasal Outcomes Test (SNOT-22). Associations were sought between lost productivity and patient-perceived CRS symptom control. To determine the association between patient-perceived longitudinal symptom control and productivity in patients with CRS. A total of 200 participants (48% male, 52% female), with a mean age of 52 years (Standard Deviation [SD]: 16) were enrolled. The mean SNOT-22 score of participants was 33.5 (SD: 22.4). Participants missed a mean of 3 days (SD: 10) of work or school due to CRS. CRS symptom control classified as "not at all" was associated with 11 days of lost productivity due to CRS on univariate analysis (β=11.16, 95% CI: 5.39-16.94, P<0.001) and 8 days of lost productivity on multivariate analysis (β=8.02, 95% CI: 1.92-14.13, P=0.011). None of the other categories of patient-reported CRS symptom control were associated with lost productivity due to CRS. Patient-perceived control of CRS symptoms, an important metric previously shown to be significantly associated with QOL in CRS patients, is independently associated with lost productivity. These results motivate longitudinal studies to determine if improvement of CRS symptom control may reduce losses in productivity. | CRS;Chronic Rhinosinusitis;Patient-perceived symptom control;Productivity;Quality of Life | pubmed |
Systems biology: old news or new stimulus for biochemistry. | In this issue of <i>Essays in Biochemistry</i>, biochemistry meets systems biology-a blind date that may hold all the promises, pitfalls and failures of a relationship where a new discipline has been sprung upon a well-established one. As the articles in this issue show, the blind date in this case has great potential to develop into a long-term relationship, where both partners share common values but can benefit from different complementary approaches. Together this partnership is well poised to address and solve some of the major challenges in modern biology. | biochemical techniques and resources;data integration;metabolic regulation;systems biology | pubmed |
Spatiotemporal analysis for detection of pre-symptomatic shape changes in neurodegenerative diseases: Initial application to the GENFI cohort. | Brain atrophy as measured from structural MR images, is one of the primary imaging biomarkers used to track neurodegenerative disease progression. In diseases such as frontotemporal dementia or Alzheimer's disease, atrophy can be observed in key brain structures years before any clinical symptoms are present. Atrophy is most commonly captured as volume change of key structures and the shape changes of these structures are typically not analysed despite being potentially more sensitive than summary volume statistics over the entire structure. In this paper we propose a spatiotemporal analysis pipeline based on Large Diffeomorphic Deformation Metric Mapping (LDDMM) to detect shape changes from volumetric MRI scans. We applied our framework to a cohort of individuals with genetic variants of frontotemporal dementia and healthy controls from the Genetic FTD Initiative (GENFI) study. Our method, take full advantage of the LDDMM framework, and relies on the creation of a population specific average spatiotemporal trajectory of a relevant brain structure of interest, the thalamus in our case. The residuals from each patient data to the average spatiotemporal trajectory are then clustered and studied to assess when presymptomatic mutation carriers differ from healthy control subjects. We found statistical differences in shape in the anterior region of the thalamus at least five years before the mutation carrier subjects develop any clinical symptoms. This region of the thalamus has been shown to be predominantly connected to the frontal lobe, consistent with the pattern of cortical atrophy seen in the disease. | Clustering;Computational anatomy;Parallel transport;Shape analysis;Spatiotemporal geodesic regression;Thalamus | pubmed |
Bioinspired, Manganese-Chelated Alginate-Polydopamine Nanomaterials for Efficient in Vivo T<sub>1</sub>-Weighted Magnetic Resonance Imaging. | Manganese-based nanomaterials are an emerging new class of magnetic resonance imaging (MRI) contrast agents (CAs) that provide impressive contrast abilities. MRI CAs that can respond to pathophysiological parameters such as pH or redox potential are also highly in demand for MRI-guided tumor diagnosis. Until now, synthesizing nanomaterials with good biocompatibility, physiochemical stability, and good contrast effects remains a challenge. This study investigated two new systems of calcium/manganese cations complexed with either alginate-polydopamine or alginate-dopamine nanogels [AlgPDA(Ca/Mn) NG or AlgDA(Ca/Mn) NG]. Under such systems, Ca cations form ionic interactions via carboxylic acids of the Alg backbone to enhance the stability of the synthetic nanogels (NGs). Likewise, complexation of Mn cations also increased the colloidal stability of the synthetic NGs. The magnetic property of the prepared CAs was confirmed with superconducting quantum interference device measurements, proving the potential paramagnetic property. Hence, the T<sub>1</sub> relaxivity measurement showed that PDA-complexed synthetic NGs reveal a strong positive contrast enhancement with r<sub>1</sub> = 12.54 mM<sup>-1</sup>·s<sup>-1</sup> in 7.0 T MRI images, whereas DA-complexed synthetic NGs showed a relatively lower T<sub>1</sub> relaxivity effect with r<sub>1</sub> = 10.13 mM<sup>-1</sup>·s<sup>-1</sup>. In addition, both the synthetic NGs exhibit negligible cytotoxicity with >92% cell viability up to 0.25 mM concentration, when incubated with the mouse macrophage (RAW 264.7) and HeLa cells, and high biocompatibility under in vivo analysis. The in vivo MRI test indicates that the synthetic NG exhibits a high signal-to-noise ratio for longer hours, which provides a longer image acquisition time for tumor and anatomical imaging. Furthermore, T<sub>1</sub>-weighted MRI results revealed that PEGylated AlgPDA(Ca/Mn) NGs significantly enhanced the signals from liver and tumor tissues. Therefore, owing to the enhanced permeability and retention effect, significantly enhanced in vitro and in vivo imagings, low cost, and one-pot synthesis method, the Mn-based biomimetic approach used in this study provides a promising and competitive alternative for noninvasive tumor detection and comprehensive anatomical diagnosis. | T1-magnetic resonance imaging (MRI);alginate;longitudinal relaxation;polydopamine;tumor diagnosis | pubmed |
Integration of Biomarkers Into a Signature Profile of Persistent Traumatic Brain Injury Involving Autoimmune Processes Following Water Hammer Injury From Repetitive Head Impacts. | To assemble an algorithm that will describe a "Signature" predictive of an individual's vulnerability to persistent traumatic brain injury (TBI). Studies of athletes and warriors who are subjected to repeated head impacts with rapid acceleration/deceleration forces are used to assist in the diagnosis and management of TBI-affected individuals. Data from multiple areas, including clinical, anatomical, magnetic resonance imaging, cognitive function, and biochemical analyses, are integrated to provide a Signature of persistent TBI. Studies to date indicate that susceptibility to TBI results from an interaction between host genetic and structural vulnerability factors and force and torque of impact on the head and torso. The host factors include molecular markers affecting immune and inflammatory responses to stress/insult as well as anatomical features such as the degree of transcortical fiber projections and vascular malformations. The host response to forceful impact includes the release of intracellular neural proteins and nucleic acids into the cerebrospinal fluid and vascular compartment as well as mobilization of cytokines and macrophages into the central nervous system with subsequent activation of microglia and inflammatory responses including autoimmune processes. Maximum impact to the base of the sulci via a "water hammer effect" is consistent with the localization of microvascular and inflammatory responses in the affected brain region. An assessment of an individuals' predisposition to persistent TBI with delayed cognitive deficits and behavioral changes requires an understanding of host vulnerability (genetic factors and brain structure) and external stressors (force and torque of impact as well as repetitive head injury and time interval between impacts). An algorithm that has utility in predicting vulnerability to TBI will include qualitative and quantitative measures of the host factors weighted against post impact markers of neural injury. Implementation of the resulting "Signature" of vulnerability at early stages of injury will help inform athletes and warriors, along with commanders and management, of the risk/benefit approaches that will markedly diminish health care costs to the nation and suffering to this population. This report attempts to define a strategy to create such an algorithm. | Autoimmune disease;Diffusion Tensor Imaging;Major Histocompatibility complex;Neuronal glial proteins;Signature of Vulnerability to TBI;Traumatic Brain Injury | pubmed |
Kojyl cinnamate esters are peroxisome proliferator-activated receptor α/γ dual agonists. | Adiponectin is an adipocytokine with insulin-sensitizing, anti-inflammatory, anti-atherosclerotic, and anti-aging properties. Compounds with the ability to promote adiponectin secretion are of interest for the development of anti-aging drugs to improve skin-aging phenotypes. In the phenotypic assay to measure adiponectin secretion during adipogenesis in human adipose tissue-derived mesenchymal stem cells (hAT-MSCs), kojyl cinnamate ester derivatives increased adiponectin secretion. A target identification study showed that the kojyl cinnamate ester derivatives competitively bound to peroxisome proliferator-activated receptor α/γ (PPARα/γ). The upregulation of adiponectin production induced by kojyl cinnamate ester derivatives was significantly correlated with PPARα and PPARγ binding activities. Kojyl cinnamate ester derivatives significantly increased the transcription of genes encoding cholesterol and fatty acid synthesizing enzymes in hAT-MSCs. Notably, the kojyl cinnamate esters upregulated the gene transcription of lipid metabolic enzymes in human epidermal keratinocytes, which are important in the integrity of skin permeability barrier. In addition, the kojyl cinnamate esters that function as PPARα/γ dual modulators inhibited ultraviolet B irradiation-induced inflammation in human epidermal keratinocytes. Therefore, kojyl cinnamate ester derivatives are a novel class of PPARα/γ dual agonists with the potential to improve skin-aging phenotypes. | Adiponectin;Human adipose tissue-derived mesenchymal stem cells;Kojyl cinnamate ester derivatives;Peroxisome proliferator-activated receptor dual modulators | pubmed |
Is functional electrical stimulation an alternative for orthotics in patients with cerebral palsy? A literature review. | Functional electrical stimulation (FES) is a well-known intervention used during walking to improve walking abilities and correct gait deviations by facilitating the proper muscle group at the appropriate timing in the gait cycle. Our aim was to study the types of surface FES currently used in a cerebral palsy (CP) population and examine the evidence of its ability to improve gait deviations, functional ability and therapeutic effects. A computerized database search was conducted from inception until 6/2016. Included were all clinical trials performing gait analysis of children with CP applying surface FES to any lower leg muscles evaluating the efficiency of the stimulation and any carry-over effect. Fifteen studies met the inclusion criteria. The most common FES stimulated the dorsi flexors muscles with a positive orthotic effect, improved dorsi flexion during the swing phase and enhanced the foot contact pattern. A smaller positive effect was found for knee extensors stimulation facilitating knee extension during the stance phase and for hip abductors stimulation improving frontal plane knee alignment. No evidence was found to support the use of plantar flexors stimulation in correcting gait deviations. There is scarce evidence of any retention effect. We encourage the clinician to evaluate the use of FES on a case to case basis. Controlled investigations with larger numbers of participants are warranted to determine the orthotic and therapeutic efficacy of FES. | Ankle foot orthoses;Cerebral palsy;Functional electrical stimulation | pubmed |
Growth and body composition in preterm newborns with bronchopulmonary dysplasia: a cohort study. | Objective To compare growth and body composition of preterm infants (gestational age <32 weeks) with and without bronchopulmonary dysplasia (BPD). Methods A prospective cohort involving three neonatal units in the public health system of the Brazilian city of Rio de Janeiro. Inclusion: newborns with gestational age <32 weeks. BPD. Anthropometric measurements were performed at birth and at 1 month of infant corrected age. Body composition was measured using an air displacement plethysmography (ADP) (PEA POD®) at 1 month of infant corrected age. Results Ninety-five newborns were eligible, of which 67 were included, 32.8% of them with BPD. Newborns with BPD presented lower gestational age at birth, greater need for resuscitation in the delivery room, received parenteral nutrition (PN) for a longer period of time, achieved lower weights during hospital stay and required more time to reach a full enteral diet. No statistically significant differences were observed in relation to anthropometric measurements and body composition at 1 month of infant corrected age between the groups with and without BPD. Conclusion This study, unlike previous ones, has shown that children who developed BPD were able to regain growth, as measured by anthropometric measures, with no change in body composition at 1 month of infant corrected age. | Body composition;bronchopulmonary dysplasia;growth;plethysmography | pubmed |
Recent progress on semiconducting polymer nanoparticles for molecular imaging and cancer phototherapy. | As a new class of organic optical nanomaterials, semiconducting polymer nanoparticles (SPNs) have the advantages of excellent optical properties, high photostability, facile surface functionalization, and are considered to possess good biocompatibility for biomedical applications. This review surveys recent progress made on the design and synthesis of SPNs for molecular imaging and cancer phototherapy. A variety of novel polymer design, chemical modification and nanoengineering strategies have been developed to precisely tune up optoelectronic properties of SPNs to enable fluorescence, chemiluminescence and photoacoustic (PA) imaging in living animals. With these imaging modalities, SPNs have been demonstrated not only to image tissues such as lymph nodes, vascular structure and tumors, but also to detect disease biomarkers such as reactive oxygen species (ROS) and protein sulfenic acid as well as physiological indexes such as pH and blood glucose concentration. The potentials of SPNs in cancer phototherapy including photodynamic and photothermal therapy are also highlighted with recent examples. Future efforts should further expand the use of SPNs in biomedical research and may even move them beyond pre-clinical studies. | Cancer therapy;Molecular imaging;Photoacoustic imaging;Phototherapy;Semiconducting polymer nanoparticles | pubmed |
Dream Recall Frequency Is Associated With Medial Prefrontal Cortex White-Matter Density. | Recent findings indicate that dream recall frequency (DRF) is associated with neurophysiological traits, and notably the regional cerebral blood flow at rest within the medial prefrontal cortex (MPFC) and the temporo-parietal junction (TPJ). To test whether, such physiological traits are rooted in anatomical specificities, we used voxel-based morphometry to compare the white matter and gray matter density in regions related to dream recall (either at the experimental or theoretical level, MPFC, TPJ, hippocampus and amygdala) between 46 high dream recallers (HR, DRF = 5.98 ± 1.25 days per week with a dream report) and 46 low dream recallers (LR, DRF = 0.34 ± 0.29). We found an increased medial prefrontal cortex white-matter density in HR compared to LR but no other significant difference between the two groups. These results are consistent with previous studies showing that lesions within the white matter of medial prefrontal cortex are associated with a partial or total cessation of dream reporting and suggest an implication of this region in dream recall or, more likely, in dream production. | DMN;MRI;amygdala;dream recall;dreaming;hippocampus;sleep;voxel-based morphometry | pubmed |
Effect of Nano-SiO<sub>2</sub> on Expression and Aberrant Methylation of Imprinted Genes in Lung and Testis. | Nanotechnology has been developing rapidly and is now used in many cutting-edge medical therapeutics. However, there is increasing concern that exposure to nanoparticles (NPs) may induce different systemic diseases as epigenetic mechanisms are associated with more and more disease. The role of NP epigenomic modification is important to disease etiology. Our study aimed to determine the epigenetic mechanisms of damage in lung and testis cells by exposing cells to SiO<sub>2</sub> NPs. We used male C57BL/6 mice to characterize the damaging effect of SiO<sub>2</sub> NPs on lung and testis cells as well as the resulting methylation state at the imprinted Dlk1/Dio3 domain region. The A549 cells exposed to SiO<sub>2</sub> NPs had cell apoptosis, and male mice exposed to SiO<sub>2</sub> NPs had altered lung and testis tissues. The genes in the imprinted domains Dlk1/Dio3 region changed in both tissues; Dlk1, Rtl1, and Dio3 are upregulated in testis while Dlk1 and Dio3 are also upregulated in lung tissues. Bisulfite sequencing PCR of male adult lung and testis were mostly hypomethylated, with a few hypermethylated CpGs. These findings indicate that nanoparticles play an important role in DNA methylation of imprinted genes. | Lung;Methylation;Nanoparticle;Testis | pubmed |
TESS DISCOVERY OF A TRANSITING SUPER-EARTH IN THE <i>π</i> MENSAE SYSTEM. | We report the detection of a transiting planet around <i>π</i> Men (HD 39091), using data from the <i>Transiting Exoplanet Survey Satellite</i> (<i>TESS</i>). The solar-type host star is unusually bright (<i>V</i> = 5.7) and was already known to host a Jovian planet on a highly eccentric, 5.7-year orbit. The newly discovered planet has a size of 2.04 ± 0.05 <i>R</i><sub>⊕</sub> and an orbital period of 6.27 days. Radial-velocity data from the HARPS and AAT/UCLES archives also displays a 6.27-day periodicity, confirming the existence of the planet and leading to a mass determination of 4.82±0.85 <i>M</i><sub>⊕</sub>. The star's proximity and brightness will facilitate further investigations, such as atmospheric spectroscopy, asteroseismology, the Rossiter-McLaughlin effect, astrometry, and direct imaging. | planetary systems;planets and satellites: detection;stars: individual (HD 39091, TIC 261136679) | pubmed |
Preparation and characterization of a novel polyethyleneimine cation-modified persimmon tannin bioadsorbent for anionic dye adsorption. | A novel and recyclable bioadsorbent (PTP) has been prepared by the cationization of persimmon tannin (PT) using polyethyleneimine (PEI) for application in the removal of the anionic dye methyl orange (MO) from aqueous solution. The physicochemical properties of the prepared PTP were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, Zeta potential measurements, Brunauer-Emmett-Teller and thermogravimetric analysis. Systematic batch adsorption experiments were carried out with pH, bioadsorbent dosage, initial MO concentration and contact time. Kinetic regression analysis indicated that the adsorption processes followed the pseudo-second order model. The equilibrium isotherm was in good fit with the Freundlich model with a maximum adsorption capacity of 225.74 mg/g. Thermodynamics data revealed that the adsorption of MO onto PTP was feasible, spontaneous and endothermic. A possible biosorption mechanism was presented where electrostatic interactions, hydrogen bonding, and π-π interactions dominated the adsorption of MO onto PTP. Moreover, the regeneration of the PTP was easily achieved and MO removal efficiency remained high (81.47%) after six cycles. The actual sewage treatment simulation was evaluated and the PTP had a good preference to adsorption MO. All these results indicated that PTP could be considered a high performance and promising candidate for the effective removal of anionic dyes from aqueous solutions. | Bioadsorbent;Cationization;Methyl orange;Persimmon tannin;Polyethyleneimine | pubmed |
Bone health and evaluation of bone mineral density in patients with premature ovarian insufficiency. | Oestrogens exert an influence on skeletal homeostasis during growth and adulthood. Regulation of osteoclasts and osteoblasts generation and apoptosis and prolongation of the lifespan of osteocytes are some of their actions on bone metabolism. Premature ovarian insufficiency (POI) and associated loss of oestrogen action on osteoclasts leads to trabecular perforation and loss of connectivity. Lack of oestrogens acting on osteoblast progenitors also causes a decrease in critical bone mass. Postmenopausal hypoestrogenism is associated with an increase in the number of lymphocyte B-cells expressing nuclear factor κB ligand (RANKL) in the bone marrow and elevated expression of RANKL by B-cells. Increased concentration of RANKL stimulates activation of osteoclasts and leads to oestrogen deficiency-associated bone loss. It has been proven that women with POI have decreased bone mineral density (BMD) measured in lumbar spine and femoral neck. The loss of bone mass associated with oestrogen deficiency is greater in trabecular than in cortical bone, thus women with POI have a significant decrease in BMD, particularly in the lumbar spine vertebrae. Smoking cessation, weight-bearing, and muscle-strengthening exercises on most days of the week, avoidance of excessive alcohol intake, and adequate supplementation of calcium and vitamin D are the main lifestyle rules necessary to avoid decline in BMD. The most important component of decreased BMD treatment in POI patients is systemic hormonal replacement therapy (HRT). HRT should provide hormonal balance and should mimic normal ovarian function as much as possible. | bone mineral density;early menopause;hormonal replacement therapy;osteopaenia;osteoporosis;premature ovarian insufficiency | pubmed |
Skeletal Fragility in Type 2 Diabetes Mellitus. | Type 2 diabetes (T2D) is associated with an increased risk of fracture, which has been reported in several epidemiological studies. However, bone mineral density in T2D is increased and underestimates the fracture risk. Common risk factors for fracture do not fully explain the increased fracture risk observed in patients with T2D. We propose that the pathogenesis of increased fracture risk in T2D is due to low bone turnover caused by osteocyte dysfunction resulting in bone microcracks and fractures. Increased levels of sclerostin may mediate the low bone turnover and may be a novel marker of increased fracture risk, although further research is needed. An impaired incretin response in T2D may also affect bone turnover. Accumulation of advanced glycosylation endproducts may also impair bone strength. Concerning antidiabetic medication, the glitazones are detrimental to bone health and associated with increased fracture risk, and the sulphonylureas may increase fracture risk by causing hypoglycemia. So far, the results on the effect of other antidiabetics are ambiguous. No specific guideline for the management of bone disease in T2D is available and current evidence on the effects of antiosteoporotic medication in T2D is sparse. The aim of this review is to collate current evidence of the pathogenesis, detection and treatment of diabetic bone disease. | Antidiabetics;Bone remodeling;Diabetes mellitus, type 2;Fracture;Sclerostin | pubmed |
XPC deficiency leads to centrosome amplification by inhibiting BRCA1 expression upon cisplatin-mediated DNA damage in human bladder cancer. | Xeroderma pigmentosum group C (XPC) is a well-known DNA damage recognition protein. Defects in XPC lead to carcinogenesis and progression of many human cancers. In the current study, we defined a novel, important role of XPC in preventing centrosome amplification during cisplatin-mediated DNA damage response. From experiments with human bladder cancer tissue, urothelial tissue from Xpc knockout mice and XPC-silenced cell lines, we found that attenuated XPC expression was associated with increased centrosome amplification in human bladder cancer. A significant increase in centrosome amplification was observed in XPC-silenced cells upon cisplatin treatment. XPC deficiency leads to reduced BRCA1 expression via upregulating its transcriptional repressor, Pit-1. The BRCA1 downregulation results in more DNA double strand breaks accumulation and persistent activation of the ATM-Chk1/Chk2 signaling, resulting in a prolonged G2/M arrest during which centrosome can over-duplicate and lead to centrosome amplification. XPC complementation in silenced cells could reduce Pit-1 expression, increase BRCA1 expression and recover the status of centrosome amplification. Our study reveals a new function for XPC in preventing chromosomal instability, providing new information on cancer chemotherapy and potential clinical significance for cancer management. | Bladder cancer;Centrosome amplification;DNA damage response;XPC | pubmed |
Chemical encoding of risk perception and predator detection among estuarine invertebrates. | An effective strategy for prey to survive in habitats rich in predators is to avoid being noticed. Thus, prey are under selection pressure to recognize predators and adjust their behavior, which can impact numerous community-wide interactions. Many animals in murky and turbulent aquatic environments rely on waterborne chemical cues. Previous research showed that the mud crab, <i>Panopeus herbstii</i>, recognizes the predatory blue crab, <i>Callinectus sapidus</i>, via a cue in blue crab urine. This cue is strongest if blue crabs recently preyed upon mud crabs. Subsequently, mud crabs suppress their foraging activity, reducing predation by blue crabs. Using NMR spectroscopy- and mass spectrometry-based metabolomics, chemical variation in urine from blue crabs fed different diets was related to prey behavior. We identified the urinary metabolites trigonelline and homarine as components of the cue that mud crabs use to detect blue crabs, with concentrations of each metabolite dependent on the blue crab's diet. At concentrations found naturally in blue crab urine, trigonelline and homarine, alone as well as in a mixture, alerted mud crabs to the presence of blue crabs, leading to decreased foraging by mud crabs. Risk perception by waterborne cues has been widely observed by ecologists, but the molecular nature of these cues has not been previously identified. Metabolomics provides an opportunity to study waterborne cues where other approaches have historically failed, advancing our understanding of the chemical nature of a wide range of ecological interactions. | blue crab;chemical ecology;metabolomics;nonconsumptive effects;predation | pubmed |
Nuclear inverse polarity papillary lesions lacking myoepithelial cells: A report of two cases. | Here, cases of a 68- (Case 1) and a 44-year-old (Case 2) female are presented. They had an abnormality in the breast, and came to our hospital for further examination and treatment. Radiologically, malignancy could not completely excluded so breast excision was performed. Histologically, both cases revealed papillary neoplastic lesions lined by fibrovascular core and nuclear inverse polarity without atypia. Loss of myoepithelial cells was observed by HE, p63, and calponin. Previous report indicate CK5/6, ER, p63 and MUC3 are important for distinguishing between papillary lesions according to the differential index (based on Allred score) of ([ER total score] + [MUC3 total score])/([CK5/6 total score] + [p63 total score] + 1). Based on this analysis, our two cases had benign lesions. However, based on immunopositivity for cell-cycle marker Cyclin-D1, Case 1 was negative, and Case 2 was about 70% positive. Additionally, the Ki-67 index was <1% in both cases, and no evidence of disease was observed after a maximum 62 months of follow-up in both cases, despite lack of additional treatment. Thus, we propose that lack of myoepithelial cells in papillary lesions do not necessarily indicate malignancy and are thought to be, at the most, uncertain malignant potential. | calponin;lack of myoepithelial cells;non-apocrine papillary lesion;nuclear inverse polarity;p63 | pubmed |
A simple quantitative chiral analysis of amino acid esters by fluorine-19 nuclear magnetic resonance using the modified James-Bull method. | A simple chiral analysis of amino acid esters by fluorine-19 nuclear magnetic resonance (<sup>19</sup> F NMR) through the modified James-Bull method is described. Thus, amino acid ester acid salt was treated with 5-fluoro-2-formylphenylboronic acid and (S)-BINOL in the presence of triethylamine (TEA) and MS4A for 10 minutes. The reaction mixture was analysed by <sup>19</sup> F NMR directly to afford good quantifications. | 19F NMR;James-bull assembly;amino acids;quantification | pubmed |
Vegetarian-style dietary pattern during adolescence has long-term positive impact on bone from adolescence to young adulthood: a longitudinal study. | The amount of bone accrued during adolescence is an important determinant of later osteoporosis risk. Little is known about the influence of dietary patterns (DPs) on the bone during adolescence and their potential long-term implications into adulthood. We examined the role of adolescent DPs on adolescent and young adult bone and change in DPs from adolescence to young adulthood. We recruited participants from the Saskatchewan Pediatric Bone Mineral Accrual Study (1991-2011). Data from 125 participants (53 females) for adolescent analysis (age 12.7 ± 2 years) and 115 participants (51 females) for adult analysis (age 28.2 ± 3 years) were included. Bone mineral content (BMC) and areal bone mineral density (aBMD) of total body (TB), femoral neck (FN) and lumbar spine (LS) were measured using dual-energy X-ray absorptiometry. Adolescent dietary intake data from multiple 24-h recalls were summarized into 25 food group intakes and were used in the principal component analysis to derive DPs during adolescence. Associations between adolescent DPs and adolescent or adult BMC/BMD were analyzed using multiple linear regression and multivariate analysis of covariance while adjusting for sex, age, the age of peak height velocity, height, weight, physical activity and total energy intake. Generalized estimating equations were used for tracking DPs. We derived five DPs including "Vegetarian-style", "Western-like", "High-fat, high-protein", "Mixed" and "Snack" DPs. The "Vegetarian-style" DP was a positive independent predictor of adolescent TBBMC, and adult TBBMC, TBaBMD (P < 0.05). Mean adolescent TBaBMD and young adult TBBMC, TBaBMD, FNBMC and FNaBMD were 5%, 8.5%, 6%, 10.6% and 9% higher, respectively, in third quartile of "Vegetarian-style" DP compared to first quartile (P < 0.05). We found a moderate tracking (0.47-0.63, P < 0.001) in DP scores at individual levels from adolescence to adulthood. There were an upward trend in adherence to "Vegetarian-style" DP and an downward trend in adherence to "High-fat, high-protein" DP from adolescence to young adulthood (P < 0.01). A "Vegetarian-style" DP rich in dark green vegetables, eggs, non-refined grains, 100% fruit juice, legumes/nuts/seeds, added fats, fruits and low-fat milk during adolescence is positively associated with bone health. | Adolescence;Bone mineral content;Bone mineral density;Dietary patterns;Vegetarian;Young adulthood | pubmed |
Thoracoscopic esophagectomy with total meso-esophageal excision reduces regional lymph node recurrence. | We investigated the operative outcomes of thoracoscopic esophagectomy (TE) in the prone position, using the concept of total meso-esophageal excision for esophageal cancer. The medical records of 140 consecutive patients with esophageal cancer who underwent radical esophagectomy by TE were reviewed retrospectively, and operative outcomes were compared between patients treated before (non-meso-esophagus; non-ME group) and after (ME group) the introduction of total meso-esophageal excision (ME). There were no significant differences between the groups in postoperative morbidity (non-ME group vs. ME group, 28.3% vs. 41.4%, p = 0.119), 30-day mortality (non-ME group vs. ME group, 0% vs. 1.1%; p = 0.433), and in-hospital mortality (non-ME group vs. ME group, 1.9% vs. 0%, p = 0.199). Although overall survival and relapse-free survival did not differ significantly between the groups, the overall recurrence rate was significantly lower in the ME group than the non-ME group (non-ME group vs. ME group, 43.4% vs. 23%, p = 0.011). In particular, the rate of regional lymph node recurrence in the mediastinum was lower in the ME group (non-ME group vs. ME group, 11.3% vs. 2.3%; p = 0.026). Our results suggest that the ME procedure might be one of the procedures that reduce regional lymph node recurrence in the mediastinum without any deterioration in short-term outcomes. | Esophageal cancer;Meso-esophagus;Minimally invasive esophagectomy;Preceding anterior approach;Thoracoscopic esophagectomy | pubmed |
Calcium-sensing receptor in nutrient sensing: an insight into the modulation of intestinal homoeostasis. | The animal gut effectively prevents the entry of hazardous substances and microbes while permitting the transfer of nutrients, such as water, electrolytes, vitamins, proteins, lipids, carbohydrates, minerals and microbial metabolites, which are intimately associated with intestinal homoeostasis. The gut maintains biological functions through its nutrient-sensing receptors, including the Ca-sensing receptor (CaSR), which activates a variety of signalling pathways, depending on cellular context. CaSR coordinates food digestion and nutrient absorption, promotes cell proliferation and differentiation, regulates energy metabolism and immune response, stimulates hormone secretion, mitigates secretory diarrhoea and enhances intestinal barrier function. Thus, CaSR is crucial to the maintenance of gut homoeostasis and protection of intestinal health. In this review, we focused on the emerging roles of CaSR in the modulation of intestinal homoeostasis including related underlying mechanisms. By elucidating the relationship between CaSR and animal gut homoeostasis, effective and inexpensive methods for treating intestinal health imbalance through nutritional manipulation can be developed. This article is expected to provide experimental data of the effects of CaSR on animal or human health. | CCK cholecystokinin; CaSR Ca-sensing receptor; ECD extracellular domain; IP3 inositol triphosphate; NHE sodium–hydrogen exchanger; PDE phosphodiesterase; PLC phospholipase C; Ror2 receptor tyrosine kinase like orphan receptor 2; TAB TAK1-binding protein; TNFR TNF-α receptor;Calcium-sensing receptor;Inflammatory responses;Intestinal barrier;Intestinal homoeostasis;Secretory diarrhoea | pubmed |
Outcomes and emergency medical services resource utilization among patients with syncope arriving to the emergency department by ambulance. | Syncope accounts for 1% of emergency department (ED) visits, yet few experience a serious adverse event (SAE). Two-thirds of syncope patients are transported to the ED by ambulance, placing considerable burden on emergency medical services (EMS), and many of these transports may be unnecessary. We estimated the proportion of syncope patients who fell into a low-risk category based on an ED diagnosis of vasovagal syncope and the absence of EMS intervention, hospitalization, or SAE. We conducted a multicentre prospective cohort study enrolling adult syncope patients transported to the ED by ambulance over 13 months. We collected demographics and EMS interventions, and followed patients for 30 days to identify all SAE, including death, dysrhythmia, myocardial infarction, aortic dissection, pulmonary embolism, subarachnoid hemorrhage, significant hemorrhage, and related procedural interventions. Of 990 (67.2%) patients transported to the ED by ambulance, 121 had EMS interventions, 137 suffered 30-day SAE, 393 (39.7%; 95%CI 36.6, 42.8) were deemed low risk, 41 patients with vasovagal syncope were lost to follow-up, and 298 patients were diagnosed with non-vasovagal syncope. During transport, 121 (12.2%; 95%CI 10.2, 14.3) patients underwent some EMS intervention, and 137 (14.6%; 95%CI 12.4, 16.9) suffered SAEs within 30 days. About 40% of patients transported to the ED by ambulance are at low risk and may not benefit from paramedic care or transport to a hospital. A robust clinical decision tool would help identify patients safe for treat-and-release, diversion to alternative care, or rapid offload into low-acuity ED areas, potentially reducing EMS workload and cost. | clinical decision aid;emergency department;emergency medical services;prehospital;resource utilization;severe adverse events;syncope | pubmed |
Planning and implementation of a countrywide campaign to deliver over 16 million long-lasting insecticidal nets in Mozambique. | In 2016/2017, Mozambique conducted a countrywide long-lasting insecticidal nets (LLINs) universal coverage campaign (UCC). This paper aims to describe the planning and implementation process of the campaign in Mozambique. A cross-sectional and descriptive design was used for reporting the planning and implementation process of the UCC. The UCC used a collaborative approach, involving institutional and non-institutional actors, namely: National Malaria Control Programme (NMCP), provincial and district health authorities, community members and civil society partners. A new household registration strategy based on coupons, stickers, and one LLIN per two persons as allocation criterion was implemented. The campaign was implemented in phases, allowing for continuous improvement of implementation quality by applying lessons learnt from each phase. A total of 7,049,894 households were registered corresponding to a total of 31,972,626 registered persons. A total of 16,557,818 LLINs were distributed between November 2016 and December 2017, corresponding to 97% of LLINs needs based on household registration, and covering 95% of the registered households (6,708,585 households), resulting in an estimated 85% of the total Mozambican population with LLIN access. The collaborative planning process and strong coordination of campaign actors allowed Mozambique's NMCP and partners to successfully carry out the first countrywide LLINs UCC in the country. The increased access to LLINs in households will likely result in increased LLIN use and a reduction of the malaria burden in the country, therefore contributing to the achievement of the 2016-2030 Global Technical Strategy for Malaria goals. | Long-lasting insecticidal nets;Mozambique;Planning and implementation;Universal coverage campaign | pubmed |
Beef quality labels: A combination of sensory acceptance test, stated willingness to pay, and choice-based conjoint analysis. | Consumer perspectives of beef quality are complex, leading to a market that is increasingly differentiating. Thus, ongoing monitoring and assessment of changes in consumer perspectives is essential to identify changing market conditions. Often only credence and search characteristics are evaluated in consumer studies; therefore the object of the present study is to examine consumer preferences and perceptions towards beef steaks, also including experience characteristics, using a mixed methods approach. For this reason, 55 consumers participated in an experiment in Germany, including a sensory acceptance test, stated willingness to pay, and choice-based conjoint analysis (CBCA). Different quality characteristics were included, but a focus on the quality labels of 'dry aged beef', 'Block House beef', and 'Angus beef' was predominant throughout the experiment with the results showing that quality labels significantly increased overall liking as well as the stated willingness to pay. Quality labels were also the one of the most important characteristics in the conjoint analysis, after origin and price. The results of all applied methods are comparable for the characteristic quality label. The combination of sensory acceptance test and CBCA were additionally able to evaluate all three kinds of beef quality characteristics, which could not be evaluated together only using a single method. This suggests that a mixture of methods should be used to gain better knowledge on the true behavior of beef consumers. Experience and credence characteristics, including beef quality labels, present opportunities for future research as well as the potential for determining product and market differentiation. | Angus beef;Beef origin;Consumer quality preferences and perception;Mixed methods approach;Top-down effect | pubmed |
Structure and evolution of double minutes in diagnosis and relapse brain tumors. | Double minute chromosomes are extrachromosomal circular DNA fragments frequently found in brain tumors. To understand their evolution, we characterized the double minutes in paired diagnosis and relapse tumors from a pediatric high-grade glioma and four adult glioblastoma patients. We determined the full structures of the major double minutes using a novel approach combining multiple types of supporting genomic evidence. Among the double minutes identified in the pediatric patient, only one carrying EGFR was maintained at high abundance in both samples, whereas two others were present in only trace amounts at diagnosis but abundant at relapse, and the rest were found either in the relapse sample only or in the diagnosis sample only. For the EGFR-carrying double minutes, we found a secondary somatic deletion in all copies at relapse, after erlotinib treatment. However, the somatic mutation was present at very low frequency at diagnosis, suggesting potential resistance to the EGFR inhibitor. This mutation caused an in-frame RNA transcript to skip exon 16, a novel transcript isoform absent in EST database, as well as about 700 RNA-seq of normal brains that we reviewed. We observed similar patterns involving longitudinal copy number shift of double minutes in another four pairs (diagnosis/relapse) of adult glioblastoma. Overall, in three of five paired tumor samples, we found that although the same oncogenes were amplified at diagnosis and relapse, they were amplified on different double minutes. Our results suggest that double minutes readily evolve, increasing tumor heterogeneity rapidly. Understanding patterns of double minute evolution can shed light on future therapeutic solutions to brain tumors carrying such variants. | Clonal evolution;Copy number alteration;Double minutes;Structural variation;Tumor heterogeneity | pubmed |
The national burden of influenza-associated severe acute respiratory illness hospitalization in Rwanda, 2012-2014. | Estimates of influenza-associated hospitalization are severely limited in low- and middle-income countries, especially in Africa. To estimate the national number of influenza-associated severe acute respiratory illness (SARI) hospitalization in Rwanda. We multiplied the influenza virus detection rate from influenza surveillance conducted at 6 sentinel hospitals by the national number of respiratory hospitalization obtained from passive surveillance after adjusting for underreporting and reclassification of any respiratory hospitalizations as SARI during 2012-2014. The population at risk was obtained from projections of the 2012 census. Bootstrapping was used for the calculation of confidence intervals (CI) to account for the uncertainty associated with all levels of adjustment. Rates were expressed per 100 000 population. A sensitivity analysis using a different estimation approach was also conducted. SARI cases accounted for 70.6% (9759/13 813) of respiratory admissions at selected hospitals: 77.2% (6783/8786) and 59.2% (2976/5028) among individuals aged <5 and ≥5 years, respectively. Overall, among SARI cases tested, the influenza virus detection rate was 6.3% (190/3022): 5.7% (127/2220) and 7.8% (63/802) among individuals aged <5 and ≥5 years, respectively. The estimated mean annual national number of influenza-associated SARI hospitalizations was 3663 (95% CI: 2930-4395-rate: 34.7; 95% CI: 25.4-47.7): 2637 (95% CI: 2110-3164-rate: 168.7; 95% CI: 135.0-202.4) among children aged <5 years and 1026 (95% CI: 821-1231-rate: 11.3; 95% CI: 9.0-13.6) among individuals aged ≥5 years. The estimates obtained from both approaches were not statistically different (overlapping CIs). The burden of influenza-associated SARI hospitalizations was substantial and was highest among children aged <5 years. | Rwanda;burden;hospitalization;influenza;severe acute respiratory illness | pubmed |
Report of Increasing Overdose Deaths that include Acetyl Fentanyl in Multiple Counties of the Southwestern Region of the Commonwealth of Pennsylvania in 2015-2016. | Acetyl fentanyl is a Schedule I controlled synthetic opioid that is becoming an increasingly detected "designer drug." Routine drug screening procedures in local forensic toxicology laboratories identified a total of 41 overdose deaths associated with acetyl fentanyl within multiple counties of the southwestern region of the state of Pennsylvania. The range, median, mean, and standard deviation of blood acetyl fentanyl concentrations for these 41 cases were 0.13-2100 ng/mL, 11 ng/mL, 169.3 ng/mL, and 405.3 ng/mL, respectively. Thirty-six individuals (88%) had a confirmed history of substance abuse, and all but one case (96%) were ruled multiple drug toxicities. This report characterizes this localized trend of overdose deaths associated with acetyl fentanyl and provides further evidence supporting an alarmingly concentrated opiate and opioid epidemic of both traditional and novel drugs within this region of the United States. | acetyl fentanyl;fentanyl;forensic science;forensic toxicology;overdose;postmortem;synthetic opioids | pubmed |
Longitudinal changes over thirty-six months in postural control dynamics and cognitive function in people with Parkinson's disease. | Postural instability is a common motor feature in people with Parkinson's disease (PD) together with non-motor features such as cognitive dysfunction. Management of postural instability is challenging as it is often resistant to dopaminergic therapy. Greater knowledge of postural control is essential to understand postural instability in PD. This study aimed to answer how postural control differs in people with PD compared to healthy older adults (HOA). Additionally, postural control changes over a 36 month period and its relationship to cognitive impairment and motor scores were investigated. The study group consisted of 50 people diagnosed with PD and 59 HOAs, recruited as part of an incident cohort study (ICICLE-GAIT). Participants stood still for 2 min, eyes open and arms by their side. A single tri-axial accelerometer (Axivity AX3, York, UK) on the lower back recorded acceleration. Measurements were taken at 18, 36 and 54 months after recruitment. Sample entropy (SampEn), which measures signal predictability, was determined for the accelerometry data. Cognitive tests included the Montreal Cognitive Assessment and the Unified Parkinson's Disease Rating Scale (UPDRS III) quantified motor function. Linear mixed models, regression analysis and correlation analysis were applied to the data. indicated that SampEn was greater for the PD group at all three time-points and along all three axes. However, there was no increase of SampEn with disease progression. Higher SampEn values were associated with greater cognitive impairment and lower UPDRS III, although correlations were weak. There was a difference between axial directions and cognitive and motor scores. People with PD exhibit decreased regularity of trunk dynamics when standing compared to HOAs. Nonlinear accelerometer metrics along all three axes are therefore a potential biomarker of PD. The relationship between trunk dynamics and cognitive function indicates common neural pathways. | Accelerometer;Cognition;Motor function;Nonlinear;Posture;Sample entropy | pubmed |
Biology-oriented drug synthesis (BIODS), in vitro urease inhibitory activity, and in silico study of S-naproxen derivatives. | Current study is based on the biology-oriented drug synthesis (BIODS) of S-naproxen (NSAID) derivatives and the evaluation of their urease inhibitory potential. In this regard, a variety of S-naproxen derivatives 2-39 including hydrazide 1, Schiff bases 2-21, aroyl substituted hydrazides 22-24, sulfohydrazides 25-34, 2-mercapto oxadiazole 35, phenacyl substituted 2-mercapto oxadiazoles 36-39 were synthesized under the umbrella of BIODS by simple chemical transformation of its pharmacophoric carboxylic group. Compounds 1-39 were evaluated for in vitro urease inhibitory activity and most of them showed good to moderate inhibitory potential in the range of IC<sub>50</sub> = 14.01 ± 0.23-76.43 ± 0.8 µM as compared to standard acetohydroxamic acid (IC<sub>50</sub> = 27.0 ± 0.5 µM). Limited structure-activity relationship (SAR) was established in order to rationalize the participation of varying groups (R) in the inhibitory potential of compounds. Molecular docking study on all active compounds was also carried out to decipher the interactions detail of the ligand with the receptors of active site of enzyme. | Biology-oriented drug synthesis (BIODS);In silico;Non-steroidal antiinflammatory drug (NSAID);S-naproxen;Ulcer;Urease inhibition | pubmed |
An Overview of the Tissue Engineering Market in the United States from 2011 to 2018. | This report seeks to provide an update of the current landscape of the tissue engineering market in the United States from an unbiased point of view by analyzing the financial reports provided by tissue engineering companies, as well as data from publicly available clinical trials with relevant tissue engineering applications. | company;industry;market;regenerative medicine;tissue engineering | pubmed |
Competing for water: A new approach to understand disintegrant performance. | The understanding of tablet disintegration is still incomplete as not all involved factors and processes are known or accounted for. E.g., the negative influence of soluble fillers, on disintegration is usually attributed to increased viscosity due to dissolved filler. When the most common filler, lactose, dissolves, the viscosity increases only slightly. The impact of binders has hardly been studied systematically. In this study, water uptake and force development as well as water sorption experiments were performed of tablets containing either a soluble or an insoluble filler, one of four different binders, and one of four different disintegrants. For both fillers, one disintegrant performed distinctly worse than the others. For the insoluble filler, dibasic calcium phosphate (DCP), sodium starch glycolate resulted in the longest disintegration, for the soluble filler, lactose, croscarmellose sodium performed worst. Based on the experimental results, the authors introduce the competition-for-water hypothesis, which takes into consideration the amount of freely available water molecules and hydration kinetics of excipients. Soluble fillers bind a large number of water molecules in hydrate shells and prevent, therefore, proper disintegrant action. Previously inconsistent observations can be approached with this hypothesis and a better understanding of the underlying processes and explanations is possible. | Binders;Disintegrants;Force development;Tablet disintegration;Water uptake | pubmed |
Needle in a haystack: lost in transition. | A lost needle during minimally invasive surgery is a cause of undue anxiety to the entire surgical team and also causes prolongation of surgical time. There is no literature reporting follow-up of any patient with needle left behind as they are considered as a 'never event' during a surgical procedure. Preventing such events needs vigilance on part of the surgeon and assistant. Here, we report a case of lost needle during performance of a robot-assisted nephron sparing surgery. The robot needed to be de-docked and converted to laparoscopy. After a thorough search, the needle was found to be lodged at an unusual place. A brief review of available literature is also provided alongside. | C-arm;Lost;Needle;Port valve;Robotic | pubmed |
Drug Delivery Systems from Self-Assembly of Dendron-Polymer Conjugates <sup>†</sup>. | This review highlights the utilization of dendron-polymer conjugates as building blocks for the fabrication of nanosized drug delivery vehicles. The examples given provide an overview of the evolution of these delivery platforms, from simple micellar containers to smart stimuli- responsive drug delivery systems through their design at the macromolecular level. Variations in chemical composition and connectivity of the dendritic and polymeric segments provide a variety of self-assembled micellar nanostructures that embody desirable attributes of viable drug delivery systems. | conjugates;dendrimer;dendron;drug delivery;nanotherapeutics;polymers | pubmed |
Architectural Designs and Synthetic Strategies of Advanced Nanocatalysts. | Advanced nanocatalysts with high compositional and structural tailorability have emerged as a new class of heterogeneous catalysts exhibiting many new technical merits over their conventional counterparts. Generally, preparation of such catalysts involves the integration of catalyst components with compositional, size, and shape controls into a larger material system in order to bring along collective and synergetic effects of individual components. Herein, a brief review of architectural designs and synthetic strategies for making these nanocatalysts is presented. Due to length constraints, only four major types of them are highlighted together with some general rules of design and synthesis. Finally, a critical outline of future perspective in this field is proposed. | composite catalysts;nanocatalysts;nanoreactors;synthesis;tailorable structures | pubmed |
Exertional dyspnea after myocardial infarction: thinking beyond the diagnosis of heart failure. | We herein present an unusual case of a pseudoaneurysm of the left ventricular myocardium, which is a rare and fatal complication of myocardial infarction. A 64-year-old man with a history of bipolar disorder and arterial hypertension was hospitalized for delayed presentation ST-elevation myocardial infarction. He was admitted to our hospital 24 hours after symptom onset. Diagnostic coronary angiography revealed 95% stenosis at the distal third of the right coronary artery, and he underwent a primary percutaneous coronary intervention to the culprit lesion. Despite administration of a diuretic and optimization of other pharmaceutical treatment, his heart failure deteriorated. Electrocardiography showed a sinus rhythm with Q-wave formation in the inferior wall leads (II, III, aVF), T-wave inversion in the same leads, and borderline QT prolongation (QTc of 490 ms). No ST elevation suggestive of left ventricular aneurysm formation was noticed. Forty days later, cardiac ultrasound revealed a dyskinetic cavity (pseudoaneurysm) in continuity with the posterior-inferior wall of the myocardium, resulting in severe mitral valve regurgitation. Unfortunately, the patient died while awaiting surgical treatment. Although most patients with left ventricular pseudoaneurysm have a relatively benign outcome, those with symptoms of heart failure must be urgently diagnosed and treated. | Pseudoaneurysm;dyskinesis;heart failure;left ventricle;myocardial infarction;percutaneous coronary intervention | pubmed |
Validation of Patient-Reported Outcomes Measurement Information System (PROMIS) computerized adaptive tests in cervical spine surgery. | OBJECTIVE The Patient-Reported Outcomes Measurement Information System (PROMIS), which is funded by the National Institutes of Health, is a set of adaptive, responsive assessment tools that measures patient-reported health status. PROMIS measures have not been validated for surgical patients with cervical spine disorders. The objective of this project is to evaluate the validity (e.g., convergent validity, known-groups validity, responsiveness to change) of PROMIS computer adaptive tests (CATs) for pain behavior, pain interference, and physical function in patients undergoing cervical spine surgery. METHODS The legacy outcome measures Neck Disability Index (NDI) and SF-12 were used as comparisons with PROMIS measures. PROMIS CATs, NDI-10, and SF-12 measures were administered prospectively to 59 consecutive tertiary hospital patients who were treated surgically for degenerative cervical spine disorders. A subscore of NDI-5 was calculated from NDI-10 by eliminating the lifting, headaches, pain intensity, reading, and driving sections and multiplying the final score by 4. Assessments were administered preoperatively (baseline) and postoperatively at 6 weeks and 3 months. Patients presenting for revision surgery, tumor, infection, or trauma were excluded. Participants completed the measures in Assessment Center, an online data collection tool accessed by using a secure login and password on a tablet computer. Subgroup analysis was also performed based on a primary diagnosis of either cervical radiculopathy or cervical myelopathy. RESULTS Convergent validity for PROMIS CATs was supported with multiple statistically significant correlations with the existing legacy measures, NDI and SF-12, at baseline. Furthermore, PROMIS CATs demonstrated known-group validity and identified clinically significant improvements in all measures after surgical intervention. In the cervical radiculopathy and myelopathic cohorts, the PROMIS measures demonstrated similar responsiveness to the SF-12 and NDI scores in the patients who self-identified as having postoperative clinical improvement. PROMIS CATs required a mean total of 3.2 minutes for PROMIS pain behavior (mean ± SD 0.9 ± 0.5 minutes), pain interference (1.2 ± 1.9 minutes), and physical function (1.1 ± 1.4 minutes) and compared favorably with 3.4 minutes for NDI and 4.1 minutes for SF-12. CONCLUSIONS This study verifies that PROMIS CATs demonstrate convergent and known-groups validity and comparable responsiveness to change as existing legacy measures. The PROMIS measures required less time for completion than legacy measures. The validity and efficiency of the PROMIS measures in surgical patients with cervical spine disorders suggest an improvement over legacy measures and an opportunity for incorporation into clinical practice. | CAT = computer adaptive test;MCID = minimally important clinical difference;MCS = mental component score;NDI = Neck Disability Index;ODI = Oswestry Disability Index;PB = pain behavior;PCS = physical component score;PF = physical function;PI = pain interference;PRO = patient-reported outcome;PROMIS;PROMIS = Patient-Reported Outcomes Measurement Information System;cervical spine;patient-reported outcomes | pubmed |
Prevention from radiation damage by natural products. | Radiotherapy is a mainstay of cancer treatment since decades. Ionizing radiation (IR) is used for destruction of cancer cells and shrinkage of tumors. However, the increase of radioresistance in cancer cells and radiation toxicity to normal tissues are severe concerns. The exposure to radiation generates intracellular reactive oxygen species (ROS), which leads to DNA damage by lipid peroxidation, removal of thiol groups from cellular and membrane proteins, strand breaks and base alterations. Plants have to deal with radiation-induced damage (UV-light of sun, other natural radiation sources). Therefore, it is worth speculating that radioprotective mechanisms have evolved during evolution of life. We hypothesize that natural products from plants may also protect from radiation damage caused as adverse side effects of cancer radiotherapy. The basis of this systematic review, we searched the relevant literature in the PubMed database. Flavonoids, such as genistein, epigallocatechin-3-gallate, epicatechin, apigenin and silibinin mainly act as antioxidant, free radical scavenging and anti-inflammatory compounds, thus, providing cytoprotection in addition to downregulation of several pro-inflammatory cytokines. Comparable effects have been found in phenylpropanoids, especially caffeic acid phenylethylester, curcumin, thymol and zingerone. Besides, resveratrol and quercetin are the most important cytoprotective polyphenols. Their radioprotective effects are mediated by a wide range of mechanisms mainly leading to direct or indirect reduction of cellular stress. Ascorbic acid is broadly used as antioxidant, but it has also shown activity in reducing cellular damage after irradiation mainly due to its antioxidant capabilities. The metal ion chelator, gallic acid, represents another natural product attenuating cellular damage caused by radiation. Some secondary metabolites from plants reveal radioprotective features against cellular damage caused by irradiation. These results warrant further analysis to develop phytochemicals as radioprotectors for clinical use. | Cancer;Phytochemical;Radioprotection;Radiotherapy;Side effects | pubmed |
Motor fatigability in persons with multiple sclerosis: Relation between different upper limb muscles, and with fatigue and the perceived use of the arm in daily life. | Motor fatigability is increasingly acknowledged in persons with MS (pwMS). It is unknown whether fatigability is generalized across upper limb muscles and relates to fatigue and perceived difficulties in upper limb use. This observational case-controlled study included twenty PwMS (median EDSS = 3, range 1.5-6.5) and twenty healthy controls who performed 30″ sustained maximal muscle contractions for index finger abduction, hand grip, elbow flexion and shoulder abduction. A static fatigue index (SFI) was calculated to assess motor fatigability for each muscle group. PwMS completed the Fatigue Severity Scale (FSS) and Modified Fatigue Index Scale (MFIS), to quantify severity and perceived impact of fatigue and the Manual Ability Measure (MAM-36) reflecting perceived difficulty in using the upper limbs. Comparisons between groups and muscles was made by t-tests. Associations between outcomes were calculated with correlation coefficients. Fatigue was highest in pwMS. PwMS showed preserved muscle strength and a greater motor fatigability in elbow flexors compared to healthy controls. SFI of elbow flexors and shoulder abductors were associated, and contributed to FSS and MFIS. SFI of elbow flexors and finger abductors predicted half of the variation in MAM-36. Increased motor fatigability was only present in elbow flexors of PwMS, indicating that expression of motor fatigability is not generalized. Fatigability was associated with perceived fatigue (impact) and daily life upper limb use. Results are preliminary given the small sample size with predominantly persons with mild MS. | Fatigability;Fatigue;Motor fatigue;Multiple sclerosis;Muscle fatigue;Muscle strength;Upper limb | pubmed |
Whole Exome Sequencing Identifies New Host Genomic Susceptibility Factors in Empyema Caused by Streptococcus pneumoniae in Children: A Pilot Study. | Pneumonia is the leading cause of death amongst infectious diseases. <i>Streptococcus pneumoniae</i> is responsible for about 25% of pneumonia cases worldwide, and it is a major cause of childhood mortality. We carried out a whole exome sequencing (WES) study in eight patients with complicated cases of pneumococcal pneumonia (empyema). An initial assessment of statistical association of WES variation with pneumonia was carried out using data from the 1000 Genomes Project (1000G) for the Iberian Peninsula (IBS) as reference controls. Pseudo-replication statistical analyses were carried out using different European control groups. Association tests pointed to single nucleotide polymorphism (SNP) rs201967957 (gene <i>MEIS1</i>; chromosome 2; <i>p</i>-value<sub>IBS</sub> = 3.71 × 10<sup>-13</sup>) and rs576099063 (gene <i>TSPAN15</i>; chromosome 10; <i>p</i>-value<sub>IBS</sub> = 2.36 × 10<sup>-8</sup>) as the best candidate variants associated to pneumococcal pneumonia. A burden gene test of pathogenicity signaled four genes, namely, <i>OR9G9</i>, <i>MUC6</i>, <i>MUC3A</i> and <i>APOB</i>, which carry significantly increased pathogenic variation when compared to controls. By analyzing various transcriptomic data repositories, we found strong supportive evidence for the role of <i>MEIS1, TSPAN15</i> and <i>APOBR</i> (encoding the receptor of the <i>APOB</i> protein) in pneumonia in mouse and human models. Furthermore, the association of the olfactory receptor gene <i>OR9G9</i> has recently been related to some viral infectious diseases, while the role of mucin genes (<i>MUC6</i> and <i>MUC3A</i>), encoding mucin glycoproteins, are well-known factors related to chronic obstructive airway disease. WES emerges as a promising technique to disentangle the genetic basis of host genome susceptibility to infectious respiratory diseases. | Streptococcus pneumoniae;infectious disease;next generation sequencing;parallel sequencing;pediatrics;transcriptome;whole exome sequencing | pubmed |
Incidence of cholecystectomy after bariatric surgery. | Bariatric surgery predisposes patients to development of cholelithiasis, and therefore the need of a subsequent cholecystectomy; however, the incidence of cholecystectomy after bariatric surgery is debated. The purpose of our study is to assess the incidence of cholecystectomy after 3 of the most common bariatric procedures. University Hospital, involving a large database in New York State. The Statewide Planning and Research Cooperative System administrative longitudinal database was used to identify all patients undergoing Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and laparoscopic adjustable gastric banding (LAGB) between 2004 and 2010. Through the use of a unique identifier patients were followed to evaluate for the need of a subsequent cholecystectomy over at least 5 years. Cox proportional hazard regression analysis was used to identify risk factors for subsequent cholecystectomy. During this time period, there were 15,301 LAGB procedures, 19,996 RYGB, and 1650 SG. There were 989 (6.5%) patients who underwent cholecystectomy after LAGB, 1931 (9.7%) patients after RYGB, and 167 (10.1%) after SG. Approximately one quarter of follow-up cholecystectomies were performed at the same institutions. LAGB and RYGB were less likely to have a subsequent cholecystectomy compared with SG (hazard ratio .5, 95% confidence interval .4-.6 for LAGB; and hazard ratio .7, 95% confidence interval .6-.9 for RYGB). Risk factors for a subsequent cholecystectomy included age, sex, race, and some co-morbidities and complications (P<.05) based on a multivariable Cox proportional hazard model. The rate of cholecystectomy after LAGB, RYGB, and SG was 6.5%, 9.7% and 10.1%, respectively. Patients should be counseled preoperatively about this risk and biliary prophylaxis should be contemplated. | Bariatric surgery;Cholecystectomy | pubmed |
Epidemiological Survey of Patients With Hemodialysis Complicated by Hepatitis C in Japan. | Nowadays, interferon-free direct-acting antiviral (DAA) treatment is the standard of care for chronic hepatitis C patients. Some DAA regimens are highly effective and safe even for those with renal dysfunction/failure including those receiving HD. However, it remains unclear to what extent HD specialists gain knowledge about advances in anti-hepatitis C virus (HCV) treatment. To clarify the current situation and identify problems in the treatment of HD patients with chronic hepatitis C, we performed a questionnaire survey at 36 HD facilities between June 2016 and September 2017. In a total of 3418 HD patients, 179 (5.2%) were positive for anti-HCV antibody, and among these patients, 110/125 (88.0%) were positive for serum HCV RNA. Of the latter, only 42/110 (38.2%) patients received antiviral therapy. Moreover, HCV serotyping or genotyping was performed in 23/110 (20.9%) patients. In 26/49 (53.1%) of the remaining 68 untreated patients, "HD specialists do not know any HCV-specific treatments" and "HD specialists have no opportunity to consult with a hepatologist" were the reasons cited for the lack of anti-HCV treatment. This epidemiological study found that some HD patients with chronic hepatitis C had not yet received antiviral treatment despite the emergence of DAAs. To overcome such undesirable circumstances, medical cooperation between HD specialists and hepatologists should be required. | Chronic kidney disease;Direct-acting antivirals;Hemodialysis;Hepatitis C virus | pubmed |
Evaluation of a novel hollow fiber membrane technique for collection of 1,1-dimethylhydrazine in air. | The purpose of this study was to develop a novel one-step method for the time-weighted average determination of 1,1-dimethylhydrazine (UDMH) in the air followed by spectrophotometric detection. For this reason, 0.1% hydrochloric acid as the absorbent was used in hollow fiber (HF) membrane for sampling of UDMH from an atmospheric standard chamber. Response surface methodology (RSM) with central composite design (CCD) was used to optimize the sampling parameters, such as flow rate and sampling time. Moreover, several analytical parameters including breakthrough (BT) volume, storage time, and carryover effect of the proposed HF were investigated. The results showed that optimal sampling rate was 9.90 mL/min. In order to validate the proposed method, it was compared with the National Institute for Occupational Safety and Health (NIOSH) 3515 method, which showed good compatibility between the two methods. Intra- and inter-day repeatability values of the HF method were in the range 0.082-0.1 and 0.091-0.12, respectively, and the limits of detection (LODs) and limits of quantitation (LOQs) were 0.002 and 0.006 ng/mL, respectively. The storage time of the proposed HF was 7 days at 2 °C. These results demonstrated that the one-step HF membrane offered a high sensitivity for sampling of UDMH in air. | 1,1-dimethylhydrazine (UDMH);Air;Hollow fiber (HF);Liquid adsorbent;Response surface methodology (RSM);Spectrophotometer | pubmed |
Conservative treatment for advanced T3-T4 laryngeal cancer: meta-analysis of key oncological outcomes. | Controversies exist regarding the treatment of advanced laryngeal carcinomas. The purpose of this systematic review was to evaluate the oncologic outcomes of both transoral laser and open partial laryngectomies for advanced (T3-T4) squamous cell laryngeal cancers management. A systematic review of literature was led searching for articles mentioning the following terms: advanced (T3-T4) laryngeal cancer AND laser; AND open partial laryngectomy; AND transoral laser microsurgery; AND cordectomy; AND conservative surgery; AND tracheohyoidopexy or tracheohyoidoepiglottopexy; AND supratracheal partial laryngectomy; AND supracricoid partial laryngectomy; AND cricohyoidopexy or cricohyoidoepiglottopexy. Then a quantitative analysis was carried on papers published after 1980. The search identified 110 publications, and a total of 21 articles satisfied inclusion criteria and were selected for quantitative synthesis. 10 out of 21 studies had a good quality score, 10 were fair and only one rated a poor score. The pooled disease-free survival (DFS) was 79% (95% CI 74-85), and pooled overall survival (OS) was 71% (95% CI 64-78) at 5 years from all 1921 patients included in the study, with significant heterogeneity (I <sup>2</sup> = 89.7% and I <sup>2</sup> = 90.4%), respectively. Significant heterogeneity value (p = 0.118) was seen by comparing transoral laser and open partial laryngectomies in terms of DFS. The two surgical techniques are both valid conservative surgical options for advanced laryngeal cancer treatment. | Advanced laryngeal carcinoma;Meta-analysis;Oncological outcomes.;Surgical conservative treatment;Systematic review | pubmed |
Analysis of short-term treatment with the phosphodiesterase type 5 inhibitor tadalafil on long bone development in young rats. | Cyclic GMP (cGMP) is an important intracellular regulator of endochondral bone growth and skeletal remodeling. Tadalafil, an inhibitor of the phosphodiesterase (PDE) type 5 (PDE5) that specifically hydrolyzes cGMP, is increasingly used to treat children with pulmonary arterial hypertension (PAH), but the effect of tadalafil on bone growth and strength has not been previously investigated. In this study, we first analyzed the expression of transcripts encoding PDEs in primary cultures of chondrocytes from newborn rat epiphyses. We detected robust expression of PDE5 as the major phosphodiesterase hydrolyzing cGMP. Time-course experiments showed that C-type natriuretic peptide increased intracellular levels of cGMP in primary chondrocytes with a peak at 2 min, and in the presence of tadalafil the peak level of intracellular cGMP was 37% greater ( P < 0.01) and the decline was significantly attenuated. Next, we treated 1-mo-old Sprague Dawley rats with vehicle or tadalafil for 3 wk. Although 10 mg·kg<sup>-1</sup>·day<sup>-1</sup> tadalafil led to a significant 52% ( P < 0.01) increase in tissue levels of cGMP and a 9% reduction ( P < 0.01) in bodyweight gain, it did not alter long bone length, cortical or trabecular bone properties, and histological features. In conclusion, our results indicate that PDE5 is highly expressed in growth plate chondrocytes, and short-term tadalafil treatment of growing rats at doses comparable to those used in children with PAH has neither obvious beneficial effect on long bone growth nor any observable adverse effect on growth plate structure and trabecular and cortical bone structure. | PDE5 inhibitor;bone;endochondral ossification;growth plate;young rat | pubmed |
Adsorption of cadmium from aqueous solutions by novel Fe<sub>3</sub>O<sub>4</sub>- newly isolated Actinomucor sp. bio-nanoadsorbent: functional group study. | A novel bio-nanocomposite was prepared by the combination of fungal biomass and Fe<sub>3</sub>O<sub>4</sub> magnetic nanoparticles. The result of XRD and EDAX analysis indicated that Fe<sub>3</sub>O<sub>4</sub> Actinomucor sp. bio-nanoadsorbent was prepared. Our experiments showed that the adsorption kinetics and isotherm of this material comply with the pseudo-second-order and the Langmuir models, respectively. The maximum adsorption capacity (q<sub>max</sub>) of this novel bio-nanoadsorbent was obtained as 29.49 mg/g. The thermodynamic analysis revealed that the adsorption of Cd<sup>2+</sup> is spontaneous and exothermic. The optimum temperature, initial concentration, contact time and pH for adsorption system of cadmium were about 45 °C, 400 mg/L, 120 min and 7, respectively. Pretreatment of adsorbent by NaOH and SDS significantly increased cadmium adsorption capacity. SEM images showed that Fe<sub>3</sub>O<sub>4</sub> nanoparticles were immobilized successfully on the fungus cell surface. Contribution of the carboxyl, hydroxyl, amine and Fe-O functional groups of the bio-nanoadsorbent in the binding to cadmium ions was revealed by FTIR analysis. Results from regeneration studies indicated reusability of the adsorbent up to 91%. According to experimental results, it could be claimed that bio-nanocomposite of Fe<sub>3</sub>O<sub>4</sub>-Actinomucor sp. is a novel efficient adsorbent for removal of metal ions from aqueous solutions, and hence it has potential to be used in the environmental pollution cleanup programs. | sp.;Cd2+;FeO;adsorption;bio-nanocomposite;cadmium | pubmed |
Toll-like receptors 2, 4 and 9 and hypoxia markers HIF-1alpha and CAIX in pancreatic intraepithelial neoplasia. | Pancreatic cancer arises from precursor lesions called pancreatic intraepithelial neoplasia (PanIN) characterized by inflammatory microenvironment. In pancreatic cancer, strong innate immunity and hypoxia responses are typical. Occurrence and relationship of these responses in human PanINs is unknown. We have studied the expression of toll-like receptors (TLR) TLR2, TLR4 and TLR9, and hypoxia markers HIF-1alpha and Carbonic anhydrase IX (CAIX) in normal and inflamed pancreatic ducts, in PanINs and in cancers. The samples of 69 surgically resected pancreatic ductal adenocarcinoma patients were stained using immunohistochemistry. We found TLR2, TLR9, HIF-1alpha and CAIX to be prominently expressed in pancreatic intraepithelial neoplasia. Expression of TLR2 showed a linear increase from PanIN1 to PanIN3, while the highest TLR4 expression was detected in inflamed ducts, and TLR9 expression in PanIN1 lesions. Within the PanIN1-group, nuclear HIF-1alpha correlated with membranous and cytoplasmic TLR2 expression (ρ = 0.982 and 0.815; p < 0.001 and p = 0.025, respectively), and in the PanIN2-group nuclear HIF-1alpha correlated with nuclear TLR9 expression 0.636, p = 0.026). Our findings show that the expression of TLRs 2, 4 and 9, and hypoxia markers HIF-1alpha and CAIX is abnormal in pancreatic intraepithelial neoplasia suggesting that both the innate immunity activation and hypoxia response are involved in early pancreatic carcinogenesis. However, these processes might be independent. | Carbonic anhydrase 9;HIF-1alpha;Toll-like receptor;hypoxia;innate immunity;pancreatic intraepithelial neoplasia | pubmed |
Interhermispheric inhibition predicts anxiety levels in multiple sclerosis: A corticospinal excitability study. | Depression and anxiety stand among the most frequent and debilitating complaints in multiple sclerosis (MS) patients. Understanding their neurophysiological correlates might improve their management. To date, no single study has addressed this issue. Patients completed the Hospital Anxiety and Depression Scale (HADS). Transcranial magnetic stimulation (TMS) was performed to obtain the following corticospinal excitability measures: resting motor threshold, short-interval intracortical inhibition and facilitation, cortical silent period and interhemispheric inhibition (IHI). Anxiety and depression scores were the primary outcomes in the univariate analysis. When obtaining significant associations between anxiety/depression and TMS measures, a multivariate analysis was performed using stepwise linear regression with anxiety and depression scores employed separately as dependent variables and TMS measures, clinical and sociodemographic data as independent variables. Due to the small sample size and the large number of studied variables, only variables with p values <0.05 in the univariate analysis were included in the multivariate analysis. Fifty patients completed the study (n = 24 women). Their mean age was 51.82 ± 12.72 years. Mean depression score was 6.08 ± 3.66. Mean anxiety score was 5.82 ± 3.42. A significant association was found between anxiety and IHI (p < 0.05), fatigue (p < 0.05), depression (p < 0.05), and female gender (p < 0.05). Stepwise linear regression analysis was performed and IHI values explained 9.10% of variance in anxiety levels (standardized β: 0.31; p < 0.01) when controlling for remaining variables. As for depression, it did not significantly correlate with any TMS measures. The results highlight the relationship between anxiety and callosal transfer as reflected by IHI values. The current findings are consistent with previous works assessing healthy participants and patients with social anxiety disorders. Compared to MS patients with aberrant callosal transfer (suggested by low IHI values), those exhibiting a relatively more efficient one (reflected by high IHI values) seem to have higher anxiety scores, a finding that merits further assessment. | Anxiety;Cortical excitability;Depression;Hospital anxiety and depression scale;Interhemispheric inhibition;Transcranial magnetic stimulation | pubmed |
Impact of Electronic Acute Kidney Injury (AKI) Alerts With Automated Nephrologist Consultation on Detection and Severity of AKI: A Quality Improvement Study. | Several electronic alert systems for acute kidney injury (AKI) have been introduced. However, their clinical benefits require further investigation. Before-and-after quality improvement study. A tertiary teaching hospital in Korea, which adopted an AKI alert system on June 1, 2014. Before and after launch of the alert system, 1,884 and 1,309 patients with AKI were included in the usual-care and alert groups, respectively. Implementation of an AKI alert system through which clinicians could generate automated consultations to the nephrology division for all hospitalized patients. Primary outcomes included overlooked AKI events, defined as not measuring the follow-up creatinine value, and the consultation pattern of clinicians. Secondary outcomes were severe AKI events; AKI recovery, defined based on the creatinine-based criterion; and patient mortality. ORs for events of overlooked AKI, early consultation, and severe AKI were calculated with logistic regression. AKI recovery rate and patient mortality were assessed using Cox regression. After introduction of the alert system, the odds of overlooked AKI events were significantly lower (adjusted OR, 0.40; 95% CI, 0.30-0.52), and the odds of an early consultation with a nephrologist were greater (adjusted OR, 6.13; 95% CI, 4.80-7.82). The odds of a severe AKI event was reduced after implementation of the alerts (adjusted OR, 0.75; 95% CI, 0.64-0.89). Furthermore, the likelihood of AKI recovery was improved in the alert group (adjusted HR, 1.70; 95% CI, 1.53-1.88). Mortality was not affected by the AKI alert system (adjusted HR, 1.07; 95% CI, 0.68-1.68). Possible unreported differences between the alert and usual-care groups. Implementation of the AKI alert system was associated with beneficial effects in terms of an improved rate of recovery from AKI. Therefore, widespread adoption of such systems could be considered in general hospitals. | AKI alarm;AKI alert;Acute kidney injury (AKI);electronic alert;electronic medical record (EMR);nephrology consultation;quality improvement report;serum creatinine | pubmed |
Comparison of perceptual properties of auditory streaming between spectral and amplitude modulation domains. | The two-tone sequence (ABA_), which comprises two different sounds (A and B) and a silent gap, has been used to investigate how the auditory system organizes sequential sounds depending on various stimulus conditions or brain states. Auditory streaming can be evoked by differences not only in the tone frequency ("spectral cue": ΔF<sub>TONE</sub>, TONE condition) but also in the amplitude modulation rate ("AM cue": ΔF<sub>AM</sub>, AM condition). The aim of the present study was to explore the relationship between the perceptual properties of auditory streaming for the TONE and AM conditions. A sequence with a long duration (400 repetitions of ABA_) was used to examine the property of the bistability of streaming. The ratio of feature differences that evoked an equivalent probability of the segregated percept was close to the ratio of the Q-values of the auditory and modulation filters, consistent with a "channeling theory" of auditory streaming. On the other hand, for values of ΔF<sub>AM</sub> and ΔF<sub>TONE</sub> evoking equal probabilities of the segregated percept, the number of perceptual switches was larger for the TONE condition than for the AM condition, indicating that the mechanism(s) that determine the bistability of auditory streaming are different between or sensitive to the two domains. Nevertheless, the number of switches for individual listeners was positively correlated between the spectral and AM domains. The results suggest a possibility that the neural substrates for spectral and AM processes share a common switching mechanism but differ in location and/or in the properties of neural activity or the strength of internal noise at each level. | Amplitude modulation;Auditory scene analysis;Bistable perception;Sequential organization of sounds | pubmed |
Detection of poliovirus infection in children with acute gastroenteritis in Chiang Mai, Thailand. | Poliovirus (PV) is typically transmitted by the fecal-oral route, which means that the risk of infection and virus distribution could be achieved by exposure to the virus contaminated in food and water. The aim of this study was to determine the occurrence of PV strains by detecting the virus in pediatric patients who admitted to the hospitals with diarrhea in Chiang Mai, Thailand during 2010-2015. By applying a reverse transcription-polymerase chain reaction and nucleotide sequencing analysis of 1,300 stool specimens collected from pediatric patients, PVs were detected at 0.61% (8 out of 1,300 specimens). Among eight PV positive samples, mixed infection with norovirus or human bocavirus was detected in one each out of eight cases. All PV strains detected in this study were characterized further by phylogenetic analysis of 343 bp of the 5' UTR and 315 bp of the partial VP1 sequences. The results revealed that eight PV strains detected in the present study two of each were PV1 and PV2, and four were PV3 serotypes of the Sabin vaccine strains. The data demonstrated the presence of PV1, PV2, and PV3 Sabin vaccine strains in children with acute gastroenteritis in Chiang Mai, Thailand. J. Med. Virol. 89:775-781, 2017. © 2016 Wiley Periodicals, Inc. | RNA extraction;fecal contaminant;poliovirus;vaccine strains | pubmed |
A meta-analytical comparison of atenolol with angiotensin-converting enzyme inhibitors on arterial stiffness, peripheral blood pressure and heart rate in hypertensive patients. | This meta-analysis of randomized parallel controlled trials was designed to compare the efficacy of atenolol with angiotensin-converting enzyme inhibitors (ACEIs) in changing pulse wave velocity (PWV), peripheral blood pressure and heart rate (HR) among patients with essential hypertension. This study was conducted according to the PRISMA guideline. Data collection was independently completed by two investigators. Statistical analyses were completed by Stata software (v12.0). Eight clinical trials were meta-analyzed in this study. Overall changes in PWV (weighted mean difference or WMD = 0.068, 95% confidence interval or CI: -0.487 to -0.623, P = 0.811) and peripheral systolic blood pressure (PSBP) (WMD = -1.281 mmHg, 95% CI: -6.936 to 4.375, P = 0.657) did not differ significantly between atenolol and ACEIs treatment. Relative to ACEIs, atenolol had a more favorable impact on peripheral diastolic blood pressure (PDBP) (WMD = -1.912 mmHg, 95% CI: -3.732 to -0.091, P = 0.040) and HR (WMD = -9.23 bpm, 95% CI: -12.53 to -5.93, P < 0.001). In stratified analyses, particularly by follow-up period, atenolol was observed to be superior over ACEIs within early 3-month treatment in PSBP (WMD = -4.097 mmHg, 95% CI: -6.589 to -1.605, P = 0.001), PDBP (WMD = -6.802 mmHg, 95% CI: -8.517 to -5.087, P < 0.001) and HR (WMD = -14.242 bpm, 95% CI: -16.427 to -12.058, P = 0.028), without heterogeneity (I<sup>2</sup> = 0.0%). There were low probabilities of publication bias for all comparisons. Our findings demonstrate that atenolol and ACEIs were equally effective in reducing PWV and PSBP, while atenolol was superior over ACEIs in improving PDBP and HR, especially within short-term treatment. | Atenolol;angiotensin-converting enzyme inhibitor;arterial stiffness;heart rate;peripheral blood pressure | pubmed |
The Injury-Related Activation of Hedgehog Signaling Pathway Modulates the Repair-Associated Inflammation in Liver Fibrosis. | Liver fibrosis is a wound healing response initiated by inflammation responding for different iterative parenchymal damages caused by diverse etiologies. Immune cells, which exert their ability of either inducing injury or promoting repair, have been regarded as crucial participants in the fibrogenic response. A characteristic feature of the fibrotic microenvironment associated with chronic liver injury is aberrant activation of hedgehog (Hh) signaling pathway. Growing evidence from a number of different studies <i>in vivo</i> and <i>in vitro</i> has indicated that immune-mediated events involved in liver fibrogenesis are regulated by Hh signaling pathway. In this review, we emphasize the impacts of injury-activated Hh signaling on liver fibrogenesis through modulating repair-related inflammation and focus on the regulatory action of aberrant Hh signaling on repair-related inflammatory responses mediated by hepatic classical and non-classical immune cell populations in the progression of liver fibrosis. Moreover, we also assess the potentiality of Hh pathway inhibitors as good candidates for anti-fibrotic therapeutic agents because of their immune regulation actions for fibrogenic liver repair. The identification of immune-modulatory mechanisms of Hh signaling pathway underlying the fibrotic process of chronic liver diseases might provide a basis for Hh-centered therapeutic strategies for liver fibrosis. | hedgehog pathway inhibitor;hedgehog signaling pathway;immune-modulatory action;liver fibrosis;repair-associated inflammation | pubmed |
Pre-treatment interleukin-6 levels strongly affect bone erosion progression and repair detected by magnetic resonance imaging in rheumatoid arthritis patients. | To examine the relationship between MRI structural damage and repair and plasma inflammatory cytokines in patients with RA. A total of 88 newly diagnosed, untreated RA patients were enrolled. Contrast MRI of the dominant hand and X-rays of the hands and feet were performed at baseline and 1 year later. MR images were evaluated using RA MRI scoring, and X-ray. Progression of bone erosion and repair were observed more frequently in MRI than in X-rays (erosion, 52% vs 26%, P < 0.001; repair, 26% vs 15%, P = 0.003, respectively). Baseline IL-6 levels and seropositivity were independent relevant factors for MRI erosion progression, with IL-6 having stronger effect than seropositivity. A receiver operating characteristic curve identified the baseline IL-6 level of 7.6 pg/ml for predicting erosion progression during 1 year, with an area under the curve of 0.82; higher IL-6 levels resulted in more erosion progression. Baseline low IL-6 was also an independent predictor for MRI erosion repair. In newly diagnosed, untreated RA patients, baseline plasma IL-6 levels are responsible for 1-year MRI bone erosion progression and repair. | IL-6;bone erosion;cytokines;magnetic resonance imaging;repair;rheumatoid arthritis | pubmed |
Different types of exercise in Multiple Sclerosis: Aerobic exercise or Pilates, a single-blind clinical study. | The aim of our study is to examine effects of aerobic and Pilates exercises on disability, cognition, physical performance, balance, depression and fatigue in relapsing-remitting Multiple Sclerosis (MS) patients as compared to healthy controls. The subjects were divided as aerobic exercise (n = 26), Pilates (n = 9), and the healthy control group (n = 21). We used MSFC, physical performance, Berg balance scale, Beck depression scale, fatigue impact scale. All evaluations were performed before and after exercise training. There are statistically meaningful differences between Nine hole testing, PASAT 3, physical performance and fatique impact scale before and after aerobic exercise. Also we found significant difference for physical performance in the Pilates group. There are no significant differences in measures of fatique impact scale and depression between aerobic exercise group and the healthy controls after exercise. We found significant differences between Pilates and control group's after measurements except depression. There were significant differences between the Pilates and aerobic group for cognitive tests in favor of the Pilates group. Aerobic exercise and clinical Pilates exercises revealed moderate changes in levels of cognitive, physical performance, balance, depression, fatigue in MS patients. | Multiple Sclerosis;aerobic exercises;balance;clinical Pilates;cognition;physical performance | pubmed |
Quantitative Analysis of Electro-Anatomical Maps: Application to an Experimental Model of Left Bundle Branch Block/Cardiac Resynchronization Therapy. | Electro-anatomical maps (EAMs) are commonly acquired in clinical routine for guiding ablation therapies. They provide voltage and activation time information on a 3-D anatomical mesh representation, making them useful for analyzing the electrical activation patterns in specific pathologies. However, the variability between the different acquisitions and anatomies hampers the comparison between different maps. This paper presents two contributions for the analysis of electrical patterns in EAM data from biventricular surfaces of cardiac chambers. The first contribution is an integrated automatic 2-D disk representation (2-D bull's eye plot) of the left ventricle (LV) and right ventricle (RV) obtained with a quasi-conformal mapping from the 3-D EAM meshes, that allows an analysis of cardiac resynchronization therapy (CRT) lead positioning, interpretation of global (total activation time), and local indices (local activation time (LAT), surrogates of conduction velocity, inter-ventricular, and transmural delays) that characterize changes in the electrical activation pattern. The second contribution is a set of indices derived from the electrical activation: speed maps, computed from LAT values, to study the electrical wave propagation, and histograms of isochrones to analyze regional electrical heterogeneities in the ventricles. We have applied the proposed methods to look for the underlying physiological mechanisms of left bundle branch block (LBBB) and CRT, with the goal of optimizing the therapy by improving CRT response. To better illustrate the benefits of the proposed tools, we created a set of synthetically generated and fully controlled activation patterns, where the proposed representation and indices were validated. Then, the proposed analysis tools are used to analyze EAM data from an experimental swine model of induced LBBB with an implanted CRT device. We have analyzed and compared the electrical activation patterns at baseline, LBBB, and CRT stages in four animals: two without any structural disease and two with an induced infarction. By relating the CRT lead location with electrical dyssynchrony, we evaluated current hypotheses about lead placement in CRT and showed that optimal pacing sites should target the RV lead close to the apex and the LV one distant from it. | Cardiac resynchronization therapy;electro-anatomical mapping system;lead placement;left bundle branch block;quantitative pattern analysis;subject-specific 2D and 3D data representation | pubmed |
Towards a chromatographic similarity index to establish localized quantitative structure-retention models for retention prediction: Use of retention factor ratio. | Quantitative Structure-Retention Relationships (QSRR) have the potential to speed up the screening phase of chromatographic method development as the initial exploratory experiments are replaced by prediction of analyte retention based solely on the structure of the molecule. The present study offers further proof-of-concept of localized QSRR modelling, in which the retention of any given compound is predicted using only the most chromatographically similar compounds in the available dataset. To this end, each compound in the dataset was sequentially removed from the database and individually utilized as a test analyte. In this study, we propose the retention factor k as the most relevant chromatographic similarity measure and compare it with the Tanimoto index, the most popular similarity measure based on chemical structure. Prediction error was reduced by up to 8 fold when QSRR was based only on chromatographically similar compounds rather than using the entire dataset. The study therefore shows that the design of a practically useful structural similarity index should select the same compounds in the dataset as does the k-similarity filter in order to establish accurate predictive localized QSRR models. While low average prediction errors (Mean Absolute Error (MAE)<0.5min) and slopes of the regression lines through the origin close to 1.00 were obtained using k-similarity searching, the use of the structural Tanimoto similarity index, considered as the gold standard in Quantitative Structure-Activity Relationships (QSAR) studies, generally resulted in much higher prediction errors (MAE>1min) and significant deviations from the reference slope of 1.0. The Tanomoto similarity index therefore appears to have limited general utility in QSRR studies. Future studies therefore aim at designing a more appropriate chromatographic similarity index that can then be applied for unknown compounds (that is, compounds which have not been tested previously on the chromatographic system used, but for which the chemical structures are known). | Automation;Quantitative Structure-Retention Relationships;Similarity searching | pubmed |
Role of Estrogen and Other Sex Hormones in Brain Aging. Neuroprotection and DNA Repair. | Aging is an inevitable biological process characterized by a progressive decline in physiological function and increased susceptibility to disease. The detrimental effects of aging are observed in all tissues, the brain being the most important one due to its main role in the homeostasis of the organism. As our knowledge about the underlying mechanisms of brain aging increases, potential approaches to preserve brain function rise significantly. Accumulating evidence suggests that loss of genomic maintenance may contribute to aging, especially in the central nervous system (CNS) owing to its low DNA repair capacity. Sex hormones, particularly estrogens, possess potent antioxidant properties and play important roles in maintaining normal reproductive and non-reproductive functions. They exert neuroprotective actions and their loss during aging and natural or surgical menopause is associated with mitochondrial dysfunction, neuroinflammation, synaptic decline, cognitive impairment and increased risk of age-related disorders. Moreover, loss of sex hormones has been suggested to promote an accelerated aging phenotype eventually leading to the development of brain hypometabolism, a feature often observed in menopausal women and prodromal Alzheimer's disease (AD). Although data on the relation between sex hormones and DNA repair mechanisms in the brain is still limited, various investigations have linked sex hormone levels with different DNA repair enzymes. Here, we review estrogen anti-aging and neuroprotective mechanisms, which are currently an area of intense study, together with the effect they may have on the DNA repair capacity in the brain. | DNA repair;brain aging;estrogen;mitochondria;neuroprotection;sex hormones | pubmed |
Serum polyunsaturated fatty acid metabolites as useful tool for screening potential biomarker of colorectal cancer. | The biomarker identification of cancer is benefit for early detection and less invasion. Polyunsaturated fatty acid (PUFA) metabolite as inflammatory mediators can affect progression and treatment of cancer. In this work, the serum was collected from colorectal cancer patients and healthy volunteers, and then we tested the change of serum PUFA metabolites in both of them by ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Of the 158 PUFA and their metabolites, we found that abnormal change of 2, 3-dinor-8-iso-PGF2α, 19-HETE and 12-keto-LTB4 from arachidonic acid were observed in colorectal cancer patients. Meanwhile, 9-HODE and 13-HODE from linoleic acid were significant lower in colorectal cancer patients. Our data suggested that some PUFA metabolites might be used as a potential biomarker of colorectal cancer, which might provide assistance in clinical diagnosis and treatment. | Colorectal cancer;Lipidomic;Mass spectrometry;Ultra-high performance liquid chromatography | pubmed |
Influence of Resin Composition on the Defect Formation in Alumina Manufactured by Stereolithography. | Stereolithography (SL) is a technique allowing additive manufacturing of complex ceramic parts by selective photopolymerization of a photocurable suspension containing photocurable monomer, photoinitiator, and a ceramic powder. The manufactured three-dimensional object is cleaned and converted into a dense ceramic part by thermal debinding of the polymer network and subsequent sintering. The debinding is the most critical and time-consuming step, and often the source of cracks. In this study, photocurable alumina suspensions have been developed, and the influence of resin composition on defect formation has been investigated. The suspensions were characterized in terms of rheology and curing behaviour, and cross-sections of sintered specimens manufactured by SL were evaluated by SEM. It was found that the addition of a non-reactive component to the photocurable resin reduced polymerization shrinkage and altered the thermal decomposition of the polymer matrix, which led to a reduction in both delamination and intra-laminar cracks. Using a non-reactive component that decomposed rather than evaporated led to less residual porosity. | DLP;ceramics;photopolymerization;stereolithography;thermal debinding | pubmed |
Proposal for a new bone marker for maxillofacial surgery. | Graphite;Medical device;Osteotomy;Surgical instruments | pubmed |
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Health, Well-Being and Energy Poverty in Europe: A Comparative Study of 32 European Countries. | Despite growing pan-European interest in and awareness of the wide-ranging health and well-being impacts of energy poverty-which is characterised by an inability to secure adequate levels of energy services in the home-the knowledge base is largely British-centric and dominated by single-country studies. In response, this paper investigates the relationship between energy poverty, health and well-being across 32 European countries, using 2012 data from the European Quality of Life Survey. We find an uneven concentration of energy poverty, poor health, and poor well-being across Europe, with Eastern and Central Europe worst affected. At the intersection of energy poverty and health, there is a higher incidence of poor health (both physical and mental) amongst the energy poor populations of most countries, compared to non-energy poor households. Interestingly, we find the largest disparities in health and well-being levels between energy poor and non-energy poor households occur within relatively equal societies, such as Sweden and Slovenia. As well as the unique challenges brought about by rapidly changing energy landscapes in these countries, we also suggest the relative deprivation theory and processes of social comparison hold some value in explaining these findings. | energy poverty;fuel poverty;health inequalities;relative deprivation;well-being | pubmed |
Effect of fermented and unfermented buckwheat flour on functional properties of gluten-free muffins. | Selected functional properties of four types of gluten-free muffins made of unfermented and fermented (by <i>Lactobacillus plantarum</i>) buckwheat flour in comparison with control muffins made using commercial gluten-free corn flour were evaluated in this study. The proximate chemical composition, antioxidant capacity analysed by ABTS, photochemiluminescence and cyclic voltammetry assays, and inhibitory activity against protein glycation in vitro in BSA/Glu systems were investigated. The content of the total phenolic compounds, available lysine, furosine, free and total FIC, browning index and antioxidant capacity of buckwheat-enhanced gluten-free muffins were higher compared to the control samples. Gluten-free muffins made of the fermented buckwheat flour showed a significantly higher antioxidant capacity, an increased activity against AGEs formation and an increased available lysine content, as well as a higher FAST index and browning index as compared to the muffins obtained with unfermented buckwheat flour. The study showed that buckwheat flour fermented by <i>L. plantarum</i> could be used as an ingredient for improving the functional properties of gluten-free muffins. | Buckwheat flour;Fermentation;Functional properties;Gluten-free muffins;Lactobacillus plantarum | pubmed |
Old age and underlying interstitial abnormalities are risk factors for development of ARDS after pleurodesis using limited amount of large particle size talc. | Talc pleurodesis is commonly performed to manage refractory pleural effusion or pneumothorax. It is considered as a safe procedure as long as a limited amount of large particle size talc is used. However, acute respiratory distress syndrome (ARDS) is a rare but serious complication after talc pleurodesis. We sought to determine the risk factors for the development of ARDS after pleurodesis using a limited amount of large particle size talc. We retrospectively reviewed patients who underwent pleurodesis with talc or OK-432 at the University of Tokyo Hospital. Twenty-seven and 35 patients underwent chemical pleurodesis using large particle size talc (4 g or less) or OK-432, respectively. Four of 27 (15%) patients developed ARDS after talc pleurodesis. Patients who developed ARDS were significantly older than those who did not (median 80 vs 66 years, P = 0.02) and had a higher prevalence of underlying interstitial abnormalities on chest computed tomography (CT; 2/4 vs 1/23, P < 0.05). No patient developed ARDS after pleurodesis with OK-432. This is the first case series of ARDS after pleurodesis using a limited amount of large particle size talc. Older age and underlying interstitial abnormalities on chest CT seem to be risk factors for developing ARDS after talc pleurodesis. | acute respiratory distress syndrome;lung cancer;lung injury;pleural disease | pubmed |
NADPH oxidase: its potential role in promotion of pulmonary arterial hypertension. | NADPH oxidases (NOXs) are a group of enzymes for superoxide anion (O<sub>2</sub><sup>·-</sup> ) generation through transferring electrons from NADPH to molecular oxygen, which is rapidly converted into hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). There are seven members in NOX family, including NOX1 to NOX5, dual oxidase1, and dual oxidase 2. Recent studies have demonstrated that NOX subtypes may have different functions in different types of pulmonary arterial hypertension (PAH). The NOX-derived reactive oxygen species (ROS) are key factors that are involved in promoting the processes of pulmonary vascular remodeling, such as endothelial dysfunction, proliferation of pulmonary arterial smooth muscle cells (PASMCs), and cellular trans-differentiation, which are the basic pathologic characteristics of PAH. Inhibition of NOX shows beneficial effect on prevention of PAH development. Thus, NOX might be a potential target for PAH therapy. The main purpose of this review is to summarize recent findings on the role of NOX, particularly the NOX subtypes, in promotion of PAH development and to list recent progress regarding the NOX-based intervention for PAH. | Apocynin;Diphenyleneiodonium;NADPH oxidases;Pulmonary arterial hypertension;Resveratrol | pubmed |
Parent Distress and the Decision to Have Another Child After an Infant's Death in the NICU. | To examine associations among parent perceptions of infant symptoms/suffering, parent distress, and decision making about having additional children after an infant's death in the NICU. Mixed-methods pilot study incorporating mailed surveys and qualitative interviews. Midwestern Level IV regional referral NICU. Participants were 42 mothers and 27 fathers whose infants died in the NICU. Parents reported on infant symptoms/suffering at end of life and their own grief and posttraumatic stress symptoms. Qualitative interviews explored decision making about having additional children. Approximately two thirds of bereaved parents had another child after their infant's death (62% of mothers, 67% of fathers). Mothers who had another child reported fewer infant symptoms at end of life compared with mothers who did not (p = .002, d = 1.28). Although few mothers exceeded clinical levels of prolonged grief (3%) and posttraumatic stress symptoms (18%), mothers who had another child endorsed fewer symptoms of prolonged grief (p = .001, d = 1.63) and posttraumatic stress (p = .009, d = 1.16). Differences between fathers mirrored these effects but were not significant. Parent interviews generated themes related to decision making about having additional children, including Impact of Infant Death, Facilitators and Barriers, Timing and Trajectories of Decisions, and Not Wanting to Replace the Deceased Child. Having another child after infant loss may promote resilience or serve as an indicator of positive adjustment among parents bereaved by infant death in the NICU. Prospective research is necessary to distinguish directional associations and guide evidence-based care. | NICU;PTSS;bereavement;decision making;grief;infant death;subsequent children | pubmed |
Impact of starter culture, ingredients, and flour type on sourdough bread volatiles as monitored by selected ion flow tube-mass spectrometry. | This study deals with the detection of volatile compounds originating from the crumb of breads made with sourdoughs obtained through starter culture-initiated fermentations, which differed in flour type (wheat and teff), ingredients (citrate and malate), fermentation time (24h or 72h), and starter culture strains (homo- and heterofermentative lactic acid bacteria species and acetic acid bacteria species) applied. Therefore, selected ion flow tube-mass spectrometry (SIFT-MS) was used. SIFT-MS is an easy-to-use and promising technique in the field of food and flavor analysis. Volatile compounds of crumb samples from the breads with sourdough were measured and compared with those of reference bread crumb samples. In general, sourdough addition had a positive effect on the concentrations of the volatile compounds measured by SIFT-MS. Furthermore, a trend toward higher concentrations of several volatiles was seen upon the addition of sourdoughs that were fermented up to 72h, compared to the addition of sourdoughs that were fermented for a shorter time. Ethanol was the major volatile compound identified tentatively, next to alcohols, aldehydes, esters, terpenes, and heterocyclic compounds. Also acetoin/ethyl acetate could be identified, but these compounds could not be distinguished. Higher alcohols showed an increase upon the use of sourdough fermented for a long time. High concentrations of acetic acid were found in breads made with Gluconobacter oxydans IMDO A845-initiated sourdough, indicating its potential for sourdough production. Breads made with teff sourdoughs were distinct from wheat-based sourdough breads as to their volatile compound profiles. | Acetic acid (PubChem CID: 176);Acetic acid bacteria;Acetoin (PubChem CID: 179);Bread;Diacetyl (PubChem CID: 650);Ethanol (PubChem CID: 702);Ethyl acetate (PubChem CID: 8857);Isoamyl acetate (PubChem CID: 31276);Lactic acid bacteria;Methyl butanol (PubChem CID: 31260);Pentanol (PubChem CID: 6276);SIFT-MS;Sourdough;Volatiles | pubmed |
Dynamic changes of serum protein in rats with acute intoxication of Chinese cobra snake venom by proteomic analysis. | To elucidate the toxic mechanism of snake venom at the protein level, proteomics technology was applied to investigate the effect of venom on circulation in the mammalian body. Temporal proteomic analysis was performed to profile the dynamic changes in the sera of Sprague-Dawley rats administered with Chinese cobra venom or saline. Using 8-plex iTRAQ analysis, 392 and 636 serum proteins were identified to be linearly upregulated or downregulated over time in the low-dose group and high-dose group, respectively. These proteins were mainly associated with the acute phase response pathway, complement system, and liver X receptor (LXR)/retinoid X receptor (RXR) and farnesoid X receptor (FXR)/RXR activation pathways. Compared with the low-dose group, the immune response and integrin pathways were inhibited in the high-dose group, although no obvious effect was observed. With consistently higher or lower expression in the high-dose group compared to the low-dose group throughout the whole process of venom poisoning, two proteins, Kininogen-1 (KNG1) and orosomucoid 1 (ORM1), which are involved in metabolism and immune response, occupied a core position in the pathway network and are considered venom dose-dependent biomarker candidates. | Forensic sciences;cobra;forensic toxicology;proteomics;rats;serum;snake bite | pubmed |
1-Carbon Cycle Metabolites Methylate Their Way to Fatty Liver. | Fatty liver is a complex disease often accompanying metabolic syndrome and Type 2 diabetes mellitus (T2DM). Hepatosteatosis may have roots in multiple metabolic abnormalities. However, metabolic dysfunction in the 1-carbon cycle (1CC), which produces the methyl donor S-adenosylmethionine (SAM) and phosphatidylcholine (PC), induces hepatic lipogenesis in model systems. Human diseases where 1CC or PC synthesis is disrupted, such as alcoholism, congenital lipodystrophy, or cystic fibrosis, often present with fatty liver. Given that the 1CC is clearly linked to this disease, it is critical to understand how the individual metabolites drive mechanisms increasing stored hepatic lipids. In this review, I summarize evidence that ties the 1CC to fatty liver disease along with data proposing mechanisms for increased lipogenesis or decreased lipid export by phosphatidylcholine. | 1-carbon cycle;fatty liver;methylation;phosphatidylcholine | pubmed |
Habitual chocolate intake and type 2 diabetes mellitus in the Maine-Syracuse Longitudinal Study: (1975-2010): Prospective observations. | Compounds in cocoa and chocolate have established cardiovascular benefits, including beneficial effects on insulin resistance, a risk factor for type 2 diabetes mellitus. The aims of this study was to investigate relations between habitual chocolate intakes and diabetes mellitus. Cross-sectional and prospective analyses were undertaken on 953 community-dwelling participants (mean age 62 years, 59% women) from the Maine-Syracuse Longitudinal Study (MSLS). Habitual chocolate intakes, measured using a food frequency questionnaire, were related to prevalence of diabetes mellitus (cross-sectionally) and with risk of diabetes measured approximately five years later (prospectively). We also examined the relation between diabetes (the predictor) and chocolate consumption (the outcome) up to 30 years later. Chocolate intake was inversely associated with type 2 diabetes. Compared to participants who consumed chocolate more than once per week, those who never or rarely ate chocolate exhibited a significantly higher odds of having type 2 diabetes 5 years later (OR: 1.91, 95% CI: 1.03, 3.55, p = 0.04), after adjustment for cardiovascular, lifestyle and dietary factors including other polyphenol-rich beverages. However, individuals diagnosed with diabetes prior to the nutritional assessment consumed lower amounts of chocolate at the time of the dietary assessment. Our findings suggest that relations between chocolate and type 2 diabetes may be bi-directional. | Chocolate;Cocoa;Type 2 diabetes | pubmed |
Smart storage technologies applied to fresh foods: A review. | Fresh foods are perishable, seasonal and regional in nature and their storage, transportation, and preservation of freshness are quite challenging. Smart storage technologies can online detection and monitor the changes of quality parameters and storage environment of fresh foods during storage, so that operators can make timely adjustments to reduce the loss. This article reviews the smart storage technologies from two aspects: online detection technologies and smartly monitoring technologies for fresh foods. Online detection technologies include electronic nose, nuclear magnetic resonance (NMR), near infrared spectroscopy (NIRS), hyperspectral imaging and computer vision. Smartly monitoring technologies mainly include some intelligent indicators for monitoring the change of storage environment. Smart storage technologies applied to fresh foods need to be highly efficient and nondestructive and need to be competitively priced. In this work, we have critically reviewed the principles, applications, and development trends of smart storage technologies. | Cold chain;fresh foods;smart;storage technology | pubmed |
Spinal cord stimulation for pain treatment failed to modify disease progression in a patient with amyotrophic lateral sclerosis. | Amyotrophic lateral sclerosis;Pain;Spinal cord stimulation | pubmed |
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Use of the augmentation index from applanation tonometry of the radial artery for assessing the extent of coronary artery calcium as assessed by coronary computed tomography. | The augmentation index (AI) obtained from applanation tonometry of the radial artery is technically the easiest and quickest of available methods for assessing arterial stiffness. We tested the hypothesis that the radial AI is associated with the extent of coronary artery calcium (CAC) as assessed by coronary computed tomography (CCT). This study included 161 patients with known or suspected coronary artery disease undergoing central hemodynamic measurements and CCT. Radial AI was recorded and was corrected in accordance with heart rate (radial AI@75). Thirty-seven patients had no CAC (CAC score = 0), 85 had low-grade CAC (CAC score = 1-399), and 39 had high-grade CAC (CAC score ≥400). Coronary risk factors, except for age and serum creatinine, were similar among the three groups. There were significant differences in brachial systolic blood pressure (SBP) (p = 0.011) and radial AI@75 (%) (p = 0.006). Multivariate analysis showed that age (β = 0.27, p = 0.001), serum creatinine (β = 0.18, p = 0.03), and radial AI@75 (β = 0.24, p = 0.005) were significantly associated with ln (CAC score + 1), whereas brachial SBP was not. Additionally, serum creatinine (odds ratio: 11.91, 95% confidence interval: 1.46-112.0, p = 0.02) and radial AI@75 (per 10%) (odds ratio: 1.76, 95% confidence interval: 1.22-2.64, p = 0.002) were independent factors associated with high-grade CAC. Our results suggest that the radial AI is better for estimating CAC than brachial SBP in patients with known or suspected coronary artery disease. | Arterial stiffness;augmentation index;central blood pressure;coronary artery calcium;coronary computed tomography | pubmed |
Increased Frequency of Rheumatoid Arthritis and Allergic Rhinitis among Pesticide Sprayers and Associations with Pesticide Use. | <i>Objective</i>: The aim of this study was to identify diseases linked with the pesticide sprayer occupation and explore possible associations with exposure history data. <i>Methods</i>: Α cross sectional study was conducted among pesticide sprayers (<i>n</i> = 80) and the general population (<i>n</i> = 90) in Thessaly (Greece). Medical history, demographic characteristics and detailed exposure history were recorded by conducting personal interviews. Lifetime exposure indicators were calculated for several pesticide chemical subclasses. Moreover, organophosphate metabolite levels were quantified in urine samples of all participants by using gas chromatography -mass spectrometry (GC-MS). Multinomial analysis was used to determine associations between occupational pesticide exposure and diseases or disorders. <i>Results</i>: In the pesticide sprayers group, significantly higher frequencies for rheumatoid arthritis (RA) and allergic rhinitis were observed compared with the control group (<i>p</i> = 0.002 and <i>p</i> = 0.024 respectively). Within the pesticide sprayers group, high lifetime pesticide exposure was associated with increased risk for reporting RA (OR: 43.07 95% CI: 3.09-600.67) and allergic rhinitis (OR: 9.72 95% CI: 2.31-40.89), compared with low pesticide exposure. Exposure to organophsphate, guanidine and quinone pesticides were associated with RA while organophosphates, pyrethroids and paraquat were associated with allergic rhinitis. Despite the higher levels of certain pesticide metabolites observed among participants with rheumatoid arthritis, the differences were not statistically significant. One metabolite (diethylthiophosphate) was found to be significantly increased in allergic rhinitis cases (<i>p</i> = 0.037). <i>Conclusion</i><i>s</i>: The results from the current study suggest a possible association of occupational pesticide exposure with RA and allergic rhinitis that should be further investigated. | allergic rhinitis;pesticides;rheumatoid arthritis;sprayers | pubmed |
Selective androgen receptor modulators: comparative excretion study of bicalutamide in bovine urine and faeces. | Besides their development for therapeutic purposes, non-steroidal selective androgen receptor modulators (non-steroidal SARMs) are also known to impact growth-associated pathways as ligands of androgenic receptors (AR). They present a potential for abuse in sports and food-producing animals as an interesting alternative to anabolic androgenic steroids (AAS). These compounds are easily available and could therefore be (mis)used in livestock production as growth promoters. To prevent such practices, dedicated analytical strategies should be developed for specific and sensitive detection of these compounds in biological matrices. The present study focused on Bicalutamide, a non-steroidal SARM used in human treatment of non-metastatic prostate cancer because of its anti-androgenic activity exhibiting no anti-anabolic effects. To select the most appropriate matrix to be used for control purposes, different animal matrices (urine and faeces) have been investigated and SARM metabolism studied to highlight relevant metabolites of such treatments and establish associated detection time windows. The aim of this work was thus to compare the urinary and faecal eliminations of bicalutamide in a calf, and investigate phase I and II metabolites. The results in both matrices showed that bicalutamide was very rapidly and mainly excreted under its free form. The concentration levels were observed as higher in faeces (ppm) than urine (ppb); although both matrices were assessed as suitable for residue control. The metabolites found were consistent with hydroxylation (phase I reaction) combined or not with glucuronidation and sulfation (phase II reactions). Copyright © 2016 John Wiley & Sons, Ltd. | LC-MS/MS;SARMs;conjugated metabolites;metabolism | pubmed |
Overexpression of ALK5 Induces Human Tenon's Capsule Fibroblasts Transdifferentiation and Fibrosis In Vitro. | To investigate the involvement of activin receptor-like kinase 5 (ALK5) in human Tenon's capsule fibroblasts (HTFs) transdifferentiation and fibrosis. (1) Cultured HTFs were treated with transforming growth factor beta 1 (TGF-β1) at different concentrations for different durations, mRNA expression of ALK5 and plasminogen activator inhibitor-1 (PAI-1) was measured by quantitative polymerase chain reaction (PCR) while protein expression of ALK5, α-smooth muscle actin (α-SMA), and extracellular matrix deposition including fibronectin (FN) and collagen I (Col1) was assessed by western blot. HTFs with or without TGF-β1 were also treated with an ALK5 activity inhibitor, SB-431542, and fibrosis-related genes were assessed. (2) HTFs were transduced with ALK5 lentivirus (ALK5-OE group) or empty lentivirus (NC-OE) with or without the treatment of SB-431542. Protein expression of ALK5, α-SMA, FN, and Col1 was evaluated. (3) HTFs in the ALK5-OE group and NC-OE group were subjected to a scratch-wound assay and their migratory activities assessed. (1) TGF-β1, in a concentration-dependent manner, upregulated ALK5 and PAI-1 expressions in the HTFs, which peaked between 24 and 36 h. These changes were associated with increases in protein levels of FN, Col1, and α-SMA. These TGF-β1 effects were blocked by the ALK5 inhibitor SB-431542. (2) Similarly, overexpression of ALK5 by lentiviral vector significantly increased protein expression of α-SMA, FN, and Col1. Addition of TGF-β1 to the ALK5-OE cells did not produce additional expression of any of the marker proteins. The upregulation of extracellular matrix and α-SMA can be reduced by SB-431542. (3) In ALK5-OE group, HTFs migration was significantly increased compared with normal control and TGF-β1 could still promote ALK5-OE cells migration. Our findings suggest that ALK5 is an important mediator of HTFs fibrosis. ALK5 is a potential therapeutic target to suppress scar formation after filtration surgery. | ALK5;TGF-β;extracellular matrix;human Tenon’s capsule fibroblasts;subconjunctival fibrosis;transdifferentiation | pubmed |
Epidemiology of Zygomycosis: Analysis of National Data from Pathological Autopsy Cases in Japan. | To identify recent trends in the frequency of zygomycosis in autopsy cases, we conducted epidemiological analysis every four years from 1989 to 2009 using national data reported in the "Annual of Pathological Autopsy Cases in Japan." 153,615 cases were autopsied, of which 6622 (4.3%) were found to have had mycosis. Among these, there were 243 cases (3.7%) of zygomycosis, which was the fourth most predominant causative agent of mycoses among the monopathogen mycoses. Of the complicated mycoses, zygomycosis accounted for 56 cases. A total of 299 cases with zygomycoses were observed. The frequency of zygomycosis appeared to be generally stable over the twenty-year period from 1989 to 2009, at around 4% of autopsy cases having mycosis. Younger patients tended to have severe and complicated infections that were characteristic of zygomycosis, compared with non-zygomycosis. The pulmonary and gastrointestinal (GI) systems were the most common foci in our analysis, reflecting the severity of zygomycosis in these sites. Hematological disease was the most frequent underlying disease, but there was a peak of neonatal infections in 2009, which was the first time that this was observed in our studies. These results of the epidemiological analysis of autopsy cases with mycosis demonstrate that clinicians should promptly recognize and treat zygomycosis. | Japan and autopsy;epidemiology;mycoses;visceral | pubmed |
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