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Electrochemical Hydrogel Lithography of Calcium-Alginate Hydrogels for Cell Culture. | Here we propose a novel electrochemical lithography methodology for fabricating calcium-alginate hydrogels having controlled shapes. We separated the chambers for Ca<sup>2+</sup> production and gel formation with alginate with a semipermeable membrane. Ca<sup>2+</sup> formed in the production chamber permeated through the membrane to fabricate a gel structure on the membrane in the gel formation chamber. When the calcium-alginate hydrogels were modified with collagen, HepG2 cells proliferated on the hydrogels. These results show that electrochemical hydrogel lithography is useful for cell culture. | calcium-alginate hydrogel;cell culture;electrochemical hydrogel lithography;electrodeposition | pubmed |
Antimicrobial activity of buttermilk and lactoferrin peptide extracts on poultry pathogens. | Antibiotics are commonly used in poultry feed as growth promoters. This practice is questioned given the arising importance of antibiotic resistance. Antimicrobial peptides can be used as food additives for a potent alternative to synthetic or semi-synthetic antibiotics. The objective of this study was to develop a peptide production method based on membrane adsorption chromatography in order to produce extracts with antimicrobial activity against avian pathogens (Salmonella enterica var. Enteritidis, Salmonella enterica var. Typhimurium, and two Escherichia coli strains, O78:H80 and TK3 O1:K1) as well as Staphylococcus aureus. To achieve this, buttermilk powder and purified lactoferrin were digested with pepsin. The peptide extracts (<10 kDa) were fractionated depending on their charges through high-capacity cation-exchange and anion-exchange adsorptive membranes. The yields of cationic peptide extracts were 6·3 and 15·4% from buttermilk and lactoferrin total peptide extracts, respectively. Antimicrobial activity was assessed using the microdilution technique on microplates. Our results indicate that the buttermilk cationic peptide extracts were bactericidal at less than 5 mg/ml against the selected avian strains, with losses of 1·7 log CFU/ml (Salm. Typhimurium) to 3 log CFU/ml (E. coli O78:H80); viability decreased by 1·5 log CFU/ml for Staph. aureus, a Gram-positive bacterium. Anionic and non-adsorbed peptide extracts were inactive at 5 mg/ml. These results demonstrate that membrane adsorption chromatography is an effective way to prepare a cationic peptide extract from buttermilk that is active against avian pathogens. | Antimicrobial peptide;avian pathogen;buttermilk;lactoferrin;membrane adsorption chromatography | pubmed |
Familial Anaphylaxis after Silkworm Ingestion. | Herein, we present a case of anaphylaxis in multiple family members after ingesting silkworms, an Asian delicacy. While food allergies, including anaphylaxis are unfortunately common, there are no previous reports of multiple family members suffering an anaphylactic reaction after eating silkworms. In addition, both family members required multiple doses of epinephrine and eventually an epinephrine infusion to improve their blood pressures. All interventions, including the epinephrine infusions, were started by emergency medical services (EMS) with on-line medical direction. Both the reaction and the required treatment are not extensively documented in the medical literature. | anaphylaxis;epinephrine;silkworms | pubmed |
Physician preference and patient satisfaction with radioactive seed versus wire localization. | Nonpalpable breast lesions require localization before excision. This is most commonly performed with a wire (WL) or a radioactive seed (SL), which is placed into the breast under radiographic guidance. Although there are advantages of each modality, there are no guidelines to address which patients should undergo WL versus SL. We investigated factors influencing the selection of SL versus WL at our institution and assessed patient satisfaction with each procedure. Patients undergoing preoperative localization of nonpalpable breast lesions from May 2014 through August 2015 were included. Physicians were surveyed on surgical scheduling to evaluate factors influencing the decision to perform SL or WL. Patient satisfaction was evaluated with a survey at the first postoperative visit. Retrospective chart review was performed. 341 patients were included: 104 (30%) patients underwent SL and 237 (70%) underwent WL. There was no difference in patient age, benign versus malignant disease, or need for concomitant axillary surgery comparing the SL versus WL groups. Physician survey indicated that 18% of patients were candidates for WL only. Of the patients who were eligible for both, 88 (41%) ultimately underwent SL and 126 (59%) had WL. The most commonly cited reason for selection of one localization method or the other was physician preference, followed by patient preference or avoiding additional visit. There was no significant difference in self-reported preoperative anxiety level, convenience of the localization procedure, pain of the localization procedure, operative experience, postoperative pain level or medication requirement, or overall patient satisfaction comparing patients who underwent SL and WL. SL and WL offer patients similar comfort and satisfaction. Factors influencing selection of one modality over the other include both logistic and clinical considerations. | Patient satisfaction;Seed localization;Wire localization | pubmed |
Repetitive Intermittent Hypoxia and Locomotor Training Enhances Walking Function in Incomplete Spinal Cord Injury Subjects: A Randomized, Triple-Blind, Placebo-Controlled Clinical Trial. | Incomplete spinal cord injuries (iSCI) leave spared synaptic pathways below the level of injury. Intermittent hypoxia (IH) elicits plasticity in the spinal cord and strengthens spared synaptic pathways, expressed as respiratory and somatic functional recovery in experimental animals and humans with iSCI. This study is a randomized, triple-blind, two-arm parallel clinical trial performed in Santiago, Chile. We compared the effects of a 4-week protocol of IH combined with body weight-supported treadmill training (BWSTT), with continuous normoxia (Nx) and BWSTT on 10-meter walk test (10MWT), 6-minute walk test (6MWT), and timed up and go (TUG) test in American Spinal Injury Association C and D individuals with iSCI. Subjects received daily IH (cycling 9%/21% O<sub>2</sub> every 1.5 min, 15 cycles/day) or continuous Nx (21% O<sub>2</sub>) combined with 45 min BWSTT for 5 consecutive days, followed by IH/Nx 3 × per week (3 × wIH/Nx) for 3 additional weeks. Subjects were assessed at day 5, weekly from weeks 2-4, and at a 2-week follow-up. Daily IH plus BWSTT enhanced walking speed, expressed as decreased 10MWT time at day 5 versus baseline (IH: -10.2 ± 3.0 vs. Nx: -1.7 ± 1.7 sec, p = 0.006), and walking endurance expressed as increased 6MWT distance at day 5 versus baseline (IH: 43.0 ± 10.7 vs. Nx: 6.1 ± 3.4 m, p = 0.012), but not TUG time. Further, 3 × wIH maintained the daily IH-induced walking speed, and enhanced the daily IH-induced walking endurance, which is maintained up to the 2-week follow-up. We conclude that daily IH enhances walking recovery in subjects with iSCI, confirming previous findings. Moreover, 3 × wIH prolonged or enhanced daily IH-induced walking speed and endurance improvements, respectively, up to 5 weeks post-daily IH. Repetitive IH may be a safe and effective therapeutic alternative for persons with iSCI. | human;intermittent hypoxia;plasticity;rehabilitation;spinal cord injuries | pubmed |
Integrative functional genomic analysis unveils the differing dysregulated metabolic processes across hepatocellular carcinoma stages. | Hepatocellular carcinoma (HCC) is a highly heterogeneous disease and the development of targeted therapeutics is still at an early stage. The 'omics' based genome-wide profiling comprising the transcriptome, miRNome and proteome are highly useful in identifying the deregulated molecular processes involved in hepatocarcinogenesis. One of the end products and processes of the central dogma being the metabolites and metabolic processes mediate the cellular functions. In recent years, metabolomics based investigations have revealed the major deregulated metabolic processes involved in carcinogenesis. However, the integrative analysis of the holistic metabolic processes with genomics is at an early stage. Since the gene-sets are highly useful in assessing the biological processes and pathways, we made an attempt to infer the deregulated cellular metabolic processes involved in HCC by employing metabolism associated gene-set enrichment analysis. Further, the metabolic process enrichment scores were integrated with the transcriptome profiles of HCC. Integrative analysis shows three distinct metabolic deregulations: i) hepatocyte function related molecular processes involving lipid/fatty acid/bile acid synthesis, ii) inflammatory processes with cytokine, sphingolipid & chondriotin sulphate metabolism and iii) enriched nucleotide metabolic process involving purine/pyrimidine & glucose mediated catabolic process, in hepatocarcinogenesis. The three distinct metabolic processes were found to occur both in tumor and liver cancer cell line profiles. Unsupervised hierarchical clustering of the metabolic processes along with clinical sample information has identified two major clusters based on AFP (alpha-fetoprotein) and metastasis. The study reveals the three major regulatory processes involved in HCC stages. | Hepatocellular carcinoma;Inflammation;Integrative genomics;Lipid metabolism;Metabolic process;Transcriptome | pubmed |
Trauma as a Cause for Hepatopathy in Newborn Göttingen Minipigs. | Routine husbandry procedures during animal toxicity studies can result in incidental pathological changes. We report on trauma-induced hepatopathy in newborn Göttingen minipigs. Sixty-four neonatal minipigs were allocated to 13- and 26-week treatment arms. There was a 4-week recovery period for both arms. The animals were divided into 2 treatment groups and a vehicle group and were dosed 3 times daily by direct oral administration using a syringe. During the feeding procedure in the first weeks, the animals had to be handled firmly. After 13 weeks, randomly distributed foci of degeneration/necrosis and focal congestion and/or hemorrhage were found in the livers of several animals from all groups. Reduced incidence and severity were evident in the recovery phase, and the lesions were absent after 26 weeks. These changes were considered as related to the manual handling of the animals. Knowledge of these findings is crucial for interpretation of studies utilizing newborn minipigs. | Göttingen;hepatopathy;incidental finding;liver;minipigs;trauma | pubmed |
Regulator of G-Protein Signaling 5 Prevents Smooth Muscle Cell Proliferation and Attenuates Neointima Formation. | Regulator of G-protein signaling 5 (RGS5) is abundantly expressed in vascular smooth muscle cells (SMCs) and inhibits G-protein signaling by enhancing the guanosine triphosphate-hydrolyzing activity of Gα-subunits. In the present study, we investigated the effects of RGS5 on vascular SMC function in vitro and neointima formation after wire-induced injury in mice and determined the underlying mechanisms. We found a robust expression of RGS5 in native arteries of C57BL/6 mice and a highly significant downregulation within neointimal lesions 10 and 21 days after vascular injury as assessed by quantitative polymerase chain reaction, immunoblotting, and immunohistochemistry. In vitro, RGS5 was found significantly downregulated after mitogenic stimulation of human coronary artery SMCs. To restore RGS5 levels, SMCs were transduced with adenoviral vectors encoding wild-type RGS5 or a nondegradable mutant. RGS5-WT and, even more prominently, the C2A-RGS5 mutant prevented SMC proliferation and migration. In contrast, the siRNA-mediated knockdown of RGS5 significantly augmented SMC proliferation. Following overexpression of RGS5, fluorescence-activated cell sorting analysis of propidium iodide-stained cells indicated cell cycle arrest in G0/G1 phase. Mechanistically, inhibition of the phosphorylation of the extracellular signal-regulated kinase 1/2 and mitogen-activated protein kinase downstream signaling was shown to be responsible for the anti-proliferative effect of RGS5. Following wire-induced injury of the femoral artery in C57BL/6 mice, adenoviral-mediated overexpression of RGS5-WT or C2A-RGS5 significantly reduced SMC proliferation and neointima formation in vivo. Downregulation of RGS5 is an important prerequisite for SMC proliferation in vitro and in vivo. Therefore, reconstitution of RGS5 levels represents a promising therapeutic option to prevent vascular remodeling processes. | neointima;proliferation;signal transduction;vascular remodeling;vascular smooth muscle | pubmed |
Intuitive Feelings of Warmth and Confidence in Insight and Noninsight Problem Solving of Magic Tricks. | The focus of the current study is on intuitive feelings of insight during problem solving and the extent to which such feelings are predictive of successful problem solving. We report the results from an experiment (N = 51) that applied a procedure where the to-be-solved problems were 32 short (15 s) video recordings of magic tricks. The procedure included metacognitive ratings similar to the "warmth ratings" previously used by Metcalfe and colleagues, as well as confidence ratings. At regular intervals during problem solving, participants indicated the perceived closeness to the correct solution. Participants also indicated directly whether each problem was solved by insight or not. Problems that people claimed were solved by insight were characterized by higher accuracy and higher confidence than noninsight solutions. There was no difference between the two types of solution in warmth ratings, however. Confidence ratings were more strongly associated with solution accuracy for noninsight than insight trials. Moreover, for insight trials the participants were more likely to repeat their incorrect solutions on a subsequent recognition test. The results have implications for understanding people's metacognitive awareness of the cognitive processes involved in problem solving. They also have general implications for our understanding of how intuition and insight are related. | aha! experience;confidence ratings;insight;intuition;magic;metacognitive feelings;problem solving;warmth ratings | pubmed |
National Utilization Patterns of Steroid Injection and Operative Intervention for Treatment of Common Hand Conditions. | To conduct a population-level analysis of practice trends and probability of surgery based on the number of steroid injections for common hand conditions. Patients aged at least 18 years receiving injection or surgery for carpal tunnel syndrome (CTS), trigger finger (TF), or de Quervain tenovaginitis (DQ) were identified for inclusion using the 2009 to 2013 Truven MarketScan databases. The researchers counted the number of injections performed and calculated the time between injection and operation for patients receiving both treatments. A multivariable logistic regression model was created to evaluate the odds of undergoing surgery based on the number of injections performed, controlling for patient age, sex, comorbidities, and insurance type. The study sample included 251,030 patients who underwent steroid injection or operative release for CTS (n = 129,917), TF (n = 102,778), and DQ (n = 18,335). Most patients with CTS were managed with immediate surgery (71%), whereas most patients with TF and DQ were managed initially with injection (74% and 84%, respectively). Among patients receiving both an injection and an operation, a single injection was the most common practice before surgery (69%, 58%, and 67% of patients with CTS, TF, and DQ, respectively). Multiple injections for DQ and TF were associated with relatively low predicted probability of surgery (17% and 26%, respectively, after 2 injections). However, the predicted probability of surgery after 2 injections was higher in patients with CTS (44%). Given the associated probability of surgery after multiple injections for the 3 hand conditions examined, the practice of repeat injections should be critically examined to determine whether underuse or overuse is present and whether efficiency and use of resources can be improved upon. Prognostic II. | Steroid injection;carpal tunnel syndrome;de Quervain tenovaginitis;treatment utilization;trigger finger | pubmed |
Shape and Charge of Gold Nanomaterials Influence Survivorship, Oxidative Stress and Moulting of Daphnia magna. | Engineered nanomaterials (ENMs) are materials with at least one dimension between 1-100 nm. The small size of ENMs results in a large surface area to volume ratio, giving ENMs novel characteristics that are not traditionally exhibited by larger bulk materials. Coupled with large surface area is an enormous capacity for surface functionalization of ENMs, e.g., with different ligands or surface changes, leading to an almost infinite array of variability of ENMs. Here we explore the effects of various shaped (spheres, rods) and charged (negative, positive) gold ENMs on <i>Daphnia magna</i> (<i>D. magna</i>) in terms of survival, ENM uptake and production of reactive oxygen species (ROS), a key factor in oxidative stress responses. We also investigate the effects of gold ENMs binding to the carapace of <i>D. magna</i> and how this may induce moulting inhibition in addition to toxicity and stress. The findings suggest that ENM shape and surface charge play an important role in determining ENM uptake and toxicity. | Daphnia magna;ecotoxicology;nano-safety;oxidative stress;surface charge | pubmed |
Single-energy metal artifact reduction in postimplant computed tomography for I-125 prostate brachytherapy: Impact on seed identification. | To evaluate the effectiveness of the single-energy metal artifact reduction (SEMAR) technique for improving the accuracy of I-125 seed identification in postimplant computed tomography (CT) after prostate brachytherapy. Postimplant CT images of 40 patients treated with I-125 prostate brachytherapy were acquired. For all patients, 2 data sets were reconstructed, 1 with SEMAR algorithms (SEMAR image), and the other without SEMAR algorithms (non-SEMAR image). Seed locations are automatically detected by the automatic seed finder tool, and their locations were compared between the SEMAR and non-SEMAR images. Dosimetric parameters using seed locations as detected were compared. The true-positive fraction of properly detected seeds on the SEMAR image as determined from a reference seed distribution defined by one investigator was significantly higher than the true-positive fraction on the non-SEMAR image (p = 0.011). The variabilities in D<sub>90</sub> (p = 0.001), V<sub>100</sub> (p = 0.007), and V<sub>150</sub> (p = 0.007) were significantly reduced for seed location on the SEMAR image as compared with non-SEMAR image. Prostate postimplant CT with SEMAR improved the accuracy of seed localization and postimplant dosimetric parameters. | Brachytherapy;I-125;Metal artifact reduction;Prostate | pubmed |
Healthcare costs of the progression of chronic kidney disease and different dialysis techniques estimated through administrative database analysis. | Chronic kidney disease (CKD) progression is associated with significant comorbidities and costs. In Italy, limited evidence of healthcare resource consumption and costs is available. We therefore aimed to investigate the direct healthcare costs in charge to the Lombardy Regional Health Service (RHS) for the treatment of CKD patients in the first year after starting hemodialysis and in the 2 years prior to dialysis. Citizens resident in the Lombardy Region (Italy) who initiated dialysis in the year 2011 (Jan 1 to Dec 31) were selected and data were extracted from Lombardy Regional databases on their direct healthcare costs in the first year after starting dialysis and in the 2 years prior to it was analyzed. Drugs, hospitalizations, diagnostic procedures and outpatient costs covered by RHS were estimated. Patients treated for acute kidney injury, or who died or stopped dialysis during the observational period were excluded. From the regional population (>9,700,000 inhabitants), 1067 patients (34.3 % females) initiating dialysis were identified, of whom 82 % underwent only hemodialysis (HD), 13 % only peritoneal dialysis (PD) and the remaining 5 % both treatments. Direct healthcare costs/patient were € 5239, € 12,303 and € 38,821 (€ 40,132 for HD vs. € 30,444 for PD patients) for the periods 24-12 months pre-dialysis, 12-0 months pre-dialysis, and in the first year of dialysis, respectively. This study highlights a significant economic burden related to CKD and an increase in direct healthcare costs associated with the start of dialysis, pointing to the importance of prevention programs and early diagnosis. | Administrative data;Chronic kidney disease;Cost;Dialysis | pubmed |
Successful transfer to sulfonylureas in KCNJ11 neonatal diabetes is determined by the mutation and duration of diabetes. | The finding that patients with diabetes due to potassium channel mutations can transfer from insulin to sulfonylureas has revolutionised the management of patients with permanent neonatal diabetes. The extent to which the in vitro characteristics of the mutation can predict a successful transfer is not known. Our aim was to identify factors associated with successful transfer from insulin to sulfonylureas in patients with permanent neonatal diabetes due to mutations in KCNJ11 (which encodes the inwardly rectifying potassium channel Kir6.2). We retrospectively analysed clinical data on 127 patients with neonatal diabetes due to KCNJ11 mutations who attempted to transfer to sulfonylureas. We considered transfer successful when patients completely discontinued insulin whilst on sulfonylureas. All unsuccessful transfers received ≥0.8 mg kg(-1) day(-1) glibenclamide (or the equivalent) for >4 weeks. The in vitro response of mutant Kir6.2/SUR1 channels to tolbutamide was assessed in Xenopus oocytes. For some specific mutations, not all individuals carrying the mutation were able to transfer successfully; we therefore investigated which clinical features could predict a successful transfer. In all, 112 out of 127 (88%) patients successfully transferred to sulfonylureas from insulin with an improvement in HbA1c from 8.2% (66 mmol/mol) on insulin, to 5.9% (41 mmol/mol) on sulphonylureas (p = 0.001). The in vitro response of the mutation to tolbutamide determined the likelihood of transfer: the extent of tolbutamide block was <63% for the p.C166Y, p.I296L, p.L164P or p.T293N mutations, and no patients with these mutations successfully transferred. However, most individuals with mutations for which tolbutamide block was >73% did transfer successfully. The few patients with these mutations who could not transfer had a longer duration of diabetes than those who transferred successfully (18.2 vs 3.4 years, p = 0.032). There was no difference in pre-transfer HbA1c (p = 0.87), weight-for-age z scores (SD score; p = 0.12) or sex (p = 0.17). Transfer from insulin is successful for most KCNJ11 patients and is best predicted by the in vitro response of the specific mutation and the duration of diabetes. Knowledge of the specific mutation and of diabetes duration can help predict whether successful transfer to sulfonylureas is likely. This result supports the early genetic testing and early treatment of patients with neonatal diabetes aged under 6 months. | ATP-sensitive potassium channel;Neonatal diabetes;Sulfonylurea receptor | pubmed |
Dysplasia discrimination in intestinal-type neoplasia of the esophagus and colon via digital image analysis. | Determining gastrointestinal tract dysplasia level is clinically important but can be difficult, and given this challenge, we investigated colonic and esophageal dysplastic progression using digital image analysis (IA). Whole slide images were obtained for colonic normal mucosa (NCM), hyperplastic polyps (HP), conventional tubular adenomas (TA), and adenomas with high-grade dysplasia (HGD), and esophageal intestinal metaplasia negative for dysplasia (IM), indefinite for dysplasia (IFD), low-grade dysplasia (LGD), and HGD. Characteristic nuclei were circumscribed, and parameters discriminating groups included nuclear circumference (μm), area (μm(2)), and 15 positive pixel count (PPC) algorithm IA measurements. In colon polyps and esophageal lesions, average nuclear area and circumference ranged 30-108.6 μm(2) and 27.5-48.9 μm, respectively. Differences for average nuclear area and circumference met statistical significance (p < 0.05) between diagnostic groups in the esophagus and colon, except for IM versus IFD nuclear area. Pixel intensity (brightness) separated lesions within both groups with statistical significance except for colonic TAs versus HPs and esophageal LGD versus IM. HGD nuclei in both groups demonstrated more pixel staining heterogeneity than other lesions. Hierarchical clustering and principal component analysis demonstrated that lesions with similar diagnoses tended to cluster together on a low- to high-grade spectrum. Our results confirm that quantitative IA is an effective adjunct reflecting dysplasia in colon polyps and Barrett esophagus lesions. Nuclear area, circumference, and PPC algorithm findings distinguished lesions in a statistically significant manner. This suggests utility for future studies on similar methods, which may provide an adjunctive ancillary technique for pathologists and enhance patient care. | Adenoma;Barrett;Colon;Digital image analysis;Dysplasia;Esophagus | pubmed |
Synthesis and antiproliferative activity of peracetylated 2-amino-1,2-dideoxy-1-nitro-d-glycero-l-manno and d-glycero-d-talo heptitols. | Michael additions between carbohydrate derived nitroalkenes and several aliphatic and aromatic amines proceeded in a stereoselective way, leading to peracetylated 2-amino-1,2-dideoxy-1-nitro-heptitols. In addition, the antiproliferative activity of some of the new adducts has been studied. The results allowed to identify lead compounds which show GI<sub>50</sub> values in the range 1.7-19μM. | Amines;Antiproliferative activity;Carbohydrates;Michael reactions;Nitroalkenes;Stereoselectivity | pubmed |
Property evaluations and application for separation of small molecules of a nanodiamond-polymer composite monolithic column. | A nanodiamond-polymer composite monolithic column was first prepared successfully with modified nanodiamond (ND) as monomer, ethylene glycol dimethacrylate (EDMA) as cross-linker, 1-dodecanol as porogenic agent and benzoyl peroxide/dimethylacetamide (BPO/DMA) as initiator at 35°C for 2.5h. There was a sharp increase of specific surface area with ND added about 22 times from 0mg (3.90m(2)/g) to 7mg (81.2m(2)/g) determined with BET. Characterizations including scanning electron microscopy (SEM), fourier-transform infrared spectra (FIRT) and mercury intrusion porosimetry (MIP) were used to determine the microstructure, group composition, pore size distribution (≃1.56μm) and porosity (≃0.7484μm) of the monolith. An excellent column stability was confirmed by permeability (1.258x10(-10)cm(2)) and good linearity (R(2)=0.998) corresponding to backpressures measured at different flow rates. The highest swelling ability of the composite was about (5%) and classical RPLC of the column obtained occurred with the acetonitrile concentration increasing from 20% to 85% in the mobile phase, above which another retention model of normal-phase chromatography appeared. The items of the eddy dispersion and the absorption-release kinetics were the decisional factors of the composite column compared with the factors of longitudinal diffusion, and the skeleton-eluent mass transfer resistance due to the finite diffusivity. Good separation of neutral and basic small molecules was obtained (24,350 plates/m for neutral molecules and 22,300 plates/m for basic ones) with the hydrophobicity retention mechanism, but not for the acidic ones except to regulate the pH of the mobile phase. | Composite;Monolithic column;Nanodiamond;Small molecules | pubmed |
Similar coding of freely chosen and externally cued intentions in a fronto-parietal network. | Intentional action is essential to human behavior, yet its neural basis remains poorly understood. In order to identify neural networks specifically involved in intentional action, freely chosen and externally cued intentions have previously been contrasted. This has led to the identification of a fronto-parietal network, which is involved in freely choosing one's intentions. However, it remains unclear whether this network encodes specific intentions, or whether it merely reflects general preparatory or control processes correlated with intentional action. Here, we used MVPA on fMRI data to identify brain regions encoding non-motor intentions that were either freely chosen or externally cued. We found that a fronto-parietal network, including the lateral prefrontal cortex, premotor, and parietal cortex, contained information about both freely chosen and externally cued intentions. Importantly, MVPA cross-classification indicated that this network represents the content of our intentions similarly, regardless of whether these intentions are freely chosen or externally cued. This finding suggests that the intention network has a general role in processing and representing intentions independent of their origin. | Free choice;Fronto-parietal cortex;Intentions;Multivoxel pattern analysis;fMRI | pubmed |
Sequence and organization of the complete mitogenome of a Siberian stone loach, Barbatula toni (Dybowsky, 1869) (Cypriniformes: Balitoridae). | In this study, we determined the complete mitogenome sequence of Siberian stone loach, Barbatula toni (Dybowsky, 1869). The total length of mitogenome is 16 623 bp, which consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 1 control region (D-loop). The genome organization and gene order were identical to that of the typical vertebrates. The control region harbors conserved sequence blocks (CSB-D, E, F, CSB-1, CBS-2 and CBS-3) and TA-nucleotide microsatellite repeats in its 3' end. The complete mitogenome may provide important molecular data for further phylogenetic analyses for higher taxa of teleost fishes, especially for the fishes in order Cypriniformes. | 1869);Balitoridae;Barbatula toni (Dybowsky;Cypriniformes;mitogenome | pubmed |
The perceived quality of interprofessional teamwork in an intensive care unit: A single centre intervention study. | This article describes a study that evaluated the quality of teamwork in a surgical intensive care unit and assessed whether teamwork could be improved significantly through a tailor-made intervention. The quality of teamwork prior to and after the intervention was assessed using the Interprofessional Practice and Education Quality Scales (IPEQS) using the PROSE online diagnostics and documenting system, which assesses three domains of teamwork: organisational factors, care processes, and team members' attitudes and beliefs. Furthermore, team members evaluated strengths and weaknesses of the teamwork through open-ended questions. Information gathered by means of the open questions was used to design a tailor-made 12-week intervention consisting of (1) optimising the existing weekly interdisciplinary meetings with collaborative decision-making and clear communication of goal-oriented actions, including the psychosocial aspects of care; and (2) organising and supporting the effective exchange of information over time between all professions involved. It was found that the intervention had a significant impact on organisational factors and care processes related to interprofessional teamwork for the total group and within all subgroups, despite baseline differences between the subgroups in interprofessional teamwork. In conclusion, teamwork, and more particularly the organisational aspects of interprofessional collaboration and processes of care, can be improved by a tailor-made intervention that takes into account the professional needs of healthcare workers. | Intensive care;interprofessional teamwork;intervention;quality of care;surveys | pubmed |
Sex differences in renal transcriptome and programmed hypertension in offspring exposed to prenatal dexamethasone. | Glucocorticoids, predominantly dexamethasone (DEX), are widely used to reduce the risk of prematurity-related chronic lung disease. However, prenatal DEX treatment links to adverse effects in later life, including hypertension. Given that sex differences exist in the blood pressure (BP) control, and that renal transcriptome is sex-specific, thus we intended to elucidate whether prenatal DEX-induced programmed hypertension is in a sex-specific manner and identify candidate genes and pathways using the whole-genome RNA next-generation sequencing (NGS) approach. Offspring were assigned to 4 groups (n=7-8/group): male control (MC), female control (FC), male DEX (MD), and female DEX (FD). Dexamethasone (0.1mg/kg body weight) or vehicle was intraperitoneally administered to pregnant SD rats from gestational day 16-22, to construct a DEX model. Rats were killed at 16weeks of age. Prenatal DEX induced sex-specific increase in BPs in male but not female adult offspring. Prenatal DEX elicited renal programming in a sex-specific fashion as demonstrated by 8 and 18 DEGs in male and female offspring, respectively. Among them, two genes, Hbb and Hba-a2, were shared. The resistance of female offspring to prenatal DEX-induced programmed hypertension is related to a lower Agt expression. Prenatal DEX induced programmed hypertension in adult male but not female offspring, which was related to renal programming affecting sex-biased genes and the RAS. Early identification of sex-specific underlying mechanisms could provide novel deprogramming strategy to reach maximal optimization in both sexes. | Glucocorticoid;Hypertension;Next generation sequencing;Renin-angiotensin system;Sex differences | pubmed |
Perinatal 6-Hydroxydopamine to Produce a Lifelong Model of Severe Parkinson's Disease. | The classic rodent model of Parkinson's disease (PD) is produced by unilateral lesioning of pars compacta substantia nigra (SNpc) in adult rats, producing unilateral motor deficits which can be assessed by dopamine (DA) D<sub>2</sub> receptor (D<sub>2</sub>-R) agonist induction of measurable unilateral rotations. Bilateral SNpc lesions in adult rats produce life-threatening aphagia, adipsia, and severe motor disability resembling paralysis-a PD model that is so compromised that it is seldom used. Described in this paper is a PD rodent model in which there is bilateral 99 % loss of striatal dopaminergic innervation, produced by bilateral intracerebroventricular or intracisternal 6-hydroxydopamine (6-OHDA) administration to perinatal rats. This procedure produces no lethality and does not shorten the life span, while rat pups continue to suckle through the pre-weaning period; and eat without impairment post-weaning. There is no obvious motor deficit during or after weaning, except with special testing, so that parkinsonian rats are indistinguishable from control and thus allow for behavioral assessments to be conducted in a blinded manner. L-DOPA (L-3,4-dihydroxyphenylalanine) treatment increases DA content in striatal tissue, also evokes a rise in extraneuronal (i.e., in vivo microdialysate) DA, and is able to evoke dyskinesias. D<sub>2</sub>-R agonists produce effects similar to those of L-DOPA. In addition, effects of both D<sub>1</sub>- and D<sub>2</sub>-R agonist effects on overt or latent receptor supersensitization are amenable to study. Elevated basal levels of reactive oxygen species (ROS), namely hydroxyl radical, occurring in dopaminergic denervated striatum are suppressed by L-DOPA treatment. Striatal serotoninergic hyperinnervation ensuing after perinatal dopaminergic denervation does not appear to interfere with assessments of the dopaminergic system by L-DOPA or D<sub>1</sub>- or D<sub>2</sub>-R agonist challenge. Partial lesioning of serotonin fibers with a selective neurotoxin either at birth or in adulthood is able to eliminate serotoninergic hyperinnervation and restore the normal level of serotoninergic innervation. Of all the animal models of PD, that produced by perinatal 6-OHDA lesioning provides the most pronounced destruction of nigrostriatal neurons, thus representing a model of severe PD, as the neurochemical outcome resembles the status of severe PD in humans but without obvious motor deficits. | 6-OHDA;6-hydroxydopamine;Animal model;Dopamine;Nigrostriatal tract;Parkinson’s disease;Receptor supersensitivity;Serotonin | pubmed |
Evaluation of a Digital Game-Based Learning Program for Enhancing Youth Mental Health: A Structural Equation Modeling of the Program Effectiveness. | Digital game-based learning (DGBL) makes use of the entertaining power of digital games for educational purposes. Effectiveness assessment of DGBL programs has been underexplored and no attempt has been made to simultaneously model both important components of DGBL: learning attainment (ie, educational purposes of DGBL) and engagement of users (ie, entertaining power of DGBL) in evaluating program effectiveness. This study aimed to describe and evaluate an Internet-based DGBL program, Professor Gooley and the Flame of Mind, which promotes mental health to adolescents in a positive youth development approach. In particular, we investigated whether user engagement in the DGBL program could enhance their attainment on each of the learning constructs per DGBL module and subsequently enhance their mental health as measured by psychological well-being. Users were assessed on their attainment on each learning construct, psychological well-being, and engagement in each of the modules. One structural equation model was constructed for each DGBL module to model the effect of users' engagement and attainment on the learning construct on their psychological well-being. Of the 498 secondary school students that registered and participated from the first module of the DGBL program, 192 completed all 8 modules of the program. Results from structural equation modeling suggested that a higher extent of engagement in the program activities facilitated users' attainment on the learning constructs on most of the modules and in turn enhanced their psychological well-being after controlling for users' initial psychological well-being and initial attainment on the constructs. This study provided evidence that Internet intervention for mental health, implemented with the technologies and digital innovations of DGBL, could enhance youth mental health. Structural equation modeling is a promising approach in evaluating the effectiveness of DGBL programs. | Internet;digital game-based learning;mental health;program evaluation | pubmed |
Trans-generational maternal effect: temperature influences egg size of the offspring in Atlantic salmon Salmo salar. | Effect of increased temperature during egg maturation on the mass of single eggs produced by the offspring was investigated experimentally in Atlantic salmon Salmo salar. Mass of eggs produced by next-generation females was larger when their mothers experienced warmer water during the last two months of egg maturation, relative to those that experienced unheated river water. There was no similar trans-generational paternal effect on offspring egg mass. | adaptive plasticity;climate change;environmental effect;epigenetics;trans-generational influence | pubmed |
Clinical Utility and Economic Impact of CYP2D6 Genotyping. | Pharmacogenetics examines an individual's genetic makeup to help predict the safety and efficacy of medications. Practical application optimizes treatment selection to decrease the failure rate of medications and improve clinical outcomes. Lack of efficacy is costly due to adverse drug reactions and increased hospital stays. Cytochrome P450 2D6 (CYP2D6) metabolizes roughly 25% of all drugs. Detecting variants that cause altered CYP2D6 enzymatic activity identifies patients at risk of adverse drug reactions or therapeutic failure with standard dosages of medications metabolized by CYP2D6. This article discusses the clinical application of pharmacogenetics to improve care and decrease costs. | CYP2D6;CYP2D6 genotyping;Pharmacoeconomics;Pharmacogenetics | pubmed |
Does pelvic floor muscle contraction early after delivery cause perineal pain in postpartum women? | Pelvic floor muscle training is effective and necessary in the prevention and treatment of pelvic floor dysfunction during pregnancy and after childbirth. But because of the high prevalence of perineal pain observed in women after childbirth, many women and caregivers fear to start pelvic floor muscle training immediately after childbirth. However, it is unknown whether pelvic floor muscle contractions (PFMC) provoke perineal pain in women shortly after childbirth. Therefore, the main objective is to study whether PFMC performed immediately after childbirth is painful or not. Observational longitudinal study. Perineal pain was assessed (1-6 days and 9 weeks postpartum) using a visual analogue scale (VAS 0-10) during PFMC and during several activities of daily living (ADL), during micturition and defecation. Descriptive statistics, Wilcoxon and McNemar tests were used. A total of 233 women participated (148 primiparous and 85 multiparous). Immediately postpartum the prevalence and intensity of pain during ADL (73%; VAS 4.9 (±2.3)), micturition (47%; VAS 3.4 (±1.7)) and defecation (19%; VAS 3.6 (±2.2)) were significantly higher (all p<0.000) than during PFMC (8%; VAS 2.2 (±0.9)). At 9 weeks postpartum, 30% experienced perineal pain during sexual intercourse (VAS 4.6 +/- 2.3) and 18% during defecation (VAS 4.7 +/- 2.3), but none during PFMC. Perineal pain is highly prevalent immediately after childbirth during ADL, micturition and defecation, but not during PFMC (only 8%). In case perineal pain occurs during PFMC, the intensity of pain is low (VAS 2). These results show that fear of perineal pain should not discourage women to start pelvic floor muscle training shortly after childbirth. | Pelvic floor muscle contraction;Pelvic floor muscle training;Perineal pain;Postpartum | pubmed |
Regulatory roles of phosphorylation in model and pathogenic fungi. | Over the past 20 years, considerable advances have been made toward our understanding of how post-translational modifications affect a wide variety of biological processes, including morphology and virulence, in medically important fungi. Phosphorylation stands out as a key molecular switch and regulatory modification that plays a critical role in controlling these processes. In this article, we first provide a comprehensive and up-to-date overview of the regulatory roles that both Ser/Thr and non-Ser/Thr kinases and phosphatases play in model and pathogenic fungi. Next, we discuss the impact of current global approaches that are being used to define the complete set of phosphorylation targets (phosphoproteome) in medically important fungi. Finally, we provide new insights and perspectives into the potential use of key regulatory kinases and phosphatases as targets for the development of novel and more effective antifungal strategies. | human fungal pathogens;kinases;phosphatases;phosphoproteome;phosphorylation | pubmed |
Flood-Ring Formation and Root Development in Response to Experimental Flooding of Young Quercus robur Trees. | Spring flooding in riparian forests can cause significant reductions in earlywood-vessel size in submerged stem parts of ring-porous tree species, leading to the presence of 'flood rings' that can be used as a proxy to reconstruct past flooding events, potentially over millennia. The mechanism of flood-ring formation and the relation with timing and duration of flooding are still to be elucidated. In this study, we experimentally flooded 4-year-old Quercus robur trees at three spring phenophases (late bud dormancy, budswell, and internode expansion) and over different flooding durations (2, 4, and 6 weeks) to a stem height of 50 cm. The effect of flooding on root and vessel development was assessed immediately after the flooding treatment and at the end of the growing season. Ring width and earlywood-vessel size and density were measured at 25- and 75-cm stem height and collapsed vessels were recorded. Stem flooding inhibited earlywood-vessel development in flooded stem parts. In addition, flooding upon budswell and internode expansion led to collapsed earlywood vessels below the water level. At the end of the growing season, mean earlywood-vessel size in the flooded stem parts (upon budswell and internode expansion) was always reduced by approximately 50% compared to non-flooded stem parts and 55% compared to control trees. This reduction was already present 2 weeks after flooding and occurred independent of flooding duration. Stem and root flooding were associated with significant root dieback after 4 and 6 weeks and mean radial growth was always reduced with increasing flooding duration. By comparing stem and root flooding, we conclude that flood rings only occur after stem flooding. As earlywood-vessel development was hampered during flooding, a considerable number of narrow earlywood vessels present later in the season, must have been formed after the actual flooding events. Our study indicates that root dieback, together with strongly reduced hydraulic conductivity due to anomalously narrow earlywood vessels in flooded stem parts, contribute to reduced radial growth after flooding events. Our findings support the value of flood rings to reconstruct spring flooding events that occurred prior to instrumental flood records. | Quercus robur;flooding;hypoxia;leaf phenology;pedunculate oak;root development;vessel development | pubmed |
Predictive performance of HAS-BLED risk score for long-term survival in patients with non-ST elevated myocardial infarction without atrial fibrillation. | Predictive value of the Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly, Drugs or alcohol use (HAS-BLED) score for clinical outcomes has been investigated in patients with and without atrial fibrillation. Many factors in the HAS-BLED model have been reported to be prognostic predictors in patients with post-myocardial infarction (MI). However, few studies have investigated the predictive value of HAS-BLED score on long-term survival in patients with post-MI. A total of 617 patients with non-ST elevation MI (NSTEMI) without atrial fibrillation were enrolled. The Thrombolysis In Myocardial Infarction (TIMI), Global Registry of Acute Coronary Events (GRACE), Can Rapid Risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE), and HAS-BLED risk scores were calculated for each patient. The C-statistics of TIMI, GRACE, CRUSADE, and HAS-BLED scores for 3-year survival were 0.658, 0.749, 0.756, and 0.765, respectively. For 3-year survival prediction, GRACE, CRUSADE, and HAS-BLED scores, respectively demonstrated superior performance than TIMI score and there was no significant difference between these three scores (GRACE vs. TIMI: z=1.615, p=0.027; CRUSADE vs. TIMI: z=1.371, p=0.043; HAS-BLED vs. TIMI: z=1.899, p=0.014; CRUSADE vs. GRACE: z=0.078, p=0.234; HAS-BLED vs. GRACE: z=0.435, p=0.166; HAS-BLED vs. CRUSADE: z=0.353, p=0.181). Multivariate analysis showed left ventricular ejection fraction <40%, old age, stroke history, bleeding history, and abnormal renal and liver function were independent predictors for 3-year mortality. HAS-BLED scoring system is similar to the GRACE and CRUSADE systems but better than TIMI system to predict long-term survival outcomes in patients with NSTEMI without atrial fibrillation. However, HAS-BLED score is easier to calculate than GRACE and CRUSADE scores. | CRUSADE;GRACE;HAS-BLED;NSTEMI;Survival;TIMI | pubmed |
Concurrent decrease of brain white matter tracts' thicknesses and fractional anisotropy after antenatal hypoxia-ischemia detected with tract-based spatial statistics analysis. | To examine the extent of gray and white matter (WM) injury following global antenatal hypoxia-ischemia (H-I) and resulting in muscle hypertonia in newborns in a rabbit cerebral palsy model. Rabbit dams (n = 15) underwent uterine ischemia procedure resulting in a global fetal H-I at embryonic day 22 (embryonic 22 days gestation). Newborn's brains underwent high resolution diffusion tensor imaging on a 14 Tesla magnet ex vivo. Fractional anisotropy (FA) in brains of hypertonic (n = 9), nonhypertonic (n = 6), and sham control (n = 5) kits were compared voxel-wise using Tract-Based Spatial Statistics (TBSS) approach. Herein, we used a novel method to assess local WM tracts' thicknesses in TBSS analysis and compare between the groups. Significant (corrected P < 0.05) reduction of WM FA was found in corpus callosum splenium (91.2%), periventricular WM (83.5%), fimbria hippocampi (78.8%), cingulum (81.4%), anterior commissure (95%), internal capsule (83.2%), and optic tract (82.9%) in the hypertonic group. Significant (corrected P < 0.05) reduction in WM tracts' thicknesses was found in corpus callosum (73.3%), periventricular WM (82.5%), cingulum (73.4%), bilaterally in the hypertonic group. WM injury in newborn hypertonic kits 10 days after global fetal H-I is widespread and involves not only motor but also limbic and commissural fibers in multiple regions. WM injury in newborn hypertonic kits is manifested by changes in microstructural properties and decreased FA, as well as reduction of WM volumes, relative to nonhypertonic kits. J. Magn. Reson. Imaging 2017;45:700-709. 1 J. Magn. Reson. Imaging 2017;45:829-838. | perinatal brain injury;tract-based spatial statistics;white matter injury | pubmed |
Carrier dynamics and the role of surface defects: Designing a photocatalyst for gas-phase CO2 reduction. | In<sub>2</sub>O<sub>3</sub><sub>-</sub><sub>x</sub>(OH)<sub>y</sub> nanoparticles have been shown to function as an effective gas-phase photocatalyst for the reduction of CO<sub>2</sub> to CO via the reverse water-gas shift reaction. Their photocatalytic activity is strongly correlated to the number of oxygen vacancy and hydroxide defects present in the system. To better understand how such defects interact with photogenerated electrons and holes in these materials, we have studied the relaxation dynamics of In<sub>2</sub>O<sub>3</sub><sub>-</sub><sub>x</sub>(OH)<sub>y</sub> nanoparticles with varying concentration of defects using two different excitation energies corresponding to above-band-gap (318-nm) and near-band-gap (405-nm) excitations. Our results demonstrate that defects play a significant role in the excited-state, charge relaxation pathways. Higher defect concentrations result in longer excited-state lifetimes, which are attributed to improved charge separation. This correlates well with the observed trends in the photocatalytic activity. These results are further supported by density-functional theory calculations, which confirm the positions of oxygen vacancy and hydroxide defect states within the optical band gap of indium oxide. This enhanced understanding of the role these defects play in determining the optoelectronic properties and charge carrier dynamics can provide valuable insight toward the rational development of more efficient photocatalytic materials for CO<sub>2</sub> reduction. | CO2 hydrogenation;indium oxide;solar fuels;surface defects;transient absorption | pubmed |
A human brain microphysiological system derived from induced pluripotent stem cells to study neurological diseases and toxicity. | Human in vitro models of brain neurophysiology are needed to investigate molecular and cellular mechanisms associated with neurological disorders and neurotoxicity. We have developed a reproducible iPSC-derived human 3D brain microphysiological system (BMPS), comprised of differentiated mature neurons and glial cells (astrocytes and oligodendrocytes) that reproduce neuronal-glial interactions and connectivity. BMPS mature over eight weeks and show the critical elements of neuronal function: synaptogenesis and neuron-to-neuron (e.g., spontaneous electric field potentials) and neuronal-glial interactions (e.g., myelination), which mimic the microenvironment of the central nervous system, rarely seen in vitro before. The BMPS shows 40% overall myelination after 8 weeks of differentiation. Myelin was observed by immunohistochemistry and confirmed by confocal microscopy 3D reconstruction and electron microscopy. These findings are of particular relevance since myelin is crucial for proper neuronal function and development. The ability to assess oligodendroglial function and mechanisms associated with myelination in this BMPS model provide an excellent tool for future studies of neurological disorders such as multiple sclerosis and other demyelinating diseases. The BMPS provides a suitable and reliable model to investigate neuron-neuroglia function as well as pathogenic mechanisms in neurotoxicology. | 3D culture;CNS;brain;microphysiological system;myelination | pubmed |
Relationship of endothelin-1 and NLRP3 inflammasome activation in HT22 hippocampal cells in diabetes. | Diabetes increases the risk and worsens the progression of cognitive decline. Diabetic rats treated with the dual endothelin receptor antagonist bosentan, have been shown to improve hippocampal-based cognitive deficits. The NLRP3 inflammasome has been implicated in vascular complications of diabetes. We hypothesized that diabetes-mediated increase in endothelin-1 (ET-1) in hippocampal cells causes NLRP3 activation and inflammation. An in vitro model was employed by exposing HT22 hippocampal cells to normal (25mM), low (5.5mM) and high (50mM) glucose conditions with and without palmitate (200μM) in the presence and absence of 10μM bosentan for 24h. NLRP3 activity was measured by western blotting for cryopyrin and caspase-1. ET-1 and IL-1β expression was determined by ELISA. HT22 cells synthesize high levels of ET-1 in normal conditions, which was reduced with palmitate and bosentan as well as low and high glucose conditions. Decreased ET-1 levels were associated with greater activation of NLRP3 and IL-1β in normal glucose. High glucose increased NLRP3 markers and activation compared to normal and low glucose. These data suggest that ET-1 may be protective to neurons. Although endothelin antagonism may be beneficial in improving vascular dysfunction and cognitive impairment, its impact on hippocampal neurons should be further explored. | Diabetes;Endothelin;Hippocampus;NLRP3 inflammasome | pubmed |
Eficiency of different doses of rituximab in rheumatoid arthritis. | Evaluate the effectiveness, cost and safety of rituximab in patients with rheumatoid arthritis (RA) depending on the dose used. Retrospective observational study conducted on 52 patients with RA treated with at least one dose of rituximab for 135.3 patient-years were included. Three treatment groups were obtained: (G1) First course and following two 1g infusions separated by 15 days; (G2) First course 2 infusions of 1g followed by 2 infusions of 500mg; (G3) First course and followed by 2 infusions of 500mg separated by 15 days. Re-treatments were administered on-demand according to the clinical activity. The retention time (Log-Rank), retreats and adverse events rates (incidence rate ratio) and treatment costs per patient-month of rituximab were analysed by groups. Group 2 showed a better cost-effectiveness ratio than group 1, as it was associated with a longer retention of rituximab (mean [95% CI] 65.7 [60.8 to 70.7] months vs 33.5 [22.7 to 44.3]; P<.001) and a lower rate of severe adverse events with only a slight increase in the rate of retreatment (courses/patient-year [95% CI] 1.66 [1.39 to 1.93] vs. 1.01 [0.69 to 1.34]; P=.005), and in the costs (median/patient-month, €484.89 vs. €473.45). Although group 3 was €41.20/patient-month cheaper than group 2, it was associated with a higher rate of re-treatments and shorter retention of rituximab (P<.001). The use of full-dose rituximab at onset, followed by reduced doses in successive courses administered on-demand retreatment may be the most cost-effective option. | Adult;Adulto;Agentes antirreumáticos/administración y dosis;Agentes antirreumáticos/efectos adversos;Agentes antirreumáticos/uso terapéutico;Antibodies, monoclonal, murine-derived;Antibodies, monoclonal/administration and dosage;Antibodies, monoclonal/adverse effects;Antibodies, monoclonal/therapeutic use;Anticuerpos, monoclonal, derivado-murino;Anticuerpos, monoclonal/administración y dosis;Anticuerpos, monoclonal/efectos adversos;Anticuerpos, monoclonal/uso terapéutico;Antirheumatic agents/administration and dosage;Antirheumatic agents/adverse effects;Antirheumatic agents/therapeutic use;Arthritis, rheumatoid/drug therapy;Arthritis, rheumatoid/immunology;Artritis, reumatoide/inmunología;Artritis, reumatoide/terapia farmacológica;Dose-response relationship, drug;Drug administration schedule;Humanos;Humans;Pauta administración fármaco;Relación dosis-respuesta, fármaco;Rituximab;Tratamiento desenlace;Treatment outcome | pubmed |
Mechanical Properties of Auxetic Cellular Material Consisting of Re-Entrant Hexagonal Honeycombs. | A preliminary study of the mechanical properties of auxetic cellular material consisting of re-entrant hexagonal honeycombs is presented. For different scales of the honeycombs, the finite element method (FEM) and experimental models are used to perform a parametric analysis on the effects of the Poisson's ratio (cell angle) and the relative density (cell thickness) of honeycombs on bearing capacity and dynamic performance of the auxetic material. The analysis demonstrates that the ultimate bearing capacity of the presented auxetic cellular material is scale-independent when the Poisson's ratio and the relative density are kept constant. The relationship between the geometric parameters and vibration level difference of the honeycombs is also revealed, which can be divided into two converse parts around the Poisson's ratio v = - 1.5 . When v is smaller than -1.5, increasing the cell thickness leads to an increase in the vibration level difference of the honeycombs. Moreover, the dynamic performance of thin-walled honeycombs is greatly influenced by the scale of the honeycombs, especially for the ones with small Poisson's ratio. These conclusions are verified by a frequency response test and a good agreement between the numerical results and experimental data is achieved. | Poisson’s ratio;auxetic cellular material;bearing capacity;dynamic performance;re-entrant honeycombs;relative density;scale | pubmed |
"I Don't Shag Dirty Girls": Marginalized Masculinities and the Use of Partner Selection as a Sexual Health Risk Reduction Strategy in Heterosexual Young Men. | Understanding and addressing the sexual risk taking of young men remains a key research, policy, and practice concern in attempts to improve the emotional and physical sexual health of young men and their sexual partners. This article explores one of the ways in which young men attempt to mitigate sexual risk through the assigning of labels to particular young women and using these as a basis for their decisions in relation to sexual activity, contraception, and condom use. The article uses the lens of hegemonic masculinities theory to increase understanding of the role played by the construction and performance of marginalized masculinities and how these in turn are influenced by social exclusionary processes. The article draws on focus group and interview data from 46 young men aged 15 to 17 years living in the northwest of England, purposively selected on the basis of the prevailing policy definitions of social inclusion and exclusion. The article describes a form of marginalized masculinity pertaining to socially excluded young men, which as a result of limited access to other tenets of hegemonic masculinity, is disproportionately reliant on sexual expertise and voracity alongside overt demonstrations of their superiority over women. It is in this context that young women are assigned the labels of "dirty" or "clean" on the basis of a selection of arbitrary judgments relating to dress, demeanor, area of residence, and perceived sexual activities. The motivations of the young men, the impact on young women, and the policy and practice implications are all discussed. | United Kingdom;adolescence;dirty/clean;labeling;masculinities;risk taking;sexual health;social exclusion | pubmed |
Protective effects of five allium derived organosulfur compounds against mutation and oxidation. | In this study, we examined the ability of five allium-derived organosulfur compounds to protect cells against mutation and oxidation. The compounds tested were 1-propylmercaptan (PM), dimethyl disulfide (DMDS), diallyl disulfide (DADS), propyl disulfide (PDS), and 2,5-dimethylthiophene (DMT). Our results showed that when used at concentrations of 100-400 μmol/l, the five compounds inhibited the mutagenicity of 4-nitroquinoline-N-oxide, a direct mutagen, and benzo[a]pyrene, an indirect mutagen, toward Salmonella typhimurium TA 98 and TA 100. Furthermore, at these concentrations, all five of the compounds protected HepG2 cells against tert-butyl hydroperoxide-induced oxidative cytotoxicity. The compounds likely enhanced cell viability by suppressing the formation of reactive oxygen species and the depletion of glutathione depletion in cells. DMT and PM inhibited mutation and oxidation to a greater extent than DMDS, DADS, and PDS. These results demonstrate for the first time that DMT and PM can contribute to the antimutagenic and the antioxidative property of Allium vegetables. | Antioxidation;Cytotoxicity;Mutation;Organosulfur compounds | pubmed |
Return to work after stroke: Important aspects shared and contrasted by five stakeholder groups. | Poor co-operation between the various stakeholders underscores the need for reviewing important factors that facilitate return to work (RTW) after stroke. To explore and describe important aspects expressed by Swedish stakeholders in the RTW process for persons post stroke and to contrast the stakeholders' aspects exploring different perspectives that may influence optimal RTW. Data from seven focus group interviews with the stakeholders were analyzed using qualitative content analysis. Three main categories made up the findings; the prolonged RTW process, the need for extended knowledge, and the assessment of work ability in the RTW process. Despite the stakeholders' agreement on these important aspects, they presented divergent views of the categories, representing their diverse agendas. A stroke coordinator may remediate the stakeholders' divergent perspectives. The coordinator should be versed in stroke specific knowledge and in a person centered approach to inform the decision process regarding RTW, while finding optimal solutions within regulatory boundary conditions. A coordinator could increase collaboration of the various stakeholders, provide support and coordinate services for the client with stroke and the employer throughout the whole process facilitating RTW after stroke. Future studies are needed to confirm this proposal. | Work;occupation;vocational rehabilitation | pubmed |
Observation of potentially troublesome (2) JCC correlations in 1,1-ADEQUATE spectra. | Despite the tremendous usage of HMBC to establish long-range (1) H-(13) C and (1) H-(15) N heteronuclear correlations, an inherent drawback of the experiment is the indeterminate nature of the (n) JXH correlations afforded by the experiment. A priori there is no reliable way of determining whether a given (n) JCH correlation is, for example, via two-, three-, or sometimes even four-bonds. This limitation of the HMBC experiment spurred the development of the ADEQUATE family of NMR experiments that rely on, in the case of 1,1-ADEQUATE, an out-and-back transfer of magnetization via the (1) JCC homonuclear coupling constant, which is significantly larger than (n) JCC (where n = 2-4) couplings in most cases. Hence, the 1,1-ADEQUATE experiment has generally been assumed to unequivocally provide the equivalent of (2) JCH correlations. The recent development of the 1,1- and 1,n-HD-ADEQUATE experiments that can provide homodecoupling for certain (1) JCC and (n) JCC correlations has increased the sensitivity of the ADEQUATE experiments significantly and can allow acquisition of these data in a fraction of the time required for the original iterations of this pulse sequence. With these gains in sensitivity, however, there occasionally come unanticipated consequences. We have observed that the collapse of proton multiplets, in addition to providing better s/n for the desired (1) JCC correlations can facilitate the observation of typically weaker (2) JCC correlations across intervening carbonyl resonances in 1,1-HD-ADEQUATE spectra. Several examples are shown, with the results supported by the measurement of the (2) JCC coupling constants in question using J-modulated-HD-ADEQUATE and DFT calculations. Copyright © 2016 John Wiley & Sons, Ltd. | 1,1-ADEQUATE;1,1-HD-ADEQUATE;2JCC correlations;J-modulated ADEQUATE | pubmed |
Mothers screening for malnutrition by mid-upper arm circumference is non-inferior to community health workers: results from a large-scale pragmatic trial in rural Niger. | Community health workers (CHWs) are recommended to screen for acute malnutrition in the community by assessing mid-upper arm circumference (MUAC) on children between 6 and 59 months of age. MUAC is a simple screening tool that has been shown to be a better predictor of mortality in acutely malnourished children than other practicable anthropometric indicators. This study compared, under program conditions, mothers and CHWs in screening for severe acute malnutrition (SAM) by color-banded MUAC tapes. This pragmatic interventional, non-randomized efficacy study took place in two health zones of Niger's Mirriah District from May 2013 to April 2014. Mothers in Dogo (Mothers Zone) and CHWs in Takieta (CHWs Zone) were trained to screen for malnutrition by MUAC color-coded class and check for edema. Exhaustive coverage surveys were conducted quarterly, and relevant data collected routinely in the health and nutrition program. An efficacy and cost analysis of each screening strategy was performed. A total of 12,893 mothers and caretakers were trained in the Mothers Zone and 36 CHWs in the CHWs Zone, and point coverage was similar in both zones at the end of the study (35.14 % Mothers Zone vs 32.35 % CHWs Zone, p = 0.9484). In the Mothers Zone, there was a higher rate of MUAC agreement (75.4 % vs 40.1 %, p <0.0001) and earlier detection of cases, with median MUAC at admission for those enrolled by MUAC <115 mm estimated to be 1.6 mm higher using a smoothed bootstrap procedure. Children in the Mothers Zone were much less likely to require inpatient care, both at admission and during treatment, with the most pronounced difference at admission for those enrolled by MUAC < 115 mm (risk ratio = 0.09 [95 % CI 0.03; 0.25], p < 0.0001). Training mothers required higher up-front costs, but overall costs for the year were much lower ($8,600 USD vs $21,980 USD.). Mothers were not inferior to CHWs in screening for malnutrition at a substantially lower cost. Children in the Mothers Zone were admitted at an earlier stage of SAM and required fewer hospitalizations. Making mothers the focal point of screening strategies should be included in malnutrition treatment programs. The trial is registered with clinicaltrials.gov (Trial number NCT01863394). | Community management of acute malnutrition;Mid-upper arm circumference;Screening by mothers;Severe acute malnutrition | pubmed |
Development of a method to rate the primary safety of vehicles using linked New Zealand crash and vehicle licensing data. | Vehicle safety rating systems aim firstly to inform consumers about safe vehicle choices and, secondly, to encourage vehicle manufacturers to aspire to safer levels of vehicle performance. Primary rating systems (that measure the ability of a vehicle to assist the driver in avoiding crashes) have not been developed for a variety of reasons, mainly associated with the difficult task of disassociating driver behavior and vehicle exposure characteristics from the estimation of crash involvement risk specific to a given vehicle. The aim of the current study was to explore different approaches to primary safety estimation, identifying which approaches (if any) may be most valid and most practical, given typical data that may be available for producing ratings. Data analyzed consisted of crash data and motor vehicle registration data for the period 2003 to 2012: 21,643,864 observations (representing vehicle-years) and 135,578 crashed vehicles. Various logistic models were tested as a means to estimate primary safety: Conditional models (conditioning on the vehicle owner over all vehicles owned); full models not conditioned on the owner, with all available owner and vehicle data; reduced models with few variables; induced exposure models; and models that synthesised elements from the latter two models. It was found that excluding young drivers (aged 25 and under) from all primary safety estimates attenuated some high risks estimated for make/model combinations favored by young people. The conditional model had clear biases that made it unsuitable. Estimates from a reduced model based just on crash rates per year (but including an owner location variable) produced estimates that were generally similar to the full model, although there was more spread in the estimates. The best replication of the full model estimates was generated by a synthesis of the reduced model and an induced exposure model. This study compared approaches to estimating primary safety that could mimic an analysis based on a very rich data set, using variables that are commonly available when registered fleet data are linked to crash data. This exploratory study has highlighted promising avenues for developing primary safety rating systems for vehicle makes and models. | consumer information;crash avoidance;primary safety;ratings system;vehicle safety | pubmed |
Disarming an Electrophilic Warhead: Retaining Potency in Tyrosine Kinase Inhibitor (TKI)-Resistant CML Lines While Circumventing Pharmacokinetic Liabilities. | Pharmacologic blockade of the activation of signal transducer and activator of transcription 3 (STAT3) in tyrosine kinase inhibitor (TKI)-resistant chronic myeloid leukemia (CML) cell lines characterized by kinase-independent resistance was shown to re-sensitize CML cells to TKI therapy, suggesting that STAT3 inhibitors in combination with TKIs are an effective combinatorial therapeutic for the treatment of CML. Benzoic acid- and hydroxamic acid-based STAT3 inhibitors SH-4-054 and SH-5-007, developed previously in our laboratory, demonstrated promising activity against these resistant CML cell lines. However, pharmacokinetic studies in murine models (CD-1 mice) revealed that both SH-4-054 and SH-5-007 are susceptible to glutathione conjugation at the para position of the pentafluorophenyl group via nucleophilic aromatic substitution (SN Ar). To determine whether the electrophilicity of the pentafluorophenyl sulfonamide could be tempered, an in-depth structure-activity relationship (SAR) study of the SH-4-054 scaffold was conducted. These studies revealed that AM-1-124, possessing a 2,3,5,6-tetrafluorophenylsulfonamide group, retained STAT3 protein affinity (Ki =15 μm), as well as selectivity over STAT1 (Ki >250 μm). Moreover, in both hepatocytes and in in vivo pharmacokinetic studies (CD-1 mice), AM-1-124 was found to be dramatically more stable than SH-4-054 (t1/2 =1.42 h cf. 10 min, respectively). AM-1-124 is a promising STAT3-targeting inhibitor with demonstrated bioavailability, suitable for evaluation in preclinical cancer models. | STAT3;chronic myeloid leukemia;covalent modification;imatinib resistance;protein-protein interactions | pubmed |
Analysis of the therapeutic evolution in the management of airway infantile hemangioma. | To analyze the evolution in the management of airway infantile hemangioma (AIH) and to report the results from 3 pediatric tertiary care institutions. A retrospective study of patients with diagnosis of AIH and treated in 3 pediatric tertiary care institutions from 1996 to 2014 was performed. Twenty-three patients with diagnosis of AIH were identified. Mean age at diagnosis was 6 mo (range, 1-27). Single therapy was indicated in 16 patients and 7 patients received combined therapy. Two therapeutic groups were identified: Group A included 14 patients who were treated with steroids, interferon, laser therapy and/or surgery; group B included 9 patients treated with oral propranolol. In group A, oral corticosteroids were used in 9 patients with a good response in 3 cases (no requiring other therapeutic option), the other patients required additional treatment options. Cushing syndrome was observed in 3 patients. One patient died of a fulminant sepsis. Open surgical excision and endoscopic therapy were performed in 11 patients (in 5 of them as a single treatment) with a response rate of 54.5%. Stridor persisted in 2 cases, and one patient died during the clinical course of bronchial aspiration. In group B, oral propranolol was used in 9 patients (in 8 of them as a single treatment) with a response rate of 100%, with an mean treatment duration of 7 mo (range, 5-10); complications were not observed. Our experience and the medical literature support the use of propranolol as a first line of treatment in AIH. | Airway;Fibrobronchoscopy;Infantile hemangioma;Propranolol;Surgery | pubmed |
Strain, Psychological Conflicts, Aspirations-Attainment Gap, and Depressive Tendencies among Youth of Mexican Immigrants. | Using Children of Immigrants Longitudinal Study (CILS), this study examined the links between strain, psychological conflicts, aspiration-attainment gap, and depressive tendencies of 755 youth of Mexican origin. Two research questions were raised: (a) What types of strain and psychological conflict induced depressive tendencies? (b) What types of aspirations were relevant to these depressive symptoms? Overall, this study showed that factors implicated by collision of values, perceived discrepancies between aspiration and attainment, and negative appraisal of self could induce depressive mood, feelings, and behaviors, an important finding revealing that this underserved population can benefit from better public health services. | Strain;aspirations;depressive tendencies;youth of Mexican immigrants | pubmed |
Enzyme activity deviates due to spatial and temporal temperature profiles in commercial microtiter plate readers. | Microtiter plates (MTP) and automatized techniques are increasingly applied in the field of biotechnology. However, the susceptibility of MTPs to edge effects such as thermal gradients can lead to high variation of measured enzyme activities. In an effort to enhance experimental reliability, to quantify, and to minimize instrument-caused deviations in enzyme kinetics between two MTP-readers, we comprehensively quantified temperature distribution in 96-well MTPs. We demonstrated the robust application of the absorbance dye cresol red as easily applicable temperature indicator in cuvettes and MTPs and determined its accuracy to ±0.16°C. We then quantified temperature distributions in 96-well MTPs revealing temperature deviations over single MTP of up to 2.2°C and different patterns in two commercial devices (BioTek Synergy 4 and Synergy Mx). The obtained liquid temperature was shown to be substantially controlled by evaporation. The temperature-induced enzyme activity variation within MTPs amounted to about 20 %. Activity deviations between MTPs and to those in cuvettes were determined to 40 % due to deviations from the set temperature in MTPs. In conclusion, we propose a better control of experimental conditions in MTPs or alternative experimental systems for reliable determination of kinetic parameters for bioprocess development. | Cresol red;Edge effect;Lactobacillus brevis ADH (LbADH);Optical thermometer;Temperature measurement | pubmed |
IFN-α potentiates the direct and immune-mediated antitumor effects of epigenetic drugs on both metastatic and stem cells of colorectal cancer. | Epigenetic alterations, including dysregulated DNA methylation and histone modifications, govern the progression of colorectal cancer (CRC). Cancer cells exploit epigenetic regulation to control cellular pathways, including apoptotic and metastatic signals. Since aberrations in epigenome can be pharmacologically reversed by DNA methyltransferase and histone deacetylase inhibitors, epigenetics in combination with standard agents are currently envisaged as a new therapeutic frontier in cancer, expected to overcome drug resistance associated with current treatments. In this study, we challenged this idea and demonstrated that the combination of azacitidine and romidepsin with IFN-α owns a high therapeutic potential, targeting the most aggressive cellular components of CRC, such as metastatic cells and cancer stem cells (CSCs), via tight control of key survival and death pathways. Moreover, the antitumor efficacy of this novel pharmacological approach is associated with induction of signals of immunogenic cell death. Of note, a previously undisclosed key role of IFN-α in inducing both antiproliferative and pro-apoptotic effects on CSCs of CRC was also found. Overall, these findings open a new frontier on the suitability of IFN-α in association with epigenetics as a novel and promising therapeutic approach for CRC management. | cancer stem cell;colorectal cancer;epigenetics;immunogenic cell death;interferon | pubmed |
Regulation of the Expression of Cytoplasmic Polyadenylation Element Binding Proteins for the Treatment of Cancer. | Regulated mRNA translation plays an important role in normal cellular functions and cytoplasmic polyadenylation element binding proteins (CPEBs) are the key factors that control the elongation of poly(A) tail during translation. The expression of various CPEBs has been noted to be linked to tumorigenesis, tumor growth, invasiveness and angiogenesis; however, different CPEBs appear to play diverse roles in cancer. The evidence from the literature suggests that CPEB1 and CPEB3 act more likely as tumor suppressors; in contrast, CPEB2 and CPEB4 mainly exert oncogenic effects. In addition, different CPEB subtypes may interact with each other to regulate tumorigenesis. All four CPEB mRNAs contain multiple microRNA (miRNA) binding sites, while the functions of CPEBs are regulated by various miRNAs. These results indicate that CPEBs play a significant role in tumorigenesis; therefore, manipulation of the expression of different subtypes of CPEBs might modulate the behavior of cancer cells and provide new therapeutic concepts for cancer therapy. However, more studies are required to clarify their definite role in tumor development. | CPEB;cancer;microRNA;review;tumorigenesis | pubmed |
Changes in Malaria Epidemiology in Africa and New Challenges for Elimination. | Although the burden of Plasmodium falciparum malaria is gradually declining in many parts of Africa, it is characterized by spatial and temporal variability that presents new and evolving challenges for malaria control programs. Reductions in the malaria burden need to be sustained in the face of changing epidemiology whilst simultaneously tackling significant pockets of sustained or increasing transmission. Large-scale, robust surveillance mechanisms that measure rather than estimate the actual burden of malaria over time from large areas of the continent where such data are lacking need to be prioritized. We review these fascinating developments, caution against complacency, and make the case that improving the extent and quality of malaria surveillance is vital for Africa as she marches on towards elimination. | Africa;Plasmodium falciparum;elimination;epidemiology;malaria control | pubmed |
Frontal Hypoactivation During a Working Memory Task in Children With 22q11 Deletion Syndrome. | Impairments in executive function, such as working memory, are almost universal in children with chromosome 22q11.2 deletion syndrome. Delineating the neural underpinnings of these functions would enhance understanding of these impairments. In this study, children and adolescents with 22q11 deletion syndrome were compared with healthy control participants in a functional magnetic resonance imaging (MRI) study of working memory. When the 2-back condition was contrasted with the 1-back and 0-back conditions, the participants with 22q11 deletion syndrome showed lower activation in several brain areas involved in working memory-notably dorsolateral prefrontal cortex, anterior cingulate, and precuneus. This hypoactivation may be due to reduced gray matter volumes or white matter connectivity in the frontal and parietal regions, differences that have previously been documented in children with 22q11 deletion syndrome. Understanding differences in brain function will provide a foundation for future interventions to address the wide range of neurodevelopmental deficits observed in 22q11 deletion syndrome. | 22q;DiGeorge;fMRI;velocardiofacial | pubmed |
A Study for Visual Realism of Designed Pictures on Computer Screens by Investigation and Brain-Wave Analyses. | In this article, the visual realism of designed pictures on computer screens is studied by investigation and brain-wave analyses. The practical electroencephalogram (EEG) measurement is always time-varying and fluctuating so that conventional statistical techniques are not adequate for analyses. This study proposes a new scheme based on "fingerprinting" to analyze the EEG. Fingerprinting is a technique of probabilistic pattern recognition used in electrical engineering, very like the identification of human fingerprinting in a criminal investigation. The goal of this study was to assess whether subjective preference for pictures could be manifested physiologically by EEG fingerprinting analyses. The most important advantage of the fingerprinting technique is that it does not require accurate measurement. Instead, it uses probabilistic classification. Participants' preference for pictures can be assessed using fingerprinting analyses of physiological EEG measurements. | EEG fingerprinting;visual preference;visual realism | pubmed |
Biomarkers in Parkinson's disease: Advances and strategies. | Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive motor disturbances and affects more than 1% of the worldwide population. Despite considerable progress in understanding PD pathophysiology, including genetic and biochemical causes, diagnostic approaches lack accuracy and interventions are restricted to symptomatic treatments. PD is a complex syndrome with different clinical subtypes and a wide variability in disorder course. In order to deliver better clinical management of PD patients and discovery of novel therapies, there is an urgent need to find sensitive, specific, and reliable biomarkers. The development of biomarkers will not only help the scientific community to identify populations at risk, but also facilitate clinical diagnosis. Furthermore, these tools could monitor progression, which could ultimately deliver personalized therapeutic strategies. The field of biomarker discovery in PD has attracted significant attention and there have been numerous contributions in recent years. Although none of the parameters have been validated for clinical practice, some candidates hold promise. This review summarizes recent advances in the development of PD biomarkers and discusses new strategies for their utilization. | Biochemical biomarkers;Diagnosis;Imaging;Parkinson's disease;Progression | pubmed |
Tumor heterogeneity of fibroblast growth factor receptor 3 (FGFR3) mutations in invasive bladder cancer: implications for perioperative anti-FGFR3 treatment. | Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer. Preclinical studies show that anti-FGFR3 treatment slows down tumor growth, suggesting that this tyrosine kinase receptor is a candidate for personalized bladder cancer treatment, particularly in patients with mutated FGFR3. We addressed tumor heterogeneity in a large multicenter, multi-laboratory study, as this may have significant impact on therapeutic response. We evaluated possible FGFR3 heterogeneity by the PCR-SNaPshot method in the superficial and deep compartments of tumors obtained by transurethral resection (TUR, n = 61) and in radical cystectomy (RC, n = 614) specimens and corresponding cancer-positive lymph nodes (LN+, n = 201). We found FGFR3 mutations in 13/34 (38%) T1 and 8/27 (30%) ≥T2-TUR samples, with 100% concordance between superficial and deeper parts in T1-TUR samples. Of eight FGFR3 mutant ≥T2-TUR samples, only 4 (50%) displayed the mutation in the deeper part. We found 67/614 (11%) FGFR3 mutations in RC specimens. FGFR3 mutation was associated with pN0 (P < 0.001) at RC. In 10/201 (5%) LN+, an FGFR3 mutation was found, all concordant with the corresponding RC specimen. In the remaining 191 cases, RC and LN+ were both wild type. FGFR3 mutation status seems promising to guide decision-making on adjuvant anti-FGFR3 therapy as it appeared homogeneous in RC and LN+. Based on the results of TUR, the deep part of the tumor needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. We conclude that studies on the heterogeneity of actionable molecular targets should precede clinical trials with these drugs in the perioperative setting. | FGFR3;bladder;cancer;heterogeneity;mutations;targeted therapy | pubmed |
Modeling and optimization of degree of folate grafted on chitosan and carboxymethyl-chitosan. | Chitosan is a cationic polysaccharide with great properties and so is considered as an attractive biopolymer. However, chitosan shows its antibacterial activity only in acidic environment and this restricts its uses. So water-soluble chitosan derivatives such as carboxymethyl chitosan could be good candidates for such biomedical applications. Modified chitosan with hydrophobic functional groups such as folate (FA) is able to make self-assembled nanoparticles in aqueous media. One of the most important factors affecting the properties of resulting nanoparticles such as size, morphology, amount and efficiency of drug loading and also drug release profile is the amount of FA groups grafted on the chitosan chains. In this study FA modified chitosan and carboxymethyl chitosan have been synthesized using folic acid, <i>N</i>-hydroxy succinimide (NHS), <i>N</i>, <i>N</i>-dicyclohexylcarbodiimide (DCC) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). The effect of molecular weight, degree of substitution of carboxymethyl hydrophilic group and primary molar ratio of folic acid to chitosan/carboxymethyl chitosan (CMCS) on degree of substitution of folate functional groups grafted on chitosan chains was modeled using a statistical software package (Design of Expert 8, Trial version). Degree of substitution of grafted folate was measured using UV/Vis spectroscopy. Results show that degree of substitution of CMC and molar ratio of folic acid to chitosan/carboxymethyl chitosan has direct effect on substitution degree of folate and molecular weight has an inverse impact. Also results show that molar ratio of folic acid to chitosan/(CMCS) has the most effect on substitution degree of folate and the proposed model is statistically valid to predict degree of substitution of FA groups on chitosan chains. | Carboxymethyl chitosan;Design experiments;Folic acid modified chitosan;Modeling of substitution degree | pubmed |
Acridinium Ester-Functionalized Carbon Nanomaterials: General Synthesis Strategy and Outstanding Chemiluminescence. | In this work, three different kinds of acridinium ester (AE)-functionalized carbon nanomaterials, including AE-functionalized carbon nanoparticles (AE-CNPs), AE-functionalized graphene oxide (AE-GO), and AE-functionalized multiwalled carbon nanotubes (AE-MCNTs), were synthesized for the first time via a simple, general, and noncovalent strategy. AE molecules were assembled on the surface of carbon nanomaterials by electrostatic interaction, π-π stacking interaction, and amide bond. The synthesized AE-CNPs, AE-GO, and AE-MCNTs with 5.0 × 10(-8) mol·L(-1) of synthetic AE concentration, which was very low compared with other chemiluminescence (CL) reagents such as luminol, N-(aminobutyl)-N-(ethylisoluminol), and lucigenin at the concentration of 3.3 × 10(-4) to 5.0 × 10(-6) mol·L(-1) used for the synthesis of CL-functionalized nanomaterials, exhibited outstanding CL activity and good stability. It was found that carbon nanomaterials as nanosized platforms could efficiently immobilize AE molecules and facilitate the formation of OH(•) and O2(•-), leading to strong light emission. Moreover, the CL intensity of AE-GO was the highest, which was about 8.7 and 3.7 times higher than that of AE-CNPs and AE-MCNTs, respectively. This mainly resulted from a difference in the amount of adsorbed AE molecules on the surface of different carbon nanomaterials. Additionally, the prepared AE-CNPs demonstrated excitation-dependent fluorescence property and good fluorescence stability against photobleaching. On the basis of the excellent CL and special fluorescence properties of AE-CNPs, a dual-mode array strategy has been proposed for the first time and seven kinds of transition-metal ions could be successfully discriminated. | acridinium ester;array;carbon nanomaterials;chemiluminescence;fluorescence;functionalization | pubmed |
Sources of polycyclic aromatic hydrocarbons are associated with gene-specific promoter methylation in women with breast cancer. | Tobacco smoke, diet and indoor/outdoor air pollution, all major sources of polycyclic aromatic hydrocarbons (PAHs), have been associated with breast cancer. Aberrant methylation may be an early event in carcinogenesis, but whether PAHs influence the epigenome is unclear, particularly in breast tissue where methylation may be most relevant. We aimed to evaluate the role of methylation in the association between PAHs and breast cancer. In a population-based case-control study, we measured promoter methylation of 13 breast cancer-related genes in breast tumor tissue (n=765-851 cases) and global methylation in peripheral blood (1055 cases/1101 controls). PAH sources (current active smoking, residential environmental tobacco smoke (ETS), vehicular traffic, synthetic log burning, and grilled/smoked meat intake) were evaluated separately. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). When comparing methylated versus unmethylated genes, synthetic log use was associated with increased ORs for CDH1 (OR=2.26, 95%CI=1.06-4.79), HIN1 (OR=2.14, 95%CI=1.34-3.42) and RARβ (OR=1.80, 95%CI=1.16-2.78) and decreased ORs for BRCA1 (OR=0.44, 95%CI=0.30-0.66). Residential ETS was associated with decreased ORs for ESR1 (OR=0.74, 95%CI=0.56-0.99) and CCND2 methylation (OR=0.65, 95%CI=0.44-0.96). Current smoking and vehicular traffic were associated with decreased ORs for DAPK (OR=0.53, 95%CI=0.28-0.99) and increased ORs for TWIST1 methylation (OR=2.79, 95%CI=1.24-6.30), respectively. In controls, synthetic log use was inversely associated with LINE-1 (OR=0.59, 95%CI=0.41-0.86). PAH sources were associated with hypo- and hypermethylation at multiple promoter regions in breast tumors and LINE-1 hypomethylation in blood of controls. Methylation may be a potential biologic mechanism for the associations between PAHs and breast cancer incidence. | Air pollution;Environmental tobacco smoke;Grilled meat.;Methylation;Smoking | pubmed |
Periungual and subungual congenital melanocytic nevus on the foot: A rare case report. | A 5-year-old caucasian child is described with a congenital melanocytic periungual and subungual nevus on the right second toe. Histopathologic examination revealed a junctional nevus. Congenital subungual nevi in this location are rare. To the best of our knowledge, this represents the first case of lesion on the right second toe to be reported in the literature. | Foot diseases;Nevi and melanomas;Nevus | pubmed |
Assessment of genotoxicity of pyrethrin in cultured human lymphocytes. | Pyrethrin is an insecticide that is obtained from the Chrysanthemum flower (Pyrethrum). In this study, we examined the genotoxic effects of pyrethrin on cultured human lymphocytes using sister chromatid exchanges (SCEs) and 8-hydroxy deoxyguanosine (8-OHdG) assays. Cultures were treated with different concentrations of pyrethrin (25, 50, and 100 μg/mL), which was dissolved in in dimethyl sulfoxide (DMSO). The results showed that treatment of cultured lymphocytes with pyrethrin at 50 μg/mL and 100 μg/mL induced significant elevation in SCEs (p < 0.05). In addition, the 100 μg/mL concentration significantly affected both mitotic and proliferative indices (p < 0.05). Finally, pyrethrin induced significant elevation in the oxidative stress marker 8-OHdG in a dose-dependent manner (p < 0.001). In conclusion, the results suggest that pyrethrin is genotoxic as measured by two independent assays on genetic toxicity. | 8-OHdG;DNA damage;Pyrethrin;sister chromatid exchange | pubmed |
Effect of temperature on continuous dry fermentation of swine manure. | Laboratory-scale experiments were performed on the dry digestion of solid swine manure in a semi-continuous mode using 4.5 L down plug-flow anaerobic reactors with an organic loading rate of 3.46 kg volatile solids (VS) m(-3) d(-1) to evaluate the effects of temperature (15, 25 and 35 °C). At 15 °C, biogas production was the poorest due to organic overload and acidification, with a methane yield of 0.036 L CH4 g(-1) VS added and a volumetric methane production rate of 0.125 L CH4 L(-1) d(-1). The methane yield and volumetric methane production rate at 25 °C (0.226 L CH4 g(-1) VS added and 0.783 L CH4 L(-1) d(-1), respectively) were 6.24 times higher than those at 15 °C. However, the methane yield (0.237 L CH4 g(-1) VS added) and the volumetric methane production rate (0.821 L CH4 L(-1) d(-1)) at 35 °C were only 4.86% higher than those at 25 °C, which indicated similar results were obtained at 25 °C and 35 °C. The lower biogas production at 35 °C in dry digestion compared with that in wet digestion could be attributed to ammonia inhibition. For a single pig farm, digestion of solid manure is accomplished in small-scale domestic or small-farm bioreactors, for which operating temperatures of 35 °C are sometimes difficult to achieve. Considering biogas production, ammonia inhibition and net energy recovery, an optimum temperature for dry digestion of solid swine manure is 25 °C. | Biogas production;Dry digestion;Swine manure;Temperature | pubmed |
Biomarkers and Targeted Therapy in Pancreatic Cancer. | Pancreatic ductal adenocarcinoma (PDAC) constitutes 90% of pancreatic cancers. PDAC is a complex and devastating disease with only 1%-3% survival rate in five years after the second stage. Treatment of PDAC is complicated due to the tumor microenvironment, changing cell behaviors to the mesenchymal type, altered drug delivery, and drug resistance. Considering that pancreatic cancer shows early invasion and metastasis, critical research is needed to explore different aspects of the disease, such as elaboration of biomarkers, specific signaling pathways, and gene aberration. In this review, we highlight the biomarkers, the fundamental signaling pathways, and their importance in targeted drug delivery for pancreatic cancers. | EGFR;EMT;KRAS;MMPs;MYC;NF-κB;PAF;PIM;RAGE;mTOR;miRNA;pancreatic cancer;pancreatic cancer stem cells | pubmed |
pKa determination of graphene-like materials: Validating chemical functionalization. | We report a novel pKa determination for different graphene-like samples: graphene oxide (GO), reduced GO (rGO), graphene nanoribbons (GNR), oxidized GNR (GONR), thiol- and imidazole-functionalized GO (GOSH and GOIMZ, respectively) and thiol-functionalized GONR (GONRSH). Using the specialized computational program BEST7 for treating titration curves, pKas for different functional groups were discriminated (confirmed by infrared spectra) and their composition quantified. Overall, three equilibria were distinguished, two relative to carboxylic acids exhibiting different acidic degrees (pKa1∼4.0 and pKa2∼6.0) and one relative to alcohols (pKa4∼10.0). Upon functionalization on carboxylate sites, thiol (pKa(GOSH/GONRSH)=6.7) and imidazole (pKa(GOIMZ)=6.6) moieties were discerned, followed by a decrease of their carboxylate percentage (compared to the precursors), thus allowing determining the degree of functionalization (48% and 36% of thiol content for GOSH and GONRSH respectively, and 29% of imidazole for GOIMZ). The proposed method is innovative and simpler when compared to the traditional tools usually employed to quantify chemical functionalization. | Graphene functionalization;Graphene nanoribbon;Titration;pK(a) determination | pubmed |
The JAK/STAT pathway in obesity and diabetes. | Diabetes mellitus are complex, multi-organ metabolic pathologies characterized by hyperglycemia. Emerging evidence shows that the highly conserved and potent JAK/STAT signaling pathway is required for normal homeostasis, and, when dysregulated, contributes to the development of obesity and diabetes. In this review, we analyze the role of JAK/STAT activation in the brain, liver, muscle, fat and pancreas, and how this affects the course of the disease. We also consider the therapeutic implications of targeting the JAK/STAT pathway in treatment of obesity and diabetes. | JAK/STAT signaling pathway;adipose tissue;brain;cytokines;diabetes;hormones;liver;muscle;obesity;pancreas | pubmed |
Lack of cooperation between physicians and dentists during osteoporosis treatment may increase fractures and osteonecrosis of the jaw. | Our previous questionnaire-based survey suggested that discontinuation of antiresorptive agents before tooth extraction may increase adverse events and disturb osteoporosis treatment without completely preventing osteonecrosis of the jaw (O.N.J.). We also found little cooperation between physicians and dentists in Japan. However, limitations of our previous study included a survey of doctors belonging to small clinics and a small sample size. Our current study aimed to confirm the results of our previous survey in doctors mainly belonging to academia. A structured questionnaire including 14 key clinical queries was sent to 1812 physicians of the Japan Osteoporosis Society, and 629 responses were received. Dentists requested discontinuation of many medications that were not associated with the incidence of O.N.J. A total of 523 respondents had received discontinuation requests from dentists. Of these, 97 respondents experienced 119 adverse events including 25 fractures and seven incidences of O.N.J. The ratios of valid responses for fractures were 3.6% and 5.3% in patients with a discontinuation of <3 and ≥3 months, respectively. Those for O.N.J. were 0.7% and 1.6%, respectively. Respondents who refused discontinuation requests reported no cases of O.N.J. Approximately 17% of respondents had patients who discontinued osteoporosis treatment following a requested drug discontinuation after tooth extraction. Approximately 62% of respondents did not request oral health care by a dentist before antiresorptive therapy, and 72% reported no cooperation between physicians and dentists in their region. This study reconfirms the results of our previous survey. Discontinuation of antiresorptive treatment may increase both fractures and O.N.J. Immediate development of a strategy for sharing information about O.N.J. among physicians, dentists, and patients is required to reduce the incidence of both O.N.J. and skeletal events in osteoporosis treatment. Study limitations were selection bias due to low response rate and possible inaccurate responses to the questionnaire. | Adverse event;Cooperation;Discontinuation;Jaw;Osteonecrosis;Osteoporosis | pubmed |
Dysfunction of the neurovascular unit in ischemic stroke and neurodegenerative diseases: An aging effect. | Current understanding on the mechanisms of brain injury and neurodegeneration highlights an appreciation of multicellular interactions within the neurovascular unit (NVU), which include the evolution of blood-brain barrier (BBB) damage, neuronal cell death or degeneration, glial reaction, and immune cell infiltration. Aging is an important factor that influences the integrity of the NVU. The age-related physiological or pathological changes in the cellular components of the NVU have been shown to increase the vulnerability of the NVU to ischemia/reperfusion injury or neurodegeneration, and to result in deteriorated brain damage. This review describes the impacts of aging on each NVU component and discusses the mechanisms by which aging increases NVU sensitivity to stroke and neurodegenerative diseases. Prophylactic or therapeutic perspectives that may delay or diminish aging and thus prevent the incidence of these neurological disorders will also be reviewed. | Aging;Ischemic stroke;Neurodegeneration;Neurovascular unit;Vulnerability | pubmed |
Prophylactic managements of hepatitis B viral infection in liver transplantation. | Liver transplantation (LT) is a considerably effective treatment for patients with end-stage hepatitis B virus (HBV)-related liver disease. However, HBV infection often recurs after LT without prophylaxis. Since the 1990s, the treatment for preventing HBV reinfection after LT has greatly progressed with the introduction of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues (NAs), resulting in improved patient survival. The combination therapy consisting of high-dose HBIG and lamivudine is highly efficacious for preventing the recurrence of HBV infection after LT and became the standard prophylaxis for HBV recurrence. However, mainly due to the high cost of HBIG treatment, an alternative protocol for reducing the dose and duration of HBIG has been evaluated. Currently, combination therapy using low-dose HBIG and NAs is considered as the most efficacious and cost-effective prophylaxis for post-LT HBV reinfection. Recently, NA monotherapy and withdrawal of HBIG from combination therapy, along with the development of new, potent high genetic barrier NAs, have provided promising efficacy, especially for low-risk recipients. This review summarizes the prophylactic protocol and their efficacy including prophylaxis of de novo HBV infection from anti-HBc antibody-positive donors. In addition, challenging approaches such as discontinuation of all prophylaxis and active immunity through hepatitis B vaccination are discussed. | Anti-hepatitis B immunoglobulin;Hepatitis B infection;Liver transplantation;Nucleos(t)ide analogue;Prophylaxis | pubmed |
Costs of Drug Therapy in Patients with Ankylosing Spondylitis in Brazil. | The Brazilian Public Health System offers free-of-charge drug treatment for ankylosing spondylitis (AS) to all Brazilian citizens. We report here the first population-based cohort study on patients with AS in Brazil. The aim of this study was to evaluate the costs of the tumour necrosis factor (anti-TNF) blockers and disease-modifying antirheumatic drugs (DMARDs) that were used in the treatments of patients with AS in Brazil between March 2010 and September 2013. A retrospective cohort study was performed using administrative databases. All patients with a diagnosis of AS who were aged 18 years or older and had been dispensed anti-TNF or DMARDs were included in the analysis. The cost analysis was carried out from the health system perspective, and the results were described as median monthly cost per capita and the annual cost over the study period. A search of the databases identified 1251 patients with AS who were treated during the study period, of whom 63.3% were male; the median age was 41 years. During the study period, 78.0% of patients initiated treatment with anti-TNF drugs and 22.0% with DMARDs. The median monthly cost per capita was US$ 1650 for anti-TNF therapy and US$ 25 for treatment with DMARDs. Among the anti-TNF drugs, therapy with etanercept was associated with the lowest cost per patient, followed by adalimumab and infliximab. No difference in monthly cost was observed in relation to gender and age. The cost per patient of treating AS in this study cohort was lower with etanercept than with adalimumab and infliximab. These results highlights the economic burden of treating patients with AS. | Administrative claims data;Ankylosing spondylitis;Anti-TNF therapy;DMARDs;Drug cost | pubmed |
Novel GM1 ganglioside-like peptide mimics prevent the association of cholera toxin to human intestinal epithelial cells in vitro. | Cholera is an acute diarrheal disease caused by infection in the gastrointestinal tract by the gram-negative bacterium, Vibrio cholerae, and is a serious public health threat worldwide. There has not been any effective treatment for this infectious disease. Cholera toxin (CT), which is secreted by V. cholerae, can enter host cells by binding to GM1, a monosialoganglioside widely distributed on the plasma membrane surface of various animal epithelial cells. The present study was undertaken to generate peptides that are conformationally similar to the carbohydrate epitope of GM1 for use in the treatment of cholera and related bacterial infection. For this purpose, we used cholera toxin B (CTB) subunit to select CTB-binding peptides that structurally mimic GM1 from a dodecamer phage-display library. Six GM1-replica peptides were selected by biopanning based on CTB recognition. Five of the six peptides showed inhibitory activity for GM1 binding to CTB. To test the potential of employing the peptide mimics for intervening with the bacterial infection, those peptides were examined for their binding capacity, functional inhibitory activity and in vitro effects using a human intestinal epithelial cell line, Caco-2 cells. One of the peptides, P3 (IPQVWRDWFKLP), was most effective in inhibiting cellular uptake of CTB and suppressing CT-stimulated cyclic adenosine monophosphate production in the cells. Our results thus provide convincing evidence that GM1-replica peptides could serve as novel agents to block CTB binding on epithelial cells and prevent the ensuing physiological effects of CT. | GM1 ganglioside;bacterial infection;cAMP;cholera toxin;epithelial cell | pubmed |
Functional Mitral Regurgitation: Appraising the Evidence Behind Recommended Treatment Strategies. | Functional mitral regurgitation (MR) is the most common type of MR encountered in clinical practice. Because the disease arises from the ventricular aspect of the mitral valve apparatus, treatment therapies are less defined and outcomes are poor. In this review, the state of evidence for medical and surgical therapy in functional MR is appraised. Future directions for research in this area are also defined. | Functional mitral regurgitation;Medical therapy;Mitraclip;Mitral valve replacement;Surgery | pubmed |
MT1-MMP Inhibits the Activity of Bst-2 via Their Cytoplasmic Domains Dependent Interaction. | Bst-2 (bone marrow stromal cell antigen 2) is a type II membrane protein, and it acts as a tetherin to inhibit virion releasing from infectious cells. Membrane type-1 matrix metalloproteinase (MT1-MMP) is a protease. It plays a pivotal role in cellular growth and migration by activating proMMP-2 into active MMP2. Our results here elaborate that MT1-MMP inhibits the tetherin activity of Bst-2 by interacting with Bst-2, and the cytoplasmic domains of both Bst-2 and MT1-MMP play critical roles within this interaction. Based on our experimental data, the assays for virion release and co-immunoprecipitation have clearly demonstrated that the activity of Bst-2 is markedly inhibited by MT1-MMP via their interaction; and both the N-terminal domain of Bst-2 and the C-terminal domain of MT1-MMP are important in the interaction. Immunostaining and Confocal Microscopy assay shows that MT1-MMP interacts with Bst-2 to form granular particles trafficking into cytoplasm from membrane and, finally, results in Bst-2 and MT1-MMP both being inhibited. In addition, mutant experiments elucidate that the N-terminal domain of Bst-2 is not only important in relating to the activity of Bst-2 itself, but is important for inhibiting the MT1-MMP/proMMP2/MMP2 pathway. These findings suggest that MT1-MMP is a novel inhibitor of Bst-2 in MT1-MMP expressed cell lines and also indicate that both the N-terminal domain of Bst-2 and the C-terminal domain of MT1-MMP are crucial in down-regulation. | Membrane type-1 matrix metalloproteinase (MT1-MMP);bone marrow stromal cell antigen 2 (Bst-2);tetherin;virus release | pubmed |
Youths' perception and knowledge towards environmental problems in a developing country: in the case of Atatürk University, Turkey. | This study explores the perception and knowledge of environmental problems among students of Atatürk University, Turkey, as a developing country, by comparing their perceptions with known facts about environmental problems at local, national, and global levels. In addition, the correlation between the student groups and their knowledge levels and the differences between the student groups according to their knowledge levels when taking age and gender into account are explored. To this end, the research designed as a case study and pursued an exploratory approach revealed that major perceived environmental problems show differences at local, national, and global levels; that consensus on both major perceived problems and knowledge decreases from a local to global level; that a weak correlation exists between the age (r (205) = -.010; .002; -.071) and gender groups (r (205) = -.099; -.125; .065) in terms of their knowledge at local, national, and global level, respectively; and that the contribution of knowledge at a national level can help to explain differences among the age groups (-.304; .102; -.148) at national level and the gender groups (.131; -.205) at national and global levels. | Environmental problems;Knowledge;Local, national and global levels;Perception;University students, Turkey | pubmed |
Symptom relief in patients with pneumonia and dementia: implementation of a practice guideline. | This study aimed to assess the degree of implementation and barriers encountered in the use of a practice guideline for optimal symptom relief for patients with dementia and pneumonia in Dutch nursing homes. A process evaluation included assessment of reach, fidelity, and dose delivered using researcher's observations, and dose received was addressed in a question "use of the practice guideline," which the physicians completed for each patient included in the study. Perceived barriers were assessed with a structured questionnaire (response 69%) and semi-structured interviews (n = 14), which were subject to qualitative content analysis. Of the 55 physicians involved in the intervention phase, 87% attended an implementation meeting; 20 physicians joined the study later (reach). The intervention was implemented as planned, and all intervention components were delivered by the researchers (fidelity and dose delivered). Thirty-six physicians included 109 patients. For 81% of the patients, the treating physician stated to have used the guideline (dose received). The guideline was perceived as providing a good overview of current practice, but some physicians had expected a more directive protocol or algorithm. Further, recommended regular observations of symptoms were rarely performed. Physician's often felt that "this is not different from what we usually do," and with the acute illness, there was not always enough time to (re)familiarize with the contents. The physicians used the practice guideline frequently despite important barriers. Future implementation may involve strategies such as multiple interactive meetings. Further, the greatest potential to alter usual practice should be emphasized, such as using observational instruments. Copyright © 2016 John Wiley & Sons, Ltd. | dementia;discomfort;nursing homes;pneumonia;process evaluation | pubmed |
Drug-induced corneal epithelial changes. | Drugs across many pharmacologic classes induce corneal epithelial changes. Many of these drugs have cationic amphiphilic structures, with a hydrophobic ring and hydrophilic cationic amine side chain that allow them to cross cell membranes. These drugs lead to intracellular phospholipid accumulation, often manifested in the cornea by vortex keratopathy, with no effect on visual acuity and few ocular symptoms. Other drugs, notably antineoplastic agents, produce a fine diffuse corneal haze, sometimes accompanied by decreased vision that can be dose limiting. Still other medications cause crystalline epithelial precipitation that might require debridement for resolution. An understanding of the variety of drugs involved, the multiple mechanisms responsible, and the systemic diseases that produce similar changes can lead to improved management strategies for patients with corneal epithelial deposits. In most cases, drug therapy need not be modified or discontinued, but if visual acuity is affected, close collaboration with the prescribing physician can result in determining an optimized dose that treats systemic disease and minimizes these deposits. Additionally, close monitoring might be required if the drug is also associated with other ocular findings, such as optic neuropathy or retinopathy. | cornea;cornea verticillata;epithelium;ocular side effects;vortex keratopathy;whorl keratopathy | pubmed |
Child mortality and poverty in three world regions (the West, Asia and Sub-Saharan Africa) 1988-2010: Evidence of relative intra-regional neglect? | Poverty kills children. This study assesses the relationship between poverty and child mortality rates (CMRs) in 71 societies from three world regions to determine whether some countries, relative to their region, neglect their children. Spearman rank order correlations were calculated to determine any association between the CMR and poverty data, including income inequality and gross national income. A current CMR one standard deviation (SD) above or below the regional average and a percentage change between 1988 and 2010 were used as the measures to assess the progress of nations. There were positive significant correlations between higher CMRs and relative poverty measures in all three regions. In Western countries, the current CMRs in the USA, New Zealand and Canada were 1 SD below the Western mean. The narrowest income inequalities, apart from Japan, were seen in the Scandinavian nations alongside low CMRs. In Asia, the current CMRs in Pakistan, Myanmar and India were the highest in their region and were 1 SD below the regional mean. Alongside South Korea, these nations had the lowest percentage reductions in CMRs. In Sub-Saharan Africa, the current CMRs in Somalia, Burkina Faso, Sierra Leone, Chad, Democratic Republic of Congo and Angola were the highest in their region and were 1 SD below the regional mean. Those concerned with the pursuit of social justice need to alert their societies to the corrosive impact of poverty on child mortality. Progress in reducing CMRs provides an indication of how well nations are meeting the needs of their children. Further country-specific research is required to explain regional differences. | Child mortality;international comparisons;poverty | pubmed |
Reproducibility of fractional ventilation derived by Fourier decomposition after adjusting for tidal volume with and without an MRI compatible spirometer. | To reduce the influence of tidal volume on fractional ventilation (FV) derived by Fourier decomposition (FD). Twelve volunteers were examined on a 1.5 Tesla scanner. Spoiled gradient echo imaging of coronal and sagittal slices of the lung were performed. The tidal volume variations between different acquisitions were studied by reproducibility and repeatability measurements. To adjust the FV derived by FD for tidal volume differences between the measurements, during all acquisitions, the lung volume changes were measured by a spirometer and used to calculate a global FV parameter. As an alternative, using the FD data, the lung area changes were calculated and used for the adjustment. Reproducibility analysis of unadjusted coronal FV showed a determination coefficient of R2 = 71% and an intraclass correlation coefficient of ICC = 93%. Differences in the measurements could be ascribed to different tidal volumes. Area adjusted values exhibited an increased R2 of 84% and a higher ICC of 97%. For the coronal middle slice/sagittal slices in free breathing, the inter-volunteer coefficient of variation was reduced from 0.23/0.28 (unadjusted) to 0.16/0.20 (spirometer) or 0.12/0.13 (area). The calculation of lung area changes is sufficient to increase the reproducibility of FV in a volunteer cohort avoiding the need for an MRI compatible spirometer. Magn Reson Med 76:1542-1550, 2016. © 2015 International Society for Magnetic Resonance in Medicine. | Fourier decomposition;lung;spirometer;tidal volume;ventilation | pubmed |
A rare presentation of hydropneumothorax in tropical pulmonary eosinophilia: cavitation and pneumonic consolidation in a child. | Tropical pulmonary eosinophilia (TPE) is a syndrome of wheezing, fever and eosinophilia seen predominantly in the Indian subcontinent and other tropical areas. The pathogenesis is due to an exaggerated immune response to the filarial antigens which includes type I, type III and type IV reactions with eosinophils playing a pivotal role. Leucocytosis with an absolute increase in eosinophils in the peripheral blood is the hallmark of TPE. Other criteria for the diagnosis of TPE include high titres of antifilarial antibodies, raised serum total IgE > 1000 ku/L and a favourable response to the antifilarial agent, diethyl-carbamazine. Although TPE runs a benign course, if left untreated, it could result in a fair degree of respiratory morbidity. | DEC;Tropical pulmonary eosinophilia;wheezing | pubmed |
Habitual Tea Consumption Reduces Prostate Cancer Risk in Vietnamese Men: a Case-Control Study | Background: An upward trend has been noted for the incidence of prostate cancer (PCa) in Vietnam, but information
is limited on modifiable factors associated with this form of cancer. This case-control study was conducted to ascertain
any relationship between habitual tea consumption and PCa risk. Materials and Methods: Two hundred and fifty-three
incident patients with histologically confirmed PCa and 419 (340 community-based and 79 hospital-based) controls,
matched by age, were recruited in Ho Chi Minh City during 2013-2015. Information on frequency, quantity and
duration of tea consumption, together with demographics, habitual diet and lifestyle characteristics, was obtained by
direct interviews using a validated questionnaire. Logistic regression analyses were performed to assess associations
between tea consumption variables and PCa risk. Results: The control subjects reported higher tea consumption levels
in terms of cumulative exposure, frequency and quantity of tea drank than the PCa patients. After accounting for
confounding factors, increasing tea consumption was found to be associated with reduced risk of PCa. The adjusted
odds ratios (95% confidence intervals) were 0.52 (95% CI 0.35-0.79) and 0.30 (95% CI 0.18-0.48) for participants
drinking 100-500 ml/day and > 500 ml/day, respectively, relative to those drinking < 100 ml/day. Significant inverse
dose-response relationships were also observed for years of drinking and number of cups consumed daily (P <0.01).
Conclusion: Habitual tea consumption is associated with a reduced risk of PCa in Vietnamese men. | Case-control study;epidemiological;prostate cancer;tea drinking;Vietnam | pubmed |
Exploring Incomplete Rating Designs With Mokken Scale Analysis. | Recent research has explored the use of models adapted from Mokken scale analysis as a nonparametric approach to evaluating rating quality in educational performance assessments. A potential limiting factor to the widespread use of these techniques is the requirement for complete data, as practical constraints in operational assessment systems often limit the use of complete rating designs. In order to address this challenge, this study explores the use of missing data imputation techniques and their impact on Mokken-based rating quality indicators related to rater monotonicity, rater scalability, and invariant rater ordering. Simulated data and real data from a rater-mediated writing assessment were modified to reflect varying levels of missingness, and four imputation techniques were used to impute missing ratings. Overall, the results indicated that simple imputation techniques based on rater and student means result in generally accurate recovery of rater monotonicity indices and rater scalability coefficients. However, discrepancies between violations of invariant rater ordering in the original and imputed data are somewhat unpredictable across imputation methods. Implications for research and practice are discussed. | Mokken scaling;missing data;performance assessment;rating quality | pubmed |
Efficient generation of dopaminergic-like neurons by overexpression of Nurr1 and Pitx3 in mouse induced Pluripotent Stem Cells. | Parkinson's disease (PD) is a neurodegenerative disorder, in which the nigro-striatal Dopaminergic (DAergic) neurons are selectively lost. Treatment of neurodegenerative diseases with Pluripotent Stem Cells (PSCs) is a big interest in cell therapy. Here, we used induced Pluripotent Stem Cells (iPSCs) expressing two master Dopaminergic (DAergic) transcription factors, i.e. Nurr1 and Pitx3, to generate functional in vitro DAergic-like neurons. After establishment and characterization of Doxycycline-inducible iPSCs from mouse fibroblasts, the cells were transduced by NURR1- and PITX3-harboring lentiviruses. The Nurr1/Pitx3 -iPSCs were differentiated through a five-stage protocol to generate DAergic-like neurons. The results confirmed the efficient expression of DAergic neuron markers in the end of protocol. Beside, the generated cells could exclusively synthesize and secrete Dopamine in response to secretagogues. In conclusion, overexpression of Nurr1 and Pitx3 in iPSCs could efficiently program iPSCs into functional DAergic-like neurons. This finding may have an impact on future stem cell therapy of PD. | Dopaminergic neurons;Induced-pluripotent stem cells;Nurr1;Parkinson’s disease;Pitx3 | pubmed |
Alien species and their zoonotic parasites in native and introduced ranges: The raccoon dog example. | The raccoon dog (Nyctereutes procyonoides) is a canid that is indigenous in East Asia and alien in Europe, where it was introduced more than half a century ago. The aim of this study was to compare the parasite faunas associated with raccoon dogs in their native and introduced ranges, and to identify zoonotic parasite species. We examined 255 carcasses of hunted raccoon dogs from Estonia and recorded a total of 17 helminth species: 4 trematodes, 4 cestodes and 9 nematodes. The most prevalent parasite species were Uncinaria stenocephala (97.6%) and Alaria alata (68.3%). Average parasite species richness was 2.86 (the highest was 9) and only two animals were not parasitized at all. Although the infection intensity was determined by weight and not by sex, all animals infected with more than five helminth species were males. We also found that animals infected with higher numbers of helminth species fed significantly more on natural plants. Intentional consumption of grass may represent a self-medicating behaviour among raccoon dogs. We included the Estonian data into a wider comparison of raccoon dog parasite faunas and found a total of 54 helminth taxa, including 28 of zoonotic potential. In Europe, raccoon dogs are infected with a minimum of 32 helminth species of which 19 are zoonotic; in the native range they are infected with 26 species of which 17 are zoonotic. Most species were nematodes or trematodes, with fewer cestodes described. The recent increase in the number and range of raccoon dogs in Europe and the relatively high number of zoonotic parasite taxa that it harbours suggests that this species should be considered an important source of environmental contamination with zoonotic agents in Europe. | Echinococcus multilocularis;Invasive species;Nyctereutes procyonoides;Parasite fauna;Self-medicating behaviour;Zoonoses | pubmed |
Diagnostic accuracy of periapical radiography and cone beam computed tomography in detecting apical periodontitis using histopathological findings as a reference standard. | To compare the diagnostic accuracy of periapical radiography (PR) and cone beam computed tomography (CBCT) in detecting apical periodontitis (AP) using histopathological findings as a reference standard. Jaw sections containing 67 teeth (86 roots) were collected from unclaimed bodies due for cremation. Imaging was carried out to detect AP by digital PR with a central view (DP group), digital PR combining central with 10˚ mesially and distally angled (parallax) views (DPS group) and CBCT scans. All specimens underwent histopathological examination to confirm the diagnosis of AP. Sensitivity, specificity and predictive values of PR and CBCT were analysed using rater mean (n = 5). Receiver-operating characteristic (ROC) analysis was carried out. Sensitivity was 0.27, 0.38 and 0.89 for DP, DPS and CBCT scans, respectively. CBCT had specificity and positive predictive value of 1.0 whilst DP and DPS had specificity and positive predictive value of 0.99. The negative predictive value was 0.39, 0.44 and 0.81 for DP, DPS and CBCT scans, respectively. Area under the curve (AUC) for the various imaging methods was 0.629 (DP), 0.688 (DPS), and 0.943 (CBCT). All imaging techniques had similar specificity and positive predictive values. Additional parallax views increased the diagnostic accuracy of PR. CBCT had significantly higher diagnostic accuracy in detecting AP compared to PR, using human histopathological findings as a reference standard. | apical periodontitis;cone beam computed tomography;histology;periapical radiography | pubmed |
Primary graft dysfunction: Long-term physical function outcomes among lung transplant recipients. | Adults with primary graft dysfunction (PGD) after lung transplantation are at increased risk for pulmonary and functional impairment. No prior studies have described the long-term (within 1.5 years of transplant) cardiopulmonary exercise testing (CPET) results in adults with grade 3 PGD. The objective of this study was to compare the functional outcomes of lung transplant patients with and without grade 3 PGD via CPET and six-minute talk tests (6MWD). 243 adults underwent lung transplantation between 2003 and 2010, 128 (53%) of whom underwent CPET and 6MWD within 12-18 months of transplantation. The primary measure of exposure was grade 3 PGD at 72 h, however grade 3 PGD within 72 h was also assessed. In addition, the impact of potential confounding variables was explored. Approximately one-third (32%) of the 243 patients experienced grade 3 PGD within 72 h; among these, 15 (6%) had grade 3 PGD at the 72 h time point. There were no differences in CPET or 6MWD between those with and without grade 3 PGD at 72 h despite a longer length of hospital stay and lower pulmonary function. Similar results were seen for patients with and without grade 3 PGD within 72 h, with the exception of a lower heart rate on CPET. Participants with grade 3 PGD are able to achieve functional outcomes comparable to those without PGD. | Exercise and pulmonary rehabilitation;Infection and inflammation;Primary graft dysfunction;Quality of life;Respiratory infections | pubmed |
Predicting mobility outcome in lower limb amputees with motor ability tests used in early rehabilitation. | Retrospective cohort study. Persons with a lower limb amputation can regain mobility using a prosthetic device. For fast and adequate prescription of prosthetic components, it is necessary to predict the mobility outcome early in rehabilitation. Currently, prosthetic prescription is primarily based on empirical knowledge of rehabilitation professionals. In this study, we explored motor ability tests, to be completed without a prosthetic device, which have predictive value for mobility outcome at the end of rehabilitation. For this study, data of 82 patients with a lower limb amputation were included. The Single-limb standing balance test (Balance test), the Lower-Extremity Motor Coordination Test and the Amputee Mobility Predictor Assessment Tool (AMPnoPRO) were used as measures for motor ability. Mobility outcome was measured using the Timed Up and Go Test, the Two-Minute Walking Test and K levels were used. The explained variance of the Balance test, the Lower-Extremity Motor Coordination Test and the AMPnoPRO was, respectively, 0.603, 0.534 and 0.649 on the Two-Minute Walking Test (linear regression); 0.597, 0.431 and 0.624 on the Timed Up and Go Test (linear regression); and 0.432, 0.420 and 0.526 on the K levels (logistic regression). The AMPnoPRO predicted mobility outcome statistically (largest amount of explained variance). Clinical relevance This study explored the possibility of statistically predicting mobility outcome in lower limb amputees at the end of rehabilitation, using motor ability tests conducted in early rehabilitation. This study suggests the use of the AMPnoPRO to predict mobility outcome in lower limb amputees. | Predicting mobility outcome;amputee;lower limb;mobility;predictors;prosthetic prescription;prosthetics;rehabilitation | pubmed |
A Role for Mitogen- and Stress-Activated Kinase 1 in L-DOPA-Induced Dyskinesia and ∆FosB Expression. | Abnormal regulation of extracellular signal-regulated kinases 1 and 2 has been implicated in 3,4-dihydroxy-l-phenylalanine (L-DOPA)-induced dyskinesia (LID), a motor complication affecting Parkinson's disease patients subjected to standard pharmacotherapy. We examined the involvement of mitogen- and stress-activated kinase 1 (MSK1), a downstream target of extracellular signal-regulated kinases 1 and 2, and an important regulator of transcription in LID. 6-Hydroxydopamine was used to produce a model of Parkinson's disease in MSK1 knockout mice and in ∆FosB- or ∆cJun-overexpressing transgenic mice, which were assessed for LID following long-term L-DOPA administration. Biochemical processes were evaluated by Western blotting or immunofluorescence. Histone H3 phosphorylation was analyzed by chromatin immunoprecipitation followed by promotor-specific quantitative polymerase chain reaction. Genetic inactivation of MSK1 attenuated LID and reduced the phosphorylation of histone H3 at Ser10 in the striatum. Chromatin immunoprecipitation analysis showed that this reduction occurred at the level of the fosB gene promoter. In line with this observation, the accumulation of ∆FosB produced by chronic L-DOPA was reduced in MSK1 knockout. Moreover, inducible overexpression of ∆FosB in striatonigral medium spiny neurons exacerbated dyskinetic behavior, whereas overexpression of ∆cJun, which reduces ∆FosB-dependent transcriptional activation, counteracted LID. Results indicate that abnormal regulation of MSK1 contributes to the development of LID and to the concomitant increase in striatal ∆FosB, which may occur via increased histone H3 phosphorylation at the fosB promoter. Results also show that accumulation of ∆FosB in striatonigral neurons is causally related to the development of dyskinesia. | Dopamine D(1) receptor;Histone;Medium spiny neurons;Mouse;Parkinson’s disease;Striatum | pubmed |
Introducing the No Preventable Harms campaign: creating the safest health care system in the world, starting with catheter-associated urinary tract infection prevention. | Endemic health care-associated safety problems, including health care-associated infection, account for substantial morbidity and mortality. We outline a regional No Preventable Harms campaign to reduce these safety problems and describe the initial results from the first initiative focusing on catheter-associated urinary tract infection (CAUTI) prevention. We formed a think tank composed of multidisciplinary experts from within a 7-hospital Midwestern Veterans Affairs network to identify hospital-acquired conditions that had strong evidence on how to prevent the harm and outcome data that could be easily collected to evaluate improvement efforts. The first initiative of this campaign focused on CAUTI prevention. Quantitative data on CAUTI rates and qualitative data from site visit interviews were used to evaluate the initiative. Quantitative data showed a significant reduction in CAUTI rates per 1,000 catheter days for nonintensive care units across the region (2.4 preinitiative and 0.8 postinitiative; P = .001), but no improvement in the intensive care unit rate (1.4 preinitiative and 2.1 postinitiative; P = .16). Themes that emerged from our qualitative data highlight the need for considering local context and the importance of communication when developing and implementing regional initiatives. A regional collaborative can be a valuable strategy for addressing important endemic patient safety problems. | Collaborative;Hospital unit culture;Hospital-acquired conditions;Patient safety;Regional medical programs | pubmed |
A simple and rapid creatinine sensing via DLS selectivity, using calix[4]arene thiol functionalized gold nanoparticles. | A new, simple, ultra-sensitive and selective approach has been reported for the "on spot" colorimetric detection of creatinine based on calix[4]arene functionalized gold nanoparticles (AuNPs) with excellent discrimination in the presence of other biomolecules. The lower detection limit of the method is 2.16nM. The gold nanoparticles and p-tert-butylcalix[4]arene were synthesized by microwave assisted method. Specifically, in our study, we used dynamic light scattering (DLS) which is a powerful method for the determination of small changes in particle size, improved selectivity and sensitivity of the creatinine detection system over colorimetric method. The nanoassembly is characterized by Transmission electron microscopy (TEM), DLS, UV-vis and ESI-MS spectroscopy, which demonstrates the binding affinity due its ability of hydrogen bonding and electrostatic interaction between -NH group of creatinine and pSDSC4. It exhibits fast response time (<60s) to creatinine and has long shelf-life (>5 weeks). The developed pSDSC4-AuNPs based creatinine biosensor will be established as simple, reliable and accurate tool for the determination of creatinine in human urine samples. | Biosensor;Calix[4]arene;Creatinine;DLS selectivity;Gold nanoparticles | pubmed |
Diabolical effects of rabies encephalitis. | Rabies is an acute encephalomyelitis in humans and animals caused by rabies virus (RABV) infection. Because the neuropathological changes are very mild in rabies, it has been assumed that neuronal dysfunction likely explains the severe clinical disease. Recently, degenerative changes have been observed in neuronal processes (dendrites and axons) in experimental rabies. In vitro studies have shown evidence of oxidative stress that is caused by mitochondrial dysfunction. Recent work has shown that the RABV phosphoprotein (P) interacts with mitochondrial Complex I leading to overproduction of reactive oxygen species, which results in injury to axons. Amino acids at positions 139 to 172 of the P are critical in this process. Rabies vectors frequently show behavioral changes. Aggressive behavior with biting is important for transmission of the virus to new hosts at a time when virus is secreted in the saliva. Aggression is associated with low serotonergic activity in the brain. Charlton and coworkers performed studies in experimentally infected striped skunks with skunk rabies virus and observed aggressive behavioral responses. Heavy accumulation of RABV antigen was found in the midbrain raphe nuclei, indicating that impaired serotonin neurotransmission from the brainstem may account for the aggressive behavior. We now have an improved understanding of how RABV causes neuronal injury and how the infection results in behavioral changes that promote viral transmission to new hosts. | Aggressive behavior;Mitochondrial dysfunction;Oxidative stress;Pathogenesis;Rabies;Serotonin;Viral encephalitis | pubmed |
Understanding the roles of the P2X7 receptor in solid tumour progression and therapeutic perspectives. | P2X7 is an intriguing ionotropic receptor for which the activation by extracellular ATP induces rapid inward cationic currents and intracellular signalling pathways associated with numerous physiological processes such as the induction of the inflammatory cascade, the survival and proliferation of cells. In contrast, long-term stimulation of P2X7 is generally associated with membrane permeabilisation and cell death. Recently, P2X7 has attracted great attention in the cancer field, and particularly in the neoplastic transformation and the progression of solid tumours. A growing number of studies were published; however they often appeared contradictory in their results and conclusions. As such, the involvement of P2X7 in the oncogenic process remains unclear so far. The present review aims to discuss the current knowledge and hypotheses on the involvement of the P2X7 receptor in the development and progression of solid tumours, and highlight the different aspects that require further clarification in order to decipher whether P2X7 could be considered as a cancer biomarker or as a target for pharmacological intervention. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers. | Biomarker;Cancer;Extracellular ATP;P2X7;Pharmacological target | pubmed |
Thalamic Responses to Nociceptive-Specific Input in Humans: Functional Dichotomies and Thalamo-Cortical Connectivity. | While nociceptive cortical activation is now well characterized in humans, understanding of the nociceptive thalamus remains largely fragmentary. We used laser stimuli and intracerebral electrodes in 17 human subjects to record nociceptive-specific field responses in 4 human thalamic nuclei and a number of cortical areas. Three nuclei known to receive spinothalamic (STT) projections in primates (ventro-postero-lateral [VPL], anterior pulvinar [PuA], and central lateral [CL]) exhibited responses with similar latency, indicating their parallel activation by nociceptive afferents. Phase coherence analysis, however, revealed major differences in their functional connectivity: while VPL and PuA drove a limited set of cortical targets, CL activities were synchronized with a large network including temporal, parietal, and frontal areas. Our data suggest that STT afferents reach simultaneously a set of lateral and medial thalamic regions unconstrained by traditional nuclear borders. The broad pattern of associated cortical networks suggests that a single nociceptive volley is able to trigger the sensory, cognitive, and emotional activities that underlie the complex pain experience. The medial pulvinar, an associative nucleus devoid of STT input, exhibited delayed responses suggesting its dependence on descending cortico-thalamic projections. Its widespread cortical connectivity suggests a role in synchronizing parietal, temporal, and frontal activities, hence contributing to the access of noxious input to conscious awareness. | cortex;human;intracerebral EEG;nociceptive stimulus;thalamus | pubmed |
Novel topical formulation of lidocaine provides significant pain relief for intrauterine device insertion: pharmacokinetic evaluation and randomized placebo-controlled trial. | To investigate the pharmacokinetics, safety, and analgesic efficacy of a novel topical formulation of lidocaine at insertion of an intrauterine device (IUD). Randomized controlled trial; phase-I and phase-II studies. University and public hospitals. Women aged ≥18 years who wanted to receive an IUD. Four women were parous in phase I; all in phase II were nulliparous. A single, 8.5-mL dose of lidocaine formulation (SHACT) was administered (to the portio, cervix, and uterus) with a specially designed applicator. The phase-I study (single-arm) was designed for pharmacokinetic assessment; the phase-II study (randomized) was intended for investigation of efficacy and safety. From the phase-I study (15 participants), mean pharmacokinetic values were: maximum plasma concentration: 351 ± 205 ng/mL; time taken to reach maximum concentration: 68 ± 41 minutes; and area under the concentration-time curve from 0 to 180 minutes: 717 ± 421 ng*h/mL. Pain relief was observed with lidocaine vs. placebo in the phase-II study (218 women, randomized). Mean visual analog scale score for maximum pain during the first 10 minutes after IUD insertion was 36% lower with lidocaine than with placebo (28.3 ± 24.6 vs. 44.2 ± 26.0). Pain intensity was also significantly lower in the lidocaine group at 30 minutes. On average, 3 of 4 patients will have less pain with lidocaine than with placebo. Adverse events were similar in the placebo and lidocaine groups. No serious adverse events were reported. Lidocaine provides pain relief lasting for 30-60 minutes for women undergoing IUD insertion, without any safety concerns. Further studies of this lidocaine formulation, for IUD insertion and other clinical applications, are planned. 2011-005660-18 and 2011-006220-20 (EudraCT). | Intrauterine device;lidocaine;pain;pharmacokinetics;topical anesthetic | pubmed |
Strand-specific community RNA-seq reveals prevalent and dynamic antisense transcription in human gut microbiota. | Metagenomics and other meta-omics approaches (including metatranscriptomics) provide insights into the composition and function of microbial communities living in different environments or animal hosts. Metatranscriptomics research provides an unprecedented opportunity to examine gene regulation for many microbial species simultaneously, and more importantly, for the majority that are unculturable microbial species, in their natural environments (or hosts). Current analyses of metatranscriptomic datasets focus on the detection of gene expression levels and the study of the relationship between changes of gene expression and changes of environment. As a demonstration of utilizing metatranscriptomics beyond these common analyses, we developed a computational and statistical procedure to analyze the antisense transcripts in strand-specific metatranscriptomic datasets. Antisense RNAs encoded on the DNA strand opposite a gene's CDS have the potential to form extensive base-pairing interactions with the corresponding sense RNA, and can have important regulatory functions. Most studies of antisense RNAs in bacteria are rather recent, are mostly based on transcriptome analysis, and have been applied mainly to single bacterial species. Application of our approaches to human gut-associated metatranscriptomic datasets allowed us to survey antisense transcription for a large number of bacterial species associated with human beings. The ratio of protein coding genes with antisense transcription ranges from 0 to 35.8% (median = 10.0%) among 47 species. Our results show that antisense transcription is dynamic, varying between human individuals. Functional enrichment analysis revealed a preference of certain gene functions for antisense transcription, and transposase genes are among the most prominent ones (but we also observed antisense transcription in bacterial house-keeping genes). | antisense RNA;human gut microbiota;metagenome;metatranscriptome;transposases | pubmed |
Effect of dysphagia rehabilitation on oral intake in elderly patients with aspiration pneumonia. | To clarify the effects of dysphagia rehabilitation on oral intake after aspiration pneumonia in older adults. The present retrospective observational study used data from the Japanese Diagnosis Procedure Combination inpatient database. We identified patients who were admitted to acute care hospitals with aspiration pneumonia. Patients were subdivided into those with and without dysphagia rehabilitation. The main outcome variable was total oral intake on discharge. We carried out multivariate logistic regression analysis to assess the effect of dysphagia rehabilitation on the outcome, with adjustment for patient backgrounds. We also carried out analyses based on pneumonia severity, and the timing and duration of dysphagia rehabilitation. We identified 22,819 patients with dysphagia rehabilitation and 75,555 patients without dysphagia rehabilitation. The rates of total oral intake on discharge were 78.0 and 75.2%, respectively. The multivariate regression model showed that the dysphagia rehabilitation group had a significantly higher proportion of total oral intake on discharge (odds ratio 1.32; P < 0.001). Mild pneumonia patients had a higher odds ratio for total oral intake associated with dysphagia rehabilitation than patients with moderate and severe pneumonia (odds ratio 2.27; P < 0.001). Among patients who underwent a short period of dysphagia rehabilitation, those with early rehabilitation were more likely to achieve total oral intake at discharge than those with late rehabilitation. The data suggest that dysphagia rehabilitation had a positive effect on total oral intake in elderly patients with aspiration pneumonia. Dysphagia rehabilitation showed greater benefit in patients with mild pneumonia than with more severe pneumonia. | aspiration pneumonia;dysphagia;elderly;oral intake;rehabilitation | pubmed |
Noninvasive Ventilation Intolerance: Characteristics, Predictors, and Outcomes. | Noninvasive ventilation (NIV) intolerance is one reason for NIV failure. However, the characteristics, predictors, and outcomes of NIV intolerance are unclear. A prospective observational study was performed in the respiratory intensive care unit of a teaching hospital. Subjects with acute respiratory failure who used NIV were enrolled. Initially, continuous use of NIV was encouraged. However, if the subject could not tolerate NIV, it was used intermittently. NIV intolerance was defined as termination of NIV due to subject refusal to receive it because of discomfort, even after intermittent use was attempted. A total of 961 subjects were enrolled in the study. Of these, 50 subjects (5.2%) experienced NIV intolerance after a median 2.4 h of NIV support. Age (OR = 0.98, 95% CI 0.963-0.996) and heart rate (OR = 1.02, 95% CI 1.006-1.030) measured before NIV were 2 independent risk factors of NIV intolerance. After 1-2 h of NIV, independent risk factors of NIV intolerance were heart rate (OR = 1.03, 95% CI 1.016-1.044) and breathing frequency (OR = 1.06, 95% CI 1.027-1.099). Intolerant subjects had no improvement in mean arterial pressure, heart rate, or breathing frequency after the NIV intervention. Moreover, intolerant subjects had a higher intubation rate (44.0% vs 25.8%, P = .008) and higher mortality (34.0% vs 22.4%, P = .08). The three most common complaints were that NIV worsened subjects' distress (46%), that NIV resulted in dyspnea (26%), and that the flow or pressure of NIV was too strong to bear (16%). NIV intolerance worsened subjects' outcomes. Younger subjects with a high heart rate and breathing frequency may be more likely to experience NIV intolerance. | intolerance;intubation;noninvasive ventilation;predictor | pubmed |
Can prenatal exposure to a 900 MHz electromagnetic field affect the morphology of the spleen and thymus, and alter biomarkers of oxidative damage in 21-day-old male rats? | We investigated the effects of a 900 Megahertz (MHz) electromagnetic field (EMF), applied during the prenatal period, on the spleen and thymus of 21-day-old male rat pups. Pregnant Sprague-Dawley rats were divided into control and EMF groups. We applied 900 MHz EMF for 1 h/day to the EMF group of pregnant rats. Newborn male rat pups were removed from their mothers and sacrificed on postnatal day 21. Spleen and thymus tissues were excised and examined. Compared to the control group, thymus tissue malondialdehyde levels were significantly higher in the group exposed to EMF, while glutathione levels were significantly decreased. Increased malondialdehyde and glutathione levels were observed in splenic tissue of rats exposed to EMF, while a significant decrease occurred in superoxide dismutase values compared to controls. Transmission electron microscopy showed pathological changes in cell morphology in the thymic and splenic tissues of newborn rats exposed to EMF. Exposure to 900 MHz EMF during the prenatal period can cause pathological and biochemical changes that may compromise the development of the male rat thymus and spleen. | electromagnetic field;electron microscopy;male;rat;spleen;thymus | pubmed |
Surfactant-enhanced spectrofluorimetric determination of total aflatoxins from wheat samples after magnetic solid-phase extraction using modified Fe₃O₄ nanoparticles. | The extraction and preconcentration of total aflatoxins (including aflatoxin B1, B2, G1, and G2) using magnetic nanoparticles based solid phase extraction (MSPE) followed by surfactant-enhanced spectrofluorimetric detection was proposed. Ethylene glycol bis-mercaptoacetate modified silica coated Fe3O4 nanoparticles as an efficient antibody-free adsorbent was successfully applied to extract aflatoxins from wheat samples. High surface area and strong magnetization properties of magnetic nanoparticles were utilized to achieve high enrichment factor (97), and satisfactory recoveries (92-105%) using only 100mg of the adsorbent. Furthermore, the fast separation time (less than 10 min) avoids many time-consuming cartridge loading or column-passing procedures accompany with the conventional SPE. In determination step, signal enhancement was performed by formation of Triton X-100 micelles around the analytes in 15% (v/v) acetonitrile-water which dramatically increase the sensitivity of the method. Main factors affecting the extraction efficiency and signal enhancement of the analytes including pH of sample solution, desorption conditions, extraction time, sample volume, adsorbent amount, surfactant concentration and volume and time of micelle formation were evaluated and optimized. Under the optimum conditions, wide linear range of 0.1-50 ng mL(-1) with low detection limit of 0.03 ng mL(-1) were obtained. The developed method was successfully applied to the extraction and preconcentration of aflatoxins in three commercially available wheat samples and the results were compared with the official AOAC method. | Fe(3)O(4) nanoparticles;Magnetic solid phase extraction;Surfactant-enhanced spectrofluorimetry;Total aflatoxins;Triton X-100 | pubmed |
The first case of Kawasaki disease in a 20-month old baby following immunization with rotavirus vaccine and hepatitis A vaccine in China: A case report. | Kawasaki disease (KD) after rotavirus and hepatitis A vaccination has not previously been reported in a baby in China. Herein, we describe a 20-month-old child who developed Kawasaki disease after receiving her second dose of Lanzhou lamb rotavirus vaccine (LLR) and her first dose of freeze-dried live attenuated hepatitis A vaccine. The case report was conducted by collecting and analyzing the hospital in-patient medical records and reviewing both the domestic and foreign pertinent literature. These findings will be important to note this possible side effect and to further investigate the association between the above 2 vaccines and Kawasaki disease. | Freeze-dried live attenuated hepatitis A vaccine;Kawasaki disease;Lanzhou lamb rotavirus | pubmed |
A prospective, randomized comparison of shock wave lithotripsy, retrograde intrarenal surgery and miniperc for treatment of 1 to 2 cm radiolucent lower calyceal renal calculi: a single center experience. | A prospective, randomized comparison of shock wave lithotripsy, retrograde intrarenal surgery and miniperc for the treatment of 1 to 2 cm radiolucent lower calyceal renal calculi was done to evaluate the safety and efficacy of these procedures. Patients with a single 1 to 2 cm radiolucent lower calyceal renal stone who underwent treatment between January 2012 and May 2013 were included in study. They were randomized to shock wave lithotripsy, retrograde intrarenal surgery and miniperc groups. Patient demographic profiles, success and re-treatment rates, auxiliary procedures and complications were analyzed. A total of 45 patients were enrolled in each of the shock wave lithotripsy, retrograde intrarenal surgery and miniperc groups. Three, 2 and 4 patients, respectively, were excluded from final analysis due to a matrix stone diagnosis. Mean procedure and fluoroscopy times were significantly greater in the miniperc group than in the other groups. Hospital stay (3.1 days vs 3.1 hours and 1.3 days, p = 0.01) and the blood transfusion rate (13.3% vs 0% and 0%, p = 0.03) were significantly higher for miniperc vs shock wave lithotripsy and retrograde intrarenal surgery, respectively. The re-treatment rate (63.4% vs 2.1% and 2.2%, p <0.001) and the auxiliary procedure rate (20.2% vs 8.8% and 6.6%, p = 0.02) were significantly greater for shock wave lithotripsy than for retrograde intrarenal surgery and miniperc, respectively. The 3-month stone-free rate of shock wave lithotripsy, retrograde intrarenal surgery and miniperc was 73.8% (31 of 42 patients), 86.1% (37 of 43) and 95.1% (39 of 41), respectively (p = 0.01). Miniperc and retrograde intrarenal surgery were more effective than shock wave lithotripsy to treat 1 to 2 cm radiolucent lower calyceal renal calculi in terms of a better stone-free rate, and lesser auxiliary and re-treatment rates. However, miniperc resulted in more complications, greater operative time and radiation exposure, and a longer hospital stay. | kidney;lithotripsy;nephrolithiasis;nephrostomy;operative;percutaneous;surgical procedures | pubmed |
Is depression associated with oral health outcomes in adults and elders? A systematic review and meta-analysis. | To systematically review the literature in order to investigate association between depression and oral diseases. Electronic searches were performed in five databases. Studies testing associations between depression and oral diseases as either exposure or outcome were included. Oral disease variable included any tooth loss or edentulism, periodontal disease, and dental caries. A total of 2504 articles were identified in the electronic database search. Sixteen studies were included in this systematic review being 14 included in the meta-analyses. Eleven studies considered oral health as outcome, whereas three studies considered depression as an outcome variable. Depression was associated to dental caries, tooth loss, and edentulism. Pooled estimates showed that depression increased the odds of dental caries (OR 1.27; 95% CI 1.13-1.44), tooth loss (OR 1.31; 95% CI 1.24-1.37), and edentulism (OR 1.17; 95% CI 1.02-1.34), respectively. When the oral diseases were tested as independent variable and depression as outcome, associations with both edentulism (OR 1.28; 95% CI 1.06-1.55) and periodontal disease (HR 1.73; 95% CI 1.58-1.89) were found. The results of our systematic review and meta-analyses show a positive association between depression and oral diseases, specifically dental caries, tooth loss, and edentulism, in adults and elders. More longitudinal studies are required to test causal and temporal relationship between depression and oral health status. Mental and oral health are among the main disabilities worldwide. This article helps to understand more about the relationship between both conditions, highlighting the importance for both clinicians and policy makers of considering individual's psychological status in management of oral health. | Dental caries;Depression;Oral health;Periodontal diseases;Periodontitis;Tooth loss | pubmed |
Evaluating bioequivalence of meloxicam tablets: is in-vitro dissolution test overdiscriminating? | The aim of the study was to assess the impact of the differences in dissolution profiles of meloxicam tablets on the in-vivo bioavailability parameters after oral administration. Compare in-vitro dissolution testing in the recommended media to evaluate in-vivo bioequivalence outcomes for the Biopharmaceutics Classification System Class II weak acidic drugs. Nine Beagle dogs received a single oral administration of each formulation (7.5 mg) in a three-way crossover design. The dissolution of meloxicam from both test products showed marked differences with that from the reference tablet in pH 1.0, 4.5 and 6.8 media at 50 or 75 rpm. Both formulations exhibiting slow or fast dissolution were then compared with the reference product for in-vivo bioequivalence study. Both products were bioequivalent with the reference tablet in either extent or rate of oral absorption. It indicated that the dissolution profiles which discriminated between the formulations in vitro did not accurately predict the in-vivo bioequivalence outcomes. Comparative dissolution profiles using similarity factor (f<sub>2</sub> ) in the recommended media should be relaxed to fulfil the requirements for the development, scale-up and postapproval changes to immediate release oral solid dosage forms of meloxicam. | bioequivalence;dissolution;formulation;meloxicam;similarity factor | pubmed |
Pharmacokinetics and drug interactions of medications used to treat hepatitis C virus infection in the setting of chronic kidney disease and kidney transplantation. | Hepatitis C infection in patients with chronic kidney disease or kidney transplant carries higher morbidity and mortality compared to noninfected patients. Historically, patients with advanced kidney disease and kidney transplant recipients were undertreated given the multiple adverse effects and limited efficacy of interferon-based therapies for chronic hepatitis C. The development of direct-acting antivirals in the past few years has opened an unprecedented opportunity for treating these populations. However, the impaired renal clearance of some of these medications in patients with kidney disease, and the potential interactions of antiviral therapies with immunosuppressants after kidney transplantation, present some challenges in choosing the proper regimen. This review provides an overview of the essential pharmacokinetics and drug interactions of relevant antiviral therapies in the treatment of chronic hepatitis C in patients with advanced kidney disease and after kidney transplantation. | Direct-acting antiviral therapies;chronic kidney disease;hepatitis C;kidney transplantation;pharmacokinetics | pubmed |
Can chronic exposure to imidacloprid, clothianidin, and thiamethoxam mixtures exert greater than additive toxicity in Chironomus dilutus? | Widespread agricultural use of neonicotinoid insecticides has resulted in frequent detection of mixtures of these compounds in global surface waters. Recent evidence suggests that neonicotinoid mixtures can elicit synergistic toxicity in aquatic insects under acute exposure conditions, however this has not been validated for longer exposures more commonly encountered in the environment. Therefore, we aimed to characterize the chronic (28-day) toxicity of imidacloprid, clothianidin, and thiamethoxam mixtures under different doses and mixture ratios to determine if the assumption of synergistic toxicity would hold under more environmentally realistic exposure settings. The sensitive aquatic insect Chironomus dilutus was used as a representative test species, and successful emergence was used as a chronic endpoint. Applying the MIXTOX modeling approach, predictive parametric models were fitted using single-compound toxicity data and statistically compared to observed toxicity in subsequent mixture tests. Imidacloprid-clothianidin, clothianidin-thiamethoxam and imidacloprid-clothianidin-thiamethoxam mixtures did not significantly deviate from concentration-additive toxicity. However, the cumulative toxicity of the imidacloprid-thiamethoxam mixture deviated from the concentration-additive reference model, displaying dose-ratio dependent synergism and resulting in up to a 10% greater reduction in emergence from that predicted by concentration addition. Furthermore, exposure to select neonicotinoid mixtures above 1.0 toxic unit tended to shift sex-ratios toward more male-dominated populations. Results indicate that, similar to acute exposures, the general assumption of joint additivity cannot adequately describe chronic cumulative toxicity of all neonicotinoid mixtures. Indeed, our observations of weak synergism and sex-ratio shifts elicited by some mixture combinations should be considered in water quality guideline development and environmental risk assessment practices for neonicotinoid insecticides, and explored in further investigations of the effects of neonicotinoid mixtures on aquatic communities. | Benthic macro invertebrates;MIXTOX;Mixture toxicity;Neonicotinoids;Synergism | pubmed |
PVA-PEG physically cross-linked hydrogel film as a wound dressing: experimental design and optimization. | The development of hydrogel films as wound healing dressings is of a great interest owing to their biological tissue-like nature. Polyvinyl alcohol/polyethylene glycol (PVA/PEG) hydrogels loaded with asiaticoside, a standardized rich fraction of Centella asiatica, were successfully developed using the freeze-thaw method. Response surface methodology with Box-Behnken experimental design was employed to optimize the hydrogels. The hydrogels were characterized and optimized by gel fraction, swelling behavior, water vapor transmission rate and mechanical strength. The formulation with 8% PVA, 5% PEG 400 and five consecutive freeze-thaw cycles was selected as the optimized formulation and was further characterized by its drug release, rheological study, morphology, cytotoxicity and microbial studies. The optimized formulation showed more than 90% drug release at 12 hours. The rheological properties exhibited that the formulation has viscoelastic behavior and remains stable upon storage. Cell culture studies confirmed the biocompatible nature of the optimized hydrogel formulation. In the microbial limit tests, the optimized hydrogel showed no microbial growth. The developed optimized PVA/PEG hydrogel using freeze-thaw method was swellable, elastic, safe, and it can be considered as a promising new wound dressing formulation. | Hydrogel film;PVA/PEG;asiaticoside;experimental design;freeze–thaw;wound dressing | pubmed |
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