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Folate deficiency in north Indian children undergoing maintenance chemotherapy for acute lymphoblastic leukemia-Implications and outcome. | Treatment-related toxicity and mortality are not uncommon during maintenance chemotherapy for childhood acute lymphoblastic leukemia (ALL), especially in the low- and middle-income countries (LMIC). Undernutrition and micronutrient deficiencies are commonly seen in children from LMICs undergoing treatment for ALL. The present study examines the prevalence and clinical implications of folate deficiency in north Indian children with ALL during the maintenance phase of treatment in view of prolonged antifolate treatment and high population prevalence of folate deficiency. Pre-cycle folate levels/deficiency as well as weight for age z-score and serum albumin level were determined and correlated with complications of treatment and mortality encountered during the maintenance phase of treatment. Twenty-nine of 52 children enrolled in the study had folate deficiency at some point during maintenance chemotherapy. Neutropenia (18 of 29 vs. 4 of 23; P = 0.002), thrombocytopenia (17 of 29 vs. 4 of 23; P = 0.005), febrile neutropenia (17 of 29 vs. 4 of 23; P = 0.005), and need for chemotherapy dose reduction (20 of 29 vs. 7 of 21; P = 0.01) were more common in folate-deficient children. Maintenance deaths were higher (8 of 29 vs. 1 of 23; P = 0.03) and survival lower (P = 0.02) in deficient children. In multivariate analysis, hypoalbuminemia (P = 0.02) and folate deficiency (P = 0.01) were associated with febrile neutropenia, and folate deficiency with maintenance deaths (P = 0.03). Folate deficiency was associated with treatment-related complications and adverse outcome in our patients. The risks and benefits of folate supplementation in deficient children during maintenance chemotherapy need to be explored with properly designed randomized studies in similar settings. | ALL maintenance;clinical implications;folate deficiency
| pubmed |
Assessment of Volumetric Distortion Artifact in Filled Root Canals Using Different Cone-beam Computed Tomographic Devices. | Artifacts in cone-beam computed tomographic (CBCT) imaging may compromise radiodiagnosis. Obturation materials for endodontic treatment may present with variable material density and thus also cause distinct artifact expression. The aim of this study was to assess the volume distortion artifact of root canal sealers using CBCT devices and micro-CT imaging as a reference. Thirty single-root mandibular central incisors were used for this study. Teeth were prepared with EndoSequence rotary nickel-titanium files (Brasseler USA, Savannah, GA) and divided into 3 groups. Canals were obturated with gutta-percha and AH Plus root canal sealer (Dentsply Maillefer, Ballaigues, Switzerland) using single-cone filling techniques. Each tooth was scanned with different CBCT devices (ie, Promax 3D Max [Planmeca Inc, Roselle, IL], NewTom VGi evo [NewTom, Verona, Italy], and 3D Accuitomo 170 [J Morita, Kyoto, Japan]) with the same voxel size (0.2 mm<sup>3</sup>) and compared with micro-CT imaging as a reference standard. The results showed a significant difference in terms of volume distortion between micro-CT and CBCT images (P < .05). There were also significant differences among CBCT devices. Promax 3D Max measurements showed significantly larger root canal volumes than the other CBCT machines (P < .05). However, NewTom VGi evo and 3D Accuitomo 170 showed similar results without any significant difference (P > .05). CBCT devices showed more volumetric distortion artifact than micro-CT imaging. The volume was variable for different CBCT devices while scanning at the same voxel size. However, to assess the effect of sealer materials on CBCT imaging, further studies should be conducted for different sealers. | Artifact;cone-beam computed tomographic machines;micro–computed tomographic imaging;root canal sealer | pubmed |
Physical activity after outpatient surgery and enhanced recovery for total knee arthroplasty. | The purpose of this study was to 'objectively' measure improvement of physical activity with the use of an activity monitor between patients who followed an enhanced recovery- or outpatient surgery pathway after total knee arthroplasty (TKA). It was hypothesized that both pathways will have comparable physical activity after TKA at 6-week follow-up. This prospective observational comparative case study was designed to investigate activity parameters (e.g. physical activity, number of steps, sit-stand transfers) of two different pathways after 6 weeks with the use of a non-invasive triaxial accelerometer activity monitor. This study included 20 patients with a mean age of 65.5 years (SD 6.1) undergoing TKA who were allocated to follow one of the two pathways: enhanced recovery (n = 10) or outpatient surgery (n = 10). Patients were monitored for 4 days pre-, 4 days during and 4 days after 5 weeks postoperatively. Patient-reported outcome measures (PROMs) and range of knee motion were obtained pre- and 6 weeks postoperatively. The activity parameters recovered steeply during the first 4 postoperative days and continued to improve within both pathways (n.s.). Preoperative and during the first 4 days and 5 weeks postoperative, activity parameters were comparable (n.s.) between both pathways but did not reach preoperative levels of physical activity and range of motion (n.s.). PROMs improved within each pathway, and no difference between both pathways was observed (n.s.). This study demonstrates that the early physical activity parameters of patients after TKA, following the outpatient surgery pathway, were similar to patients who followed the standard enhanced recovery pathway. The activity monitor is an added value for a more detailed and objective analysis of the physical performance in patients after TKA. III. | Accelerometer;Activity monitor;Day care surgery;Enhanced recovery;Fast track;Outpatient surgery;Pathway;Physical activity;Total knee arthroplasty | pubmed |
4-Benzyl-1-(4-nitro-phen-yl)-1<i>H</i>-1,2,3-triazole: crystal structure and Hirshfeld analysis. | The mol-ecule in the title compound, C<sub>15</sub>H<sub>12</sub>N<sub>4</sub>O<sub>2</sub>, has a twisted <i>L</i>-shape with the dihedral angle between the aromatic rings of the N-bound benzene and C-bound benzyl groups being 70.60 (9)°. The nitro group is co-planar with the benzene ring to which it is connected [C-C-N-O torsion angle = 0.4 (3)°]. The three-dimensional packing is stabilized by a combination of methyl-ene-C-H⋯O(nitro), methyl-ene-C-H⋯π(phen-yl), phenyl-C-H⋯π(triazol-yl) and nitro-O⋯π(nitro-benzene) inter-actions, along with weak π(triazol-yl)-π(nitrobenzene) contacts [inter-centroid distance = 3.8386 (10) Å]. The importance of the specified inter-molecular contacts has been verified by an analysis of the calculated Hirshfeld surface. | 1,2,3-triazole;Hirshfeld surface analysis;crystal structure | pubmed |
Prolonged acyclovir treatment in a child with opercular syndrome related to herpes simplex encephalitis. | HSV 1 encephalitis is the most common cause of sporadic and focal viral encephalitis. Opercular syndrome is characterized by swallowing and speech difficulties which are associated with deterioration of voluntary control of face, pharynx, tongue and chewing muscles. It can be developed in patients with Herpes simplex encephalitis (HSE). Here, a twelve-year-old boy who was diagnosed with HSE and Opercular syndrome, is presented. The patient recovered without sequela as a result of 30 days of intravenous and 10 days of oral acyclovir treatment. It might be important as well, to personalize and elongate the treatment in terms of prognosis. | Acyclovir;Encephalitis;Opercular syndrome | pubmed |
Size, Shape, and Sequence-Dependent Immunogenicity of RNA Nanoparticles. | RNA molecules have emerged as promising therapeutics. Like all other drugs, the safety profile and immune response are important criteria for drug evaluation. However, the literature on RNA immunogenicity has been controversial. Here, we used the approach of RNA nanotechnology to demonstrate that the immune response of RNA nanoparticles is size, shape, and sequence dependent. RNA triangle, square, pentagon, and tetrahedron with same shape but different sizes, or same size but different shapes were used as models to investigate the immune response. The levels of pro-inflammatory cytokines induced by these RNA nanoarchitectures were assessed in macrophage-like cells and animals. It was found that RNA polygons without extension at the vertexes were immune inert. However, when single-stranded RNA with a specific sequence was extended from the vertexes of RNA polygons, strong immune responses were detected. These immunostimulations are sequence specific, because some other extended sequences induced little or no immune response. Additionally, larger-size RNA square induced stronger cytokine secretion. 3D RNA tetrahedron showed stronger immunostimulation than planar RNA triangle. These results suggest that the immunogenicity of RNA nanoparticles is tunable to produce either a minimal immune response that can serve as safe therapeutic vectors, or a strong immune response for cancer immunotherapy or vaccine adjuvants. | RNA nanoparticle;RNA nanotechnology;RNA polygon;immune response;immunogenicity;immunomodulation;nanobiotechnology;pRNA 3WJ | pubmed |
MEK inhibitors under development for treatment of non-small-cell lung cancer. | The mitogen-activated protein kinase (MAPK) pathway is intimately implicated in the molecular pathogenesis of non-small-cell lung cancer (NSCLC). Aberrant MAPK signaling resulting from the upstream activating mutations converges on mitogen-activated protein kinase kinase 1/2 (MEK1/2), making MEK inhibition an attractive strategy for the treatment of NSCLC. Several MEK inhibitors have demonstrated anticancer activity in patients with NSCLC. In this article, we discuss the biological rationale for the use of MEK inhibitors and summarize the clinical experience with MEK1/2 inhibitors for the treatment of NSCLC, from initial phase I studies to phase II/III studies, both as monotherapy or in combination with other anticancer agents. Trametinib in combination with the BRAF inhibitor dabrafenib represents the first MEK1/2 inhibitor containing regimen that is approved for advanced BRAF<sup>V600E</sup>-mutant NSCLC. Other MEK1/2 inhibitors that are also in advanced stages of clinical development include selumetinib, cobimetinib, and binimetinib. Several studies of MEK inhibitor combination therapies are underway, including trials using combined MEK inhibition and immune checkpoint blockade. Further research aimed at discovering biomarkers of response and resistance to MEK1/2 inhibitors will be needed to develop rational combination strategies for the treatment of NSCLC driven by aberrant MAPK signaling. | BRAF;KRAS;MAPK;MEK inhibitor;non-small-cell lung cancer | pubmed |
Evaluation of the ERIC-PCR as a probable method to differentiate Avibacterium paragallinarum serovars. | Infectious coryza, an upper respiratory tract disease in chickens, caused by Avibacterium paragallinarum, leads to huge economic losses. The disease is controlled through vaccination; but vaccination efficacy is dependent on correct identification of the infecting serovar, as limited cross-protection is reported amongst some serovars. Current identification methods include the heamagglutination inhibition test, which is demanding and could be subjective. To overcome this, molecular typing methods proposed are the Multiplex polymerase chain reaction (PCR) and Restriction Fragment Length Polymorphism-PCR, but low reproducibility is reported. Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR has been suggested for molecular groupings of various bacterial species. This study focuses on evaluating the ERIC-PCR as a probable method to differentiate between different Av. paragallinarum serovars by grouping with reference isolates, based on clonal relations. The ERIC-PCR was performed on 12 reference isolates and 41 field isolates originating from South Africa and South America. The data indicate that the ERIC-PCR is not ideal for the differentiation or for molecular typing of Av. paragallinarum serovars, as no correlation is drawn upon comparison of banding patterns of field isolates and reference strains. However, the results do indicate isolates from the same origin sharing unique banding patterns, indicating potential clonal relationship; but when compared to the reference isolates dominant in the specific area, no correlation could be drawn. Furthermore, although the ERIC-PCR serves a purpose in epidemiological studies, it has proved to have little application in differentiating amongst serovars of Av. paragallinarum and to group untyped field strains with known reference strains. | Avibacterium paragallinarum;ERIC-PCR;molecular typing;serovar differentiation;species-specific PCR | pubmed |
The naturally occurring xanthone α-mangostin induces ROS-mediated cytotoxicity in non-small scale lung cancer cells. | Small cell lung cancer (NSCLC) accounts for 85% of total deaths globally, and recent studies indicate the increasing risks of NSCLC in China and South Asian countries. Hence, development of new therapeutics against NSCLC has been a major concern. α-Mangostin, a naturally occurring xanthone, found abundantly in pericarps of mangosteen fruit is well known for its medicinal importance. The anticancer properties of α-mangostin against several types of cancer are also well documented. But the mechanism of action of α-mangostin against lung cancer is not well understood and requires further investigation. Therefore in the present study, we explored the therapeutic potential of α-mangostin against A549 cells. Treatment of A549 cells with α-mangostin resulted in a dose-dependent loss of cell viability, while the non-malignant cells such as <i>h</i>PBMC and WI-38 remained unaffected. Further we observed that the ROS plays an important role in α-mangostin -induced apoptosis in A549 cells, and administration of N-acetyl cysteine significantly abrogates α-mangostin -mediated cytotoxicity in lung cancer cells. Overall, α-mangostin induces ROS-mediated cytotoxicity in NSCLC cells. | Apoptosis;NSCLC;ROS;α-Mangostin | pubmed |
HMGCR inhibits the early stage of PCV2 infection, while PKC enhances the infection at the late stage. | Porcine circovirus type 2 (PCV2) is the smallest DNA virus, which causes porcine circovirus diseases and porcine circovirus-associated diseases (PCVD/PCVAD). Due the small size of viral genomic DNA, PCV2 replication predominantly relies on the host factors. In this study, effects of PKC and HMGCR on PCV2 infection were evaluated using real time PCR and western blot. We found that PKC and HMGCR participated in different stages of PCV2 infection. HMGCR works on the early stage of the infection to inhibit the virus infection, while PKC enhances the infection at the late stage. Furthermore, PKC enhances PCV2 replication by activating JNK1/2 and inactivating HMGCR via regulating phosphorylation of these two proteins, while HMGCR can suppress phosphorylation of JNK1/2. The results in the present study will provide new sights in the pathogenesis of PCV2 infection, as well as interactions between host factors during PCV2 infection. | 3-hydroxy-3-methylglutaryl coenzyme a reductase (HMGCR);Porcine circovirus 2 (PCV2);Protein kinase C (PKC) | pubmed |
Anomalous White Matter Structure and the Effect of Age in Down Syndrome Patients. | Neural tissue alterations in Down syndrome are fully expressed at relatively late developmental stages. In addition, there is an early presence of neurodegenerative changes in the late life stages. The aims of this study were both to characterize white matter abnormalities in the brain of adult Down syndrome patients using diffusion tensor imaging (DTI) and to investigate whether degenerative alterations in white matter structure are detectable before dementia is clinically evident. Forty-five adult non-demented Down syndrome patients showing a wide age range (18-52 years) and a matched 45-subject control group were assessed. DTI fractional anisotropy (FA) brain maps were generated and selected cognitive tests were administered. Compared with healthy controls, non-demented Down syndrome patients showed lower DTI FA in white matter involving the major pathways, but with more severe alterations in the frontal-subcortical circuits. White matter FA decreased with age at a similar rate in both DS and control groups. Our results contribute to characterizing the expression of white matter structural alterations in adult Down syndrome. However, an accelerated aging effect was not demonstrated, which may suggest that the FA measurements used are not sufficiently sensitive or, alternatively, age-related white matter neurodegeneration is not obvious prior to overt clinical dementia. | Accelerated aging;diffusion tensor imaging;magnetic resonance imaging;neurodegeneration | pubmed |
Stochastic hyperelastic constitutive laws and identification procedure for soft biological tissues with intrinsic variability. | In this work, we address the constitutive modeling, in a probabilistic framework, of the hyperelastic response of soft biological tissues. The aim is on the one hand to mimic the mean behavior and variability that are typically encountered in the experimental characterization of such materials, and on the other hand to derive mathematical models that are almost surely consistent with the theory of nonlinear elasticity. Towards this goal, we invoke information theory and discuss a stochastic model relying on a low-dimensional parametrization. We subsequently propose a two-step methodology allowing for the calibration of the model using standard data, such as mean and standard deviation values along a given loading path. The framework is finally applied and benchmarked on three experimental databases proposed elsewhere in the literature. It is shown that the stochastic model allows experiments to be accurately reproduced, regardless of the tissue under consideration. | Biological material;Calibration;Constitutive law;Hyperelasticity;Information theory;Variability | pubmed |
Neural plasticity following lesions of the primate occipital lobe: The marmoset as an animal model for studies of blindsight. | For nearly a century it has been observed that some residual visually guided behavior can persist after damage to the primary visual cortex (V1) in primates. The age at which damage to V1 occurs leads to different outcomes, with V1 lesions in infancy allowing better preservation of visual faculties in comparison with those incurred in adulthood. While adult V1 lesions may still allow retention of some limited visual abilities, these are subconscious-a characteristic that has led to this form of residual vision being referred to as blindsight. The neural basis of blindsight has been of great interest to the neuroscience community, with particular focus on understanding the contributions of the different subcortical pathways and cortical areas that may underlie this phenomenon. More recently, research has started to address which forms of neural plasticity occur following V1 lesions at different ages, including work using marmoset monkeys. The relatively rapid postnatal development of this species, allied to the lissencephalic brains and well-characterized visual cortex provide significant technical advantages, which allow controlled experiments exploring visual function in the absence of V1. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 314-327, 2017. | V1;V1 lesion;lateral geniculate nucleus;pulvinar;visual cortex | pubmed |
Cancer-related microangiopathic haemolytic anaemia. | breast cancer;malignant and benign haematology | pubmed |
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PREVIEW: Prevention of Diabetes through Lifestyle Intervention and Population Studies in Europe and around the World. Design, Methods, and Baseline Participant Description of an Adult Cohort Enrolled into a Three-Year Randomised Clinical Trial. | Type-2 diabetes (T2D) is one of the fastest growing chronic diseases worldwide. The PREVIEW project has been initiated to find the most effective lifestyle (diet and physical activity) for the prevention of T2D, in overweight and obese participants with increased risk for T2D. The study is a three-year multi-centre, 2 × 2 factorial, randomised controlled trial. The impact of a high-protein, low-glycaemic index (GI) vs. moderate protein, moderate-GI diet in combination with moderate or high-intensity physical activity on the incidence of T2D and the related clinical end-points are investigated. The intervention started with a two-month weight reduction using a low-calorie diet, followed by a randomised 34-month weight maintenance phase comprising four treatment arms. Eight intervention centres are participating (Denmark, Finland, United Kingdom, The Netherlands, Spain, Bulgaria, Australia, and New Zealand). Data from blood specimens, urine, faeces, questionnaires, diaries, body composition assessments, and accelerometers are collected at months 0, 2, 6, 12, 18, 24, and 36. In total, 2326 adults were recruited. The mean age was 51.6 (SD 11.6) years, 67% were women. PREVIEW is, to date, the largest multinational trial to address the prevention of T2D in pre-diabetic adults through diet and exercise intervention. Participants will complete the final intervention in March, 2018. | carbohydrate;diet;glycaemic index;obesity;physical activity;protein | pubmed |
Public exposure to radioactivity levels in the Lebanese environment. | In the framework of a National Environmental Radiation Survey Program, a total of 950 samples were collected and analyzed over 7 years. The program covers different compartment of Lebanese environment, rivers, wells, marine samples, soil, and foodstuff. Air was monitored continuously through a radiation early warning network system. Data collected from 2009 to 2015 are presented in this work. Gross alpha/gross beta values in well samples were below the guidance levels stated by the WHO. Cesium-137 was detected in milk samples, whey, and jam. However, its content was much lower than the national permissible level, while its activity concentration in marine samples was lower than the values reported in studies carried out in the Mediterranean Sea. The activity concentration of <sup>40</sup>K in food samples was comparable to studies carried out in neighboring countries and higher than the content determined in non Mediterranean countries. Concerning marine environment, the activity concentrations of natural radionuclides <sup>238</sup>U, <sup>232</sup>Th, and <sup>40</sup>K were comparable to those reported in other studies carried out in different countries. As well as their content in rivers and sediments was lower than those reported in neighboring region. Potassium-40 in food and <sup>210</sup>Po in fish were the main contributors to the internal dose. The average annual effective dose due to external exposure and internal, excluding radon gas which constitutes around 43 % of the total dose, was found to be lower than the total worldwide value, 2.4 mSv year<sup>-1</sup>. Iodine-131 was detected in grass samples, collected in 2011 during Fukushima accident; its content ranged from 0.40 ± 0.06 to 0.9 ± 0.1 Bq kg<sup>-1</sup>, as well as <sup>137</sup>Cs was detected in some seafood samples imported from Japan and neighboring countries. Its activity concentration varied between 0.15 ± 0.04 and 0.40 ± 0.02 Bq kg<sup>-1</sup>. | Alpha spectroscopy;Annual effective dose;Environmental radiation survey program;Gamma spectroscopy;Liquid scintillation counter;Radiation baseline levels | pubmed |
Contribution of whole platelet aggregometry to the endovascular management of unruptured aneurysms: an institutional experience. | Stent-assisted coiling of intracranial aneurysms is an efficient alternative treatment to surgical clipping but requires prolonged antiplatelet therapy. Some patients are non-responsive to aspirin and/or clopidogrel. To analyze the implications of this assessment using the 'whole blood aggregometry (WBA) by impedance' technique. The Southwestern Tertiary Aneurysm Registry was reviewed between 2002 and 2012 for patients with unruptured aneurysms treated with stent-assisted coiling. The study population was divided into patients who were tested preoperatively for platelet responsiveness to aspirin and clopidogrel ('tested' patients) and those who were not ('non-tested'). Where necessary, tested patients received additional doses of antiplatelet drugs to achieve adequate platelet inhibition. Endpoints included the incidence of non-responsiveness, the rates of thrombotic and hemorrhagic complications, and the rates of permanent morbidity and mortality. A total of 266 patients fulfilled our selection criteria: 114 non-tested patients who underwent 121 procedures, and 152 tested patients who underwent 171 procedures. The two groups did not vary significantly in patient age, gender, and aneurysms location. Aspirin non-responsiveness was detected in 3 patients (1.75%) and clopidogrel non-responsiveness in 21 patients (12.3%). Non-tested patients had an 11.6% rate of thrombotic complications with a 4.1% permanent morbidity or mortality rate versus 2.3% and 0.6% in tested patients (p=0.0013). The incidence of hemorrhagic complications was similar between the two groups. Preoperative platelet inhibition testing using WBA can be useful to assess and correct antiaggregant non-responsiveness, and may reduce postoperative mortality and permanent morbidity. | Aneurysm;Angiography;Complication;Stent;Stroke | pubmed |
Baseline and treatment-related changes in thrombin generation in patients with multiple myeloma. | The prothrombotic risk in multiple myeloma (MM) could be potentially assessed by thrombin generation (TG) assays. TG was performed using Calibrated Automated Thrombography with 5 and 1 pM tissue factor. We compared baseline TG among 24 MM patients, 19 MGUS, and 50 healthy controls, and assessed change in TG in MM patients during the initial treatment period at 1, 2, and 3 months. MM subjects demonstrated increased FVIII and VWF:Ag levels pretreatment, and a prothrombotic TG phenotype with increased velocity index, reduced lag time and time-to-peak, and increased resistance to thrombomodulin inhibition. There were no significant changes in TG with treatment for the majority of parameters, however, MM subjects exhibited persistent elevation of velocity index throughout treatment. Two subjects developed thrombosis during the study period despite thromboprophylaxis. This study provides information on the optimal conditions for examining TG as a predictor of thrombotic risk in MM patients. | Monoclonal gammopathy;hypercoagulability;multiple myeloma;thrombin generation;venous thromboembolism | pubmed |
Randomized clinical trial for the biological evaluation of two nanostructured biphasic calcium phosphate biomaterials as a bone substitute. | The presence of nonresorbable residual granules of hydroxyapatite (HA) may decrease the bone/implant interface. To balance resorption and bone formation biphasic calcium phosphate ceramics compounds applied at different rates have been studied. The aim of this trial was to compare the clinical, histological, and histomorphometric responses of two new biphasic calcium phosphate biomaterials in fresh dental sockets after 3 and 6 months. Forty-eight volunteers were divided randomly and double-blindly into 4 groups of 12 individuals: Clot (C), BoneCeramic (BC), Biomaterial 1 (B1), and Biomaterial 2 (B2) groups. Three and six months later, samples were obtained, and histological and histomorphometric sections were evaluated, focusing on the presence of fibrous connective tissue (CT) and newly formed bone. Statistical analysis was performed (P < .05%). The quantification of crystalline phases showed B1 composed of HA (60.28%) and β-TCP (39.72%); B2 composed of HA (78.21%) and β-TCP (21.79%); and BC composed of HA (61%) and β-TCP (39%). The B1 group showed the most newly formed bone (69.3% ± 6.03%), followed by the BC (51.6 ± 12.34%), B2 (46.6 ± 7.66%), and C groups (45.4 ± 7.98%), and less connective tissue and biomaterial remained in the B1 group after 6 months. B1 group showed the greatest amount of newly formed bone after 6 months. | bone repair;bone substitute;calcium phosphate;clinical trial;dental implants | pubmed |
The Effectiveness of Articaine and Lidocaine Single Buccal Infiltration versus Conventional Buccal and Palatal Injection Using Lidocaine during Primary Maxillary Molar Extraction: A Randomized Control Trial. | Despite the advent of modern injection techniques, palatal injection continues to be a painful experience for children. To compare the pain experienced during extraction of maxillary primary molars with conventional lignocaine anesthesia versus lignocaine and articaine buccal infiltration in children aged 6-14 years. A prospective randomized triple blinded study was conducted with ninety children (<i>n</i> = 90), randomly allocated to receive lignocaine conventional anesthesia (Group I [control group]), and buccal infiltration using articaine (Group II [articaine group]) or lignocaine (Group III [lignocaine group]). A composite score of self-report (faces pain scale-revised), behavioral measure (face legs activity cry consolability scale), and a physiological response (pulse rate) was measured following maxillary primary molar extraction. To test the mean difference between two groups, Students' <i>t</i>-test was used and among the three groups, one-way ANOVA with <i>post hoc</i> test was used. Articaine group had significantly lower pain scores for self-report (<i>P</i> < 000.1) and behavioral measures (<i>P</i> < 000.1) while there was no significant difference (<i>P</i> > 0.05) between articaine and control groups during primary maxillary molar extraction. Maxillary primary molar extraction procedure can be successfully accomplished by bypassing the palatal injection. Articaine buccal infiltration can be considered as an alternative to conventional local anesthesia for the extraction of maxillary primary molars. | Articaine;buccal administration;children;lignocaine;local anesthesia;maxillary primary molars;palatal injection | pubmed |
Interventions for reducing fear of childbirth: A systematic review and meta-analysis of clinical trials. | Fear of childbirth is a problematic mental health issue during pregnancy. But, effective interventions to reduce this problem are not well understood. To examine effective interventions for reducing fear of childbirth. The Cochrane Central Register of Controlled Trials, PubMed, Embase and PsycINFO were searched since inception till September 2017 without any restriction. Randomised controlled trials and quasi-randomised controlled trials comparing interventions for treatment of fear of childbirth were included. The standardized mean differences were pooled using random and fixed effect models. The heterogeneity was determined using the Cochran's test and I<sup>2</sup> index and was further explored in meta-regression model and subgroup analyses. Ten studies inclusive of 3984 participants were included in the meta-analysis (2 quasi-randomized and 8 randomized clinical trials). Eight studies investigated education and two studies investigated hypnosis-based intervention. The pooled standardized mean differences of fear for the education intervention and hypnosis group in comparison with control group were -0.46 (95% CI -0.73 to -0.19) and -0.22 (95% CI -0.34 to -0.10), respectively. Both types of interventions were effective in reducing fear of childbirth; however our pooled results revealed that educational interventions may reduce fear with double the effect of hypnosis. Further large scale randomized clinical trials and individual patient data meta-analysis are warranted for assessing the association. | Antenatal class education;Fear of childbirth;Hypnosis;Meta-analysis;Systematic-review | pubmed |
Human Stem Cell-Derived Endothelial-Hepatic Platform for Efficacy Testing of Vascular-Protective Metabolites from Nutraceuticals. | Atherosclerosis underlies many cardiovascular and cerebrovascular diseases. Nutraceuticals are emerging as a therapeutic moiety for restoring vascular health. Unlike small-molecule drugs, the complexity of ingredients in nutraceuticals often confounds evaluation of their efficacy in preclinical evaluation. It is recognized that the liver is a vital organ in processing complex compounds into bioactive metabolites. In this work, we developed a coculture system of human pluripotent stem cell-derived endothelial cells (hPSC-ECs) and human pluripotent stem cell-derived hepatocytes (hPSC-HEPs) for predicting vascular-protective effects of nutraceuticals. To validate our model, two compounds (quercetin and genistein), known to have anti-inflammatory effects on vasculatures, were selected. We found that both quercetin and genistein were ineffective at suppressing inflammatory activation by interleukin-1β owing to limited metabolic activity of hPSC-ECs. Conversely, hPSC-HEPs demonstrated metabolic capacity to break down both nutraceuticals into primary and secondary metabolites. When hPSC-HEPs were cocultured with hPSC-ECs to permit paracrine interactions, the continuous turnover of metabolites mitigated interleukin-1β stimulation on hPSC-ECs. We observed significant reductions in inflammatory gene expressions, nuclear translocation of nuclear factor κB, and interleukin-8 production. Thus, integration of hPSC-HEPs could accurately reproduce systemic effects involved in drug metabolism in vivo to unravel beneficial constituents in nutraceuticals. This physiologically relevant endothelial-hepatic platform would be a great resource in predicting the efficacy of complex nutraceuticals and mechanistic interrogation of vascular-targeting candidate compounds. Stem Cells Translational Medicine 2017;6:851-863. | Coculture;Endothelial cells;Hepatocytes;Human pluripotent stem cells;Metabolism;Nutraceutical testing | pubmed |
Genomic and Molecular Characterization of Brain Tumors in Asian and Non-Asian Patients of Los Angeles: A Single Institution Analysis. | Worldwide, approximately 2% of new cancers are of the brain. Five-year survival rates among brain cancer patients have been reported as a little over a third. Differences in clinical outcomes between brain tumor patients of different races remain poorly understood. A retrospective chart review was performed on brain tumor resection patients≥18 years old. Demographics, treatment variables, and survival outcomes were collected. Primary outcomes were length of stay, recurrence rate, progression-free survival (PFS), and overall survival (OS). A total of 452 patients were included in analysis. Females and males had nearly a 1:1 ratio (n=242 and n=220, respectively). Mean age was 54.8 years (SD: 14.5 range: 18-90). Females composed 69% (n=48) of Asian patients; males constituted 31% (n=22). Mean age of the Asian patients was 55.9 years (SD: 14.6 range: 26-89). Asian-only cohort tumor pathologies included glioblastoma (GBM) (n=14), high-grade glioma (n=7), low-grade glioma (n=4), meningioma (n=38), and metastases (n=7). Of the 185 meningioma patients, non-Asian patients comprised 79% of the group (n=146). Of the 65 GBM patients in total, non-Asian patients made up 89% of the GBM cohort (n=58). There were no statistically significant differences between these groups of both cohorts in recurrence (<i>p</i>=0.1580 and <i>p</i>=0.6294, respectively), PFS (<i>p</i>=0.9662 and <i>p</i>=0.4048, respectively), or OS (<i>p</i>=0.3711 and <i>p</i>=0.8183, respectively). Studies evaluating the survival between patients of different racial backgrounds against several tumor varieties are rare. Patients of certain racial backgrounds may need additional consideration when being attended to despite the same mutational composition as their counterparts. Repeated studies using national databases may yield more conclusive results. | Biomarkers;Brain neoplasms;Glioblastoma;Meningioma;Race | pubmed |
Measurement and evaluation of fetal fat layer in the prediction of fetal macrosomia in pregnancies complicated by gestational diabetes. | To explore the predictive power of measuring the abdominal fetal fat layer (FFL) as a soft tissue marker at 31, 34, and 37 weeks' gestation to improve the detection of fetal macrosomia in pregnant women with GDM, in addition to the biometric values with close monitoring of maternal blood sugar level and BMI changes. We conducted a prospective observational study at the Department of Obstetrics, University Hospitals, Campus Kiel, Germany, in collaboration with diabetic clinic staff. Participants underwent a third-trimester scan and extra FFL measurements were performed at 31, 34, and 37 weeks of gestation. The clinical outcomes of pregnancy and birth weight were collected from the obstetric record. All of the enrolled women had an early pregnancy ultrasound scan to confirm gestational age. The FFL at 34 and 37 weeks, with respective cutoff values of >0.48 cm and >0.59 cm, showed a very good sensitivity of 60% for both gestational points, and specificity of 89.3 and 90.6%, respectively. The probability of fetal macrosomia could be more than doubled if the FFL at 34 weeks was more than 0.48 cm. However, the probability of macrosomia dropped to 16% if the FFL was ≤0.48 cm. The median FFLs of macrosomic fetuses at 34 and 37 weeks were 0.50 (IQR 0.10) and 0.60 (IQR 0.25) cm, respectively. The mean age of the study population (n = 80) was 32.26 (SD = 5.06) years. In our study population, ten newborns were born with birth weight >4000 g. The body mass index (BMI) for the mothers of later-onset macrosomic newborns showed higher median values of 30 (IQR 8), 32 (IQR 5), and 33 (IQR 9) at 31, 34, and 37 weeks, respectively, in comparison to mothers of non-macrosomic newborn. However, the BMI did not show any statistically significant difference from those with normal-weight newborn and did not show any specific sensitivity for predicting macrosomia. Measuring the FFL at 34 and 37 weeks of gestation, in addition to the standard measurement, might be useful for predicting macrosomia and is worth further evaluation. | Abdominal fetal fat layer (FFL);Fetal macrosomia;Gestational diabetes;Soft-tissue marker | pubmed |
Prevention and treatment of cancer-associated thrombosis in France: A national survey among vascular disease and supportive care specialists. | Long-term use of low-molecular-weight heparins (LMWH) for the treatment of cancer-associated thrombosis (CAT) has been well-established. Conversely, the use of thromboprophylaxis in patients with cancer remains controversial in the absence of homogeneous guidelines. Our aim was to assess the awareness of treatment guidelines and the management of patients with CAT in daily clinical practice. A national survey based on an open questionnaire developed by a panel of health professionals including specialists in vascular medicine, oncology, supportive care and pharmacy, was proposed on line to 2104 specialists experts in the management of CAT with the objective to collect at least 400 answers. Clinical practice assessment included the treatment of lung adenocarcinoma-associated thrombosis, the use of thromboprophylaxis and factors influencing the management of patients with CAT. A total of 401 questionnaires were completed by specialists of vascular medicine (68%), oncology (12%) and other (20%). LMWH was the preferred option for over 90% of the participants for the treatment of recent overt proximal pulmonary embolism or deep-vein thrombosis. Up to 70% of the participants considered treatment duration for 6 months and more than 12 months in case of active malignancy. Patient management in the setting of incidental VTE and thromboprophylaxis were heterogeneous in the absence of clear guidance while VTE risk scores would be used by only 14% of participants. Patients with CAT are properly managed based on clear and consistent guidelines. Patient care is heterogeneous regarding treatment duration beyond 6 months and thromboprophylaxis while VTE risk scores are misused. Identification of referent health care professionals for CAT management and more clear guidelines are required. | Cancer;Héparine de bas poids moléculaire;Low-molecular-weight heparin;Maladie veineuse thromboembolique;Recommandations;Treatment guidelines;Venous thromboembolism | pubmed |
Triterpenoids with antioxidant activities from Myricaria squamosa. | A new triterpenoid, namely myricarin C (compound 1), together with three known compounds myricarin A (compound 2) and myricarin B (compound 3), 3α-hydroxy-D-friedoolean-14-en-28-oic acid (compound 4), was isolated from the overground part of Myricaria squamosa. Compound 2 and compound 3 existed in the solution by the form of cis-trans isomers. Their structures were elucidated by means of extensive spectroscopic methods, including 1D-NMR, 2D-NMR, and HR-ESI-MS. The antioxidant properties of all compounds were calculated based on the DPPH radical scavenging activities. Results showed that myricarin A and myricarin C had general antioxidant activities with EC<sub>50</sub> values of 40.90 μg/ml, 42.22 μg/ml, respectively, compared to the control, rutin (5.17 μg/ml). The EC<sub>50</sub> values of myricarin B was 195.81 μg/ml. Compound 4 had no antioxidant activities. | DPPH radical scavenging activity;Myricaria squamosa;semi-preparative reversed phase liquid chromatography (RPLC);triterpenoid | pubmed |
A male and female RNA marker to infer sex in forensic analysis. | In forensics, DNA profiling is used for the identification of the donor of a trace, while messenger RNA (mRNA) profiling can be applied to identify the cellular origin such as body fluids or organ tissues. The presence of male cell material can be readily assessed by the incorporation of Y-chromosomal markers in quantitation or STR profiling systems. However, no forensic marker exists to positively identify female cell material; merely the presence of female DNA is deduced from the absence of a Y peak, or unbalanced X-Y signals at the Amelogenin locus or unbalanced response of the total and Y-specific quantifier. The presence of two X-chromosomes in female cells invokes dosage compensation, which is achieved through inactivation of one of the X-chromosomes in females. Since this process involves specific RNA molecules, identification of female cellular material may be possible through RNA profiling. Additionally, male material may be identified through RNAs expressed from the Y-chromosome. RNAs preferentially expressed in either sex were assessed for their potential to act as sex markers in forensic RNA assays. To confirm sex-specificity, body fluids and organ tissues of multiple donors of either sex were tested. Additionally, sensitivity of the markers and the suitability of positively identifying male-female mixtures were assessed and degraded samples were used to assess performance of the markers in forensic settings. The addition of sex-specific markers is of added informative value in any RNA profiling system and both markers were incorporated into existing RNA assays that either target body fluids or organs. These are the first forensic assays that enable positive identification of female cellular material. | Body fluid identification;Forensic science;Organ tissue identification;Sex-biased genes;Sex-specific RNA marker;mRNA profiling | pubmed |
Passive in-vehicle driver breath alcohol detection using advanced sensor signal acquisition and fusion. | The research objective of the present investigation is to demonstrate the present status of passive in-vehicle driver breath alcohol detection and highlight the necessary conditions for large-scale implementation of such a system. Completely passive detection has remained a challenge mainly because of the requirements on signal resolution combined with the constraints of vehicle integration. The work is part of the Driver Alcohol Detection System for Safety (DADSS) program aiming at massive deployment of alcohol sensing systems that could potentially save thousands of American lives annually. The work reported here builds on earlier investigations, in which it has been shown that detection of alcohol vapor in the proximity of a human subject may be traced to that subject by means of simultaneous recording of carbon dioxide (CO<sub>2</sub>) at the same location. Sensors based on infrared spectroscopy were developed to detect and quantify low concentrations of alcohol and CO<sub>2</sub>. In the present investigation, alcohol and CO<sub>2</sub> were recorded at various locations in a vehicle cabin while human subjects were performing normal in-step procedures and driving preparations. A video camera directed to the driver position was recording images of the driver's upper body parts, including the face, and the images were analyzed with respect to features of significance to the breathing behavior and breath detection, such as mouth opening and head direction. Improvement of the sensor system with respect to signal resolution including algorithm and software development, and fusion of the sensor and camera signals was successfully implemented and tested before starting the human study. In addition, experimental tests and simulations were performed with the purpose of connecting human subject data with repeatable experimental conditions. The results include occurrence statistics of detected breaths by signal peaks of CO<sub>2</sub> and alcohol. From the statistical data, the accuracy of breath alcohol estimation and timing related to initial driver routines (door opening, taking a seat, door closure, buckling up, etc.) can be estimated. The investigation confirmed the feasibility of passive driver breath alcohol detection using our present system. Trade-offs between timing and sensor signal resolution requirements will become critical. Further improvement of sensor resolution and system ruggedness is required before the results can be industrialized. It is concluded that a further important step toward completely passive detection of driver breath alcohol has been taken. If required, the sniffer function with alcohol detection capability can be combined with a subsequent highly accurate breath test to confirm the driver's legal status using the same sensor device. The study is relevant to crash avoidance, in particular driver monitoring systems and driver-vehicle interface design. | Passive breath alcohol detection;automotive safety;contactless measurement;infrared gas sensor | pubmed |
A paper-based nanomodified electrochemical biosensor for ethanol detection in beers. | Herein, we report the first example of a paper-based screen-printed biosensor for the detection of ethanol in beer samples. Common office paper was adopted to fabricate the analytical device. The properties of this paper-based screen-printed electrode (SPE) were investigated by cyclic voltammetry, electrochemical impedance spectroscopy, and scanning electron microscopy, and they were compared with the well-established polyester-based SPEs as well. Paper demonstrated similar properties when compared with polyester, highlighting suitability towards its utilization in sensor development, with the advantages of low cost and simple disposal by incineration. A nanocomposite formed by Carbon Black (CB) and Prussian Blue nanoparticles (PBNPs), namely CB/PBNPs, was utilized as an electrocatalyst to detect the hydrogen peroxide generated by the enzymatic reaction between alcohol oxidase (AOx) and ethanol. After optimizing the analytical parameters, such as pH, enzyme, concentration, and working potential, the developed biosensor allowed a facile quantification of ethanol up to 10 mM (0.058 %<sub>vol</sub>), with a sensitivity of 9.13 μA/mM cm<sup>2</sup> (1574 μA/%<sub>vol</sub> cm<sup>2</sup>) and a detection limit equal to 0.52 mM (0.003%<sub>vol</sub>). These satisfactory performances rendered the realized paper-based biosensor reliable over the analysis of ethanol contained in four different types of beers, including Pilsner, Weiss, Lager, and alcohol-free. The proposed manufacturing approach offers an affordable and sustainable tool for food quality control and for the realization of different electrochemical sensors and biosensors as well. | Carbon black;Ethanol oxidase;Paper-based screen-printed electrode;Prussian blue nanoparticles;Wax printing | pubmed |
Asymmetric Catalytic Aza-Diels-Alder/Ring-Closing Cascade Reaction Forming Bicyclic Azaheterocycles by Trienamine Catalysis. | An asymmetric catalytic aza-Diels-Alder/ring-closing cascade reaction between acylhydrazones and in situ formed trienamines is presented. The reaction proceeds through a formal aza-Diels-Alder cycloaddition, followed by a ring-closing reaction forming the hemiaminal ring leading to chiral bicyclic azaheterocycles in moderate to good yield (up to 71 %), good enantio- (up to 92 % ee) and diastereoselectivity (up to >20:1 d.r.). Furthermore, transformations are presented to show the potential application of the formed product. | asymmetric catalysis;cycloaddition;heterocycles;organocatalysis;synthetic methods | pubmed |
Intrauterine device visualized as extrinsic bladder mass on cystoscopy. | Intrauterine device migration;Intrauterine devices;Intrauterine devices, medicated | pubmed |
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Validation of a method for retroperitoneal tumor segmentation. | In 2005, an application for surgical planning called AYRA[Formula: see text] was designed and validated by different surgeons and engineers at the Virgen del Rocío University Hospital, Seville (Spain). However, the segmentation methods included in AYRA and in other surgical planning applications are not able to segment accurately tumors that appear in soft tissue. The aims of this paper are to offer an exhaustive validation of an accurate semiautomatic segmentation tool to delimitate retroperitoneal tumors from CT images and to aid physicians in planning both radiotherapy doses and surgery. A panel of 6 experts manually segmented 11 cases of tumors, and the segmentation results were compared exhaustively with: the results provided by a surgical planning tool (AYRA), the segmentations obtained using a radiotherapy treatment planning system (Pinnacle[Formula: see text]), the segmentation results obtained by a group of experts in the delimitation of retroperitoneal tumors and the segmentation results using the algorithm under validation. 11 cases of retroperitoneal tumors were tested. The proposed algorithm provided accurate results regarding the segmentation of the tumor. Moreover, the algorithm requires minimal computational time-an average of 90.5% less than that required when manually contouring the same tumor. A method developed for the semiautomatic selection of retroperitoneal tumor has been validated in depth. AYRA, as well as other surgical and radiotherapy planning tools, could be greatly improved by including this algorithm. | CT;Continuous convex relaxation;Radiotherapy planning;Retroperitoneal tumor;Surgical planning | pubmed |
Conceptual disorganization weakens links in cognitive pathways: Disentangling neurocognition, social cognition, and metacognition in schizophrenia. | Disentangling links between neurocognition, social cognition, and metacognition offers the potential to improve interventions for these cognitive processes. Disorganized symptoms have shown promise for explaining the limiting relationship that neurocognition holds with both social cognition and metacognition. In this study, primary aims included: 1) testing whether conceptual disorganization, a specific disorganized symptom, moderated relationships between cognitive processes, and 2) examining the level of conceptual disorganization necessary for links between cognitive processes to break down. To accomplish these aims, comprehensive assessments of conceptual disorganization, neurocognition, social cognition, and metacognition were administered to 67 people with schizophrenia-spectrum disorders. We found that conceptual disorganization significantly moderated the relationship between neurocognition and metacognition, with links between cognitive processes weakening when conceptual disorganization is present even at minimal levels of severity. There was no evidence that conceptual disorganization-or any other specific disorganized symptom-drove the limiting relationship of neurocognition on social cognition. Based on our findings, conceptual disorganization appears to be a critical piece of the puzzle when disentangling the relationship between neurocognition and metacognition. Roles of specific disorganized symptoms in the neurocognition - social cognition relationship were less clear. Findings from this study suggest that disorganized symptoms are an important treatment consideration when aiming to improve cognitive impairments. | Conceptual disorganization;Metacognition;Neurocognition;Schizophrenia;Social cognition | pubmed |
Challenges and Issues in the Evaluation of Teaching Quality: How Does it Affect Teachers' Professional Practice? A UK Perspective. | Evaluation of the quality of higher education is undertaken for the purposes of ensuring accountability, accreditation, and improvement, all of which are highly relevant to veterinary teaching institutions in the current economic climate. If evaluation is to drive change, it needs to be able to influence teaching practice. This article reviews the literature relating to evaluation of teaching quality in higher education with a particular focus on teachers' professional practice. Student evaluation and peer observation of teaching are discussed as examples of widely used evaluation processes. These approaches clearly have the potential to influence teachers' practice. Institutions should strive to ensure the development of a supportive culture that prioritizes teaching quality while being aware of any potential consequences related to cost, faculty time, or negative emotional responses that might result from the use of different evaluation methods. | evaluation of teaching;peer observation;quality in higher education | pubmed |
Association of Body Mass Index Changes during Neoadjuvant Chemotherapy with Pathologic Complete Response and Clinical Outcomes in Patients with Locally Advanced Breast Cancer. | The purpose of this study was to determine the association between body mass index (BMI) measurements (baseline BMI and changes in BMI during neoadjuvant systemic treatment [NST]) and clinical efficacy (pathologic complete response [pCR] rate and survival outcomes) in locally advanced breast cancer (LABC). We hypothesized that high baseline BMI and increases in BMI during NST are associated with lower pCR rates and poorer clinical outcomes in LABC. We retrospectively reviewed the medical records of 1002 patients, 204 with primary inflammatory breast cancer (IBC) and 798 with stage III non-IBC, who underwent standard NST and definitive surgery between November 1, 2006, and December 31, 2012. The median follow-up time for the survivors was 19.6 months (0.4 - 67.8 months). The pCR rates of patients whose BMI increased or decreased were 23.2% and 18.1%, respectively, (p=0.048). The unadjusted overall survival (OS) was significantly better in the group with increased BMI (p=0.006). However, increased BMI was not an independent predictor of pCR and clinical outcomes (recurrence-free survival and OS) after adjusting for other clinical variables. In subset analyses, increased BMI as a continuous variable was an independent predictor of higher pCR rates in the normal BMI/underweight group (odds ratio [OR]=1.35, 95% confidence interval [CI]: 1.06-0.71, p=0.015). Increased BMI (BMI change ≥0 vs. <0) was also an independent predictor of pCR (OR=1.65, 95% CI: 1.00-2.72, p=0.049) in the postmenopausal group. Our results show that increasing BMI shows improved clinical outcome in terms of better pCR rates in normal BMI/underweight group and in the postmenopausal group. These results contradict previously reported findings on the association between high BMI and poor clinical efficacy regarding pCR rate and survival outcomes in early-stage breast cancer. Thus, the role of BMI in breast cancer may depend on patients' clinical characteristics such as advanced stage. | Body mass index;Body mass index change;Breast cancer;Inflammatory breast cancer;Pathological complete response;Predictive factor | pubmed |
HIV with non-communicable diseases in primary care in Kibera, Nairobi, Kenya: characteristics and outcomes 2010-2013. | Antiretroviral therapy (ART) has increased the life expectancy of people living with HIV (PLHIV); HIV is now considered a chronic disease. Non-communicable diseases (NCDs) and HIV care were integrated into primary care clinics operated within the informal settlement of Kibera, Nairobi, Kenya. We describe early cohort outcomes among PLHIV and HIV-negative patients, both of whom had NCDs. A retrospective analysis was performed of routinely collected clinic data from January 2010 to June 2013. All patients >14 years with hypertension and/or diabetes were included. Of 2206 patients included in the analysis, 210 (9.5%) were PLHIV. Median age at enrollment in the NCD program was 43 years for PLHIV and 49 years for HIV-negative patients (p<0.0001). The median duration of follow up was 1.4 (IQR 0.7-2.1) and 1.0 (IQR 0.4-1.8) years for PLHIV and HIV-negative patients, respectively (p=0.003). Among patients with hypertension, blood pressure outcomes were similar, and for those with diabetes, outcomes for HbA1c, fasting glucose and cholesterol were not significantly different between the two groups. The frequency of chronic kidney disease (CKD) was 12% overall. Median age for PLHIV and CKD was 50 vs 55 years for those without HIV (p=0.005). In this early comparison of PLHIV and HIV-negative patients with NCDs, there were significant differences in age at diagnosis but both groups responded similarly to treatment. This study suggests that integrating NCD care for PLHIV along with HIV-negative patients is feasible and achieves similar results. | Africa;Chronic kidney disease;Diabetes;HIV;Hypertension;Non-communicable diseases | pubmed |
Molecular and Functional Characterization of Thioredoxin 1 from Korean Rose Bitterling (Rhodeus uyekii). | Thioredoxin is a multifunctional antioxidant enzyme that belongs to the reductase family. In this study, we cloned and characterized thioredoxin 1 cDNA from the Korean rose bitterling Rhodeus uyekii (RuTrx). The full-length RuTrx cDNA consists of 674 bp with a 324 nt open reading frame (ORF) encoding a 107 aa protein. The deduced RuTrx amino acid sequence indicated a characteristic redox active site, (31)WCGPC(35). Pairwise alignment revealed RuTrx amino acid identity (55.1%-83.2%) with orthologs from various species of mammalia, amphibia, fish and bird. Phylogenetic analysis was conducted to determine the evolutionary position of RuTrx. Expression analysis showed that RuTrx transcripts were present in all of the tissues examined, and was high in the hepatopancreas of R. uyekii. During early development, the expression of RuTrx transcripts was increased. Recombinant RuTrx protein (rRuTrx) was tested for its capacity to serve as an antioxidant enzyme using a metal-catalyzed oxidation (MCO) system. The ability of rRuTrx to protect against supercoiled DNA cleavage due to oxidative nicking increased in a dose-dependent manner. In Raw264.7 cells, Dihydroethidium (DHE) staining for ROS production indicated the antioxidant activity of rRuTrx. Together, these findings suggest that RuTrx may play a role in maintaining the redox state balance in Korean rose bitterling R. uyekii. | Korean rose bitterling;MCO assay;ROS detection;Rhodues uyekii;anti-oxidant;expression analysis;thioredoxin | pubmed |
Therapeutic effects of Ventolin versus hypertonic saline 3% for acute bronchiolitis in children. | Complications of Ventolin as the most common drug used for bronchiolitis are widely known. The present study was conducted to determine the efficacy of hypertonic saline 3%, compared with Ventolin, for treatment of acute bronchiolitis in children. This double-blinded clinical trial study was conducted in Hajar Hospital, Shahrekord, Iran, from 2011 to 2012. A total of 70 patients under the age of two years with bronchiolitis were divided into two groups of 35 each. Ventolin nebulizer and hypertonic saline 3% nebulizer three times per day were administered in the first (Ventolin) and second (Hypersaline) group, respectively. The length of recovery was compared between the two groups. The data were analyzed by SPSS software (version 22) using chi-square, t-test, paired t-test, and Mann-Whitney. The mean±SD length of recovery was 4.14±0.9 and 3.06±0.6 in the Ventolin and hypersaline groups, respectively. The mean duration of recovery was significantly lower in the hypersaline group (p<0.001). Hypertonic saline 3% nebulizer has more pleasant therapeutic effects on acute bronchiolitis than Ventolin. Therefore, use of hypertonic saline 3% nebulizer is recommended for the treatment of acute bronchiolitis in children under two years old. | Bronchiolitis;Hypertonic saline solution;Pediatric;Ventolin-albuterol | pubmed |
The Effects of Transcranial Direct-Current Stimulation on Cognition in Stroke Patients. | To investigate whether transcranial direct-current stimulation (tDCS) can improve cognition in stroke patients. Forty-five stroke patients (20 males and 25 females, average age: 62.7 years) with cognitive dysfunction were included in this prospective, double-blinded, randomized case-control study. All patients were right-handed and the mean elapsed time after stroke was 39.3 days. Three different treatments groups were used: (1) anodal stimulation of the left anterior temporal lobe, (2) anodal stimulation of the right anterior temporal lobe, and (3) sham stimulation. tDCS was delivered for 30 minutes at 2 mA with 25 cm(2) electrodes, five times/week, for a total of 3 weeks, using a Phoresor II Auto Model PM 850 (IOMED(®)). The evaluation of cognitive impairment was based on a Computerized Neuropsychological Test (CNT), Korean Mini-Mental State Examination (K-MMSE). The Korean version of the Modified Barthel Index (K-MBI) was used to assess activities of daily living functionality. These evaluations were conducted in all patients before and after treatment. Each group included 15 patients. Pre-treatment evaluation showed no significant differences between the three groups for any of the parameters. There was significant improvement in the verbal learning test on the CNT in the left anodal stimulation group (P < 0.05). There were, however, no significant differences in the K-MMSE or K-MBI scores among the three groups. These results demonstrated the beneficial effects of anodal tDCS on memory function. Thus, tDCS can successfully be used as a treatment modality for patients with cognitive dysfunction after stroke. | Cognition;Stroke;Transcranial direct stimulation | pubmed |
Lipid emulsions for parenteral nutrition in critical illness. | Critical illness is a life-threatening multisystem process that can result in significant morbidity and mortality. In most patients, critical illness is preceded by a physiological deterioration, characterized by a catabolic state and intense metabolic changes, resulting in malnutrition and impaired immune functions. In this context, parenteral lipid emulsions may modulate inflammatory and immune reactions, depending on their fatty acid composition. These effects appear to be based on complex modifications in the composition and structure of cell membranes, through eicosanoid and cytokine synthesis and by modulation of gene expression. The pathophysiological mechanisms underlying these fatty acid-induced immune function alterations in critical ill patients are however complex and partially understood. Indeed, despite a very abundant literature, experimental and clinical data remain contradictory. The optimization of lipid emulsion composition thus represents a major challenge for clinical medicine, to adequately modulate the inflammatory pathways. In the present review, we first address the metabolic response to aggression, the effects of parenteral lipid emulsions on inflammation and immunity, and finally the controversial place of these lipid emulsions during critical illness. The analysis furthermore highlights the pathophysiological mechanisms underlying the differential effects of lipid emulsions and their potential for improving the handling of critically ill patients. | ARDS;Critical illness;Lipid emulsion;Parenteral nutrition;Post-surgery;Septic shock;n−3 PUFAs | pubmed |
Shorter ischaemic time and improved survival with pre-hospital STEMI diagnosis and direct transfer for primary PCI. | We sought to determine if our regional program for pre-hospital STEMI diagnosis and direct transfer for primary PCI (PPCI) was associated with shorter ischaemic times and improved survival compared with ED diagnosis. STEMI diagnosis was made at the scene by pre-hospital ECG or in local EDs depending on patient presentation. Ambulance ECGs were transmitted to our ED for cath lab activation. Patient variables and outcomes at 12 months were recorded. We treated 782 consecutive patients with PPCI during January 2008-June 2013. Cath lab activation was initiated prior to hospital arrival (pre-hospital) in 24% of cases and by ED in 76% of cases. Median total ischaemic time was 154 min for pre-hospital and 211 minutes for ED patients (p<0.0001). Mortality at 12 months was 7.9% in the ED group compared with 3.7% in the pre-hospital group (p=0.036). On multivariate Cox regression analysis including baseline and procedural variables, pre-hospital activation remained an independent predictor of mortality (HR 0.45, 95% CI 0.20-1.0, p=0.03). Pre-hospital diagnosis of STEMI and direct transfer to the cath lab reduced total ischaemic time by 57 minutes and mortality by >50% following PPCI. Further efforts are needed to increase the proportion of STEMI patients treated using this strategy. | Ambulances;Myocardial infarction;Myocardial reperfusion;Pre-hospital triage;Primary percutaneous coronary intervention;STEMI | pubmed |
Impaired expression of neuronal nitric oxide synthase in the gracile nucleus is involved in neuropathic changes in Zucker Diabetic Fatty rats with and without 2,5-hexanedione intoxication. | These studies examined the influence of 2,5-hexanedione (2,5-HD) intoxication on expression of neuronal nitric oxide synthase (nNOS) in the brainstem nuclei in Zucker Diabetic Fatty (ZDF) vs. lean control (LC) rats. Functional neuropathic changes were also investigated following axonal damage and impaired axonal transport induced by the treatment. Animals were intoxicated by i.p. injection of 2,5-HD plus unilateral administration of 2,5-HD over the sciatic nerve. The mechanical thresholds and withdrawal latencies to heat and cold stimuli on the foot were measured at baseline and after intoxication. The medulla sections were examined by nNOS immunohistochemistry and NADPH-diaphorase histochemistry at the end of the treatments. The mechanical thresholds and withdrawal latencies were significantly decreased while nNOS immunostained neurons and NADPH-diaphorase positive cells were selectively reduced in the gracile nucleus at baseline in ZDF vs. LC rats. NADPH-diaphorase reactivity and nNOS positive neurons were increased in the ipsilateral gracile nucleus in LC rats following 2,5-HD intoxication, but its up-regulation was attenuated in ZDF rats. These results suggest that diabetic and chemical intoxication-induced nNOS expression is selectively reduced in the gracile nucleus in ZDF rats. Impaired axonal damage-induced nNOS expression in the gracile nucleus is involved in neuropathic pathophysiology in type II diabetic rats. | 2,5-HD intoxication;Diabetic neuropathy;Dorsal medulla;Immunohistochemistry;Nitric oxide synthase;Sensory functions | pubmed |
Genome-wide Association Study of Autism Spectrum Disorder in the East Asian Populations. | Autism spectrum disorder is a heterogeneous neurodevelopmental disorder with strong genetic basis. To identify common genetic variations conferring the risk of ASD, we performed a two-stage genome-wide association study using ASD family and healthy control samples obtained from East Asian populations. A total of 166 ASD families (n = 500) and 642 healthy controls from the Japanese population were used as the discovery cohort. Approximately 900,000 single nucleotide polymorphisms (SNPs) were genotyped using Affymetrix Genome-Wide Human SNP array 6.0 chips. In the replication stage, 205 Japanese ASD cases and 184 healthy controls, as well as 418 Chinese Han trios (n = 1,254), were genotyped by TaqMan platform. Case-control analysis, family based association test, and transmission/disequilibrium test (TDT) were then conducted to test the association. In the discovery stage, significant associations were suggested for 14 loci, including 5 known ASD candidate genes: GPC6, JARID2, YTHDC2, CNTN4, and CSMD1. In addition, significant associations were identified for several novel genes with intriguing functions, such as JPH3, PTPRD, CUX1, and RIT2. After a meta-analysis combining the Japanese replication samples, the strongest signal was found at rs16976358 (P = 6.04 × 10(-7)), which is located near the RIT2 gene. In summary, our results provide independent support to known ASD candidate genes and highlight a number of novel genes warranted to be further investigated in a larger sample set in an effort to improve our understanding of the genetic basis of ASD. | autism;autism spectrum disorder;common variation;genetics;genome-wide association study | pubmed |
Janus Solid-Liquid Interface Enabling Ultrahigh Charging and Discharging Rate for Advanced Lithium-Ion Batteries. | LiFePO4 has long been held as one of the most promising battery cathode for its high energy storage capacity. Meanwhile, although extensive studies have been conducted on the interfacial chemistries in Li-ion batteries,1-3 little is known on the atomic level about the solid-liquid interface of LiFePO4/electrolyte. Here, we report battery cathode consisted with nanosized LiFePO4 particles in aqueous electrolyte with an high charging and discharging rate of 600 C (3600/600 = 6 s charge time, 1 C = 170 mAh g(-1)) reaching 72 mAh g(-1) energy storage (42% of the theoretical capacity). By contrast, the accessible capacity sharply decreases to 20 mAh g(-1) at 200 C in organic electrolyte. After a comprehensive electrochemistry tests and ab initio calculations of the LiFePO4-H2O and LiFePO4-EC (ethylene carbonate) systems, we identified the transient formation of a Janus hydrated interface in the LiFePO4-H2O system, where the truncated symmetry of solid LiFePO4 surface is compensated by the chemisorbed H2O molecules, forming a half-solid (LiFePO4) and half-liquid (H2O) amphiphilic coordination environment that eases the Li desolvation process near the surface, which makes a fast Li-ion transport across the solid/liquid interfaces possible. | LiFePO4;ab initio calculations;aqueous electrolyte;organic electrolyte;rate performance;solid−liquid interface | pubmed |
Effect of Aggregation and Cage Setting on Some Life-History Parameters of Aleurodicus Rugioperculatus (Hemiptera: Aleyrodidae). | Fecundity is defined as the number of progeny produced by an organism. In our study, we used three different experimental settings to measure the fecundity of rugose spiraling whitefly (Aleurodicus rugioperculatus Martin), a recent invasive insect in Florida, on Strelitzia nicolai host plants. The adult longevity was significantly different among treatments, with females surviving significantly longer in groups in whole-plant cages and individual females in clip cages compared with individual females in whole-plant cages. Females laid 34.5 ± 8.4, 156.4 ± 18.3, and 225.2 ± 18 eggs, on average, when kept individually in whole-plant cages, in a group in whole-plant cages, and individually in clip cages, respectively. In all treatments, there was a significant correlation between the longevity and fecundity of females. Males emerged earlier than females in all treatments. Virgin females produced only males in the F1, while mated females produced both males and females, which suggests an arrhenotokous parthenogenesis. The egg-to-adult survival of the whitefly was 29 ± 4%, and the highest mortality occurred at the crawler stage when reared on S. nicolai. The results showed a significant effect of aggregation and cage setting on longevity and fecundity of this whitefly. To conclude, the experimental setting of the group fecundity treatment is more similar to what occurs in the landscape. Such a significant effect of cage setting and aggregation on the life-history parameters should be always taken into account when designing experiments or interpreting results. | Aleurodicus rugioperculatus;cage setting;fecundity;longevity;survival | pubmed |
Battery-powered bone drill: caution needed in densely blastic lesions. | Image-guided biopsies play an important role for pathologic diagnosis of bone tumors. Recently, motorized, battery powered bone marrow biopsy devices have been used to biopsy focal bone lesions with high accuracy. We present here two cases of densely blastic metastases where the biopsy sample could not be removed from the needle. These two cases suggest that if the lesion is densely blastic, then the sample should be small (<5 mm) to ensure that the biopsy specimen will not be stuck within the biopsy needle. | CT-guided biopsy;Metastases;Tumor | pubmed |
"Nothing About Me Without Me": An Interpretative Review of Patient Accessible Electronic Health Records. | Patient accessible electronic health records (PAEHRs) enable patients to access and manage personal clinical information that is made available to them by their health care providers (HCPs). It is thought that the shared management nature of medical record access improves patient outcomes and improves patient satisfaction. However, recent reviews have found that this is not the case. Furthermore, little research has focused on PAEHRs from the HCP viewpoint. HCPs include physicians, nurses, and service providers. We provide a systematic review of reviews of the impact of giving patients record access from both a patient and HCP point of view. The review covers a broad range of outcome measures, including patient safety, patient satisfaction, privacy and security, self-efficacy, and health outcome. A systematic search was conducted using Web of Science to identify review articles on the impact of PAEHRs. Our search was limited to English-language reviews published between January 2002 and November 2014. A total of 73 citations were retrieved from a series of Boolean search terms including "review*" with "patient access to records". These reviews went through a novel scoring system analysis whereby we calculated how many positive outcomes were reported per every outcome measure investigated. This provided a way to quantify the impact of PAEHRs. Ten reviews covering chronic patients (eg, diabetes and hypertension) and primary care patients, as well as HCPs were found but eight were included for the analysis of outcome measures. We found mixed outcomes across both patient and HCP groups, with approximately half of the reviews showing positive changes with record access. Patients believe that record access increases their perception of control; however, outcome measures thought to create psychological concerns (such as patient anxiety as a result of seeing their medical record) are still unanswered. Nurses are more likely than physicians to gain time efficiencies by using a PAEHR system with the main concern from physicians being the security of the PAEHRs. This review implements a novel scoring system, which shows there is a lack of rigorous empirical testing that separates the effect of record access from other existing disease management programs. Current research is too targeted within certain clinical groups' needs, and although there are positive signs for the adoption of PAEHRs, there is currently insufficient evidence about the effect of PAEHRs on health outcomes for patients or HCPs. | online record access;patient accessible electronic health records | pubmed |
Perceptions of Determinants of Successful Aging Among Older U.S. Veterans: Results from the National Health and Resilience in Veterans Study. | To conduct a qualitative study of older American veterans' subjective perceptions of factors that contribute to successful physical, emotional, and cognitive aging. A nationally representative sample of 2,025 veterans aged 60 or older (range: 60-96; 96.9% male, 39.4% combat veterans) participated in the National Health and Resilience in Veterans Study. Using qualitative analysis software, the authors coded responses to three open-ended questions, inductively developed categories, aggregated similar categories into factors, and grouped factors into broader themes. A total of 53, 56, and 61 categories of responses was identified in response to questions about successful physical, cognitive, and emotional aging, respectively, with 10 aggregate factors linking these categories. The most prominent theme overall was "What you do," which received 2,295, 2,210, and 1,247 mentions for each of these domains of successful aging, with health behaviors the most common factor for both successful physical and cognitive aging and social engagement the most common for successful emotional aging. The theme "Who you are" was the second-most common factor (discerned from 376, 247, and 943 total mentions, respectively), with the factors that comprise this theme-personality and explanatory style, moral compass, and emotional dispositions-more commonly endorsed for successful emotional aging. External factors such as healthcare were least commonly endorsed across all domains. Older U.S. Veterans emphasize health behaviors, social engagement, and dispositional characteristics as key determinants of successful aging. Prevention and treatment initiatives that target these potentially modifiable factors may help promote successful aging in this growing segment of the population. | Successful aging;inductive thematic analysis;older U.S. veterans | pubmed |
Encouraging employees to report verbal violence in primary health care in Serbia: A cross-sectional study. | Workplace violence is a serious and multidimensional problem that adversely affects professional and personal lives of employees. The aim of this study was to assess the prevalence and characteristics of verbal violence as a part of psychological violence among employees in primary health care in Belgrade, and to identify contributing factors of verbal violence in the workplace. In this cross-sectional study, the final analysis included 1526 employees, using multi-stage sampling. Data were collected using the questionnaire Workplace Violence in the Health Sector Country Case Studies Research, developed by ILO/ICN/WHO/PSI. Descriptive statistics and logistic regression analysis were used to analyse the data. The general response rate was 86.8% (1526/1757). It was found that 47.8% of the participants were subjected to verbal violence. The main source of verbal violence was patient/client, 55.6% of employees did not report the incident. Among those who did not report the incident, 74.9% believed that reporting violence was useless. The interaction with patients (OR, 1.45; 95% CI, 1.02-2.06) and work between 6pm and 7am (OR, 1.27; 95% CI, 1.01-1.60) were significant contributing factors of verbal violence. The results are indicative of a high prevalence of verbal violence against employees in primary health centres, which could have undesirable consequences. Conducting a better organizational measure and encouraging employees to report workplace violence could reduce the prevalence of verbal violence. | contributing factors;health workers;verbal workplace violence | pubmed |
Evaluating the Efficacy of a Registry linked to a Consent to Re-Contact Program and Communication Strategies for Recruiting and Enrolling Participants into Clinical Trials. | Although registries can rapidly identify clinical study participants, it is unknown which follow up methods for recruiting are most effective. Our goal is to examine the efficacy of three communication strategies for recruiting and enrolling patients who were identified via a contact registry (i.e., registry linked to a consent to re-contact program). Patients who met the study criteria were identified via the contact registry and targeted for recruitment. In condition 1, patients established in the university hepatology specialty clinics were contacted one time via phone call by the study coordinator and asked to participate (C1). In condition 2, non-established specialty clinic patients were mailed an IRB-approved letter with study information and instructions for calling the study coordinator to participate (C2). Condition 2A included patients who called within two weeks of receiving the letter (C2A); condition 2B included patients who did not call after receiving the letter but were subsequently contacted via phone call. A registry identified 1,060 patients, of which 661were eligible and targeted for recruiting. All 37 patients were reached in C1 and 17 (45.9%) were recruited. Nineteen of the 624 patients in C2A were reached and 10 were recruited whereas 120 of the 605 patients in C2B were reached and 53 (8.7%) were recruited. Seventy patients enrolled with C2B being the most effective (total, cost) recruitment strategy (<i>n</i> = 50) (<i>p</i> < .001). The efficacy of enrolling patients identified via a contact registry into clinical trials varies based on the communication strategies used for recruiting. | broad consent;communication;patient recruitment;registry | pubmed |
Peri-SRS Administration of Immune Checkpoint Therapy for Melanoma Metastatic to the Brain: Investigating Efficacy and the Effects of Relative Treatment Timing on Lesion Response. | To investigate the efficacy of immune checkpoint therapy (ICT) administered with stereotactic radiosurgery (SRS) and determine the effects of relative treatment timing on lesion response. A prospective institutional database of all patients with intact brain metastases treated with SRS from 2008 to 2015 was reviewed for patients diagnosed with malignant melanoma. Lesion response was determined using a modified RECIST v1.1 criteria. Patients were grouped according to if they received ICT and the timing of ICT relative to SRS. Cox regression was used to identify predictors of lesion failure (LF) and distant brain failure (DBF). The Wilcoxon rank-sum test was used to compare median lesion regression after SRS between treatment groups. Fifty-one patients with 167 metastases were evaluated. Eighteen patients (59 lesions) were treated with peri-SRS ICT with anticytotoxic T-lymphocyte-associated protein 4 or antiprogrammed cell death protein 1 therapy. Peri-SRS ICT was a significant favorable predictor for reduced hazard of LF (hazard ratio, 0.131; confidence interval, 0.028-0.610). Concurrent ICT given with SRS (hazard ratio, 0.364; confidence interval, 0.161-0.825) significantly predicted freedom from DBF. When quantitative lesion response was examined, peri-SRS ICT resulted in a significantly greater median percent lesion regression than did SRS alone at 1.5 (-30.7% vs. -14.6%; P = 0.018), 4 (-42.3% vs. -18.8%; P = 0.031), and 5 months after SRS (-52.01 vs. -14.9%; P = 0.002). ICT combined with SRS was associated with greater lesion regression of melanoma brain metastases and decreased LF. When given concurrently, combined SRS and ICT may result in improved freedom from DBF. | Brain metastases;Immunotherapy;Lesion response;Melanoma;SRS | pubmed |
Contact-force-guided vs. contact-force-blinded catheter ablation of typical atrial flutter: a prospective study. | It remains unknown whether contact force (CF) sensing technology is of value for cavotricuspid isthmus (CTI) ablation. We prospectively evaluated procedural parameters and outcomes of CF-guided vs. CF-blinded CTI ablation for typical atrial flutter (AFL). A total of 70 consecutive patients (62.5 ± 10.9 years) undergoing CTI ablation for AFL were prospectively enrolled, 35 in CF-blinded and 35 in CF-guided groups. A CF-sensing catheter (power 25-35 W) was used in all. In the CF-guided group, CF target range was 10-25 g, whereas in the CF-blinded group, the operator was blinded to CF. The isthmus was divided into anterior, middle, and posterior segments for region-specific CF analysis. The procedural endpoint of bidirectional isthmus block following a 20-min observation period was achieved in all. A trend towards lower fluoroscopy and procedure duration was observed when the CF-guided group was compared with the CF-blinded group. The total radiofrequency (RF) energy delivery time required to achieve bidirectional block was significantly lower in the CF-guided vs. CF-blinded group [10.0 min (IQR 8.3;15.1) vs. 15.9 min (IQR 9.6;24.7), P= 0.0020], with a significant inverse correlation between CF and total RF delivery time (r = -0.36; P= 0.0027). Mean CF measurements significantly increased from anterior to posterior anatomical zones of CTI in the CF-blinded group (ANOVA P= 0.0466). Catheter ablation of AFL guided by real-time CF assessment results in a significant reduction in total RF delivery time. Real-time CF measurements facilitate the maintenance of homogenous efficient contact all along the CTI, particularly in the anterior segment where CF is generally lower. | Ablation;Atrial flutter;Cavotricuspid isthmus;Contact force;Three-dimensional electroanatomic mapping | pubmed |
Auditory Sensitivity and Decision Criteria Oscillate at Different Frequencies Separately for the Two Ears. | Many behavioral measures of visual perception fluctuate continually in a rhythmic manner, reflecting the influence of endogenous brain oscillations, particularly theta (∼4-7 Hz) and alpha (∼8-12 Hz) rhythms [1-3]. However, it is unclear whether these oscillations are unique to vision or whether auditory performance also oscillates [4, 5]. Several studies report no oscillatory modulation in audition [6, 7], while those with positive findings suffer from confounds relating to neural entrainment [8-10]. Here, we used a bilateral pitch-identification task to investigate rhythmic fluctuations in auditory performance separately for the two ears and applied signal detection theory (SDT) to test for oscillations of both sensitivity and criterion (changes in decision boundary) [11, 12]. Using uncorrelated dichotic white noise to induce a phase reset of oscillations, we demonstrate that, as with vision, both auditory sensitivity and criterion showed strong oscillations over time, at different frequencies: ∼6 Hz (theta range) for sensitivity and ∼8 Hz (low alpha range) for criterion, implying distinct underlying sampling mechanisms [13]. The modulation in sensitivity in left and right ears was in antiphase, suggestive of attention-like mechanisms sampling alternatively from the two ears. | alpha rhythm;attention;auditory perception;perceptual oscillations;signal detection theory;theta rhythm | pubmed |
Risk factors of immunoglobulin resistance and coronary complications in children with Kawasaki disease. | The risk of immunoglobulin resistance is still likely to occur in Kawasaki disease (KD) despite adequate treatment. The Kobayashi score (KS) is used to predict unresponsiveness to treatment although the usefulness of the score in populations other than Asian seems to be debatable. The analysis of clinical and laboratory parameters predisposing to immunoglobulin resistance and coronary complica-tions in children hospitalised due to KD. The data of children hospitalised due to KD between 2003 and 2016 underwent analysis. Clinical and laboratory parameters were analysed, including all parameters present in KS in relation to the risk of intravenous immunoglobulin (IVIG) resistance and the occurrence of coronary complications in the form of aneurysms and dilatations. Seventy-three children (51 boys; aged 1.5-135 months) with KD were hospitalised. In eight (11%) patients IVIG re-sistance was observed. We reported aneurysms or coronary dilatations in 13 (17.8%) children. The criterion for increased risk of IVIG resistance based on KS (≥ 4 points) was fulfilled by 21 (29%) children. Resistance to IVIG and coronary complications were observed in four (19.1%) and two (9.5%) children with the score ≥ 4 points, respectively, and four (7.7%) and 11 (21.6%) from the group < 4 points in KS, respectively. The prevalence of IVIG resistance and coronary artery complications was not different between the group with ≥ 4 and the group with < 4 points (p = 0.22, p = 0.32, respectively). A higher risk of IVIG resistance was confirmed in children with a longer duration of fever (13.0 days with IVIG resistance vs. 9.2 days with a good response to IVIG, p = 0.04). For the prediction of the occurrence of coronary artery aneurysms the following were of great importance: the day of diagnosis (which was usually the day of the beginning of treatment), the number of symptoms, and the maximal platelet count (p = 0.001; p = 0.019 and p = 0.026, respectively). In our study population we did not demonstrate the usefulness of KS to predict IVIG resistance or the risk of the occurrence of coronary artery aneurysms. However, prolonged fever, late diagnosis, poorly symptomatic course of the disease, and a high platelet count at the time of the follow-up remain independent risk factors. | Kawasaki disease;Kobayashi score;coronary artery aneurysms;immunoglobulin resistance | pubmed |
Post-polypectomy bleeding after colonoscopy on uninterrupted aspirin/non steroideal antiflammatory drugs: Systematic review and meta-analysis. | The aim of this systematic review and meta-analysis was to assess the risk of post-polypectomy bleeding (PPB) in patients that underwent colorectal polypectomy and exposed to ASA/NSAIDs. Relevant publications were identified in MEDLINE/EMBASE for the period 1950-2016. Studies with specified ASA/NSAIDs exposure and bleeding rate were included. Study quality was ascertained according to Newcastle-Ottawa Scale. Forest plot was based on fixed or random effect models in relation to the heterogeneity. 11 studies (4 prospective and 7 retrospective) including 9307 patients were included in the analyses. Overall, 344 patients (OR 1.8; 95% CI 1.2-2.7; p-value 0.001, I<sup>2</sup> 52%) experienced rectal bleeding after procedure. While the rate of immediate PPB on aspirin and/or NSAIDs was not increased (OR 1.1; CI 95% 0.6-2.1; d.f.=1, p=0.64, I<sup>2</sup> 0%), the risk of delayed PPB was augmented (OR 1.7; 95% CI 1.2-2.2; d.f.=8, p=0.127, I<sup>2</sup> 36%). ASA/NSAIDs are not a risk factor for immediate PPB but the chance of delayed is increased. | Acetilsalicil acid;Adverse event;Antinflammatory non steroideal drugs;Bleeding;Colonic polyp;Colonoscopy;Hemorrhage | pubmed |
Attentive pointing in natural scenes correlates with other measures of attention. | Finger pointing is a natural human behavior frequently used to draw attention to specific parts of sensory input. Since this pointing behavior is likely preceded and/or accompanied by the deployment of attention by the pointing person, we hypothesize that pointing can be used as a natural means of providing self-reports of attention and, in the case of visual input, visual salience. We here introduce a new method for assessing attentional choice by asking subjects to point to and tap the first place they look at on an image appearing on an electronic tablet screen. Our findings show that the tap data are well-correlated with other measures of attention, including eye fixations and selections of interesting image points, as well as with predictions of a saliency map model. We also develop an analysis method for comparing attentional maps (including fixations, reported points of interest, finger pointing, and computed salience) that takes into account the error in estimating those maps from a finite number of data points. This analysis strengthens our original findings by showing that the measured correlation between attentional maps drawn from identical underlying processes is systematically underestimated. The underestimation is strongest when the number of samples is small but it is always present. Our analysis method is not limited to data from attentional paradigms but, instead, it is broadly applicable to measures of similarity made between counts of multinomial data or probability distributions. | Attention;Fixations;Interest points;Natural scenes;Pointing;Probability density estimation;Probability distributions;Salience;Saliency map;Tapping | pubmed |
How do Mediterranean shrub species cope with shade? Ecophysiological response to different light intensities. | Under natural conditions, light exposure for Mediterranean shrubs can be highly variable, especially during cloudy days or under a canopy, and can interfere with other environmental factors such as temperature and water availability. With the aim of decoupling the effect of radiation and temperature from water availability, we conducted an experiment where two perennial and three summer semi-deciduous shrub species were subjected to different levels of irradiation. In order to follow plant responses to light exposure, we measured gas exchange, photosystem II photochemical efficiency, photosynthetic pigments and leaf mass area in spring and summer. Results showed that all study species presented a plastic response to different light conditions, and that light-related traits varied in a coordinated manner. Summer semi-deciduous species exhibited a more opportunistic response, with higher photosynthesis rates in full sun, but under shade conditions, the two strategies presented similar assimilation rates. Stomatal conductance did not show such a drastic response as photosynthetsis, being related to changes in WUE. Daily cycles of F<sub>v</sub> /F<sub>m</sub> revealed a slight photoinhibitory response during summer, mainly in perennial species. In all cases photosynthetic pigments adjusted to the radiation level; leaves had lower chlorophyll content, higher pool of xanthophylls and higher proportion of the de-epoxydaded state of xanthophylls under sun conditions. Lutein content increased in relation to the xanthophyll pool under shade conditions. Our results evidenced that radiation is an important driving factor controlling morphological and physiological status of Mediterranean shrub species, independently of water availability. Summer semi-deciduous species exhibit a set of traits with higher response variability, maximising their photosynthetic assimilation under different sun conditions. | Chlorophyll;light availability;lutein;photochemical efficiency;photosynthetic rate;xanthophyll cycle | pubmed |
Mycophenolate mofetil improves renal haemodynamics, microvascular oxygenation, and inflammation in a rat model of supra-renal aortic clamping-mediated renal ischaemia reperfusion injury. | Ischaemia/reperfusion (I/R) is one of the main causes of acute kidney injury (AKI), which is characterized by sterile inflammation and oxidative stress. Immune cell activation can provoke overproduction of inflammatory mediators and reactive oxygen species (ROS), leading to perturbation of the microcirculation and tissue oxygenation associated with local and remote tissue injury. This study investigated whether the clinically employed immunosuppressant mycophenolate mofetil (MMF) was able to reduce I/R-induced renal oxygenation defects and oxidative stress by preventing sterile inflammation. Rats were divided into three groups (n=6/group): (1) a sham-operated control group; (2) a group subjected to renal I/R alone (I/R); and (3) a group subjected to I/R and MMF treatment (20 mg/kg prior to I/R) (I/R+MMF). Ischaemia was induced by a vascular occluder placed on the abdominal aorta for 30 minutes, followed by 120 minutes of reperfusion. Renal I/R deteriorated renal oxygenation (P<.001) and oxygen delivery (P<.01), reduced creatinine clearance (P<.01) and tubular sodium reabsorption (P<.001), and increased iNOS, renal tissue injury markers (P<.001), and IL-6 (P<.001). Oral MMF administration prior to insult restored renal cortical oxygenation (P<.05) and iNOS, renal injury markers, and inflammation parameters (P<.001) to near-baseline levels without affecting renal function. MMF exerted a prophylactic effect on renal microvascular oxygenation and abrogated tissue inflammation and renal injury following lower body I/R-induced AKI. These findings may have clinical implications during major vascular or renal transplant surgery. | immunosuppression;inflammation;ischaemia/reperfusion;microvascular oxygenation;mycophenolate mofetil | pubmed |
Videofluoroscopic assessment of the pathophysiology of chronic poststroke oropharyngeal dysphagia. | Oropharyngeal dysphagia (OD) is a major complaint following stroke, associated with poor clinical outcome and high mortality rates. We aimed at characterizing the kinematics of swallow response associated with unsafe swallowing in chronic poststroke patients with OD. Consecutive poststroke patients with a positive volume-viscosity swallow test for OD 3 months following stroke were studied by videofluoroscopy (VFS). Demographical and clinical factors and kinematics of swallow response were compared between those poststroke patients with safe swallow (penetration-aspiration scale, PAS≤2) and those with unsafe swallow (PAS≥3). Receiver operating characteristic (ROC) curves were drawn for laryngeal vestibule closure (LVC) time which predicts unsafe swallow. We studied 73 poststroke patients (76.7±9.3 years, 53.4% male) by VFS (60.4% with impaired safety, PAS=4.47±1.44, and 95.9% with impaired efficacy of swallow). Poststroke patients with unsafe swallow presented a poorer functional (Rankin 2.2±1.6 vs 1.2±1.0, P<.012) and nutritional status (MNA-sf≤11, 34.2% vs 7.4%, P<.05) than poststroke patients with safe swallow. Poststroke patients with unsafe swallow presented a significant delay in LVC time (406.4±99.5 ms vs 318.9±80.4 ms; P<.05) and weaker tongue bolus propulsion forces (0.771±0.450 mJ vs 1.638±3.212 mJ; P=.043). LVC time ≥340 ms predicts unsafe swallow in chronic poststroke patients with a diagnostic accuracy of 0.78. Impaired safety of swallow in chronic poststroke patients is caused by specific impairments in swallow response including delayed timing of airway protection mechanisms and weak tongue propulsion forces. Treatments aiming to restore swallowing function in poststroke patients with OD should be targeted to improve these critical biomechanical events. | deglutition disorders;kinematics;risk factors;stroke | pubmed |
DeepIED: An epileptic discharge detector for EEG-fMRI based on deep learning. | Presurgical evaluation that can precisely delineate the epileptogenic zone (EZ) is one important step for successful surgical resection treatment of refractory epilepsy patients. The noninvasive EEG-fMRI recording technique combined with general linear model (GLM) analysis is considered an important tool for estimating the EZ. However, the manual marking of interictal epileptic discharges (IEDs) needed in this analysis is challenging and time-consuming because the quality of the EEG recorded inside the scanner is greatly deteriorated compared to the usual EEG obtained outside the scanner. This is one of main impediments to the widespread use of EEG-fMRI in epilepsy. We propose a deep learning based semi-automatic IED detector that can find the candidate IEDs in the EEG recorded inside the scanner which resemble sample IEDs marked in the EEG recorded outside the scanner. The manual marking burden is greatly reduced as the expert need only edit candidate IEDs. The model is trained on data from 30 patients. Validation of IEDs detection accuracy on another 37 consecutive patients shows our method can improve the median sensitivity from 50.0% for the previously proposed template-based method to 84.2%, with false positive rate as 5 events/min. Reproducibility validation on 15 patients is applied to evaluate if our method can produce similar hemodynamic response maps compared with the manual marking ground truth results. We explore the concordance between the maximum hemodynamic response and the intracerebral EEG defined EZ and find that both methods produce similar percentage of concordance (76.9%, 10 out of 13 patients, electrode was absent in the maximum hemodynamic response in two patients). This tool will make EEG-fMRI analysis more practical for clinical usage. | Deep learning;EEG-fMRI;Epilepsy;GLM;IED detection | pubmed |
Understanding the impact of relapses in the overall course of MS; refinement of the 2 stage natural history model. | Recent studies suggest a need for refinement of the traditional two phase model of relapse onset multiple sclerosis (RMS) to include dynamically changing subgroups within the broad category of secondary progressive MS (SPMS). These studies challenge the traditional notion that relapses play a minor role in comparison to a secondary progressive (perhaps degenerative) process. Patients fulfilling the broad definition for SPMS may take several courses, including variable rates and patterns of overall worsening. New paradigms or models for mapping the trajectory of disability in RMS and SPMS (clinical phenotyping), including periods of remission, may impact our understanding of the underlying pathology, and will be important in assessing treatments. | Multiple sclerosis (MS);Natural history;Progression;Progression of disability;Progressive;Relapse | pubmed |
Posterior column ataxia with retinitis pigmentosa coexisting with sensory-autonomic neuropathy and leukemia due to the homozygous p.Pro221Ser FLVCR1 mutation. | FLVCR1 encodes for a ubiquitous heme exporter, whose recessive mutations cause posterior column ataxia with retinitis pigmentosa (PCARP). Recently, FLVCR1 recessive mutations were also found in two sporadic children with hereditary sensory-autonomic neuropathy (HSAN). We report the unique case of a 33-year-old Italian woman with a combination of typical PCARP, sensory-autonomic neuropathy with sensory loss to all modalities and multiple autonomic dysfuctions, and acute lymphocytic leukemia. Molecular analysis demonstrated homozygosity for the previously identified FLVCR1 p.Pro221Ser variation. The same variation, in combination with a frameshift mutation, was previously identified in an Italian child with HSAN. Functional studies carried out on patient-derived lymphoblastoid cell lines showed decreased FLVCR1a transcript, increased reactive oxygen species, excessive intracellular heme accumulation, and increased number of Annexin V positive cells. This indicates that the homozygous p.Pro221Ser FLVCR1 variation compromises the ability of FLVCR1a to export heme leading to enhanced susceptibility to programmed cell death. Our study demonstrates the existence of a phenotypic continuum among the discrete disorders previously linked to FLVCR1 mutations, and suggests that the related alteration of heme metabolism may lead to the degeneration of specific neuronal cell populations. | FLVCR1a;FLVCR1b;HSAN;heme;retinitis pigmentosa;sensory neuropathy | pubmed |
Glyphosate-induced oxidative stress in Arabidopsis thaliana affecting peroxisomal metabolism and triggers activity in the oxidative phase of the pentose phosphate pathway (OxPPP) involved in NADPH generation. | Glyphosate is a broad-spectrum systemic herbicide used worldwide. In susceptible plants, glyphosate affects the shikimate pathway and reduces aromatic amino acid synthesis. Using Arabidopsis seedlings grown in the presence of 20μM glyphosate, we analyzed H<sub>2</sub>O<sub>2</sub>, ascorbate, glutathione (GSH) and protein oxidation content as well as antioxidant catalase, superoxide dismutase (SOD) and ascorbate-glutathione cycle enzyme activity. We also examined the principal NADPH-generating system components, including glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), NADP-malic enzyme (NADP-ME) and NADP-isocitrate dehydrogenase (NADP-ICDH). Glyphosate caused a drastic reduction in growth parameters and an increase in protein oxidation. The herbicide also resulted in an overall increase in GSH content, antioxidant enzyme activity (catalase and all enzymatic components of the ascorbate-glutathione cycle) in addition to the two oxidative phase enzymes, G6PDH and 6PGDH, in the pentose phosphate pathway involved in NADPH generation. In this study, we provide new evidence on the participation of G6PDH and 6PGDH in the response to oxidative stress induced by glyphosate in Arabidopsis, in which peroxisomal enzymes, such as catalase and glycolate oxidase, are positively affected. We suggest that the NADPH provided by the oxidative phase of the pentose phosphate pathway (OxPPP) should serve to maintain glutathione reductase (GR) activity, thus preserving and regenerating the intracellular GSH pool under glyphosate-induced stress. It is particularly remarkable that the 6PGDH activity was unaffected by pro-oxidant and nitrating molecules such as H<sub>2</sub>0<sub>2</sub>, nitric oxide or peroxynitrite. | 6-Phosphogluconate dehydrogenase;Catalase;Glucose-6-phosphate dehydrogenase;Glyphosate;Nitric oxide;Oxidative stress;Peroxisome | pubmed |
Diagnosis of Infective Endocarditis After TAVR: Value of a Multimodality Imaging Approach. | PET/CT;TAVI;TAVR;infective endocarditis;multi-imaging | pubmed |
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The association between rehabilitation programs and metabolic syndrome in chronic inpatients with schizophrenia. | The correlation between different rehabilitation programs and the prevalence of metabolic syndrome in people with schizophrenia is unclear. We tested the association in chronic inpatients with schizophrenia of a psychiatric hospital in Taiwan. Patients with schizophrenia and age from 20 to 65 years old were included. The criteria of metabolic syndrome were according to the adapted Adult Treatment Protocol for Asians. According to different types of rehabilitations, patients were divided into work group, occupational therapy group and daily activities group. A total of 359 chronic inpatients with schizophrenia were recruited. Participants had a mean age of 45.9 years and the prevalence of metabolic syndrome was 37.3%. There was a significantly higher prevalence of metabolic syndrome in the work group than in the daily activity group (adjusted odds ratio (aOR) = 1.91, 95% CI = 1.019-3.564, p < 0.05) after adjusted related confounders. Other factors associated with higher prevalence of metabolic syndrome included old age, female gender, low psychotic symptoms severity and clozapine user. This study identified a high prevalence of metabolic syndrome in chronic inpatients with schizophrenia especially in patients with good occupational function. Further investigation of the relationship between the occupational function and metabolic syndrome is necessary for chronic inpatients with schizophrenia. | Chronic inpatients;Metabolic syndrome;Rehabilitation;Schizophrenia | pubmed |
Seroadaptive Strategies of Vancouver Gay and Bisexual Men in a Treatment as Prevention Environment. | British Columbia's treatment as prevention policy has provided free access to highly active antiretroviral therapy (HAART) to all HIV-positive provincial residents since 1996. One outcome is an increase in HIV-positive gay and bisexual men (GBM) with suppressed viral loads. Previous cross-sectional analyses indicated that some Vancouver GBM now recognize condomless anal sex with men on HAART who report a suppressed viral load as a seroadaptive strategy. To test the hypothesis that this new strategy, termed viral load sorting (VLS), is recognized and used among by GBM in the Momentum Health Study, we analyzed longitudinal data for HIV-negative/unknown (n = 556) and HIV-positive (n = 218) serostatus participants. Analyses indicated that both groups reported VLS, and that serostatus and Treatment Optimism Scale scores were significant determinants in frequency and use. Results exemplify the medicalization of sex and Rogers' Diffusion Of Preventative Innovations Model, and they have important implications for HIV research and GBM sexual decision-making. | Treatment as prevention;diffusion of preventative innovations;seroadaptation;treatment optimism | pubmed |
Cancer Rehabilitation: An Overview of Current Need, Delivery Models, and Levels of Care. | The relevance of cancer rehabilitation as a public health issue grows steadily as cancer incidence, survival, and mean patient age increase. Reported rates of physical impairment and disability are already high, prior to the anticipated influx of aged cancer survivors. Despite the high prevalence of cancer-related disablement, treatment rates, even for readily remediable physical impairments, are as low as 1-2%. In addition to low referral rates, a challenge to patient-centric cancer rehabilitation is a fractured system that requires multiple visits to a range of specialists to address even a single issue, and cancer survivors generally have several. Effective solutions must acknowledge the limited cancer rehabilitation clinical work force and its clustering in tertiary centers, as well as the lack of consensus regarding the essential and effective components of a cancer rehabilitation program. A number of models of cancer rehabilitation service delivery have been developed, but, as yet, none have been empirically validated. This paper describes these models and proposes a taxonomy for stratifying the needs of cancer survivors. Modalities used to preserve or restore function among survivors range from simple, relatively intuitive activities to complex, integrated programs that include diagnostic and multi-modal pharmacological, manual, and even procedural interventions. Criteria for determining a survivor's needs across this spectrum are proposed, and the role of the physiatrist as a vital advocate and champion discussed. | Cancer rehabilitation;Delivery models;Levels of care | pubmed |
When Patient Engagement and Research Ethics Collide: Lessons from a Dementia Forum. | The importance of patient engagement in research has been gaining recognition since the turn of the 21st century. However, little is known about the perspectives of people with dementia on the process of discovery. To fill this gap and to inform priorities in patient engagement in the context of dementia research, the Clinic for Alzheimer Disease and Related Disorders at the University of British Columbia hosted an interactive session for members of the patient community and of the general public to share their views on various ethical aspects of the research process. Results from the session indicate that several current research ethics policies and norms in dementia research are not in line with participants' preferences. Here we discuss the importance of bridging the gap between researchers and patients and call for reforms in current standards of dementia research. | Alzheimer’s disease;dementia;ethics;informed consent;public policy;research ethics | pubmed |
Optimization of high-yielding protocol for DNA extraction from the forest rhizosphere microbes. | Soil is major reservoir for microbes and harbors a vast microbial diversity. Soil microbiota plays a pivotal role in biogeochemical cycles, bioremediation, and in health and disease states of humans, animals, and plants. It is imperative to understand the microbial signatures which are specific in such an ecosystem to unravel their potential role and impact on environment. During the recent years, exploration of soil microbial communities has been geared up with the advent of advanced sequencing technologies. Introduction of custom-made protocols and optimized procedures have enhanced the accuracy levels along with cost-effectiveness of DNA extraction. Standardization of DNA extraction method from soil microbiota has its own limitations due to different nature of soils and the complexity of ecosystems. Though a few standardized protocols are in usage, huge variations and complexities among the microbial communities frequently suggest the optimization, based on various known and unknown factors. Therefore, a set of four standardized DNA isolation protocols was comparatively analyzed with respect to our custom-made protocol owing to the scientific fact that the same protocol does not hold good for all soil samples. Furthermore, the developed protocol has been successfully applied for the identification of efficient plant-specific Rhizobial stains for five legume plants from the soils of various locations under same geographical region. Out of 40 Badrachalam forest soils, five samples, KPFS36, CHFS17, TPFS33, GVFS06, and GPFS40, one for each of Arachis hypogaea, Vigna radiata, Vigna mungo, Glycine max, and Cicer arietinum plants, were selected, respectively, for the soil DNA extraction. A considerable improvement in the DNA yield was identified using the modified protocol with a yield of 21.08 μg/g providing abundant DNA fragments for further investigation on Rhizobial species. | DNA protocol optimization;Forest soil DNA;Rhizobial species;Root nodules;Soil DNA extraction | pubmed |
Curcumin Inhibits Chondrocyte Hypertrophy of Mesenchymal Stem Cells through IHH and Notch Signaling Pathways. | Using tissue engineering technique to repair cartilage damage caused by osteoarthritis is a promising strategy. However, the regenerated tissue usually is fibrous cartilage, which has poor mechanical characteristics compared to hyaline cartilage. Chondrocyte hypertrophy plays an important role in this process. Thus, it is very important to find out a suitable way to maintain the phenotype of chondrocytes and inhibit chondrocyte hypertrophy. Curcumin deriving from turmeric was reported with anti-inflammatory and anti-tumor pharmacological effects. However, the role of curcumin in metabolism of chondrocytes, especially in the chondrocyte hypertrophy remains unclear. Mesenchymal stem cells (MSCs) are widely used in cartilage tissue engineering as seed cells. So we investigated the effect of curcumin on chondrogenesis and chondrocyte hypertrophy in MSCs through examination of cell viability, glycosaminoglycan synthesis and specific gene expression. We found curcumin had no effect on expression of chondrogenic markers including Sox9 and Col2a1 while hypertrophic markers including Runx2 and Col10a1 were down-regulated. Further exploration showed that curcumin inhibited chondrocyte hypertrophy through Indian hedgehog homolog (IHH) and Notch signalings. Our results indicated curcumin was a potential agent in modulating cartilage homeostasis and maintaining chondrocyte phenotype. | Indian hedgehog homolog;chondrocyte hypertrophy;curcumin;mesenchymal stem cell;neurogenic locus notch homolog | pubmed |
The effectiveness of optimised clinical medication reviews for geriatric patients: Opti-Med a cluster randomised controlled trial. | Inappropriate drug use is a frequent problem in older patients and associated with adverse clinical outcomes and an important determinant of geriatric problems. Clinical medication reviews (CMR) may reduce inappropriate drug use. The aim of this study is to investigate the effectiveness of CMR on quality of life (QoL) and geriatric problems in comparison with usual care in older patients with geriatric problems in the general practice. We performed a cluster randomised controlled trial in 22 Dutch general practices. Patients of ≥65 years were eligible if they newly presented with pre-specified geriatric symptoms in general practice and the chronic use of ≥1 prescribed drug. The intervention consisted of CMRs which were prepared by an independent expert team and discussed with the patient by the general practitioner. Primary outcomes: QoL and the presence of self-reported geriatric problems after a follow-up period of 6 months. 518 patients were included. No significant differences between the intervention and control group and over time were found for QoL, geriatric problems, satisfaction with medication and self-reported medication adherence. After 6 months the percentage of solved Drug Related Problems (DRPs) was significantly higher in the intervention group compared to the control group [B 22.6 (95%CI 14.1-31.1), P < 0.001]. The study intervention did not influence QoL and geriatric problems. The higher percentage of solved DRPs in the intervention group did not result in effects on the patient's health. CMRs on a large scale seem not meaningful and should be reconsidered. | Aged;drug utilization review;inappropriate prescribing;primary health care;quality of life;randomized clinical trial | pubmed |
Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains. | H3N2 viruses continuously acquire mutations in the hemagglutinin (HA) glycoprotein that abrogate binding of human antibodies. During the 2014-2015 influenza season, clade 3C.2a H3N2 viruses possessing a new predicted glycosylation site in antigenic site B of HA emerged, and these viruses remain prevalent today. The 2016-2017 seasonal influenza vaccine was updated to include a clade 3C.2a H3N2 strain; however, the egg-adapted version of this viral strain lacks the new putative glycosylation site. Here, we biochemically demonstrate that the HA antigenic site B of circulating clade 3C.2a viruses is glycosylated. We show that antibodies elicited in ferrets and humans exposed to the egg-adapted 2016-2017 H3N2 vaccine strain poorly neutralize a glycosylated clade 3C.2a H3N2 virus. Importantly, antibodies elicited in ferrets infected with the current circulating H3N2 viral strain (that possesses the glycosylation site) and humans vaccinated with baculovirus-expressed H3 antigens (that possess the glycosylation site motif) were able to efficiently recognize a glycosylated clade 3C.2a H3N2 virus. We propose that differences in glycosylation between H3N2 egg-adapted vaccines and circulating strains likely contributed to reduced vaccine effectiveness during the 2016-2017 influenza season. Furthermore, our data suggest that influenza virus antigens prepared via systems not reliant on egg adaptations are more likely to elicit protective antibody responses that are not affected by glycosylation of antigenic site B of H3N2 HA. | antibody;hemagglutinin;influenza;vaccine | pubmed |
Multiple receptor conformers based molecular docking study of fluorine enhanced ethionamide with mycobacterium enoyl ACP reductase (InhA). | A major limitation in current molecular docking method is that of failure to account for receptor flexibility. Herein we report multiple receptor conformers based molecular docking as a practical alternative to account for the receptor flexibility. Multiple (forty) conformers of Mycobacterium Enoyl ACP Reductase (InhA) are generated from Molecular Dynamics simulation and twenty crystallographic structures of InhA bound to different inhibitors are obtained from the Protein Data Bank. Fluorine directed modifications are performed to currently available anti-tuberculosis drug ethionamide. The modified drugs are optimized using B3LYP 6-31G (d,p) level of theory. Dipole moment, frontier orbital gap and thermodynamical properties such as electronic energy, enthalpy and Gibbs free energy of these optimized drugs are investigated. These drugs are subsequently docked against the conformers of InhA. Molecular docking against multiple InhA conformations show variation in ligand binding affinity and suggest that Ser94, Gly96, Lys165 and Ile194 amino acids play critical role on strong drug-InhA interaction. Modified drug N1 showed greater binding affinity compared to EN in most conformations. Structure of PDB ID: 2NSD and snapshot conformer at 5.5ns show most favorable binding with N1 compared to other conformers. Fluorine participates in forming fluorine bonds and contributes significantly in increasing binding affinity. Our study reveal that addition of trifluoromethyl group explicitly shows promise in improving thermodynamic properties and in enhancing hydrogen bonding and non-bonded interactions. Molecular dynamics (MD) simulation show that EN and N1 remained in the binding pocket similar to the docked pose of EN-InhA and E1-InhA complexes and also suggested that InhA binds to its inhibitor in inhibitor-induced folding manner. ADMET calculations predict modified drugs to have improved pharmacokinetic properties. Our study concludes that multiple receptor conformers based molecular docking can be an alternative to study the effect of receptor flexibility in ligand binding and fluorine directed modifications can improve drug efficacy. | Drug design;Enoyl ACP reductase (InhA);Ensemble-based docking;Molecular docking;Molecular dynamics;Quantum calculation | pubmed |
Atrial flutter presenting as broad complex tachycardia in a patient with right sided pneumonectomy. | A 71-year-old man with no history of coronary artery disease presented with palpitations to the emergency department. The 12-lead ECG showed a regular tachycardia with wide QRS complexes (220 bpm) suggestive of ventricular tachycardia. Instead invasive electrophysiological investigation revealed typical atrial flutter as underlying arrhythmia. The altered QRS morphology resulted from displacement of the heart into the right hemithorax due to right-sided pneumonectomy in combination with bundle branch block. | Atrial flutter;Broad complex tachycardia;Supraventricular tachycardia;Ventricular tachycardia | pubmed |
Aged chimpanzees exhibit pathologic hallmarks of Alzheimer's disease. | Alzheimer's disease (AD) is a uniquely human brain disorder characterized by the accumulation of amyloid-beta protein (Aβ) into extracellular plaques, neurofibrillary tangles (NFT) made from intracellular, abnormally phosphorylated tau, and selective neuronal loss. We analyzed a large group of aged chimpanzees (n = 20, age 37-62 years) for evidence of Aβ and tau lesions in brain regions affected by AD in humans. Aβ was observed in plaques and blood vessels, and tau lesions were found in the form of pretangles, NFT, and tau-immunoreactive neuritic clusters. Aβ deposition was higher in vessels than in plaques and correlated with increases in tau lesions, suggesting that amyloid build-up in the brain's microvasculature precedes plaque formation in chimpanzees. Age was correlated to greater volumes of Aβ plaques and vessels. Tangle pathology was observed in individuals that exhibited plaques and moderate or severe cerebral amyloid angiopathy, a condition in which amyloid accumulates in the brain's vasculature. Amyloid and tau pathology in aged chimpanzees suggests these AD lesions are not specific to the human brain. | Alzheimer's disease;Amyloid-beta protein;Chimpanzee;Neurofibrillary tangle;Primate;Tau | pubmed |
Estradiol Regulation of Brown Adipose Tissue Thermogenesis. | Physiologically, estrogens carry out a myriad of functions, the most essential being the regulation of the reproductive axis. Currently, it is also dogmatic that estrogens play an important role modulating energy balance and metabolism. In this sense, it is well known that low estrogens levels, occurring due to ovarian insufficiency, in conditions such as menopause or ovariectomy (OVX), are associated with increased food intake and decreased energy expenditure, leading to weight gain and obesity at long term. Concerning energy expenditure, the main effect of estradiol (E2) is on brown adipose tissue (BAT) thermogenesis. Thus, acting through a peripheral or a central action, E2 activates brown fat activity and increases body temperature, which is negatively associated with body weight. Centrally, the hypothalamic AMP-activated protein kinase (AMPK) mediates the E2 action on BAT thermogenesis. In this chapter, we will summarize E2 regulation of BAT thermogenesis and how this can influence energy balance and metabolism in general. | Brown adipose tissue;Energy expenditure;Estradiol;Hypothalamus;Obesity | pubmed |
Objectively measured physical activity and kidney function in older men; a cross-sectional population-based study. | kidney function declines in older adults and physical activity levels are low. We investigated whether higher levels of physical activity and lower levels of sedentary behaviour were associated with lower odds of low kidney function in older men. cross-sectional study of 1,352 men from the British Regional Heart Study, mean (standard deviation) age 78.5 (4.6) year. Physical activity and sedentary behaviour were measured using Actigraph GT3X accelerometers. Kidney function was measured by estimated Glomerular filtration rate (eGFR) using the chronic kidney disease-EPI creatinine-cystatin equation. Associations between physical (in)activity and kidney function were investigated using regression models. higher levels of physical activity and lower levels of sedentary behaviour were associated with reduced odds ratios (ORs) for lower eGFR (<45 versus ≥45 ml/min per 1.73 m2) after adjustment for covariates. Each additional 1,000 steps, 30 min of light physical activity and 10 min of moderate/vigorous physical activity per day were associated with a lower odds (95% confidence interval (CI)) of a low eGFR; OR 0.81 (0.73, 0.91), OR 0.87 (0.78, 0.97) and OR 0.84 (0.76, 0.92), respectively. Each additional 30 min of sedentary behaviour per day was associated with a higher odds of a low eGFR (1.16 95% CI 1.06, 1.27). Associations between moderate/vigorous physical activity and lower kidney function persisted after adjustment for light physical activity or sedentary behaviour. physical activity is associated with kidney function in older men and could be of public health importance in this group who are at increased risk of poor kidney function and low physical activity. More evidence is needed on whether the association is causal. | glomerular filtration rate;kidney function;older people;physical activity;sedentary behaviour | pubmed |
Multifunctional Hybrid Nanoparticles for Traceable Drug Delivery and Intracellular Microenvironment-Controlled Multistage Drug-Release in Neurons. | Innovative nanoparticles hold promising potential for disease therapy as drug delivery systems. For brain-disease therapy, a drug delivery system that can sustainably control drug-release and monitor fluorescence of the drug cargos is highly desirable. In this study, a light-traceable and intracellular microenvironment-responsive drug delivery system was developed based on the combination of glutathione-responsive autoflurescent nanogel, dendrimer-like mesoporous silica nanoparticles, and gold nanoparticles. The resulting hybrid nanoparticles represent a new class of delivery system that can efficiently load, transport, and control multistage-release of sulfydryl-containing drugs into neurons, with light-traceable monitoring for future brain-disease therapy. | multistage controlled release;neurons;responsive drug delivery;sulfydryl-containing drugs;traceable drug delivery | pubmed |
Morphological novelty and modest developmental truncation in Barboides, Africa's smallest vertebrates (Teleostei: Cyprinidae). | Miniaturization, the evolution of extremely small adult body size, is widespread amongst animals and commonly associated with novel ecological, physiological, and morphological attributes. The phenotypes of miniaturized taxa are noteworthy because they combine reductions and structural simplifications with novel traits not developed in their larger relatives. Previous research on miniature cyprinid fishes (focused predominantly on South and South East Asian taxa of a single subfamily) has identified two distinct classes of miniature taxa: proportioned dwarves and developmentally truncated miniatures. Miniaturization has also occurred independently in the subfamily Cyprininae, particularly in African lineages. We investigate the skeletal anatomy of Barboides, a genus of miniature African cyprinids that includes Africa's smallest known species of vertebrates, to assess whether miniaturization has resulted in similar organismal outcomes in different lineages of the Cyprinidae. The skeleton of Barboides is characterized by the complete absence of a number of dermal and endochondral ossifications, and marked reduction in size and/or complexity of other skeletal elements, particularly those of the dermatocranium. Absent skeletal elements in Barboides include those which develop relatively late in the ossification sequence of the non-miniature African relative 'Barbus' holotaenia suggesting that their absence in Barboides can be explained by a simple scenario of developmental truncation. In contrast to this theme of loss and reduction, the os suspensorium of Barboides is enlarged and the outer arm distally trifid and associated with a novel bulbous muscle in males. An evaluation of the skeleton of Barboides provides further evidence for a link between developmental truncation and evolutionary morphological novelty in Cyprinidae. In the spectrum of miniature cyprinids ranging from proportioned dwarves with few bones missing to highly progenetic taxa with dozens of missing bones, the two species of Barboides range roughly in the middle showing that the extremes are connected by intermediate levels of truncatedness. | miniaturization;ossification sequence;progenesis | pubmed |
Methylglyoxal-Derived Advanced Glycation Endproducts in Multiple Sclerosis. | Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). The activation of inflammatory cells is crucial for the development of MS and is shown to induce intracellular glycolytic metabolism in pro-inflammatory microglia and macrophages, as well as CNS-resident astrocytes. Advanced glycation endproducts (AGEs) are stable endproducts formed by a reaction of the dicarbonyl compounds methylglyoxal (MGO) and glyoxal (GO) with amino acids in proteins, during glycolysis. This suggests that, in MS, MGO-derived AGEs are formed in glycolysis-driven cells. MGO and MGO-derived AGEs can further activate inflammatory cells by binding to the receptor for advanced glycation endproducts (RAGE). Recent studies have revealed that AGEs are increased in the plasma and brain of MS patients. Therefore, AGEs might contribute to the inflammatory status in MS. Moreover, the main detoxification system of dicarbonyl compounds, the glyoxalase system, seems to be affected in MS patients, which may contribute to high MGO-derived AGE levels. Altogether, evidence is emerging for a contributing role of AGEs in the pathology of MS. In this review, we provide an overview of the current knowledge on the involvement of AGEs in MS. | advanced glycation endproducts;glyoxalase system;methylglyoxal;multiple sclerosis;receptor for advanced glycation endproduct | pubmed |
Association of vertebral compression fractures with physical performance measures among community-dwelling Japanese women aged 40 years and older. | Numerous reported studies have shown that vertebral compression fractures are associated with impaired function or disability; however, few examined their association with objective measures of physical performance or functioning. We examined the association of vertebral compression fractures with physical performance measures in 556 Japanese women aged 40-89 years. Lateral spine radiographs were obtained and radiographic vertebral compression fractures were assessed by quantitative morphometry, defined as vertebral heights more than 3 SD below the normal mean. Measures of physical performance included walking speed, chair stand time and functional reach. Adjusted means of performance-based measures according to the number and severity of vertebral compression fractures were calculated using general linear modeling methods. After adjusting for age, body mass index, back pain, number of painful joints, number of comorbidities and regular physical activities, the walking speed of women with two or more compression fractures (1.17 m/s) was significantly slower than that of women without compression fracture (1.24 m/s) (p = 0.03). Compared with women without compression fracture, chair stand time was longer in women with two or more compression fractures (p = 0.01), and functional reach was shorter (p = 0.01). No significant differences were observed in walking speed, chair stand time, or functional reach between women with one compression fracture and those without compression fracture. Having multiple vertebral compression fractures affects physical performance in community-dwelling Japanese women. Poor physical functioning may lead to functional dependence, accelerated bone loss, and increased risk for falls, injuries, and fractures. Preventing vertebral compression fracture is considered important for preserving the independence of older adults. | Chair stand time;Functional reach test;Physical performance;Vertebral compression fractures;Walking speed | pubmed |
Surgeons' views on preoperative medical evaluation: a qualitative study. | There is substantial variation in the practice of preoperative medical evaluation (PME) and limited evidence for its benefit, which raises concerns about overuse. Surgeons have a unique role in this multidisciplinary practice. The objective of this qualitative study was to explore surgeons' practices and their beliefs about PME. We conducted of semi-structured interviews with 18 surgeons in Baltimore, Maryland. Surgeons were purposively sampled to maximize diversity in terms of practice type (academic vs. private practice), surgical specialty, gender, and experience level. General topics included surgeons' current PME practices, perceived benefits and harms of PME, the surgical risk assessment, and potential improvements and barriers to change. Interviews were audio-recorded and transcribed. Transcripts were analyzed using content analysis to identify themes, which are presented as assertions. Transcripts were re-analyzed to identify supporting and opposing instances of each assertion. A total of 15 themes emerged. There was wide variation in surgeons' described PME practices. Surgeons believed that PME improves surgical outcomes, but not all patients benefit. Surgeons were cognizant of the financial cost of the current system and the potential inconvenience that additional tests and office visits pose to patients. Surgeons believed that PME has minimal to no risk and that a normal PME is reassuring to them and patients. Surgeons were confident in their ability to assess surgical risk, and risk assessment by non-surgeons rarely affected their surgical decision-making. Hospital and anesthesiology requirements were a major driver of surgeons' PME practices. Surgeons did not receive much training on PME but perceived their practices to be similar to their colleagues. Surgeons believed that PME provides malpractice protection, welcomed standardization, and perceived there to be inadequate evidence to significantly change their current practice. Views of surgeons should be considered in future research on and reforms to the PME process. | Medical overuse;Preoperative care;Risk assessment | pubmed |
From Bench to Bed: New Gastrin-Releasing Peptide Receptor-Directed Radioligands and Their Use in Prostate Cancer. | Gastrin-releasing peptide receptors (GRPRs) are overexpressed in prostate and breast cancer, and are therefore attractive molecular targets for diagnosis and therapy with radiolabeled GRPR-directed peptide probes. The amphibian tetradecapeptide bombesin or the mammalian gastrin-releasing peptide and neuromedin C have been modified with a variety of chelators. As a result, labeling with radiometals attractive for SPECT or PET imaging and for radionuclide therapy has led to the development of peptide radioligands suitable for in vivo targeting of prostate cancer. A shift of paradigm from internalizing GRPR-agonists to antagonists has occurred owing to the higher biosafety and superior pharmacokinetics of radioantagonists. | Clinical translation;Gastrin-releasing peptide receptor targeting;Preclinical design;Prostate cancer;Theranostics | pubmed |
Regulation of human feto-placental endothelial barrier integrity by vascular endothelial growth factors: competitive interplay between VEGF-A<sub>165</sub>a, VEGF-A<sub>165</sub>b, PIGF and VE-cadherin. | The human placenta nourishes and protects the developing foetus whilst influencing maternal physiology for fetal advantage. It expresses several members of the vascular endothelial growth factor (VEGF) family including the pro-angiogenic/pro-permeability VEGF-A<sub>165</sub>a isoform, the anti-angiogenic VEGF-A<sub>165</sub>b, placental growth factor (PIGF) and their receptors, VEGFR1 and VEGFR2. Alterations in the ratio of these factors during gestation and in complicated pregnancies have been reported; however, the impact of this on feto-placental endothelial barrier integrity is unknown. The present study investigated the interplay of these factors on junctional occupancy of VE-cadherin and macromolecular leakage in human endothelial monolayers and the perfused placental microvascular bed. Whilst VEGF-A<sub>165</sub>a (50 ng/ml) increased endothelial monolayer albumin permeability (<i>P</i><0.0001), equimolar concentrations of VEGF-A<sub>165</sub>b (<i>P</i>>0.05) or PlGF (<i>P</i>>0.05) did not. Moreover, VEGF-A<sub>165</sub>b (100 ng/ml; <i>P</i><0.001) but not PlGF (100 ng/ml; <i>P</i>>0.05) inhibited VEGF-A<sub>165</sub>a-induced permeability when added singly. PlGF abolished the VEGF-A<sub>165</sub>b-induced reduction in VEGF-A<sub>165</sub>a-mediated permeability (<i>P</i>>0.05); PlGF was found to compete with VEGF-A<sub>165</sub>b for binding to Flt-1 at equimolar affinity. Junctional occupancy of VE-cadherin matched alterations in permeability. In the perfused microvascular bed, VEGF-A<sub>165</sub>b did not induce microvascular leakage but inhibited and reversed VEGF-A<sub>165</sub>a-induced loss of junctional VE-cadherin and tracer leakage. These results indicate that the anti-angiogenic VEGF-A<sub>165</sub>b isoform does not increase permeability in human placental microvessels or HUVEC primary cells and can interrupt VEGF-A<sub>165</sub>a-induced permeability. Moreover, the interplay of these isoforms with PIGF (and s-flt1) suggests that the ratio of these three factors may be important in determining the placental and endothelial barrier in normal and complicated pregnancies. | VE-cadherin;permeability;placenta;vascular endothelial growth factor | pubmed |
In-Office Application of Fluoride Gel or Varnish: Cost-Effectiveness and Expected Value of Perfect Information Analysis. | Application of fluoride gel/varnish (FG/FV) reduces caries increments but generates costs. Avoiding restorative treatments by preventing caries might compensate for these costs. We assessed the cost-effectiveness of dentists applying FG/FV in office and the expected value of perfect information (EVPI). EVPI analyses estimate the economic value of having perfect knowledge, assisting research resource allocation. A mixed public-private-payer perspective in Germany was adopted. A population of 12-year-olds was followed over their lifetime, with caries increments modelled using wide intervals to reflect the uncertainty of caries risk. Biannual application of FV/FG until age 18 years was compared to no fluoride application. Effectiveness parameters and their uncertainty were derived from systematic reviews. The health outcome was caries increment (decayed, missing, or filled teeth; DMFT). Cost calculations were based on fee catalogs or microcosting, including costs for individual-prophylactic fluoridation and, for FG, an individualized tray, plus material costs. Microsimulations, sensitivity, and EVPI analyses were performed. On average and applied to a largely low-risk population, no application of fluoride was least costly but also least effective (EUR 230; 11 DMFT). FV was more costly and effective (EUR 357; 7 DMFT). FG was less effective than FV and also more costly when using individualized trays. FV was the best choice for payers willing to invest EUR 39 or more per avoided DMFT. This cost-effectiveness will differ in different settings/countries or if FG/FV is applied by other care professionals. The EVPI was mainly driven by the individual's caries risk, as FV/FG were significantly more cost-effective in high-risk populations than in low-risk ones. Future studies should focus on caries risk prediction. | Computer modeling;Fluoride;Public dental health;Topical fluorides;Varnish | pubmed |
Astakines in arthropods-phylogeny and gene structure. | Astakine1 was isolated as a hematopoietic cytokine in the freshwater crayfish Pacifastacus leniusculus. In this study we detect and compare 79 sequences in GenBank, which we consider to be possible astakine orthologs, among which eleven are crustacean, sixteen are chelicerate and 52 are from insect species. Available arthropod genomes are searched for astakines, and in conclusion all astakine sequences in the current study have a similar exon containing CCXX(X), thus potentially indicating that they are homologous genes with the structure of this exon highly conserved. Two motifs, RYS and YP(N), are also conserved among the arthropod astakines. A phylogenetic analysis reveals that astakine1 and astakine2 from P. leniusculus and Procambarus clarkii are distantly related, and may have been derived from a gene duplication occurring early in crustacean evolution. Moreover, a structural comparison using the Mamba intestinal toxin (MIT1) from Dendroaspis polylepis as template indicates that the overall folds are similar in all crustacean astakines investigated. | Astakine;Astakine-like;Prokineticin | pubmed |
Influence of β2- and β3-adrenoceptor agonists on contractile activity of the porcine myometrium in the luteal phase and the first days of pregnancy. | This study analysed the relaxant properties of salbutamol (β2-adrenoceptors agonist) and BRL 37344 (β3-adrenoceptors agonist) regarding the contractility of porcine myometrium on days 10-14 of the oestrous cycle (cyclic group; n = 10) and on days 3-5 of pregnancy (early pregnant group; n = 6). The activity of myometrial strips (tension, frequency and amplitude) was recorded under isometric conditions using force transducers. The contractility was assessed further following the administration of increasing concentrations of the agonists (10-9-10-4 M), both with and without β-adrenoceptor antagonists (butaxamine - a selective β2- adrenoceptor antagonist, propranolol- a non-selective β1- and β2-adrenoceptor antagonist and bupranolol - a non-selective β1-, β2- and β3-adrenoceptor antagonist) at a concentration of 10-4 M. Although neither salbutamol nor BRL 37344 caused changes in the tension, at the highest concentrations they decreased the frequency and amplitude of contractions. These changes were more evident after salbutamol treatment and in the early pregnant group. Antagonists given alone did not cause changes in the parameters examined but changed some activity of the agonists. Butoxamine reduced the decrease in frequency and amplitude induced by salbutamol and produced a decrease in the tension after BRL 37344 treatment in the early pregnant group. Propranolol reduced the decrease in frequency and amplitude induced by salbutamol in both examined groups and did not cause significant changes in BRL 37344 activity. The administration of bupranolol before salbutamol treatment caused an increase in the tension and reduced the decrease in the frequency in the cyclic group. Moreover, bupranolol eliminated a decrease in frequency and induced an increase in amplitude caused by BRL 37344 in both groups and these changes were more evident in the early pregnant group. The data indicates that both β2- and β3-adenoreceptors are involved in the regulation of the contractility in both groups, but the changes after agonists and antagonists treatment are more evident in the early pregnant myometrium. | beta adrenoceptors;cyclic pigs;early pregnancy;uterine contractility | pubmed |
Trauma patient discharge and care transition experiences: Identifying opportunities for quality improvement in trauma centres. | Challenges delivering quality care are especially salient during hospital discharge and care transitions. Severely injured patients discharged from a trauma centre will go either home, to rehabilitation or another acute care hospital with complex management needs. This purpose of this study was to explore the experiences of trauma patients and families treated in a regional academic trauma centre to better understand and improve their discharge and care transition experiences. A qualitative study using inductive thematic analysis was conducted between March and October 2016. Telephone interviews were conducted with trauma patients and/or a family member after discharge from the trauma centre. Data collection and analysis were completed inductively and iteratively consistent with a qualitative approach. Twenty-four interviews included 19 patients and 7 family members. Participants' experiences drew attention to discharge and transfer processes that either (1) Fostered quality discharge or (2) Impeded quality discharge. Fostering quality discharge was ward staff preparation efforts; establishing effective care continuity; and, adequate emotional support. Impeding discharge quality was perceived pressure to leave the hospital; imposed transfer decisions; and, sub-optimal communication and coordination around discharge. Patient-provider communication was viewed to be driven by system, rather than patient need. Inter-facility information gaps raised concern about receiving facilities' ability to care for injured patients. The quality of trauma patient discharge and transition experiences is undermined by system- and ward-level processes that compete, rather than align, in producing high quality patient-centred discharge. Local improvement solutions focused on modifiable factors within the trauma centre include patient-oriented discharge education and patient navigation; however, these approaches alone may be insufficient to enhance patient experiences. Trauma patients encounter complex barriers to quality discharge that likely require a comprehensive, multimodal intervention. | Care transfer;Discharge;Injured patients;Patient experience;Qualitative research;Quality improvement;Trauma centre | pubmed |
Fragile X Syndrome: Prevalence, Treatment, and Prevention in China. | Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and the leading monogenic cause of autism spectrum disorder. Although FXS has been studied for several decades, there is relatively little basic science or clinical research being performed on FXS in China. Indeed, there is a large gap between China and Western countries in the FXS field. China has a potentially large number of FXS patients. However, many of them are underdiagnosed or even misdiagnosed, and treatments are not always administered in the Chinese population. This review discusses the prevalence, treatment, and prevention of FXS in China to facilitate an understanding of this disease in the Chinese population. | China;fragile X syndrome;prevalence;prevention;treatment | pubmed |
Developmental changes in hypothalamic SF-1, POMC, and ERα mRNA expression and their sensitivity to fasting in male and female rats. | Estrogen plays pivotal roles in body weight regulation through its effects on central estrogen receptor-α (ERα) expression. ERα is found on neurons that express the hypothalamic anorexigenic factors steroidogenic factor-1 (SF-1) and pro-opiomelanocortin (POMC) mediate these effects of estrogen. As the gonadal hormonal milieu is drastically altered during the developmental period, the expression levels of SF-1 and POMC might also change during this period. In this study, we showed that hypothalamic SF-1 and ERα mRNA expression did not change during the neonatal to pre-pubertal period (from postnatal day 10 to 30), and there were no significant differences in the hypothalamic mRNA expression levels of these molecules between males and females at any examined age. On the other hand, hypothalamic POMC mRNA expression and the serum estradiol (E2) level increased during development in both males and females. Significant positive correlations were detected between the serum E2 level and hypothalamic POMC mRNA expression in both males and females. Hypothalamic ERα and POMC mRNA expression were decreased by fasting in male rats at all examined ages, whereas fasting had no effect on hypothalamic ERα or POMC mRNA expression in the female rats. These results indicate that the regulatory system involving E2 and hypothalamic POMC expression might already be established in the neonatal period and that the roles of POMC and ERα in body weight regulation during development might differ slightly between males and females. | ERα;Hypothalamus;POMC;SF-1 | pubmed |
The impact of non-genetic and genetic factors on a stable warfarin dose in Thai patients. | The aim of this study was to investigate the contributions of non-genetic and genetic factors on the variability of stable warfarin doses in Thai patients. A total of 250 Thai patients with stable warfarin doses were enrolled in the study. Demographics and clinical data, e.g., age, body mass index, indications for warfarin and concomitant medications, were documented. Four single nucleotide polymorphisms in the VKORC1 - 1639G > A, CYP2C9*3, CYP4F2 rs2108622, and UGT1A1 rs887829 genes were detected from gDNA using TaqMan allelic discrimination assays. The patients with variant genotypes of VKORC1 - 1639G > A required significantly lower warfarin stable weekly doses (SWDs) than those with wild-type genotype (p < 0.001). Similarly, the patients with CYP2C9*3 variant allele required significantly lower warfarin SWDs than those with homozygous wild-type (p = 0.006). In contrast, there were no significant differences in the SWDs between the patients who carried variant alleles of CYP4F2 rs2108622 and UGT1A1 rs887829 as compared to wild-type allele carriers. Multivariate analysis, however, showed that CYP4F2 rs2108622 TT genotype accounted for a modest part of warfarin dose variability (1.2%). In contrast, VKORC1 - 1639G > A, CYP2C9*3, CYP4F2 rs2108622 genotypes and non-genetic factors accounted for 51.3% of dose variability. VKORC1 - 1639G > A, CYP2C9*3, and CYP4F2 rs2108622 polymorphisms together with age, body mass index, antiplatelet drug use, amiodarone use, and current smoker status explained 51.3% of individual variability in stable warfarin doses. In contrast, the UGT1A1 rs887829 polymorphism did not contribute to dose variability. | CYP2C9;CYP4F2;Non-genetic factors;UGT1A1;VKORC1;Warfarin | pubmed |
Redox-Responsive Biodegradable Polycation Poly(amido amine) Used As Intranasal Vaccine Delivery Systems. | Polycations such as polyethylenimine and chitosan have been widely used as mucosal vaccine delivery systems due to their permeation enhancement effect. Preferably, environmentally responding biodegradable polycations would be better carrier materials for mucosal vaccine delivery. Disulfide bond-based redox-sensitive polycations could respond to the higher intracellular glutathione concentration and degrade in the cytoplasm via the breakage of the disulfide bonds, which are particularly suitable for antigen delivery. In this work, we evaluated the potential of redox-sensitive, biodegradable polycation poly(amido amine) (PAA) as mucosal vaccine carriers. From the primary studies with ovalbumin used as a model protein antigen, it is found that PAA could complex with and encapsulate protein antigen via electrostatic attraction, enhance the cellular uptake of antigen by dendritic cell line DC2.4, prolong antigen residence in nasal cavity, and promote antigen permeation into nasal submucosal layer. Further, Balb/c mice were intranasally immunized with PAA-delivered recombinant hemagglutinin (HA) antigen protein of H7N9 influenza virus. The PAA/HA formulations induced significantly more potent systemic IgG response and mucosal IgA response, higher splenocyte proliferation activity, higher secretion levels of cytokines IFN-γ and IL-4 by splenocytes, more memory CD4<sup>+</sup> and CD8<sup>+</sup> T cells, and more DCs expressing MHC II molecule. From the results, the redox-responsive polycation PAA as vaccine carriers helped elicit more potent cellular and humoral immune responses. Particularly, PAA induced much higher cellular immune response compared with previously reported carrier materials. The intelligent PAA could be developed as efficient mucosal vaccine delivery systems for clinical applications. | mucosal immunization;poly(amido amine);redox-responsive;vaccine delivery systems | pubmed |
Visualization of Phosphatidylinositol 3,5-Bisphosphate Dynamics by a Tandem ML1N-Based Fluorescent Protein Probe in Arabidopsis. | Phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] is a low-abundance phospholipid known to be associated with a wide variety of physiological functions in plants. However, the localization and dynamics of PI(3,5)P2 in plant cells remain largely unknown, partially due to the lack of an effective fluorescent probe. Using Arabidopsis transgenic plant expressing the PI(3,5)P2-labeling fluorescent probe (tagRFP-ML1N*2) developed based on a tandem repeat of the cytosolic phosphoinositide-interacting domain (ML1N) of the mammalian lysosomal transient receptor potential cation channel, Mucolipin 1 (TRPML1), here we show that PI(3,5)P2 is predominantly localized on the limited membranes of the FAB1- and SNX1-positive late endosomes, but rarely localized on the membranes of plant vacuoles or trans-Golgi network/early endosomes of cortical cells of the root differentiation zone. The late endosomal localization of tagRFP-ML1N*2 is reduced or abolished by pharmacological inhibition or genetic knockdown of expression of genes encoding PI(3,5)P2-synthesizing enzymes, FAB1A/B, but markedly increased with FAB1A overexpression. Notably, reactive oxygen species (ROS) significantly increase late endosomal levels of PI(3,5)P2. Thus, tandem ML1N-based PI(3,5)P2 probes can reliably monitor intracellular dynamics of PI(3,5)P2 in Arabidopsis cells with less binding activity to other endomembrane organelles. | Arabidopsis;Fluorescent protein probe;Late endosomes;ML1N*2;PI(3,5)P2;YM201636 | pubmed |
Percutaneous closure of the left atrial appendage in patients with diabetes mellitus. | Left atrial appendage closure is a preventive treatment of atrial fibrillation-related thrombo-embolism. Patients with diabetes mellitus have increased risk for a negative outcome in percutaneous cardiac interventions. We assessed whether percutaneous left atrial appendage closure is safe and effective in patients with diabetes mellitus. We included 78 patients (mean age of 74.4 ± 8.3 years) with indication for left atrial appendage closure in an open-label observational single-centre study. Patients with diabetes mellitus ( n = 31) were at higher thrombo-embolic and bleeding risk (CHA<sub>2</sub>DS<sub>2</sub>-VASc: 4.5 ± 0.9, HAS-BLED: 4.7 ± 0.7) compared to patients without diabetes mellitus ( n = 47, CHA<sub>2</sub>DS<sub>2</sub>-VASc: 3.5 ± 1.0, HAS-BLED: 4.1 ± 0.8; p < 0.001 for both). Pre- and periprocedural risk was elevated in patients with diabetes mellitus (Euro II-Score: 6.6 ± 3.7 vs 3.9 ± 1.9, p < 0.01; Society of Thoracic Surgeons (STS)-Score: 4.0 ± 2.5 vs 2.6 ± 1.2, p < 0.01). Procedural success was similar. Periprocedural major adverse cardiac and cerebrovascular events occurred in one patient from the control group (2.1%), whereas patients with diabetes mellitus had no events ( p = 0.672). Follow-up of 6 months revealed no bleeding complication in both groups. No stroke occurred in follow-up, and left atrial appendage flow velocity reduction (55.6 ± 38.6 vs 51.4 ± 19.1 cm/s, p = 0.474) and rate of postinterventional leakage in the left atrial appendage were comparable (0% vs 2.1%, p = 0.672). Despite patients with diabetes mellitus are high-risk patients, the outcome of percutaneous left atrial appendage closure is similar to patients without diabetes mellitus. | Percutaneous closure of left atrial appendage;atrial fibrillation;diabetes mellitus;structural interventions | pubmed |
Effects of Adjuvant-Induced Inflammation on Disposition of Diclofenac and Its Metabolites in Perfused Rat Liver. | The reactive metabolites of diclofenac (DF) such as 1-O-acyl glucuronide (DF-Glu) are hypothesized to result in idiosyncratic hepatotoxicity. However, it is unclear whether inflammation affects the hepatic disposition of DF and its metabolites. To clarify the alterations in the disposition of DF and its metabolites in inflammatory conditions, we performed in situ perfused rat liver experiments. Using adjuvant arthritis rats as a model of inflammation, the elimination of DF, 4'-hydroxydiclofenac, and DF-Glu from the perfusate was observed to be delayed in comparison with the control. Parameter sensitivity analysis for hepatic DF disposition revealed that the area under the plasma concentration-time curve (AUC) and the maximum concentration (C<sub>max</sub>) of DF-Glu in the liver markedly increased along with a decrease in intrinsic excretion clearance of DF-Glu (CL<sub>int,bile,Glu</sub>) and an increase in intrinsic glucuronidation clearance (CL<sub>int,Glu</sub>) of DF-Glu. It is possible that the elimination of DF-Glu from the perfusate in adjuvant arthritis rats was delayed via reduction of biliary excretion of DF-Glu. | MRP;biliary excretion;disposition;metabolism;transporters | pubmed |
Factors affecting water resistance of alginate/gellan blend films on paper cups for hot drinks. | Enhanced film water resistance of paper cups was achieved by physically blending sodium alginate (NaAlg) and gellan gum with crosslinking treatment. Pure and blended films were prepared and characterized via Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and positron annihilation lifetime spectroscopy (PALS). Results demonstrated excellent compatibility between the two polysaccharides. Total mixed solution concentration, component ratio, glycerol content, Ca<sup>2+</sup> concentration, crosslinking time, and dry temperature affected water resistance. Water permeability (WP) and swelling degree (SD) were tested. Optimal conditions were as follows: total mixed solution concentration, 2.4% (m/v); component ratio, 2:1; glycerol content, 0.5% (m/v); Ca<sup>2+</sup> concentration, 5% (m/v); crosslinking time, 5min; and dry temperature, 50°C. WP and SD values were 78.1×10<sup>-8</sup>g/msPa and 66.3%, respectively. Properties of the films showed the synergistic effect between NaAlg and gellan, which can be used for water-resistant film coating on paper cups for hot drinks. | Alginate;Blend films;Factor;Gellan;Hot drinks;Water resistance | pubmed |
Selection is required for efficient Cas9-mediated genome editing in Fusarium graminearum. | Genome engineering using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated nucleases, such as Cas9 (CRISPR-associated protein 9), are revolutionising molecular biology. In this study, we established a Cas9-based genome editing system in Fusarium graminearum, a highly destructive fungal pathogen of cereal crops. Although the molecular toolkit of F. graminearum is well developed compared to other fungi, Cas9-mediated engineering offers a number of potential benefits, such as the ability to create marker free mutants in this species. Here we have used a codon-optimised Cas9 nuclease and dual ribozyme-based expression of a single guide RNA (sgRNA) to induce mutations. Cas9-mediated mutations were identified through a fungicide resistance-based phenotypic screen, which selects for null mutations in the FgOs1 gene encoding an osmosensor histidine kinase. In the absence of selection, however, mutations were identified at very low frequency. Examination of the mutant alleles identified suggests that, a microhomology-mediated end joining (MMEJ) DNA repair pathway is likely to be the predominant process involved in erroneous repairing of Cas9-induced double-stranded breaks in F. graminearum. | CRISPR;Fusarium head blight;MMEJ;Os1 | pubmed |
Exercise program design considerations for head and neck cancer survivors. | The present study aimed to establish exercise preferences, barriers, and perceived benefits among head and neck cancer survivors, as well as their level of interest in participating in an exercise program. Patients treated for primary squamous cell carcinoma of the head and neck between 2010 and 2014 were identified from the hospital database and sent a postal questionnaire pack to establish exercise preferences, barriers, perceived benefits, current physical activity levels, and quality of life. A postal reminder was sent to non-responders 4 weeks later. The survey comprised 1021 eligible patients of which 437 (43%) responded [74% male, median (interquartile range) age, 66 (60-73) years]. Of the respondents, 30% said 'Yes' they would be interested in participating in an exercise program and 34% said 'Maybe'. The most common exercise preferences were a frequency of three times per week, moderate-intensity, and 15-29 min per bout. The most popular exercise types were walking (68%), flexibility exercises (35%), water activites/swimming (33%), cycling (31%), and weight machines (19%). Home (55%), outdoors (46%) and health club/gym (33%) were the most common preferred choices for where to regularly exercise. Percieved exercise benefits relating to improved physical attributes were commonly cited, whereas potential social and work-related benefits were less well-acknowledged. The most commonly cited exercise barriers were dry mouth or throat (40%), fatigue (37%), shortness of breath (30%), muscle weakness (28%) difficulty swallowing (25%), and shoulder weakness and pain (24%). The present findings inform the design of exercise programs for head and neck cancer survivors. | Exercise barriers;Exercise benefits;Exercise preferences;Oncology;Physical activity;Rehabilitation | pubmed |
Bioavailability of coated and uncoated ZnO nanoparticles to cucumber in soil with or without organic matter. | There is a gap of knowledge for the fate, effects and bioavailability of coated and uncoated ZnO nanoparticles (NPs) in soil. Moreover, little is known about the effects of soil properties on effects of NPs on plants. In this study, the availability ZnO NPs in two soils with different organic matter content (one treated with cow manure (CM) and the other as untreated) was compared with their bulk particles. Results showed that coated and uncoated ZnO NPs can be more bioaccessible than their bulk counterpart and despite their more positive effects at low concentration (< 100mgkg<sup>-1</sup>), they were more phytotoxic for plants compared to the bulk ZnO particles at high concentration (1000mgkg<sup>-1</sup>) in the soil untreated with CM. The concentration of 1000mgkg<sup>-1</sup> of ZnO NPs, decreased shoot dry biomass (52%) in the soil untreated with CM but increased shoot dry biomass (35%) in CM-treated soil compared to their bulk counterpart. In general, plants in the CM-treated soil showed higher Zn concentration in their tissues compared with those in untreated soil. The difference in shoot Zn concentration between CM-treated and untreated soil for NPs treatments was more than bulk particles treatment. This different percentage at 100mgkg<sup>-1</sup> of bulk particles was 20.6% and for coated and uncoated NPs were 37% and 32%, respectively. Generally, the distribution of ZnO among Zn fractions in soil (exchangeable, the metal bound to carbonates, Fe-Mn oxides, organic matter and silicate minerals and the residual fraction) changed based on applied Zn concentration, Zn source and soil organic matter content. The root tip deformation under high concentration of NPs (1000mgkg<sup>-1</sup> treatment<sup>)</sup> was observed by light microscopy in plants at the soil untreated with CM. It seems that root tip deformation is one of the specific effects of NPs which in turn inhibits plant growth and nutrients uptake by root. The transmission electron microcopy image showed the aggregation of NPs inside the plant cytoplasm and their accumulation adjacent to the cell membrane. | Soil fractionation;Uptake;Zinc oxide nano particles | pubmed |
Clinicopathological analysis of renal inflammatory pseudotumors presenting as the unilateral solitary masses. | Renal inflammatory lesions rarely present as unilateral solitary mass. These types of lesions are often misdiagnosed as renal tumors that lead to unnecessary nephrectomy. So far there are very few comprehensive studies about both their clinical features and pathologic characteristics of these inflammatory pseudotumors. Six renal inflammatory pseudotumors were identified in atotal of 1195 radical or partial nephrectomy cases retrospectively reviewed in our institution. The inflammatory lesions included xanthogranulomatous pyelonephritis (2 cases), renal tuberculosis (1 case), renal malakoplakia (1 case), IgG4-related tubulointerstitial nephritis (1 case), and renal Wegener's granulomatosis (1 case). All patients underwent radical nephrectomy because they had the unilateral renal solitary mass by the imaging examination. Following the postoperative pathological diagnosis, these patients received anti-inflammatory therapy according to their specific etiology. In conclusion, the attention must be paid for rare renal inflammatory pseudotumors that may mimic tumors since these diseases require a total different treatment strategy from neoplastic diseases. | Kidney;clinicopathological features;differential diagnosis;inflammatory pseudotumor;renal tumor | pubmed |
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