Characterization of lung fibroblasts more than two decades after mustard gas exposure

Purpose: In patients with short-term exposure to the sulfur mustard gas, the delayed cellular effects on lungs have not been well understood yet. The lung pathology shows a dominant feature consistent with obliterative bronchiolitis, in which fibroblasts play a central role. This study aims to characterize alterations to lung fibroblasts, at the cellular level, in patients with delayed respiratory complications after short-term exposure to the sulfur mustard gas. Methods: Fibroblasts were isolated from the transbronchial biopsies of patients with documented history of exposure to single high-dose sulfur mustard during 1985-7 and compared with the fibroblasts of control subjects. Results: Compared with controls, patients' fibroblasts were thinner and shorter, and showed a higher population doubling level, migration capacity and number of filopodia. Sulfur mustard decreased the in vitro viability of fibroblasts and increased their sensitivity to induction of apoptosis, but did not change the rate of spontaneous apoptosis. In addition, higher expression of alpha smooth muscle actin showed that the lung's microenvironment in these patients is permissive for myofibroblastic differentiation. Conclusions: These findings suggest that in patients under the study, the delayed pulmonary complications of sulfur mustard should be considered as a unique pathology, which might need a specific management by manipulation of cellular components. © 2015 Pirzad Jahromi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Protection of hippocampal CA1 neurons against ischemia/Reperfusion injury by exercise preconditioning via modulation of Bax/Bcl-2 ratio and prevention of Caspase-3 Activation

Introduction: Ischemia leads to loss of neurons by apoptosis in specific brain regions, especially in the hippocampus. The purpose of this study was investigating the effects of exercise preconditioning on expression of Bax, Bcl-2, and caspase-3 proteins in hippocampal CA1 neurons after induction of cerebral ischemia. Methods: Male rats weighing 260-300 g were randomly allocated into three groups (sham, exercise, and ischemia). The rats in exercise group were trained to run on atreadmill 5 days a week for 4 weeks. Ischemia was induced by the occlusion of both common carotid arteries (CCAs) for 20 min. Levels of expression of Bax, Bcl-2, and caspase-3 proteins in CA1 area of hippocampus were determined by immunohistochemical staining . Results: The number of active caspase-3-positive neurons in CA1 area were significantly increased in ischemia group, compared to sham-operated group (P<0.001), and exercise preconditioning significantly reduced the ischemia/reperfusion-induced caspase-3 activation, compared to the ischemia group (P<0.05). Also, results indicated a significant increase in Bax/Bcl-2 ratio in ischemia group, compared to sham-operated group (P<0.001). Discussion: This study indicated that exercise has a neuroprotective effects against cerebral ischemia when used as preconditioning stimuli

PVDF membrane for oil-in-water separation via cross-flow ultrafiltration process

The objective of this study is to investigate the potential of ultrafiltration polyvinylidene fluoride (PVDF)-titanium dioxide (TiO2) membrane for oil-in-water separator. PVDF polymeric matrix membrane is excellent in term of chemical and thermal stabilities, which make it very promising to be used as a membrane matrix for water separation. However, poor hydrophilic property of the PVDF has led to the severe fouling during operation. Thus, current work was performed to investigate the effect of incorporation of two additives i.e. polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG) in PVDF-TiO2 membrane, which fabricated using dry/wet phase inversion technique. Membranes characterizations were performed using field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM), contact angle and UV-vis spectrophotometer. Accordingly, modified PVDF membrane possessed good hydrophilicity property when the additives were added into PVDF-TiO2 membrane matrix. In term of filtration performance, the experimental results showed that oil rejection using PVDF-TiO2/PVP membrane were ~99.7%, which met the requirement for discharge. On the other hand, PVDF-TiO2/PEG membrane was shown more enhancement in terms of permeate flux by given over 64 (L/m2h) at pressure of 2 bar gauge

Barriers to Family Caregivers’ Coping With Patients With Severe Mental Illness in Iran

The broad spectrum of problems caused by caring for a patient with mental illness imposes a high burden on family caregivers. This can affect how they cope with their mentally ill family members. Identifying caregivers’ experiences of barriers to coping is necessary to develop a program to help them overcome these challenges. This qualitative content analysis study explored barriers impeding family caregivers’ ability to cope with their relatives diagnosed with severe mental illness (defined here as schizophrenia, schizoaffective disorders, and bipolar affective disorders). Sixteen family caregivers were recruited using purposive sampling and interviewed using a semi-structured in-depth interview method. Data were analyzed by a conventional content analytic approach. Findings consisted of four major categories: the patient’s isolation from everyday life, incomplete recovery, lack of support by the mental health care system, and stigmatization. Findings highlight the necessity of providing support for caregivers by the mental health care delivery service system.The study was supported by Grant TBZMED·REC.5825 from the deputy of research in Tabriz University of Medical Sciences

Evaluating The Association Between Serum Hsp27 Antibody and Hypertension in Patients without Underlying Cardiovascular Disease

Introduction: An association between heat shock protein 27 (Hsp27) antigen with cardiovascular risk factors has been shown previously. Furthermore, higher levels of serum anti-HSP27 antibodies are also related to higher cardiovascular morbidity and mortality. In the current study, we looked at the relationship between serum Hsp27 antibodies and hypertension, as an important cardiovascular risk factor, in individuals without evidence of cardiovascular disease (CVD).Methods: A sub-population of hypertensive patients (HTN+) without underlying CVD were recruited from the Mashhad stroke and atherosclerosis heart disease (MASHAD) study to assess the association between serum Hsp27 antibodies and hypertension; independent of other cardiovascular risk factors. A total of 1599 people were studied of whom 288 individuals had hypertension and 1311 were used as controls (HTN-).Results: Mean serum Hsp27 antibody titers were 0.20 (0.27) OD in the whole population sample and was not significantly different in the normotensive (HTN-) compared to HTN+ individuals with different degrees of hypertension.Conclusion: There were no significant associations between serum anti-Hsp27 concentrations and either the presence or severity of hypertension. Future studies are warranted to explore the association of anti-Hsp27 antibody and antigen levels and other cardiovascular risk factors

The Effects of Cognitive Therapy versus ‘No Intervention’ for Major Depressive Disorder

BACKGROUND: Major depressive disorder afflicts an estimated 17% of individuals during their lifetimes at tremendous suffering and costs. Cognitive therapy may be an effective treatment option for major depressive disorder, but the effects have only had limited assessment in systematic reviews. METHODS/PRINCIPAL FINDINGS: We used The Cochrane systematic review methodology with meta-analyses and trial sequential analyses of randomized trials comparing the effects of cognitive therapy versus 'no intervention' for major depressive disorder. Participants had to be older than 17 years with a primary diagnosis of major depressive disorder to be eligible. Altogether, we included 12 trials randomizing a total of 669 participants. All 12 trials had high risk of bias. Meta-analysis on the Hamilton Rating Scale for Depression showed that cognitive therapy significantly reduced depressive symptoms (four trials; mean difference -3.05 (95% confidence interval (Cl), -5.23 to -0.87; P<0.006)) compared with 'no intervention'. Trial sequential analysis could not confirm this result. Meta-analysis on the Beck Depression Inventory showed that cognitive therapy significantly reduced depressive symptoms (eight trials; mean difference on -4.86 (95% CI -6.44 to -3.28; P = 0.00001)). Trial sequential analysis on these data confirmed the result. Only a few trials reported on 'no remission', suicide inclination, suicide attempts, suicides, and adverse events without significant differences between the compared intervention groups. DISCUSSION: Cognitive therapy might be an effective treatment for depression measured on Hamilton Rating Scale for Depression and Beck Depression Inventory, but these outcomes may be overestimated due to risks of systematic errors (bias) and random errors (play of chance). Furthermore, the effects of cognitive therapy on no remission, suicidality, adverse events, and quality of life are unclear. There is a need for randomized trials with low risk of bias, low risk of random errors, and longer follow-up assessing both benefits and harms with clinically relevant outcome measures

Crowdsourced mapping of unexplored target space of kinase inhibitors

Despite decades of intensive search for compounds that modulate the activity of particular protein targets, a large proportion of the human kinome remains as yet undrugged. Effective approaches are therefore required to map the massive space of unexplored compound-kinase interactions for novel and potent activities. Here, we carry out a crowdsourced benchmarking of predictive algorithms for kinase inhibitor potencies across multiple kinase families tested on unpublished bioactivity data. We find the top-performing predictions are based on various models, including kernel learning, gradient boosting and deep learning, and their ensemble leads to a predictive accuracy exceeding that of single-dose kinase activity assays. We design experiments based on the model predictions and identify unexpected activities even for under-studied kinases, thereby accelerating experimental mapping efforts. The open-source prediction algorithms together with the bioactivities between 95 compounds and 295 kinases provide a resource for benchmarking prediction algorithms and for extending the druggable kinome. The IDG-DREAM Challenge carried out crowdsourced benchmarking of predictive algorithms for kinase inhibitor activities on unpublished data. This study provides a resource to compare emerging algorithms and prioritize new kinase activities to accelerate drug discovery and repurposing efforts

The effects of cognitive therapy versus 'treatment as usual' in patients with major depressive disorder

BACKGROUND: Major depressive disorder afflicts an estimated 17% of individuals during their lifetimes at tremendous suffering and costs. Cognitive therapy may be an effective treatment option for major depressive disorder, but the effects have only had limited assessment in systematic reviews. METHODS/PRINCIPAL FINDINGS: Cochrane systematic review methodology, with meta-analyses and trial sequential analyses of randomized trials, are comparing the effects of cognitive therapy versus 'treatment as usual' for major depressive disorder. To be included the participants had to be older than 17 years with a primary diagnosis of major depressive disorder. Altogether, we included eight trials randomizing a total of 719 participants. All eight trials had high risk of bias. Four trials reported data on the 17-item Hamilton Rating Scale for Depression and four trials reported data on the Beck Depression Inventory. Meta-analysis on the data from the Hamilton Rating Scale for Depression showed that cognitive therapy compared with 'treatment as usual' significantly reduced depressive symptoms (mean difference -2.15 (95% confidence interval -3.70 to -0.60; P<0.007, no heterogeneity)). However, meta-analysis with both fixed-effect and random-effects model on the data from the Beck Depression Inventory (mean difference with both models -1.57 (95% CL -4.30 to 1.16; P = 0.26, I(2) = 0) could not confirm the Hamilton Rating Scale for Depression results. Furthermore, trial sequential analysis on both the data from Hamilton Rating Scale for Depression and Becks Depression Inventory showed that insufficient data have been obtained. DISCUSSION: Cognitive therapy might not be an effective treatment for major depressive disorder compared with 'treatment as usual'. The possible treatment effect measured on the Hamilton Rating Scale for Depression is relatively small. More randomized trials with low risk of bias, increased sample sizes, and broader more clinically relevant outcomes are needed