Assessment of myofascial pain syndrome among married female healthcare workers: a cross sectional comparative study in a tertiary care centre

Background: Myofascial pain syndrome (MPS) is common among females between ages 20-40 years. Psychosomatic and mechanical reasons are attributed as causative factors. Female health care workers (FHW) in hospitals with rapid patient turn over are vulnerable to develop MPS. Our aim was to ascertain the prevalence of MPS in married FHW working in various departments of the hospital and its association with poor sleep and work stress. Methods: We selected married FHWs in 20-50 years age group and divided them into two groups, medical and paramedical (those involved directly and indirectly with patient care respectively). MPS was diagnosed after detailed personal interview and clinical examination. Sleep duration was divided into less than 5 hours and more than 5hours. Presence of work-related stress and other medical parameters were also recorded. Results: A total of 150 medical and 150 paramedical FHWs were included in the study. Overall prevalence of MPS among FHWs was 42%, of which, medical group was 32% and paramedical was 52%. The paramedical group showed significantly higher prevalence of MPS (p: 0.02). Sleep was less than 5 hours in 29.3% of medical FHW and 13.3% of paramedical. This difference didn’t show any association to MPS (p=0.8). 38% FHW perceived excessive work stress, 40% were paramedical and 36% were medical. This didn’t correlate with prevalence of MPS (p=0.2) among them. Conclusions: Paramedical FHW experienced more MPS than medical and it was more of mechanical type and not due to work stress or sleep deprivation

Epigenetic and transcriptional dysregulation in CD4+ T cells in patients with atopic dermatitis

Atopic dermatitis (AD) is one of the most common skin disorders among children. Disease etiology involves genetic and environmental factors, with 29 independent AD risk loci enriched for risk allele-dependent gene expression in the skin and CD4+ T cell compartments. We investigated the potential epigenetic mechanisms responsible for the genetic susceptibility of CD4+ T cells. To understand the differences in gene regulatory activity in peripheral blood T cells in AD, we measured chromatin accessibility (an assay based on transposase-accessible chromatin sequencing, ATAC-seq), nuclear factor kappa B subunit 1 (NFKB1) binding (chromatin immunoprecipitation with sequencing, ChIP-seq), and gene expression levels (RNA-seq) in stimulated CD4+ T cells from subjects with active moderate-to-severe AD, as well as in age-matched non-allergic controls. Open chromatin regions in stimulated CD4+ T cells were highly enriched for AD genetic risk variants, with almost half of the AD risk loci overlapping AD-dependent ATAC-seq peaks. AD-specific open chromatin regions were strongly enriched for NF-κB DNA-binding motifs. ChIP-seq identified hundreds of NFKB1-occupied genomic loci that were AD- or control-specific. As expected, the AD-specific ChIP-seq peaks were strongly enriched for NF-κB DNA-binding motifs. Surprisingly, control-specific NFKB1 ChIP-seq peaks were not enriched for NFKB1 motifs, but instead contained motifs for other classes of human transcription factors, suggesting a mechanism involving altered indirect NFKB1 binding. Using DNA sequencing data, we identified 63 instances of altered genotype-dependent chromatin accessibility at 36 AD risk variant loci (30% of AD risk loci) that might lead to genotype-dependent gene expression. Based on these findings, we propose that CD4+ T cells respond to stimulation in an AD-specific manner, resulting in disease- and genotype-dependent chromatin accessibility alterations involving NFKB1 binding

Psychotherapy as a treatment modality for psychiatric disorders: Perceptions of general public of Karachi, Pakistan

<p>Abstract</p> <p>Background</p> <p>Psychiatric disorders affect about 450 million individuals worldwide. A number of treatment modalities such as psychotropic medications, psychotherapy and electroconvulsive therapy can be used to treat these disorders. Attitudes of general public play a pivotal role in effective utilization of mental health services. We explored the perceptions of general public of Karachi, Pakistan regarding psychotherapy.</p> <p>Methods</p> <p>A cross-sectional study was conducted in Karachi, Pakistan during July-August, 2008. A three-step sampling strategy and a structured questionnaire were employed to survey knowledge and perceptions of adult general public about psychotherapy. Descriptive statistics were used for baseline characteristics. Logistic regression models were used to investigate any significant associations between baseline characteristics of the participants and their perceptions.</p> <p>Results</p> <p>The study sample comprised of 985 individuals (536 males; 531 financially independent) with an average age of 36.7 years (SD 13.54 years) and 12.5 years (SD 3.09 years) of education were included. Majority (59.4%; n = 585) claimed to be aware of psychotherapy as a treatment option for psychiatric disorders but 47.5% of these (n = 278/585) failed to identify its correct definition. Concerns voiced by the participants about psychotherapy included stigma (48.7%) and breech in confidentiality (39.5%); 60.7% opined it cost effective and 86.5% favored its use as an adjuvant modality. A preference for psychotherapy as the treatment strategy for psychiatric disorders was demonstrated by 46.6% (n = 459/985). Younger, more educated, financially independent and female participants were more likely to prefer psychotherapy as were those who deemed it cost effective.</p> <p>Conclusion</p> <p>Positive attitudes regarding the acceptability, clinical utility and cost-effectiveness of psychotherapy were observed in a sample representative of general public of Karachi, Pakistan. These findings highlight its potential utility for devising pragmatic mental health strategies in the face of limited resources.</p

A new heat propagation velocity prevails over Brownian particle velocities in determining the thermal conductivities of nanofluids

An alternative insight is presented concerning heat propagation velocity scales in predicting the effective thermal conductivities of nanofluids. The widely applied Brownian particle velocities in published literature are often found too slow to describe the relatively higher nanofluid conductivities. In contrast, the present model proposes a faster heat transfer velocity at the same order as the speed of sound, rooted in a modified kinetic principle. In addition, this model accounts for both nanoparticle heat dissipation as well as coagulation effects. This novel model of effective thermal conductivities of nanofluids agrees well with an extended range of experimental data

Obesity is associated with insulin resistance and components of the metabolic syndrome in Lebanese adolescents

adolescents has been reported to range between 18–42%, depending on country of origin, thus suggesting an ethnicbased association between obesity and MS. Aim: This study aims to investigate the magnitude of the association between obesity, insulin resistance and components of MS among adolescents in Lebanon. Subjects and methods: The sample included 263 adolescents at 4 th and 5 th Tanner stages of puberty (104 obese; 78 overweight; 81 normal weight). Anthropometric, biochemical and blood pressure measurements were performed. Body fat was assessed using dual-energy X-ray absorptiometry. Results: According to International Diabetes Federation criteria, MS was identified in 21.2 % of obese, 3.8 % of overweight and 1.2 % of normal weight subjects. The most common metabolic abnormalities among subjects having MS were elevated waist circumference (96.2%), low HDL (96.2%) and hypertriglyceridemia (73.1%). Insulin resistance was identified in all subjects having MS. Regression analyses showed that percentage body fat, waist circumference and BMI were similar in their ability to predict the MS in this age group. Conclusions: MSwas identified in asubstantial proportion of Lebanese obese adolescents, thus highlighting the importance of early screening for obesity-associated metabolic abnormalities and of developing successful multi-component interventions addressing adolescent obesity

Human BRCA1-BARD1 ubiquitin ligase activity counters chromatin barriers to DNA resection

The opposing activities of 53BP1 and BRCA1 influence pathway choice of DNA double-strand break repair. How BRCA1 counters the inhibitory effect of 53BP1 on DNA resection and homologous recombination is unknown. Here we identify the site of BRCA1-BARD1 required for priming ubiquitin transfer from E2~ubiquitin. We demonstrate that BRCA1-BARD1’s ubiquitin ligase activity is required for repositioning 53BP1 on damaged chromatin. We confirm H2A ubiquitylation by BRCA1-BARD1 and show that an H2A-ubiquitin fusion protein promotes DNA resection and repair in BARD1 deficient cells. We show BRCA1-BARD1 function in homologous recombination requires the chromatin remodeler SMARCAD1. SMARCAD1 binding to H2A-ubiquitin, optimal localization to sites of damage and activity in DNA repair requires its ubiquitin-binding CUE domains. SMARCAD1 is required for 53BP1 repositioning and the need for SMARCAD1 in Olaparib or camptothecin resistance is alleviated by 53BP1 loss. Thus BRCA1- BARD1 ligase activity and subsequent SMARCAD1-dependent chromatin remodeling are critical regulators of DNA repair

Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship

Epigenetic understanding of gene-environment interactions in psychiatric disorders: a new concept of clinical genetics

Epigenetics is a mechanism that regulates gene expression independently of the underlying DNA sequence, relying instead on the chemical modification of DNA and histone proteins. Although environmental and genetic factors were thought to be independently associated with disorders, several recent lines of evidence suggest that epigenetics bridges these two factors. Epigenetic gene regulation is essential for normal development, thus defects in epigenetics cause various rare congenital diseases. Because epigenetics is a reversible system that can be affected by various environmental factors, such as drugs, nutrition, and mental stress, the epigenetic disorders also include common diseases induced by environmental factors. In this review, we discuss the nature of epigenetic disorders, particularly psychiatric disorders, on the basis of recent findings: 1) susceptibility of the conditions to environmental factors, 2) treatment by taking advantage of their reversible nature, and 3) transgenerational inheritance of epigenetic changes, that is, acquired adaptive epigenetic changes that are passed on to offspring. These recently discovered aspects of epigenetics provide a new concept of clinical genetics

Sgs1 and Exo1 Redundantly Inhibit Break-Induced Replication and De Novo Telomere Addition at Broken Chromosome Ends

In budding yeast, an HO endonuclease-inducible double-strand break (DSB) is efficiently repaired by several homologous recombination (HR) pathways. In contrast to gene conversion (GC), where both ends of the DSB can recombine with the same template, break-induced replication (BIR) occurs when only the centromere-proximal end of the DSB can locate homologous sequences. Whereas GC results in a small patch of new DNA synthesis, BIR leads to a nonreciprocal translocation. The requirements for completing BIR are significantly different from those of GC, but both processes require 5′ to 3′ resection of DSB ends to create single-stranded DNA that leads to formation of a Rad51 filament required to initiate HR. Resection proceeds by two pathways dependent on Exo1 or the BLM homolog, Sgs1. We report that Exo1 and Sgs1 each inhibit BIR but have little effect on GC, while overexpression of either protein severely inhibits BIR. In contrast, overexpression of Rad51 markedly increases the efficiency of BIR, again with little effect on GC. In sgs1Δ exo1Δ strains, where there is little 5′ to 3′ resection, the level of BIR is not different from either single mutant; surprisingly, there is a two-fold increase in cell viability after HO induction whereby 40% of all cells survive by formation of a new telomere within a few kb of the site of DNA cleavage. De novo telomere addition is rare in wild-type, sgs1Δ, or exo1Δ cells. In sgs1Δ exo1Δ, repair by GC is severely inhibited, but cell viaiblity remains high because of new telomere formation. These data suggest that the extensive 5′ to 3′ resection that occurs before the initiation of new DNA synthesis in BIR may prevent efficient maintenance of a Rad51 filament near the DSB end. The severe constraint on 5′ to 3′ resection, which also abrogates activation of the Mec1-dependent DNA damage checkpoint, permits an unprecedented level of new telomere addition