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One hundred 100 raw milk samples (70 shops and 30 dairy farms) were collected from Quetta City and were subjected to microbiological assessment. Out of the 100 samples, 94 were found positive for bacterial contamination. Out of the positive samples, 25 different bacterial species were identified. The most frequent bacteria were Escherichia coli (60%), Streptococcus faecalis (26%), Entrobacter cloacae (16%), Bacillus cereus (10%), Lactobacillus bulgaricus (6%) and many of Staphylococcus and Streptococcus species. Statistical analysis revealed a significant association (P<0.05) in the occurrence of different bacteria in the raw milk samples sold under prevailing traditional managmental system. These results clearly indicate the heavy contamination of raw milk sold in shops and dairy farms in Quetta posing serious threat to public health. [ABSTRACT FROM AUTHOR]

Background: Intensive care unit (ICU) staff have faced unprecedented challenges during the coronavirus disease 2019 (COVID-19) pandemic, which could significantly affect their mental health and well-being. The present study aimed to investigate perceived stress and post-traumatic stress disorder (PTSD) symptoms reported by ICU staff working directly with COVID-19 patients., Methods: The Perceived Stress Scale was used to assess perceived stress, the PTSD Diagnostic Scale for the Diagnostic and Statistical Manual of Mental Disorders (5th edition) was used to determine PTSD symptoms, and a sociodemographic questionnaire was used to record different sociodemographic variables., Results: Altogether, 124 participants (57.2% of whom were men) were included in the analysis. The majority of participants perceived working in the ICU with COVID-19 patients as moderately to severely stressful. Moreover, 71.4% of doctors and 74.4% of nurses experienced moderate-to-severe perceived stress. The staff with previous ICU experience were less likely to have a probable diagnosis of PTSD than those without previous ICU experience., Conclusions: Assessing perceived stress levels and PTSD among ICU staff may enhance our understanding of COVID-19-induced mental health challenges. Specific strategies to enhance ICU staff's mental well-being during the COVID-19 pandemic should be employed and monitored regularly. Interventions aimed at alleviating sources of anxiety in a high-stress environment may reduce the likelihood of developing PTSD., (© 2021. The Author(s).)

A fraction of the transcriptome is translated into proteins. The rest is classified as non-protein coding RNA (Ribonucleic Acid) but has gained increased attention as functional and regulatory group of transcripts. The gene regulatory role of non-coding RNAs (ncRNAs) has now been widely accepted in diverse biological processes in both physiology and disease. MicroRNAs fall into this latter group and are widely known for their diverse post-transcriptional regulatory role. MicroRNA sequences are embedded in the long ncRNAs, known as primary microRNAs, are processed into precursor microRNAs and are typically transported out of the nucleus for maturation and loading into a protein complex forming RNA-induced silencing complex (RISC) that either drives the degradation of messenger RNA (mRNA) or blocks its translation. A new phenomenon is emerging where microRNAs have active roles within the nucleus. The presence of RISC components including microRNAs in the nucleus supports this notion. They may integrate with chromatin modifiers, microprocessing machinery and mRNA stabilizing transcripts to play a multifunctional role in the nucleus. Although a limited number of studies appreciate this novel activity of microRNAs relevant to the cardiovascular system, they provide proof-of-concept that requires consideration while targeting miRNAs with therapeutic potential., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Rationale: Hyperglycemia -induced reactive oxygen species are key mediators of cardiac dysfunction. JunD (Jund proto-oncogene subunit), a member of the AP-1 (activator protein-1) family of transcription factors, is emerging as a major gatekeeper against oxidative stress. However, its contribution to redox state and inflammation in the diabetic heart remains to be elucidated., Objective: The present study investigates the role of JunD in hyperglycemia-induced and reactive oxygen species-driven myocardial dysfunction., Methods and Results: JunD mRNA and protein expression were reduced in the myocardium of mice with streptozotocin-induced diabetes mellitus as compared to controls. JunD downregulation was associated with oxidative stress and left ventricular dysfunction assessed by electron spin resonance spectroscopy as well as conventional and 2-dimensional speckle-tracking echocardiography. Furthermore, myocardial expression of free radical scavenger superoxide dismutase 1 and aldehyde dehydrogenase 2 was reduced, whereas the NOX2 (NADPH [nicotinamide adenine dinucleotide phosphatase] oxidase subunit 2) and NOX4 (NADPH [nicotinamide adenine dinucleotide phosphatase] oxidase subunit 4) were upregulated. The redox changes were associated with increased NF-κB (nuclear factor kappa B) binding activity and expression of inflammatory mediators. Interestingly, mice with cardiac-specific overexpression of JunD via the α MHC (α- myosin heavy chain) promoter (α MHC JunD tg ) were protected against hyperglycemia-induced cardiac dysfunction. We also showed that JunD was epigenetically regulated by promoter hypermethylation, post-translational modification of histone marks, and translational repression by miRNA (microRNA)-673/menin. Reduced JunD mRNA and protein expression were confirmed in left ventricular specimens obtained from patients with type 2 diabetes mellitus as compared to nondiabetic subjects., Conclusions: Here, we show that a complex epigenetic machinery involving DNA methylation, histone modifications, and microRNAs mediates hyperglycemia-induced JunD downregulation and myocardial dysfunction in experimental and human diabetes mellitus. Our results pave the way for tissue-specific therapeutic modulation of JunD to prevent diabetic cardiomyopathy.

Aims: Impairments of retinal vessel diameter are associated with major adverse cardiovascular (CV) events. Promoter DNA methylation is a repressor of the mitochondrial adaptor p66Shc gene transcription, a key driver of ageing-induced reactive oxygen species. The study aimed to investigate whether high-intensity interval training (HIIT) affects retinal microvascular phenotype as well as p66Shc expression and oxidative stress in ageing subjects with increased CV risk from the EXAMIN AGE cohort., Methods and Results: Eighty-four sedentary subjects (mean age 59.4 ± 7.0 years) with ≥2 CV risk factors were randomized into either a 12-week HIIT or standard physical activity recommendations. Retinal arteriolar and venular diameters were measured by use of a retinal vessel analyser. As a marker of oxidative stress plasma 3-nitrotyrosine (3-NT) level was determined by ELISA. Gene expression of p66Shc and DNA methylation were assessed in mononuclear cells by RT-qPCR and methylated-DNA capture (MethylMiner Enrichment Kit) coupled with qPCR, respectively. High-intensity interval training reduced body mass index, fat mass, low-density lipoprotein and increased muscle mass, as well as maximal oxygen uptake (VO2max). Moreover, HIIT restored microvascular phenotype by inducing retinal arteriolar widening (pre: 175 ± 14 µm vs. post: 181 ± 13 µm, P = 0.001) and venular narrowing (pre: 222 ± 14 µm vs. post: 220 ± 14 µm, P = 0.007). After HIIT, restoration of p66Shc promoter methylation (P = 0.034) reduced p66Shc gene expression (P = 0.037) and, in turn, blunted 3-NT plasma levels (P = 0.002)., Conclusion: High-intensity interval training rescues microvascular dysfunction in ageing subjects at increased CV risk. Exercise-induced reprogramming of DNA methylation of p66Shc gene may represent a putative mechanistic link whereby exercise protects against age-related oxidative stress., Clinical Trial Registration: ClinicalTrials.gov: NCT02796976 (https://clinicaltrials.gov/ct2/show/NCT02796976)., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Clonal chromosome changes are often found in the bone marrow (BM) of patients with Shwachman-Diamond syndrome (SDS). The most frequent ones include an isochromosome of the long arm of chromosome 7, i (7)(q10), and an interstitial deletion of the long arm of chromosome 20, del (20)(q). These two imbalances are mechanisms of somatic genetic rescue. The literature offers few expression studies on SDS., Results: We report the expression analysis of bone marrow (BM) cells of patients with SDS in relation to normal karyotype or to the presence of clonal chromosome anomalies: del (20)(q) (five cases), i (7)(q10) (one case), and other anomalies (two cases). The study was performed using the microarray technique considering the whole transcriptome (WT) and three gene subsets selected as relevant in BM functions. The expression patterns of nine healthy controls and SDS patients with or without chromosome anomalies in the bone marrow showed clear differences., Conclusions: There is a significant difference between gene expression in the BM of SDS patients and healthy subjects, both at the WT level and in the selected gene sets. The deletion del (20)(q), with the EIF6 gene consistently lost, even in patients with the smallest losses of material, changes the transcription pattern: a low proportion of abnormal cells led to a pattern similar to SDS patients without acquired anomalies, whereas a high proportion yields a pattern similar to healthy subjects. Hence, the benign prognostic value of del (20)(q). The case of i (7)(q10) showed a transcription pattern similar to healthy subjects, paralleling the positive prognostic role of this anomaly as well., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2019.)

In the heart, primary microRNA-208b (pri-miR-208b) and Myheart (Mhrt) are long non-coding RNAs (lncRNAs) encoded by the cardiac myosin heavy chain genes. Although preclinical studies have shown that lncRNAs regulate gene expression and are protective for pathological hypertrophy, the mechanism underlying sex-based differences remains poorly understood. In this study, we examined DNA- and RNA-methylation-dependent regulation of pri-miR-208b and Mhrt. Expression of pri-miR-208b is elevated in the left ventricle of the female heart. Despite indistinguishable DNA methylation between sexes, the interaction of MeCP2 on chromatin is subject to RNase digestion, highlighting that affinity of the methyl-CG reader is broader than previously thought. A specialized procedure to isolate RNA from soluble cardiac chromatin emphasizes sex-based affinity of an MeCP2 co-repressor complex with Rest and Hdac2. Sex-specific Mhrt methylation chromatinizes MeCP2 at the pri-miR-208b promoter and extends the functional relevance of default transcriptional suppression in the heart., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Infection due to hepatitis C virus (HCV) is a major cause of fibrosis and hepatocellular carcinoma in Pakistan. In the current review, pattern of HCV genotypes and subtypes in Khyber Pakhtunkhwa province was ascertained in light of the available literature. After thorough analysis, genotype 3 (58.27%) was determined to be the leading HCV genotype, followed by genotypes 2 (12.39%), 1 (9.54%) and 4 (0.86%). The proportions of genotypes 5 and 6 were recorded as 0.09% and 0.22% respectively. Subtype wise, 3a accounted for 48.67%, followed by subtype 2a (10.91%), 3b (9.43%), 1a (5.84%), 1b (3.66%), 2b (1.45%) and genotype 4 with its undefined subtypes contributed a portion of 0.86%. The cumulative share of subtypes 1c, 2c, 3c, 5a and 6a was less than 1%. In 11.51% cases, the subtype was untypeable while in 7.17% cases mixed subtypes were recorded. Gender wise, proportions of most HCV subtypes were marginally higher among males as compared to females. On the basis of studied groups, 3a was pervasive among all groups except in intravenous drug users where 2a was the major HCV subtype. Similarly, based on various geographical locations (provincial divisions), subtype 3a revealed a ubiquitous distribution. Conclusively, HCV 3a persists to be the principal subtype across the province of Khyber Pakhtunkhwa. The considerable number of untypeable subtypes in most studies urges for an improved genotyping system on the basis of local sequence data and practice of sequencing for determination of underlying subtype in untypeable cases. Further, studies on identification of subtypes transmission pattern are imperative for assessment of transmission origin and reinforcement of efficient control strategies. In addition, the current review emphasizes the need of attention toward HCV risk groups and ignored southern side of Khyber Pakhtunkhwa province for better holistic understanding of HCV genotype distribution pattern in the province., (Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.)

The postural tachycardia syndrome (POTS) is characterised clinically by symptoms of light-headedness, palpitations, fatigue and exercise intolerance occurring with standing and relieved by lying down. Symptoms occur in association with an inappropriate rise in heart rate in the absence of a fall in blood pressure with the assumption of standing. The pathophysiology of POTS is complicated and poorly understood. Plasma norepinephrine (NE) is often elevated in patients with POTS, resulting in consideration of dysfunction of the norepinephrine transporter (NET) encoded by SLC6A2 gene. Whilst some studies have implicated a defect in the SLC6A2 gene, the cause of reduced SLC6A2 expression and function remains unclear. The search to explain the molecular mechanism of NET dysfunction has focused on genetic variation in the SLC6A2 gene and remains inconclusive. More recent studies show epigenetic mechanisms implicated in the regulation of SLC6A2 expression. In this article, we discuss the epigenetic mechanisms involved in SLC6A2 repression and highlight the potential therapeutic application of targeting these mechanisms in POTS., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The Ministry of Health and Family Welfare (MOHFW) of the Government of Bangladesh embarked on a sector-wide approach (SWAp) modality for the health, nutrition and population (HNP) sector in 1998. This programmatic shift initiated a different set of planning disciplines and practices along with institutional changes in the MOHFW. Over the years, the SWAp modality has evolved in Bangladesh as the MOHFW has learnt from its implementation and refined the program design. This article explores the progress made, both in terms of achievement of health outcomes and systems strengthening results, since the implementation of the SWAp for Bangladesh's health sector. Secondary analyses of survey data from 1993 to 2011 as well as a literature review of published and grey literature on health SWAp in Bangladesh was conducted for this assessment. Results of the assessment indicate that the MOHFW made substantial progress in health outcomes and health systems strengthening. SWAps facilitated the alignment of funding and technical support around national priorities, and improved the government's role in program design as well as in implementation and development partner coordination. Notable systemic improvements have taken place in the country systems with regards to monitoring and evaluation, procurement and service provision, which have improved functionality of health facilities to provide essential care. Implementation of the SWAp has, therefore, contributed to an accelerated improvement in key health outcomes in Bangladesh over the last 15 years. The health SWAp in Bangladesh offers an example of a successful adaptation of such an approach in a complex administrative structure. Based on the lessons learned from SWAp implementation in Bangladesh, the MOHFW needs to play a stronger stewardship and regulatory role to reap the full benefits of a SWAp in its subsequent programming., (© The Author 2015. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.)

A significant proportion of the worldwide population is of the elderly people living with chronic diseases that result in high health-care cost. To provide continuous health monitoring with minimal health-care cost, Wireless Body Sensor Networks (WBSNs) has been recently emerged as a promising technology. Depending on nature of sensory data, WBSNs might require a high level of Quality of Service (QoS) both in terms of delay and reliability during data reporting phase. In this paper, we propose a data-centric routing for intra WBSNs that adapts the routing strategy in accordance with the nature of data, temperature rise issue of the implanted bio-medical sensors due to electromagnetic wave absorption, and high and dynamic path loss caused by postural movement of human body and in-body wireless communication. We consider the network models both with and without relay nodes in our simulations. Due to the multi-facet routing strategy, the proposed data-centric routing achieves better performance in terms of delay, reliability, temperature rise, and energy consumption when compared with other state-of-the-art.

Recently sink mobility has been exploited in numerous schemes to prolong the lifetime of wireless sensor networks (WSNs). Contrary to traditional WSNs where sensory data from sensor field is ultimately sent to a static sink, mobile sink-based approaches alleviate energy-holes issues thereby facilitating balanced energy consumption among nodes. In mobility scenarios, nodes need to keep track of the latest location of mobile sinks for data delivery. However, frequent propagation of sink topological updates undermines the energy conservation goal and therefore should be controlled. Furthermore, controlled propagation of sinks' topological updates affects the performance of routing strategies thereby increasing data delivery latency and reducing packet delivery ratios. This paper presents a taxonomy of various data collection/dissemination schemes that exploit sink mobility. Based on how sink mobility is exploited in the sensor field, we classify existing schemes into three classes, namely path constrained, path unconstrained, and controlled sink mobility-based schemes. We also organize existing schemes based on their primary goals and provide a comparative study to aid readers in selecting the appropriate scheme in accordance with their particular intended applications and network dynamics. Finally, we conclude our discussion with the identification of some unresolved issues in pursuit of data delivery to a mobile sink.

Wireless Body Sensor Networks (WBSNs) constitute a subset of Wireless Sensor Networks (WSNs) responsible for monitoring vital sign-related data of patients and accordingly route this data towards a sink. In routing sensed data towards sinks, WBSNs face some of the same routing challenges as general WSNs, but the unique requirements of WBSNs impose some more constraints that need to be addressed by the routing mechanisms. This paper identifies various issues and challenges in pursuit of effective routing in WBSNs. Furthermore, it provides a detailed literature review of the various existing routing protocols used in the WBSN domain by discussing their strengths and weaknesses.

Objective: To determine the outcome of various techniques of vascular repair in terms of repair related complications and limb salavagibility., Methods: From January 1999 to December 2005, this retrospective study was conducted in the Department of General Surgery, Lahore General Hospital, Lahore, Pakistan. The patients, who underwent various surgical interventions for extremity vascular trauma, were included in this study. Those, who underwent primary amputation due to non-salvageable injuries or who presented with late complications of vascular injuries were excluded., Results: Ninety-three patients underwent different surgical procedures for extremity vascular trauma. Majority of the patients were young, (mean, 29.4 years) male (91.3%). Penetrating trauma was the most common mode of injury (77.4%). The median time interval between injury and repair was 4.5 hours. Superficial femoral artery was the most frequently injured artery (26.8%). Graft repair was carried out in 41 patients (46.6%), while (34.1%) of the patients had end-to-end anastomosis. Wound infection was the most common complication (18.2%). Seven patients (7.5%) had secondary amputations and 3 (3.2%) died from other injuries. Vascular reconstruction was successful in 89.3% of the patients., Conclusion: Early revascularization by employing simple repair or interposition autogenous vein graft repair results in successful limb salvage with acceptable complication rate.