Association study of two interleukin-1 gene loci with essential hypertension in a Pakistani Pathan population

An association study of IL-1 beta -511C/T and IL-1 RN 86 bp VNTR polymorphisms with essential hypertension was carried out in a sample population of 500 Pakistani Pathan subjects selected randomly, comprising groups of 235 subjects with hypertension and 265 controls. The distribution of both genotypes and alleles was not statistically different in cases and controls. In conclusion, IL-1 beta -511C/T and IL-1 RN 86 bp VNTR do not contribute to the aetiology of essential hypertension in the Pakistani Pathan population investigated here

RNA-Seq analysis uncovers transcriptomic variations between morphologically similar in vivo- and in vitro-derived bovine blastocysts

<p>Abstract</p> <p>Background</p> <p>A valuable tool for both research and industry, in vitro fertilization (IVF) has applications range from gamete selection and preservation of traits to cloning. Although IVF has achieved worldwide use, with approximately 339,685 bovine embryos transferred in 2010 alone, there are still continuing difficulties with efficiency. It is rare to have more than 40% of fertilized in vitro cattle oocytes reach blastocyst stage by day 8 of culture, and pregnancy rates are reported as less than 45% for in vitro produced embryos. To investigate potential influences in-vitro fertilization (IVF) has on embryonic development, this study compares in vivo- and in vitro-derived bovine blastocysts at a similar stage and quality grade (expanded, excellent quality) to determine the degree of transcriptomic variation beyond morphology using RNA-Seq.</p> <p>Results</p> <p>A total of 26,906,451 and 38,184,547 fragments were sequenced for in vitro and in vivo embryo pools, respectively. We detected expression for a total of 17,634 genes, with 793 genes showing differential expression between the two embryo populations with false discovery rate (FDR) < 0.05. There were also 395 novel transcribed units found, of which 45 were differentially expressed (FDR < 0.05). In addition, 4,800 genes showed evidence of alternative splicing, with 873 genes displaying differential alternative splicing between the two pools (FDR < 0.05). Using GO enrichment analysis, multiple biological pathways were found to be significantly enriched for differentially expressed genes (FDR < 0.01), including cholesterol and sterol synthesis, system development, and cell differentiation.</p> <p>Conclusions</p> <p>Thus, our results support that IVF may influence at the transcriptomic level and that morphology is limited in full characterization of bovine preimplantation embryos.</p

Awareness and Use of Benzodiazepines in Healthy Volunteers and Ambulatory Patients Visiting a Tertiary Care Hospital: A Cross Sectional Survey

Background: Indiscriminate prescription of Benzodiazepines in Pakistan and subsequent availability over-the-counter without prescription is a major public health problem, requiring systematic inquiry through research. Additionally, there is limited data on the awareness and use of Benzodiazepines from developing countries making it impossible to devise meaningful health policies. Methodology/Principal Findings: This was an Observational, Cross-Sectional study. conducted at Aga Khan University. A total of 475 (58.5 % males, 41.5 % females) people visiting a tertiary care hospital were interviewed by means of a structured questionnaire. The results showed that majority of population was aware of one or more Benzodiazepines (80.4%) and 30.4 % had used them at some point in life. 42.4 % of the users had been using it for more than a year. Commonest reason for use was sleep disturbance. Frequency of usage was higher for females, married individuals, educated (.Grade12), high socioeconomic status and housewives. More (59%) were prescribed than not and of them most by GP (58.5%). Only 36.5% of them were particularly told about the long-term addiction potential by the use of these drugs. Conclusion: Easy availability, access to re-fills without prescription and self prescription compounded with the lack of understanding of abuse potential of benzodiazepines constitutes a significant problem demanding serious consideratio

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Investigating socio-economic-demographic determinants of tobacco use in Rawalpindi, Pakistan

<p>Abstract</p> <p>Background</p> <p>To investigate the socio-economic and demographic determinants of tobacco use in Rawalpindi, Pakistan.</p> <p>Methods</p> <p>Cross sectional survey of households (population based) with 2018 respondent (1038 Rural; 980 Urban) was carried out in Rawalpindi (Pakistan) and included males and females 18–65 years of age. Main outcome measure was self reported daily tobacco use.</p> <p>Results</p> <p>Overall 16.5% of the study population (33% men and 4.7% women) used tobacco on a daily basis. Modes of tobacco use included cigarette smoking (68.5%), oral tobacco(13.5%), hukka (12%) and cigarette smoking plus oral tobacco (6%). Among those not using tobacco products, 56% were exposed to Environmental tobacco smoke.</p> <p>The adjusted odds ratio of tobacco use for rural residence compared to urban residence was 1.49 (95% CI 1.1 2.0, p value 0.01) and being male as compared to female 12.6 (8.8 18.0, p value 0.001). Illiteracy was significantly associated with tobacco use. Population attributable percentage of tobacco use increases steadily as the gap between no formal Education and level of education widens.</p> <p>Conclusion</p> <p>There was a positive association between tobacco use and rural area of residence, male gender and low education levels. Low education could be a proxy for low awareness and consumer information on tobacco products. As Public health practitioners we should inform the general public especially the illiterate about the adverse health consequences of tobacco use. Counter advertisement for tobacco use, through mass media particularly radio and television, emphasizing the harmful effects of tobacco on human health is very much needed.</p

Effects of a lifestyle intervention programme after 1 year of follow-up among South Asians at high risk of type 2 diabetes: a cluster randomised controlled trial

© Author(s) (or their employer(s)) 2021. Introduction South Asians are at high risk of type 2 diabetes (T2D). We assessed whether intensive family-based lifestyle intervention leads to significant weight loss, improved glycaemia and blood pressure in adults at elevated risk for T2D. Methods This cluster randomised controlled trial (iHealth-T2D) was conducted at 120 locations across India, Pakistan, Sri Lanka and the UK. We included 3684 South Asian men and women, aged 40–70 years, without T2D but with raised haemoglobin A1c (HbA1c) and/or waist circumference. Participants were randomly allocated either to the family-based lifestyle intervention or control group by location clusters. Participants in the intervention received 9 visits and 13 telephone contacts by community health workers over 1-year period, and the control group received usual care. Reductions in weight (aim >7% reduction), waist circumference (aim ≥5 cm reduction), blood pressure and HbA1C at 12 months of follow-up were assessed. Our linear mixed-effects regression analysis was based on intention-to-treat principle and adjusted for age, sex and baseline values. Results There were 1846 participants in the control and 1838 in the intervention group. Between baseline and 12 months, mean weight of participants in the intervention group reduced by 1.8 kg compared with 0.4 kg in the control group (adjusted mean difference −1.10 kg (95% CI −1.70 to −1.06), p<0.001). The adjusted mean difference for waist circumference was −1.9 cm (95% CI −2.5; to 1.3), p<0.001). No overall difference was observed for blood pressure or HbA1c. People who attended multiple intervention sessions had a dose-dependent effect on waist circumference, blood pressure and HbA1c, but not on weight. Conclusion An intensive family-based lifestyle intervention adopting low-resource strategies led to effective reduction in weight and waist circumference at 12 months, which has potential long-term benefits for preventing T2D. A higher number of attended sessions increased the effect on waist circumference, blood pressure and HbA1c. Trial registration number EudraCT: 2016-001350-18; ClinicalTrials.gov: NCT02949739.The iHealth-T2D trial was funded by the European Commission (grant award 643774)

The iHealth-T2D study, prevention of type 2 diabetes amongst South Asians with central obesity and prediabetes: study protocol for a randomised controlled trial

Copyright © 2021 The Author(s). Background: People from South Asia are at increased risk of type 2 diabetes (T2D). There is an urgent need to develop approaches for the prevention of T2D in South Asians that are cost-effective, generalisable and scalable across settings. Hypothesis: Compared to usual care, the risk of T2D can be reduced amongst South Asians with central obesity or raised HbA1c, through a 12-month lifestyle modification programme delivered by community health workers. Design: Cluster randomised clinical trial (1:1 allocation to intervention or usual care), carried out in India, Pakistan, Sri Lanka and the UK, with 30 sites per country (120 sites total). Target recruitment 3600 (30 participants per site) with annual follow-up for 3 years. Entry criteria: South Asian, men or women, age 40–70 years with (i) central obesity (waist circumference ≥ 100 cm in India and Pakistan; ≥90 cm in Sri Lanka) and/or (ii) prediabetes (HbA1c 6.0–6.4% inclusive). Exclusion criteria: known type 1 or 2 diabetes, normal or underweight (body mass index < 22 kg/m2); pregnant or planning pregnancy; unstable residence or planning to leave the area; and serious illness. Endpoints: The primary endpoint is new-onset T2D at 3 years, defined as (i) HbA1c ≥ 6.5% or (ii) physician diagnosis and on treatment for T2D. Secondary endpoints at 1 and 3 years are the following: (i) physical measures: waist circumference, weight and blood pressure; (ii) lifestyle measures: smoking status, alcohol intake, physical activity and dietary intake; (iii) biochemical measures: fasting glucose, insulin and lipids (total and HDL cholesterol, triglycerides); and (iv) treatment compliance. Intervention: Lifestyle intervention (60 sites) or usual care (60 sites). Lifestyle intervention was delivered by a trained community health worker over 12 months (5 one-one sessions, 4 group sessions, 13 telephone sessions) with the goal of the participants achieving a 7% reduction in body mass index and a 10-cm reduction in waist circumference through (i) improved diet and (ii) increased physical activity. Usual care comprised a single 30-min session of lifestyle modification advice from the community health worker. Results: We screened 33,212 people for inclusion into the study. We identified 10,930 people who met study entry criteria, amongst whom 3682 agreed to take part in the intervention. Study participants are 49.2% female and aged 52.8 (SD 8.2) years. Clinical characteristics are well balanced between intervention and usual care sites. More than 90% of follow-up visits are scheduled to be complete in December 2020. Based on the follow-up to end 2019, the observed incidence of T2D in the study population is in line with expectations (6.1% per annum). Conclusion: The iHealth-T2D study will advance understanding of strategies for the prevention of diabetes amongst South Asians, use approaches for screening and intervention that are adapted for low-resource settings. Our study will thus inform the implementation of strategies for improving the health and well-being of this major global ethnic group. IRB approval: 16/WM/0171 Trial registration: EudraCT 2016-001350-18. Registered on 14 April 2016. ClinicalTrials.govNCT02949739. Registered on 31 October 2016, First posted on 31/10/2016.European Union H2020 program (iHealth-T2D, 643774); National Institute for Health Research (NIHR) (16/136/68) using UK aid from the UK Government to support global health research

Dead on arrival in a low-income country: results from a multicenter study in Pakistan

BACKGROUND: This study assessed the characteristics of dead on arrival (DOA) patients in Pakistan. METHODS: Data about the DOA patients were extracted from Pakistan National Emergency Department Surveillance study (Pak-NEDS). This study recruited all ED patients presenting to seven tertiary care hospitals during a four-month period between November 2010 and March 2011. This study included patients who were declared dead-on-arrival by the ED physician. RESULTS: A total of 1,557 DOA patients (7 per 1,000 visits) were included in the Pak-NEDS. Men accounted for two-thirds (64%) of DOA patients. Those aged 20-49 years accounted for about 46% of DOA patients. Nine percent (n = 72) of patients were brought by ambulance, and most patients presented at a public hospital (80%). About 11% of DOA patients had an injury. Factors significantly associated (p \u3c 0.05) with ambulance use were men (adjusted odds ratio [aOR] = 2.72), brought to a private hospital (OR = 2.74), and being injured (aOR = 1.89). Cardiopulmonary resuscitation (CPR) was performed on 6% (n = 42) of patients who received treatment. Those brought to a private hospital were more likely to receive CPR (aOR = 2.81). CONCLUSION: This study noted a higher burden of DOA patients in Pakistan compared to other resourceful settings (about 1 to 2 per 1,000 visits). A large proportion of patients belonging to productive age groups, and the low prevalence of ambulance and CPR use, indicate a need for improving the prehospital care and basic life support training in pakistan

Low uptake of COVID-19 prevention behaviours and high socioeconomic impact of lockdown measures in South Asia: Evidence from a large-scale multi-country surveillance programme

Background South Asia has become a major epicentre of the COVID-19 pandemic. Understanding South Asians’ awareness, attitudes and experiences of early measures for the prevention of COVID-19 is key to improving the effectiveness and mitigating the social and economic impacts of pandemic responses at a critical time for the Region. Methods We assessed the knowledge, behaviours, health and socio-economic circumstances of 29,809 adult men and women, at 93 locations across four South Asian countries. Data were collected during the national lockdowns implemented from March to July 2020, and compared with data collected prior to the pandemic as part of an ongoing prospective surveillance initiative. Results Participants were 61% female, mean age 45.1 years. Almost half had one or more chronic disease, including diabetes (16%), hypertension (23%) or obesity (16%). Knowledge of the primary COVID-19 symptoms and transmission routes was high, but access to hygiene and personal protection resources was low (running water 63%, hand sanitisers 53%, paper tissues 48%). Key preventive measures were not widely adopted. Knowledge, access to, and uptake of COVID-19 prevention measures were low amongst people from disadvantaged socio-economic groups. Fifteen percent of people receiving treatment for chronic diseases reported loss of access to long-term medications; 40% reported symptoms suggestive of anxiety or depression. The prevalence of unemployment rose from 9.3% to 39.4% (P < 0.001), and household income fell by 52% (P < 0.001) during the lockdown. Younger people and those from less affluent socio-economic groups were most severely impacted. Sedentary time increased by 32% and inadequate fruit and vegetable intake increased by 10% (P < 0.001 for both), while tobacco and alcohol consumption dropped by 41% and 80%, respectively (P < 0.001), during the lockdown. Conclusions Our results identified important knowledge, access and uptake barriers to the prevention of COVID-19 in South Asia, and demonstrated major adverse impacts of the pandemic on chronic disease treatment, mental health, health-related behaviours, employment and household finances. We found important sociodemographic differences for impact, suggesting a widening of existing inequalities. Our findings underscore the need for immediate large-scale action to close gaps in knowledge and access to essential resources for prevention, along with measures to safeguard economic production and mitigate socio-economic impacts on the young and the poor

Importance of Non-Selective Cation Channel TRPV4 Interaction with Cytoskeleton and Their Reciprocal Regulations in Cultured Cells

BACKGROUND: TRPV4 and the cellular cytoskeleton have each been reported to influence cellular mechanosensitive processes as well as the development of mechanical hyperalgesia. If and how TRPV4 interacts with the microtubule and actin cytoskeleton at a molecular and functional level is not known. METHODOLOGY AND PRINCIPAL FINDINGS: We investigated the interaction of TRPV4 with cytoskeletal components biochemically, cell biologically by observing morphological changes of DRG-neurons and DRG-neuron-derived F-11 cells, as well as functionally with calcium imaging. We find that TRPV4 physically interacts with tubulin, actin and neurofilament proteins as well as the nociceptive molecules PKCepsilon and CamKII. The C-terminus of TRPV4 is sufficient for the direct interaction with tubulin and actin, both with their soluble and their polymeric forms. Actin and tubulin compete for binding. The interaction with TRPV4 stabilizes microtubules even under depolymerizing conditions in vitro. Accordingly, in cellular systems TRPV4 colocalizes with actin and microtubules enriched structures at submembranous regions. Both expression and activation of TRPV4 induces striking morphological changes affecting lamellipodial, filopodial, growth cone, and neurite structures in non-neuronal cells, in DRG-neuron derived F11 cells, and also in IB4-positive DRG neurons. The functional interaction of TRPV4 and the cytoskeleton is mutual as Taxol, a microtubule stabilizer, reduces the Ca2+-influx via TRPV4. CONCLUSIONS AND SIGNIFICANCE: TRPV4 acts as a regulator for both, the microtubule and the actin. In turn, we describe that microtubule dynamics are an important regulator of TRPV4 activity. TRPV4 forms a supra-molecular complex containing cytoskeletal proteins and regulatory kinases. Thereby it can integrate signaling of various intracellular second messengers and signaling cascades, as well as cytoskeletal dynamics. This study points out the existence of cross-talks between non-selective cation channels and cytoskeleton at multiple levels. These cross talks may help us to understand the molecular basis of the Taxol-induced neuropathic pain development commonly observed in cancer patients