Implications of the 375W mutation for HIV-1 tropism and vaccine development.

Understanding how different amino acids affect the HIV-1 envelope (Env) trimer will greatly help the design and development of vaccines that induce broadly neutralizing antibodies (bnAbs). A tryptophan residue at position 375 that opens the CD4 binding site without modifying the trimer apex was identified using our saturation mutagenesis strategy. 375W was introduced into a large panel of 27 transmitted/founder, acute stage, chronic infection, and AIDS macrophage-tropic and non-macrophage-tropic primary envelopes from different clades (A, B, C, D, and G) as well as complex and circulating recombinants. We evaluated soluble CD4 and monoclonal antibody neutralization of WT and mutant Envs together with macrophage infection. The 375W substitution increased sensitivity to soluble CD4 in all 27 Envs and macrophage infection in many Envs including an X4 variant. Importantly, 375W did not impair or abrogate neutralization by potent bnAbs. Variants that were already highly macrophage tropic were compromised for macrophage tropism, indicating that other structural factors are involved. Of note, we observed a macrophage-tropic (clade G) and intermediate macrophage-tropic (clades C and D) primary Envs from the blood and not from the central nervous system (CNS), indicating that such variants could be released from the brain or evolve outside the CNS. Our data also indicate that "intermediate" macrophage-tropic variants should belong to a new class of HIV-1 tropism. These Envs infected macrophages more efficiently than non-macrophage-tropic variants without reaching the high levels of macrophage-tropic brain variants. In summary, we show that 375W is ideal for inclusion into HIV-1 vaccines, increasing Env binding to CD4 for widely diverse Envs from different clades and disease stages.IMPORTANCESubstitutions exposing the CD4 binding site (CD4bs) on HIV-1 trimers but still occluding non-neutralizing, immunogenic epitopes are desirable to develop HIV-1 vaccines. If such substitutions induce similar structural changes in trimers across diverse clades, they could be exploited for the development of multi-clade envelope (Env) vaccines. We show that the 375W substitution increases CD4 affinity for envelopes of all clades, circulating recombinant forms, and complex Envs tested, independent of disease stage. Clade B and C Envs with an exposed CD4bs were described for macrophage-tropic strains from the central nervous system (CNS). Here, we show that intermediate (clades C and D) and macrophage-tropic (clade G) envelopes can be detected outside the CNS. Vaccines targeting the CD4bs will be particularly effective against such strains and CNS disease.

Assessment of physical literacy in 8- to 12-year-old Pakistani school children: reliability and cross-validation of the Canadian assessment of physical literacy-2 (CAPL-2) in South Punjab, Pakistan.

BACKGROUND: The increasing prevalence of physical inactivity, declining fitness, and rising childhood obesity highlight the importance of physical literacy (PL), as a foundational component for fostering lifelong health and active lifestyle. This recognition necessitates the development of effective tools for PL assessment that are applicable across diverse cultural landscapes. AIM: This study aimed to translate the Canadian Assessment of Physical Literacy-2 (CAPL-2) into Urdu and adapt it for the Pakistani cultural context, to assess PL among children aged 8-12 years in Pakistan. METHOD: The Urdu version of CAPL-2 was administered among 1,360 children aged 8-12 from 87 higher secondary schools across three divisions in South Punjab province, Pakistan. Statistical analysis includes test-retest reliability and construct validity, employing confirmatory factor analysis to evaluate the tool's performance both overall and within specific subdomains. RESULTS: The Urdu version of CAPL-2 demonstrated strong content validity, with a Content Validity Ratio of 0.89. Confirmatory factor analysis supported the four-factor structure proposed by the original developers, evidenced by excellent model fit indices (GFI = 0.984, CFI = 0.979, TLI = 0.969, RMSEA = 0.041). High internal consistency was observed across all domains (α = 0.988 to 0.995), with significant correlations among most, excluding the Knowledge and Understanding domains. Notably, gender and age significantly influenced performance, with boys generally scoring higher than girls, with few exceptions. CONCLUSION: This study marks a significant step in the cross-cultural adaptation of PL assessment tools, successfully validating the CAPL-2 Urdu version for the Pakistani context for the first time. The findings affirm the tool's suitability for assessing PL among Pakistani children, evidencing its validity and reliability across the Pakistani population.

Youth-led co-production of mental health promotion in Pakistan: intergenerational influences.

Youth with mental health needs face barriers in seeking and accessing help, especially in resource-constrained settings in Majority World Countries. Community engagement is thus important for mental health promotion, particularly in addressing stigma. Engagement can be enhanced by involving peer educators and by relating to intergenerational experiences in the sociocultural context of the community. The aim of this study was to explore how intergenerational experiences and perspectives can inform the co-production of youth-led mental health promotion in a Majority World Country, Pakistan. We recruited 11 families (one grandmother, mother and granddaughter in each family) as advisers from two disadvantaged areas of Karachi, and 14 peer educators. Training for peer educators included seminars, experiential activities, three participatory workshops with family advisers and supervision. A sub-sample of family advisers and peer educators attended four focus groups, and peer educators completed reflective diaries following each activity. Data were integrated and subjected to thematic codebook analysis. The three themes related to enabling and hindering factors towards co-production of mental health promotion, incorporation of intergenerational resilience and cascading knowledge to communities. The findings highlighted potential benefits of youth-led mental health promotion that contextualizes intergenerational experiences for those communities. Peer educator roles should be supported by training, and mental health promotion should be integrated within local service systems.

Central centrifugal cicatricial alopecia: a deeper insight into the disease.

Central centrifugal cicatricial alopecia (CCCA) is a scarring alopecia of multifactorial etiology that presents on the vertex as patchy areas of hair loss, spreading centrifugally over the scalp. It most commonly affects women of African descent, but cases among other ethnicities have also been reported. CCCA typically starts with thinning and breaking of the hair as the first sign of presentation, which eventually progresses to hair loss over the central part of the scalp, spreading symmetrically outwards to involve a larger area. Currently, there is no definitive cure for the disease; however, multiple management options are available, which should aim to be tailored to the individual patient. Owing to its cosmetic outcomes, the quality of life (QoL) of patients with central centrifugal cicatricial alopecia is also disturbed, as patients may face psychological and social stress due to their permanent hair loss. This article focuses on various aspects of the pathogenesis, clinical trials, quality of life, barriers faced by patients, and treatment of central centrifugal cicatricial alopecia.

What Should Personalised Mental Health Support Involve? Views of Young People with Lived Experience and Professionals from Eight Countries.

Research demonstrates that young people value mental health support that is tailored to their needs and preferences, rather than a "one size fits all" offer, which is often not equitably accessible (National Children's Bureau, 2021). Understanding young people's lived experiences across different sociocultural contexts is important. The aim of this research was to conduct an international qualitative study on the views of young people with lived experience and professionals, on proposed aspects of personalised support for anxiety and/or depression. Participatory action focus groups were conducted with N = 120 young people with lived experience of anxiety and/or depression (14-24 years) and with N = 63 professionals in Brazil, India, Kenya, Pakistan, Portugal, South Africa, Turkey, and the United Kingdom. Data were analysed using the rigorous and accelerated data reduction (RADaR) technique. Overall, although some country-specific differences were found in terms of what aspects of support young people found to be most important, individual preferences were considered stronger, furthering the view that support should be personalised to the needs of the individual young person. Young people experiencing anxiety and/or depression should be able to choose for themselves which aspects of support they would prefer in their own care and support plans, with families and mental health professionals providing guidance where appropriate, rather than removing the young person from the decision-making process altogether. It should also be ensured that the aspects of personalised support can be understood by young people and professionals from different contexts, including marginalised and minoritised groups and communities.

Influence of puberty on relationships between body composition and blood pressure: a cross-sectional study.

BACKGROUND: Fat mass (FM) and fat-free mass (FFM) are positively associated with blood pressure (BP) in youth. Yet, how puberty, independent of age, affects these relationships remains unclear. Given puberty may be a crucial period for cardiometabolic health, we examined how pubertal development moderates the associations of FM/FFM with BP. METHODS: Pubertal development, resting BP, and body composition were assessed in a convenience sample of youth (5.5-17 years). General linear models were conducted to assess if pubertal development moderated the relationships between FM/FFM and systolic/diastolic BP standardized for age, sex, and height (SBPz/DBPz). RESULTS: Among participants (N = 1405; age: M = 13.3 ± 2.9 years; 65.4% female; 53.2% racial/ethnic minority), FM/FFM were positively associated with SBPz and DBPz (ps ≤ 0.02). Pubertal development moderated the associations between FFM and BPz (ps ≤ 0.01), but not FM (ps > 0.43). For early/mid and late pubertal participants, there were positive associations between FFM and BP (DBPz: ßs = 0.10-0.18, ps ≤ 0.01; SBPz: ßs = 0.33-0.43, ps < 0.001); however, these relationships were attenuated, especially for prepubertal DBPz (DBPz: ß = 0.01, p = 0.91; SBPz: ß = 0.24, p = 0.001). CONCLUSIONS: Puberty moderated the relationships between FFM and SBPz/DBPz in analyses that separately modeled the contributions of age and sex. These data suggest that the FFM-DBPz association may potentially be impacted by increasing sex hormone concentrations during puberty. IMPACT: Fat mass (FM) and blood pressure (BP) were positively associated throughout puberty. Fat-free mass (FFM) and BP were positively associated throughout puberty; however, puberty moderated the FFM-BP relationship, such that there was a positive relationship in early/mid and late puberty, but the relationship was attenuated for prepubertal children. These findings contribute further insight into physiological and cardiometabolic changes occurring during puberty. Changes in hormone concentrations may explain the impact puberty has on the FFM-BP relationship. Understanding predictors of BP are important as childhood BP is associated with future cardiometabolic outcomes.

Intra-urban risk assessment of occupational injuries and illnesses associated with current and projected climate: Evidence from three largest Australian cities.

BACKGROUND: Increased risk of occupational injuries and illnesses (OI) is associated with ambient temperature. However, most studies have reported the average impacts within cities, states, or provinces at broader scales. METHODS: We assessed the intra-urban risk of OI associated with ambient temperature in three Australian cities at statistical area level 3 (SA3). We collected daily workers' compensation claims data and gridded meteorological data from July 1, 2005, to June 30, 2018. Heat index was used as the primary temperature metric. We performed a two-stage time series analysis: we generated location-specific estimates using Distributed Lag Non-Linear Models (DLNM) and estimated the cumulative effects with multivariate meta-analysis. The risk was estimated at moderate heat (90th percentile) and extreme heat (99th percentile). Subgroup analyses were conducted to identify vulnerable groups of workers. Further, the OI risk in the future was estimated for two projected periods: 2016-2045 and 2036-2065. RESULTS: The cumulative risk of OI was 3.4% in Greater Brisbane, 9.5% in Greater Melbourne, and 8.9% in Greater Sydney at extreme heat. The western inland regions in Greater Brisbane (17.4%) and Greater Sydney (32.3%) had higher risk of OI for younger workers, workers in outdoor and indoor industries, and workers reporting injury claims. The urbanized SA3 regions posed a higher risk (19.3%) for workers in Greater Melbourne. The regions were generally at high risk for young workers and illness-related claims. The projected risk of OI increased with time in climate change scenarios. CONCLUSIONS: This study provides a comprehensive spatial profile of OI risk associated with hot weather conditions across three cities in Australia. Risk assessment at the intra-urban level revealed strong spatial patterns in OI risk distribution due to heat exposure. These findings provide much-needed scientific evidence for work, health, and safety regulators, industries, unions, and workers to design and implement location-specific preventative measures.

UHPLC-MS and GC-MS phytochemical profiling, amelioration of pain and inflammation with chloroform extract of Funaria hygrometrica Hedw. via modulation of inflammatory biomarkers.

People of Pakistan have undisturbed customs for the employment of medicinal plants for healthcare requisites. Chloroform extract of F. hygrometrica (CE FH) was examined for its ability to reduce inflammation and to produce analgesia. Carrageenan and formalin-induced paw edema model for inflammatory activity, hot-plate and tail-flick methods to assess analgesic activity were executed. Phytochemical analysis was done by UHPLC-MS and GC-mass spectrometer. The results demonstrated that in carrageenan-induced paw edema, maximum reduction in inflammation was observed at 5th hour at the dose 100 mg/kg; while at doses 250 and 500 mg/kg, maximum response was observed at 5th and 6th hours. Analgesic activity results indicated that maximum analgesia was observed up to 120 min at 100 mg/kg, while up to 90 min in case of 250 and 500 mg/kg doses. The formalin-induced rat paw edema showed significant (p < 0.05) anti-inflammatory activity after 5 days treatment. After, testing period of 10 days, the biochemical parameters such as CBC, CRP, serum enzymes like CAT, SOD, GSH and inflammatory mediators like TNF-α, IL-6, IL-4 and IL-10 were estimated. The administration of formalin resulted in an increase in the level of leucocytes, total WBC, CRP, serum enzymes and in the diameters of paw thickness, while pre-treatment with CE FH at dose levels of 100, 250 and 500 mg/kg exhibited a diminution in the levels of SOD, GSH, CAT, total RBC and HB. Acute inflammatory mediators such as TNFα, IL -6 and IL-4 were reduced, and IL-10 was upregulated in the treated group as compared to the control. Many phytoconstituents, i.e., chitobiose, chlorovulone III, γ-tocotrienol, emmotin, cassine, hexacosanedioic acid, neophytadiene, fumaric acid, neophytadiene, hexadecanoic acid, phytol and stigmasterol were detected during UHPLC-MS and GC-MS analysis seems to be responsible for the said activity in correlation with the already reported data about these compounds. The results concluded that CE FH possess noteworthy anti-inflammatory and central analgesic action at different doses (100, 250 and 500 mg/kg).

Life of an amputee: predictors of quality of life after lower limb amputation.

Lower limb amputations (LLA) have a significant impact on global morbidity. Approximately 2 million people are living with lower limb amputation in the United States and this figure is expected to rise. LLA lead to physical disabilities and can cause restriction in functionalities in the everyday life of amputees. Patients lose their independence, which can be very debilitating and eventually causes physical, behavioral, and psychical changes. These changes after amputations should be properly addressed and must be incorporated into rehabilitation to improve and regain better adjustment to life among amputees. This article focuses on determining various factors and their effect on quality of life after lower limb amputations.

Impact of domestic and industrial effluent on marine environment at Karachi Port Trust (KPT) coastal area, Pakistan.

The extent of aquatic pollution of Karachi Port Trust (KPT) coastal area located at the south of Pakistan coast has increased considerably in the last few decades due to unrestricted discharge of sanitary waste. The current study lays emphasis on the identification of vulnerable zones severely impacted by pollution in the KPT coastal area using laboratory monitoring, geospatial techniques, and statistical analysis. During 2019, sampling was conducted along the KPT coastal area, and 54 samples of seawater were collected during pre- and post-monsoon seasons. The outcomes of physical and chemical analysis revealed that the concentrations of BOD (biochemical oxygen demand), COD (chemical oxygen demand), nitrate, phosphate, phenol, cyanide, and oil and grease frequently exceeded the permitted limit of international norms and reached much greater levels. The levels of perilous metals in the seawater samples were in the order Ni>Cr>Cu>Pb>Cd>As in both phases and also reached to elevated levels as a consequence of the indiscriminate discharge of untreated industrial and domestic wastewater. Based on detailed examination during pre- and post-monsoon, six sites near KPT, Lyari River outfall, and Karachi Harbour were identified as highly polluted zones due to heavy discharge of sanitary effluents at these sites. In particular, the industrial zones present in the formal and informal sectors of Karachi are responsible for the deterioration of the KPT coastal area. Therefore, it is advised to design and build a submerged drainage system to transport and distribute massive amounts of treated municipal and industrial waste to the deep open sea in order to minimize the high pollutant levels in these locations.

The fate of health professions education as a profession: a road less travelled.

OBJECTIVE: To explore the views of academics about the identity of Health Professions Education as a discipline, its fate and sustainability as a profession. METHODS: The qualitative exploratory study was conducted from February to July 2021 after approval from the ethics review committee of Islamic International Medical College, Riphah International University, Rawalpindi, Pakistan, and comprised both fulltime and part-time health professions educationists of either gender teaching in different institutions of seven cities of Pakistan; Taxila, Kamrah, Rawalpindi, Peshawar, Lahore, Multan and Karachi. Using Professional Identity theory, data was collected through semi-structured one-on-one interviews which were conducted online. The interviews were transcribed verbatim, coded and thematically analysed. RESULTS: Of the 14 participants, 7(50%) had qualifications and experience of other specialities as well, while 7(50%) were pure health professions educationists. Overall, 5(35%) subjects were from Rawalpindi, 3(21%) were serving in multiple cities including Peshawer, 2(14%) were from Taxilla and 1(7.5%) each was from Lahore, Karachi, Kamrah and Multan. Accumulated data led to 31 codes with 3 themes and 15 sub-themes. The main themes were identity of health professions education as a discipline, its fate and sustainability. CONCLUSIONS: Health professions education has established its identity as a discipline in Pakistan, with independent, fully functioning departments in medical and dental colleges across the country.

Dry eye disease and high disease activity score (DAS-28) in rheumatoid arthritis: An underrated combination.

OBJECTIVE: To determine the association of dryness of eyes with rheumatoid arthritis severity. METHODS: The cross-sectional, observational study was conducted at the Jinnah Medical College Hospital, Karachi, from December 2020 to May 2021, and comprised adult patients of either gender with rheumatoid arthritis who were diagnosed on the basis of clinical and serological investigations. Data was collected using a structured pre-tested questionnaire. Ocular Surface Disease Index questionnaires with Tear Film Breakup Time were used to assess the severity of dry eyes. Disease Activity Score-28 with erythrocyte sedimentation rate was used to assess the severity of rheumatoid arthritis. Association between the two was explored. Data was analysed using SPSS 22. RESULTS: Of the 61 patients, 52(85.2%) were females and 9(14.8%) were males. The overall mean age was 41.7±12.8 years, with 4(6.6%) aged <20 years, 26(42.6%) aged 21-40 years, 28(45.9%) aged 41-60 years and 3(4.9%) aged >60years. Further, 46(75.4%) subjects had sero-positive rheumatoid arthritis, 25(41%) had high severity, 30(49.2%) had severe Occular Surface Density Index score and 36(59%) had decreased Tear Film Breakup Time. Logistic Regression analysis showed there were 5.45 times higher odds of having severe disease among the people with Occular Surface Density Index score >33 (p=0.003). In patients with positive Tear Film Breakup Time, there were 6.25 higher odds of having increased disease activity score (p=0.001). CONCLUSIONS: Disease activity scores of rheumatoid arthritis were found to have strong association with dryness of eyes, high Ocular Surface Disease Index score and increased erythrocyte sedimentation rate.

Exploring knowledge, attitudes and perceived myths towards foetal programming and factors affecting it among the public and health professionals in Pakistan: a needs assessment study.

OBJECTIVE: To explore knowledge, attitudes and practices of laypersons and health professionals towards foetal programming, and factors affecting it. METHODS: The mixed methods study was conducted at the Aga Khan University, Karachi, from January 20, 2021 to May 13, 2022, and comprised adults of either gender with access to social media platforms. Data was collected using an online survey questionnaire in English and Urdu developed to capture responses from a diverse pool of participants. The survey tool was circulated through WhatsApp, Facebook and Instagram. Two focus group discussions were conducted; one with laypersons in group A and the other with health and allied professionals in group B. Data was analysed using SPSS 21, while data related to focus group discussions was subjected to thematic analysis. RESULTS: Of the 358 participants, 173(48.3%) were in group A and 185(51.7%) were in group B. There were 34(18.4) subjects in group A and 27(15.6) in group B who had knowledge of foetal programming (p>0.05). Only factors related to father's health and dietary elements on the foetus were significantly different between the groups (p<0.05). Thematic analysis led to the formation of 3 overarching themes: parent's lifestyle, comorbidity and diet on foetal health; myths and cultural beliefs regarding foetal development; and the need for training / awareness for practitioners and community. CONCLUSIONS: Lack of knowledge and misinformation about foetal programming and development was common among health professionals and laypersons.

Relationship Between Genetic Variant Of OXTR (Rs53576) And MTNR1B (Rs1387153) And Symptoms Of Psychological Stress In Females With Gestational Diabetes Mellitus.

Objective: To assess the association of oxytocin receptor (rs53576) and melatonin hormone receptor 1B (rs1387153) gene single nucleotide polymorphisms with psychological symptoms in women with gestational diabetes mellitus. METHODS: The case-control study was conducted from May 1 to June 1, 2022, at the Department of Physiology, University of Karachi, in collaboration with the Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, and the Department of Obstetrics and Gynaecology, Jinnah Postgraduate Medical Centre, Karachi. Fifty gestational diabetic pregnant women and ninety healthy pregnant women were recruited. Sanger sequencing was performed to assess the genotypic frequency and polymorphic variation of all subjects. Perceived stress scale and diabetes-related distress scale were used to assess the stress levels. Data was analysed using SPSS 23. RESULTS: Of the 140 subjects, 90 (64.3%) were controls with mean age 24.96±4.35 years, and 50 (35.7%) were cases with mean age 28.78±5.25 (p<0.05). Mean body weight and mean gestational age were not significantly different between the groups (p>0.05). Melatonin hormone receptor 1B rs1387153 frequency was significantly different between the groups (p<0.05). Among the cases, a significant mean difference for regimen distress scores between AA and GG was observed for oxytocin receptor rs53576 (p=0.04). A significant mean difference in sum of PSS, diabetes-related stress, total diabetes- related stress and emotional distress was noted between CC and TT genotypes for melatonin hormone receptor 1B rs1387153 (p=0.001). Conclusion: MTNR1B rs1387153 genotypes were associated with perceived stress, diabetes-related stress, diabetic distress, and emotional burden, while OXTR rs53576 genotypes were associated with regimen distress in GDM women.

Maternal and fetal outcomes in women undergoing induction of labor with low dose vaginal misoprostol.

Objective: To determine Maternal and Fetal outcome in women undergoing induction of labour with low dose misoprostol. Method: A cross-sectional study was carried out to determine the efficacy of Misoprostol for induction of labor (IOL) in MTI, Lady Reading Hospital (LRH), Peshawar from 21st January to 31st December 2021. All pregnant women with singleton pregnancy and cephalic presentation admitted for Induction of Labor were included in the study. Maternal and Fetal outcome was noted. Induction of labor was started with 25 micrograms of Misoprostol, repeated every six hours depending on Bishop Score. Results: Three hundred and thirty-seven women were included in this study. The majority of females (76%) were in 18-35 years age group. In 92.3% of females, the Bishop score was less than six. The maximum number of females (33.5%) delivered after eight hours of IOL. Sixty-six (66.46%) of females had gestational age of 37-40 weeks. Premature rupture of membranes was the most common indication (32.9%). Three doses of misoprostol were required in 31.2% of females. Only 5.6% of females required six doses of misoprostol for induction. With Misoprostol 85.1% of females delivered spontaneously, 2.37% required forceps delivery, 1.7% required vacuum delivery, and 10.68% delivered by Caesarean Section. APGAR score was 8 /10 in 84% of neonates at birth. Eighty-seven %(87.8%) of neonates did not require NICU admission. Conclusion: Misoprostol is a safe medicine to be used to induce labor in females. It can help shorten the duration of labor, with good fetomaternal outcome.

Primary Norfloxacin Prophylaxis for APASL-Defined Acute-on-Chronic Liver Failure: A Placebo-Controlled Double-Blind Randomized Trial.

INTRODUCTION: This study aimed to evaluate the role of prophylactic norfloxacin in preventing bacterial infections and its effect on transplant-free survival (TFS) in patients with acute-on-chronic liver failure (ACLF) identified by the Asian Pacific Association for the Study of the Liver criteria. METHODS: Patients with ACLF included in the study were randomly assigned to receive oral norfloxacin 400 mg or matched placebo once daily for 30 days. The incidence of bacterial infections at days 30 and 90 was the primary outcome, whereas TFS at days 30 and 90 was the secondary outcome. RESULTS: A total of 143 patients were included (72 in the norfloxacin and 71 in the placebo groups). Baseline demographics, biochemical variables, and severity scores were similar between the 2 groups. On Kaplan-Meier analysis, the incidence of bacterial infections at day 30 was 18.1% (95% confidence interval [CI], 10-28.9) and 33.8% (95% CI, 23-46) (P = 0.03); and the incidence of bacterial infections at day 90 was 46% (95% CI, 34-58) and 62% (95% CI, 49.67-73.23) in the norfloxacin and placebo groups, respectively (P = 0.02). On Kaplan-Meier analysis, TFS at day 30 was 77.8% (95% CI, 66.43-86.73) and 64.8% (95% CI, 52.54-75.75) in the norfloxacin and placebo groups, respectively (P = 0.084). Similarly, TFS at day 90 was 58.3% (95% CI, 46.11-69.84) and 43.7% (95% CI, 31.91-55.95), respectively (P = 0.058). Thirty percent of infections were caused by multidrug-resistant organisms. More patients developed concomitant candiduria in the norfloxacin group (25%) than in the placebo group (2.63%). DISCUSSION: Primary norfloxacin prophylaxis effectively prevents bacterial infections in patients with ACLF.

Obesity-associated metabolites in relation to type 2 diabetes risk: A prospective nested case-control study of the CARRS cohort.

AIMS: To determine whether obesity-associated metabolites are associated with type 2 diabetes (T2DM) risk among South Asians. MATERIALS AND METHODS: Serum-based nuclear magnetic resonance imaging metabolomics data were generated from two South Asian population-based prospective cohorts from Karachi, Pakistan: CARRS1 (N = 4017) and CARRS2 (N = 4802). Participants in both cohorts were followed up for 5 years and incident T2DM was ascertained. A nested case-control study approach was developed to select participants from CARRS1 (Ncases  = 197 and Ncontrols  = 195) and CARRS2 (Ncases  = 194 and Ncontrols  = 200), respectively. First, we investigated the association of 224 metabolites with general obesity based on body mass index and with central obesity based on waist-hip ratio, and then the top obesity-associated metabolites were studied in relation to incident T2DM. RESULTS: In a combined sample of the CARRS1 and CARRS2 cohorts, out of 224 metabolites, 12 were associated with general obesity and, of these, one was associated with incident T2DM. Fifteen out of 224 metabolites were associated with central obesity and, of these, 10 were associated with incident T2DM. The higher level of total cholesterol in high-density lipoprotein (HDL) was associated with reduced T2DM risk (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.53, 0.86; P = 1.2 × 10-3 ), while higher cholesterol esters in large very-low-density lipoprotein (VLDL) particles were associated with increased T2DM risk (OR 1.90, 95% CI 1.40, 2.58; P = 3.5 × 10-5 ). CONCLUSION: Total cholesterol in HDL and cholesterol esters in large VLDL particles may be an important biomarker in the identification of early development of obesity-associated T2DM risk among South Asian adults.

State negative affect in relation to loss-of-control eating among children and adolescents in the natural environment.

Affect regulation theory proposes that loss-of-control (LOC)-eating is preceded by increases and followed by decreases in negative affect (NA), but empirical tests of this theory among pediatric samples in the natural environment are needed. Using an ecological momentary assessment approach, we conducted post-hoc analyses to examine LOC-eating severity reported during post-meal surveys in relation to the intensity of composite NA and NA components (anger, anxiety, depression, guilt) throughout the day for two weeks in a cohort of healthy children and adolescents. Multilevel models tested the associations among LOC-eating severity and NA components reported at pre-meal surveys (t-1), post-meal surveys (t), and lagged post-meal surveys (t+1). Models were adjusted for sex, age, race/ethnicity, height, fat mass, socioeconomic status, and time between the occurrence and report of eating episodes; post-meal analyses were also adjusted for pre-meal NA. Participants age 8-17 (N = 100; 55% female; 45% male; 12.83 ± 2.73y; 24% with overweight/obesity) recorded 2410 eating episodes. Pre-meal composite NA and NA components were not associated with LOC-eating severity at the subsequent meal. LOC-eating severity was positively associated with post-meal depression (ß = 0.042, 95% CI = 0.007, 0.076) and guilt (ß = 0.056, 95% CI = 0.017, 0.095), but not composite negative affect, anger, or anxiety. The positive association among LOC-eating severity and guilt persisted in lagged post-meal analyses (ß = 0.075, 95% CI = 0.021, 0.128). Contrary to affect regulation theory and laboratory data, but consistent with prior ecological momentary assessment data in children and adolescents, pre-meal NA was not linked to subsequent LOC-eating. Increased guilt following meals may be a mechanism for the development of exacerbated disordered eating. Longitudinal studies may elucidate how NA is implicated in the etiology of pediatric eating disorders.

Assessment during Covid-19: quality assurance of an online open book formative examination for undergraduate medical students.

BACKGROUND: The spread of COVID-19 pandemic in early 2020 compelled all the educational activities, including medical education to be shifted from face-to-face interaction to a virtual platform. This shift provided opportunities for exploring online assessment modalities. One such assessment method is an online open book exam which is a unique concept in medical education of Pakistan. Limited information is available in literature regarding open book exam for the basic science subjects. Hence, the objective of the study was to determine the quality of the open book exam administered as a pilot project to the first-year medical students. METHODS: It was a cross-sectional analytical study that included 99 students of first year MBBS. The students were administered an online unrestricted type of open book exam as a formative assessment. The exam consisted of 30 open-ended, short answer type questions. The scores of the exam were analyzed for psychometric quality. RESULTS: The mean score was 47.24 ± 15.30 SD %. The reliability of the exam was 0.79. The majority (66.6%) of items were found to be moderately difficult with their difficulty index ranging from 31 to 80%. The majority (86.6%) items were in the range of moderate to high discrimination. There were no questions with negative discrimination. CONCLUSIONS: The exam was found to be reliable and can be implemented with training of faculty and students. Online open book exam provides a good format for remote and formative assessment of students with minimum proctoring during times of constraints such as COVID-19 pandemic.

Relationship between Moderate-to-Vigorous Physical Activity with Health-Related Physical Fitness Indicators among Pakistani School Adolescents: Yaali-Pak Study.

Background: The current study is the foremost study exploring the relationships between moderate-to-vigorous physical activity and health-related physical fitness indicators among 12-16-year-old adolescents of the South Punjab region of Pakistan. Methods: The researcher adopted the cross-sectional research design for the study. A total of 2970 participants (1477 boys and 1493 girls) aged adolescents from South Punjab, Pakistan, completed health-related physical fitness indicators measuring strength, endurance, and aerobic capacity through a hand-grip strength test, modified pull-up test, plank test, and 20-m shuttle run test, and physical activity were subjectively assessed by International Physical Activity Questionnaire Short Form (IPAQ-SF). Linear regression models were used to explore the between moderate-to-vigorous physical activity (MVPA) with health-related physical fitness indicators. Results: Positive associations were observed between hand-grip strength (p < 0.001), modified pull-up (p < 0.001), plank exercise (p < 0.001), and 20-m shuttle run test (p < 0.001), with MVPA. The gender-specific comparison also indicated a significant (p < 0.001) and positive relationship. The results revealed that as MVPA increases, body composition, muscular strength, core muscular endurance, and aerobic capacity could improve in both genders. Conclusions: MVPA appears to be an effective and reliable predictor of health-related physical fitness among school adolescents.