Current Clinical Profile of Acute Rheumatic Fever and Recurrent Acute Rheumatic Fever in Pakistan.

Inclusion of echocardiography as diagnostic tool and polyarthralgia and monoarthritis as major criteria for high-risk populations in the Revised Jones Criteria 2015 is likely to surface substantial variability in clinical manifestations among various populations. This study aimed to compare clinical profile of patients presenting with first and recurrent episodes of acute rheumatic fever (ARF) using most recent criteria. 130 consecutive patients with ARF were included in the study from August 2019 to March 2022. World Heart Federation standardized echocardiographic criteria were used for cardiac evaluation. The socio-demographic variables, clinical details and relevant investigations were recorded. Median age was 13(6-26) years. Male to female ratio was 1.6:1. Majority was of low socioeconomic status (90%) and with > 5 family members in a house (83.8%). 27 patients (20.8%) were with ARF while 103 (79.2%) with recurrent ARF. Carditis was the most common presenting feature (n = 122, 93.8%), followed by polyarthralgia (n = 46, 35.4%), polyarthritis (n = 32, 24.6%), subcutaneous nodules (n = 10, 7.7%), monoarthritis (n = 10, 7.7%), and chorea (n = 5, 3.8%). Monoarthralgia was more common in ARF than recurrence (29.4% vs. 3.2%, p = 0.004). Carditis (97.1% vs. 81.5%, p = 0.01) and congestive cardiac failure (18.5% vs. 5.9%, p = 0.001) were more common in recurrent ARF than ARF. Diagnostic categorization of Jones criteria for different populations has highlighted important variability in clinical presentation of ARF. Monoarthralgia is common in first episode of ARF. Carditis is the most common feature in recurrent ARF. Polyarthralgia is seen with higher frequency that polyarthritis. Subcutaneous nodules seem to be more common in our population.

Maternal and environmental Impact assessment on Neurodevelopment in Early childhood years (MINE): a prospective cohort study protocol from a low, middle-income country.

INTRODUCTION: Environmental and psychosocial adversities negatively impact children's developmental outcomes. When these factors are experienced in early childhood-a sensitive period of development-the developing brain can be altered. While these associations have been drawn in high-income countries, it is necessary to understand child growth, neurodevelopment, and the role of environmental factors in developmental trajectories in low-income settings. The objective of this study is to longitudinally assess how demographic factors, maternal health, maternal development, and child health, are related to child development on a behavioural, cognitive, and neuroimaging level in low-socioeconomic communities. METHODS AND ANALYSIS: Mother-child dyads will be identified in the peri-urban field sites of Rehri Goth and Ibrahim Hyderi, Karachi, Pakistan. Dyads will undergo yearly assessments for 4 years beginning when the child is 1 month, 3 months or 6 months of age (+≤30 days of age) (depending on group assignment). Maternal assessments include anthropometry, behavioural, cognitive, and developmental assessments (Edinburgh Postnatal Depression Scale; Parenting Stress Index; Maternal Autonomy Index; Hurt, Insult, Threaten, Scream Tool; Reynolds Intellectual Assessment Scales (RIAS)), and biological samples collection (breast milk, blood, stool, hair). Children's assessments include anthropometry, developmental assessments (Global Scales for Early Development (GSED); RIAS), MRI brain assessments, and biological sample collection (blood, stool, hair). Using cross-sectional and longitudinal data with statistical analysis tools, associations will be quantified between brain structure (MRI) and connectivity (resting state connectivity and diffusion tensor imaging), general cognitive skills (RIAS, GSED) and environmental influences (nutrition via biological samples, maternal mental health via questionnaires) through repeated measures analysis of variance tests and χ2 tests. Quantile regression and cortical analyses will be conducted to understand how demographic factors are related to the associations found. ETHICS AND DISSEMINATION: The study has received ethical approval from the Aga Khan University Ethics Review Committee. The study's findings will be disseminated through scientific publications and project summaries for the participants.

Expanding the Horizon of Bio-Inspired Catalyst Design with Tactical Incorporation of Drug Molecules.

The development of potent H2 production catalysts is a key aspect in our journey toward the establishment of a sustainable carbon-neutral power infrastructure. Hydrogenase enzymes provide the blueprint for designing efficient catalysts by the rational combination of central metal core and protein scaffold-based outer coordination sphere (OCS). Traditionally, a biomimetic catalyst is crafted by including natural amino acids as OCS features around a synthetic metal motif to functionally imitate the metalloenzyme activity. Here, we have pursued an unconventional approach and implanted two distinct drug molecules (isoniazid and nicotine hydrazide) at the axial position of a cobalt core to create a new genre of synthetic catalysts. The resultant cobalt complexes are active for both electrocatalytic and photocatalytic H2 production in near-neutral water, where they significantly enhance the catalytic performance of the unfunctionalized parent cobalt complex. The drug molecules showcased a dual effect as they influence the catalytic HER by improving the surrounding proton relay along and exerting subtle electronic effects. The isoniazid-ligated catalyst C1 outperformed the nicotine hydrazide-bound complex C2, as it produced H2 from water (pH 6.0) at a rate of 3960 s-1 while exhibiting Faradaic efficiency of about 90 %. This strategy opens up newer avenues of bio-inspired catalyst design beyond amino acid-based OCS features.

COVID-19 stress and wellbeing: A phenomenological qualitative study of Pakistani Medical Doctors.

The COVID-19 stress and increased job pressure have largely affected healthcare professionals' various life domains. This study particularly explores the effect of stress caused by treating COVID-19 patients on medical doctors' wellbeing. To explore this phenomenon, we interviewed 12 doctors treating COVID-19 patients in hospitals of metropolitan cities in Pakistan. The thematic analysis using NVivo V.12 Plus software of interviews resulted in four major themes, COVID-19 Stressors, Effects of Stress, Nature and Personality, Stress Relievers, and Stress Coping Strategies. Physicians were physically and emotionally stressed as a result of the intense work. Although they were carrying a lot of pain and hurt on their insides, participants demonstrated a sense of professional determination to overcome obstacles. Physicians are currently dealing with their emotional issues, and they should have access to complete professional help to ensure their wellbeing. The COVID-19 pandemic's mental health effects are anticipated to last far longer than the physical health effects. This study is well-positioned to investigate frontline physicians' opinions and attitudes concerning the COVID-19 and its impact on their daily lives and mental health. This research will help implement context-specific innovative mental health solutions to help the frontline workers.

Angiogenic potential and wound healing efficacy of chitosan derived hydrogels at varied concentrations of APTES in chick and mouse models.

Chitosan (Cs) based biomaterials seem to be indispensable for neovasculogenesis and angiogenesis that ensure accelerated wound healing. Cs/poly (vinyl alcohol) (PVA) bio-constructs were cross-linked and investigated with varying concentrations of aminopropyltriethoxysilane (APTES). This study comprised of three phases: fabrication of hydrogels, characterization, assessment of angiogenic potential along with toxico-pathological effects, wound healing efficacy in chick and mice, respectively. The hydrogels were characterized by FTIR, SEM and TGA and the swelling response was examined in different solvents. The hydrogels swelling ratio was decreased with increasing amount of APTES, showed the highest swelling at acidic and basic pH while low swelling at neutral pH. Chorioallantoic membranes (CAM) assay was performed to study in-vivo angiogenesis, toxicological, morphological, biochemical and histological analyses in developing chicks. The results showed remarkably improved angiogenesis with little deviations in morphological, histological features and liver enzymes of chick embryos at higher concentrations of APTES. Besides, full thickness wounds were excised on mice dorsolateral skin to assess the wound healing. The rate of wound size reduction was significantly higher after topical application of hydrogels with elevated levels of crosslinker. Hence, the hydrogels showed enhanced angiogenesis, accelerated wound healing with little or no observable in-vivo toxicity.

CD4+CD25(hi) regulatory T cells in healthy males and females mediate gender difference in the prevalence of autoimmune diseases.

BACKGROUND: It is generally acknowledged that autoimmune diseases are more prevalent in females worldwide. These diseases are caused by interaction of genetic and environmental factors that result in the failure of immune mechanisms responsible for self-tolerance. One of these mechanisms includes regulatory T cells which play an essential role in maintaining peripheral tolerance. These cells are a subset of CD4+ helper T cells which express high levels of CD25 on their surface. These cells suppress cells of both innate and adaptive immune systems in an antigen nonspecific manner through cell-cell contact and production of cytokines. As females have a higher incidence of autoimmune diseases and regulatory T cells play a crucial role in preventing autoimmunity, it was reasonable to hypothesize that the females might have a lower number of T(reg) as compared to males. METHODS: 50 apparently healthy males and 47 females aged 19 - 26 years were recruited for the study. The percentage of regulatory T cells in their peripheral blood was determined using flow cytometery. Mann Whitney rank sum test was applied to estimate the significance of gender related difference in their frequency. RESULTS: Significant difference was observed in regulatory T cells percentages of males and females, p < 0.02 showing that there is a lower regulatory T cell percentage in females than in males (2.89 +/- 1.46% vs. 3.32 +/- 1.39%). CONCLUSIONS: This study shows a significant difference in the frequency of regulatory T cells among males and females which could be one of the reasons for increased predisposition of females to autoimmune diseases.