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Purpose of Review South Asia is highly vulnerable to the impacts of climate change, owing to the high dependency on climate-sensitive livelihoods and recurrent extreme events. Consequently, an increasing number of households are adopting labour migration as a livelihood strategy to diversify incomes, spread risks, and meet aspirations. Under the Collaborative Adaptation Research Initiative in Africa and Asia (CARIAA) initiative, four research consortia have investigated migration patterns and their inherent linkages to adaptation to climate change in climate hotspots. This article synthesizes key findings in regional context of South Asia. Recent Findings The synthesis suggests that in climate-sensitive hotspots, migration is an important livelihood diversification strategy and a response to various risks, including climate change. Typically, one or more household members, often young men, migrated internally or internationally to work in predominantly informal sectors. Remittances helped spatially diversify household income, spread risks, and insure against external stressors. The outcomes of migration are often influenced by who moves, where to, and what capacities they possess. Summary Migration was found to help improve household adaptive capacity, albeit in a limited capacity. Migration was mainly used as a response to risk and uncertainty, but with potential to have positive adaptation co-benefits.

doi: https://doi.org/10.12669/pjms.38.8.6854 How to cite this:Sultan H, Ishaq G. Bad Touch in Childhood is associated with unexplained Gastroenteritis. Pak J Med Sci. 2022;38(8):---. doi: https://doi.org/10.12669/pjms.38.8.6854

Most of the breast cancers are estrogen receptor-positive recurring with a steady rate of up to 20 years dysregulating the normal cell cycle. Dinaciclib is still in clinical trials and considered as a research drug against such cancers targeting CDK2. The major goal of this study was to identify the potential inhibitors of CDK-2 present in Moringa oleifera for treating hormonal receptor positive breast cancers. For this purpose, in silico techniques; molecular docking, MM-GBSA and molecular dynamics simulations were employed to screen Moringa oleifera compounds and their anticancer potential was determined against CDK-2 protein targets. Among 36 compounds of Moringa oleifera reported in literature, chlorogenic acid (1), quercetin (2), ellagic acid (3), niazirin (4), and kaempferol (5) showed good affinity with the target. The interaction of the compounds was visualized using PYMOL software. The profiles of absorption, distribution, metabolism, excretion (ADME) and toxicity were determined using SWISS and ProTox II webservers. The MTT assay was performed in-vitro using MCF-7 cancer cell lines to validate the anticancer potential of Moringa oleifera leaf extract. MTT assay results revealed no significant change in proliferation of Mcf-7 cells following 24 h treatment with fraction A (petroleum ether). However, significant antiproliferative effect was observed at 200 µg/mL dose of fraction B (ethyl acetate) and cell viability was reduced to 40%. In conclusion, the data suggested that all the compounds with highest negative docking score than the reference could be the potential candidates for cyclin dependent kinase-2 (CDK-2) inhibition while ellagic acid, chlorogenic acid and quercetin being the most stable and potent inhibitors to treat estrogen receptor positive breast cancer targeting CDK-2. Moreover, the data suggested that further investigation is required to determine the optimum dose for significant antiproliferative effects using in-vivo models to validate our findings of in-silico analysis.

Background Fluctuations in pH of saliva during a prolonged treatment course influences the enamel demineralization progress, which is one of the complications of fixed orthodontic treatment. This randomized clinical trial aimed to evaluate and compare the short-term effects of stainless steel (SS) versus elastomeric (EM) ligatures on salivary pH in patients scheduled for fixed orthodontic treatment. Methods Seventy participants were enrolled in the study (54 female, 16 male) aged 19–36 years who met specific inclusion criteria. They were randomly selected and allocated into two equal groups through computer-generated randomization. All patients received fixed orthodontic treatment using conventional orthodontic brackets. Two commonly used archwire ligature methods were used: SS and EMs. An unstimulated (resting) salivary sample was collected before tying of the ligatures at T0 (baseline), 2 weeks, 6 (weeks), and 12 (weeks). Salivary pH was measured using a digital pH meter. The level of significance was set at p value < 0.05. Results The salivary pH level was stable between T0 and T1 (6.72 ± 0.14), then significantly and progressively increased from T1 to T2 (6.78 ± 0.13) and from T2 to T3 (6.81 ± 0.14) with (p < 0.05) in the SS group. In the EM group, the salivary pH level was significantly decreased in all follow-up periods; T0 (6.77 ± 0.16), T1 (6.72 ± 0.14), T2 (6.67 ± 0.13) and T3 (6.64 ± 0.13). Conclusion The EM ligatures showed a significant decrease in salivary pH to an unfavorable level, which increased the risk of enamel demineralization. Therefore, EMs as ligature material is preferably should not be recommended in patients with high caries index or inadequate oral hygiene. Trial registration ANZCTR.org. (ACTRN12618001647224) http://www.anzctr.org.au/ACTRN12618001647224.aspx . Registration Date: 5/10/2018, “Retrospectively registered”.

A new species, Allium sulaimanicum , is described from northern Balochistan and southern Khyber Pakhtunkhwa in Pakistan based on morphological, molecular, and cytological studies. The new species is characterised by long runner-like cylindrical rhizomes of adult plants, cylindrical bulbs, linear leaves with minute soft hairs along veins, campanulate perigonium, and white to creamy white, ovate to elliptical, 4.5–5-mm-long acute tepals, with brownish to purplish nerves, stamens as long as to slightly longer than tepals, yellow to brick red anthers, hexagonal ovary, and white and papillate/warty along angles. The presence of long herbaceous rhizomes indicated serious isolation of the new species; hence, a new section Sulaimanicum is proposed to accommodate the new species. The new species is diploid with a chromosome number of 2n = 16. Detailed morphological description, illustrations, phylogenetic analyses based on sequences of plastid spacers ( rpl 32- trn L (UAG) and trn Q- rps 16) and nuclear ITS, karyotype features, and a distribution map of the new species are provided.

Background The bromodomain (BRD) proteins play a pivotal role in regulating gene expression by recognizing acetylated lysine residues and acting as chromatin-associated post-translational modification-inducing proteins. Although BRD proteins have been extensively studied in mammals, they have also been characterized in plants like Arabidopsis thaliana and Oryza sativa , where they regulate stress-responsive genes related to drought, salinity, and cold. However, their roles in cotton species remain unexplored. Results In this genome-wide comparative analysis, 145 BRD genes were identified in the tetraploid species ( Gossypium hirsutum and G. barbadense ), compared with 82 BRD genes in their diploid progenitors ( G. arboreum and G. raimondii ), indicating that polyploidization significantly influenced BRD gene evolution. Gene duplication analysis revealed 78.85% of duplications were segmental and 21.15% were tandem among 104 in-paralogous gene pairs, contributing to BRD gene expansion. Gene structure, motif, and domain analyses demonstrated that most genes were intron-less and conserved throughout evolution. Syntenic analysis revealed a greater number of orthologous gene pairs in the Dt sub-genome than in the At sub-genome. The abundance of regulatory, hormonal, and defense-related cis -regulatory elements in the promoter region suggests that BRD genes play a role in both biotic and abiotic stress responses. Protein-protein interaction analysis indicated that global transcription factor group E (GTE) transcription factors regulate BRD genes. Expression analysis revealed that BRD genes are predominantly involved in ovule development, with some genes displaying specific expression patterns under heat, cold, and salt stress. Furthermore, qRT-PCR analysis demonstrated significant differential expression of BRD genes between the tolerant and sensitive genotype, underscoring their potential role in mediating drought and salinity stress responses. Conclusions This study provides valuable insights into the evolution of BRD genes across species and their roles in abiotic stress tolerance, highlighting their potential in breeding programs to develop drought and salinity tolerant cotton varieties.

BackgroundPrimary Biliary Cholangitis (PBC) is a rare autoimmune liver disease that causes liver inflammation and damage, potentially leading to cirrhosis and liver failure. Ursodeoxycholic acid (UDCA) is the standard treatment, but up to 40% of patients are non-responders. Due to the limited treatment options, there is a need to explore alternative therapies. This study evaluates the efficacy and safety of PPAR agonists for PBC management.MethodsA systematic review and meta-analysis were performed, including eight randomized controlled trials (RCTs) evaluating selective PPAR agonists (fenofibrate, seladelpar) and multi-subtype PPAR agonists (bezafibrate, saroglitazar, elafibranor). The primary outcome was alkaline phosphatase (ALP), while secondary outcomes included GGT, ALT, AST, total bilirubin (TBil), triglycerides (Tg), and pruritus. Subgroup analyses were conducted based on the type of PPAR agonists used in the trials.ResultsThe analysis revealed that PPAR agonists significantly reduced ALP levels compared to placebo (SMD = -0.66, p = 0.0005), indicating a notable improvement in liver function. Similarly, there was a significant reduction in GGT levels (SMD = -0.45, p = 0.02), which is a marker of liver injury and cholestasis. The overall reduction in total bilirubin (TBil) was also significant (SMD = -0.77, p = 0.006), suggesting improved biliary function. Triglyceride levels showed a significant decrease with PPAR agonists (MD = -0.99, p = 0.003), consistent with the lipid-regulating effects of PPAR activation. However, no significant changes were found for ALT (p = 0.07) or AST (p = 0.99), indicating that PPAR agonists may not significantly impact these liver enzymes in PBC. Subgroup analysis demonstrated that both selective PPAR agonists (such as fenofibrate and seladelpar) and multi-subtype PPAR agonists (like bezafibrate and elafibranor) led to significant reductions in ALP and GGT compared to placebo. Interestingly, selective PPAR agonists exhibited minimal heterogeneity for TBil levels (I² = 0%), while multi-subtype agonists maintained high heterogeneity. The analysis of pruritus found no significant difference between PPAR agonists and placebo (p = 0.6), despite some trials reporting variable effects on pruritus severity.Abstract P219 Figure 1Forest plot of change in ALP levels from baseline[Figure omitted. See PDF]ConclusionPPAR agonists are effective in reducing key biochemical markers of liver dysfunction in PBC, particularly ALP, GGT, TBil, and triglycerides. However, their effect on ALT, AST, and pruritus remains limited. Further studies with larger sample sizes and longer durations are required to fully explore the therapeutic potential of PPAR agonists in managing PBC.

BackgroundChronic Hepatitis B (CHB) is a global health concern, with significant risks of liver-related complications and mortality. Antiviral treatments such as Tenofovir Disoproxil Fumarate (TDF) and Tenofovir Alafenamide (TAF) are commonly used for HBV suppression. TAF is a newer formulation designed to offer similar efficacy to TDF while improving safety profiles, especially in terms of bone and renal health. This meta-analysis aimed to compare the efficacy and safety of TAF and TDF in treating CHB.MethodsA systematic literature search was conducted in August 2023, focusing on randomised controlled trials (RCTs) comparing TAF and TDF for the treatment of CHB. Four RCTs involving 1,960 patients were included. The primary outcome was the proportion of patients achieving HBV DNA suppression to levels <15-29 IU/ml. Secondary outcomes included ALT normalisation, changes in bone mineral density (BMD), serum creatinine levels, estimated glomerular filtration rate (eGFR), and LDL cholesterol levels. Pooled data were analysed using relative risk (RR) and mean difference (MD) with 95% confidence intervals (CIs).Abstract O31 Figure 1Effect of TAF compared to TDF on virological suppression[Figure omitted. See PDF]ResultsPrimary Outcome: Both TAF and TDF demonstrated similar efficacy in achieving virological suppression, with no significant difference in HBV DNA reduction (RR=1.00; 95% CI 0.96 to 1.05; p=0.82).Secondary Outcomes:ALT Normalisation: TAF was more effective in achieving ALT normalisation (RR=1.38; 95% CI 1.16 to 1.64; p=0.0002).Bone Mineral Density (BMD): TAF showed significantly less reduction in hip (MD=1.44; 95% CI 0.98 to 1.91; p<0.00001) and spine BMD (MD=1.93; 95% CI 1.42 to 2.44; p<0.00001).Kidney Function: TAF caused less elevation in serum creatinine (MD=-0.02; 95% CI -0.03 to -0.01; p<0.00001) and less decline in eGFR (MD=3.55; 95% CI 2.97 to 4.14; p<0.0001).LDL Cholesterol: TAF was associated with higher LDL cholesterol levels compared to TDF (RR=4.95; 95% CI 1.21 to 20.29; p=0.03).ConclusionTAF demonstrated comparable efficacy to TDF in HBV DNA suppression but showed superior outcomes in terms of ALT normalisation, bone mineral density preservation, and kidney function. However, TAF led to higher LDL cholesterol levels, which may require monitoring. These findings suggest that TAF could be a safer alternative to TDF for CHB patients, particularly in those at risk for bone and renal complications. Further long-term studies are needed to confirm these results, particularly in special populations.

Primary biliary cholangitis (PBC), an autoimmune liver disease, has the potential to advance to liver cirrhosis and result in fatality. Ursodeoxycholic acid (UDCA) is the first-line treatment, while obeticholic acid (OCA) serves as a second-line option because of moderate UDCA nonresponsiveness and cirrhosis-related concerns. Additional therapies are necessary because of recent warnings regarding OCA usage in patients with cirrhosis. This study aimed to evaluate the efficacy and safety of peroxisome proliferator-activated receptor (PPAR) agonists in PBC. We searched PubMed, Google Scholar, and the Cochrane Library until October 2023. We included all randomized controlled trials (RCTs) that studied the efficacy and safety of PPAR agonists in treating PBC. The primary outcome of interest was change in alkaline phosphatase (ALP) levels. In contrast, the secondary outcomes were changes in gamma-glutamyl transferase (GGT), alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), triglyceride levels, and pruritis. We used a random-effects model to calculate the risk ratio (RR) and standardized mean difference (SMD) with 95% CI. A total of eight RCTs ( = 515) were eligible for the analysis. Pooled data showed beneficial effects of PPAR agonists compared with placebo for change in ALP level (SMD = -2.81, 95%CI = -4.10 to - 1.51; < 0.0001, I = 96%), GGT level (SMD = -1.29, 95%CI = -2.09 to - 0.48; = 0.002, I = 92%), TBil level (SMD = -0.77, 95%CI = -1.32 to - 0.22; = 0.006, I = 86%), and Tg level (SMD = -0.99, 95%CI = -1.63 to - 0.35; = 0.003, I = 83%). There was no significant difference between PPAR agonists and placebo for ALT level (SMD = -0.93, 95%CI = -1.94 to 0.08; = 0.07, I = 95%), AST level (SMD = -0.01, 95%CI = -0.67 to 0.66; = 0.99, I = 91%), and pruritus (RR = 0.77, 95%CI = 0.29 to 2.06; = 0.60, I = 34%). Our study found a superior efficacy of PPAR agonists compared with placebo for change in ALP, GGT, TBil, and Tg levels, highlighting the potentially beneficial effect of PPAR agonists on liver health.

Solanum rostratum Dunal is native to the United States of America and northern and central Mexico. Solanum rostratum has been observed in various localities in Zhob district of northern part of Balochistan Province of Pakistan. These observations represent first record of this species from Balochistan or Pakistan. Its description and illustrations are provided for easy identification.