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Background. Hyperpigmentation is a common side effect of different drugs with many of these having a well-explained mechanism and some even having a characteristic distribution. However, it is a rare side effect of sertraline, a selective serotonin reuptake inhibitor (SSRI), with only a few reported cases. In addition, there are no specific characteristics of the lesions or the risk factors. Case Summary. This is a case report of a 24-year-old male with panic disorder, who developed hyperpigmentation over the face after 5 days of increasing the dosage of sertraline to 100 mg/day. There were no other significant findings from the physical examination or investigations. The patient was treated as a case of sertraline-induced hyperpigmentation, and the dose was reduced to 75 mg/day and maintained at 50 mg/day after 1 week along with tablet propranolol 20 mg/day. He was also prescribed tablet tranexamic acid 500 mg/day and sunscreen with sun protection factor 50. The hyperpigmentation disappeared within 2 months, and the medication was gradually tapered after 7 months of treatment. Conclusion. Hyperpigmentation is a rare but distressing side effect of sertraline. It is a potentially curable side effect if recognized early. Early recognition and intervention can decrease unnecessary investigations and treatment. There are limited studies highlighting this unusual adverse effect of this commonly used SSRI. Hence, further studies are needed to better understand various aspects of this condition including the characteristics, patients at risk, and possible management. The development of diagnostic and treatment guidelines would decrease the dilemma of identification and management.

This study is the first time to perform molecular characterization in indigenous chickens, Sakini, of Nepal for studying genetic diversity and its relationship with its assumed progenitors. The first 522 nucleotides of hypervariable I (HVI) segment of the D-loop from 33 individuals were PCR amplified and subsequently sequenced. Fourteen haplotypes out of 33 sequences were identified from 20 polymorphic sites. Haplotype (gene) diversity (Hd) is 0.813 with SD 0.065 and nucleotide diversity (Pi) is 0.00525 with SD 0.00091. The neighbour joining tree indicated that Red Jungle Fowl from India is the progenitor of the Nepalese Sakini chicken. NETWORK analysis revealed that it can be grouped into four distinct Haplogroups (A1, E1, E2, and E3) respectively. Seventeen individuals belonged to E1, eight to E3, seven to E2, and one to A1. The high mitochondrial D-loop diversity in Nepalese Sakini chicken with multiple maternal origins serves the scientific basis for the development of rational policies supporting conservation efforts and provides directions for future research for developing sustainable genetic improvement approaches.

Type 1 cGMP-dependent protein kinases (PKGs) play important roles in human cardiovascular physiology, regulating vascular tone and smooth-muscle cell phenotype. A mutation in the human PRKG1 gene encoding cGMP-dependent protein kinase 1 (PKG1) leads to thoracic aortic aneurysms and dissections. The mutation causes an arginine-to-glutamine (RQ) substitution within the first cGMP-binding pocket in PKG1. This substitution disrupts cGMP binding to the pocket, but it also unexpectedly causes PKG1 to have high activity in the absence of cGMP via an unknown mechanism. Here, we identified the molecular mechanism whereby the RQ mutation increases basal kinase activity in the human PKG1α and PKG1β isoforms. Although we found that the RQ substitution (R177Q in PKG1α and R192Q in PKG1β) increases PKG1α and PKG1β autophosphorylation in vitro, we did not detect increased autophosphorylation of the PKG1α or PKG1β RQ variant isolated from transiently transfected 293T cells, indicating that increased basal activity of the RQ variants in cells was not driven by PKG1 autophosphorylation. Replacement of Arg-177 in PKG1α with alanine or methionine also increased basal activity. PKG1 exists as a parallel homodimer linked by an N-terminal leucine zipper, and we show that the WT chain in WT-RQ heterodimers partly reduces basal activity of the RQ chain. Using hydrogen/deuterium-exchange MS, we found that the RQ substitution causes PKG1β to adopt an active conformation in the absence of cGMP, similar to that of cGMP-bound WT enzyme. We conclude that the RQ substitution in PKG1 increases its basal activity by disrupting the formation of an inactive conformation.

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have enormous potential for the study of human cardiac disorders. However, their physiological immaturity severely limits their utility as a model system and their adoption for drug discovery. Here, we describe maturation media designed to provide oxidative substrates adapted to the metabolic needs of human iPSC (hiPSC)-CMs. Compared with conventionally cultured hiPSC-CMs, metabolically matured hiPSC-CMs contract with greater force and show an increased reliance on cardiac sodium (Na+) channels and sarcoplasmic reticulum calcium (Ca2+) cycling. The media enhance the function, long-term survival, and sarcomere structures in engineered heart tissues. Use of the maturation media made it possible to reliably model two genetic cardiac diseases: long QT syndrome type 3 due to a mutation in the cardiac Na+ channel SCN5A and dilated cardiomyopathy due to a mutation in the RNA splicing factor RBM20. The maturation media should increase the fidelity of hiPSC-CMs as disease models.

Climate change phenomena, such as droughts, floods, heat waves, hurricanes, and wildfires, have a deleterious effect on nature and the health of the people, especially on vulnerable population cohorts, such as persons with disabilities (PwD). PwD are disproportionately affected by the health effects of climate change and experience a greater burden due to various physiological, socio-economic and health-related factors. Rehabilitation professionals as trusted care providers/educators have an integral role in global efforts to educate, advocate and protect vulnerable people from the adverse impact of climate change. They are in a distinctive position as they are experts in understanding the complex medical, physiological and psychosocial needs of PwD. Although the impact of climate change on health is widely documented, the literature on the effect of climatic factors on PwD is sparse. Further, specific rehabilitation and disability-inclusive climate action plans are yet to be developed and/or implemented globally. As the climate-change-related health burdens continue to grow the critical importance of rehabilitation services is apparent. The challenge ahead is to build a structured people-centered approach to building rehabilitation-inclusive climate-resilient health systems to improve the adaptive capacity and resilience of the most susceptible people with distinct healthcare needs.

Introduction: The world has faced a disastrous period at the time of the pandemic of corona virus- 19. The education system was hampered along with all the sectors of life and therefore, it was realized that a switch from the conventional way of teaching to online teaching is needed. The current study was done to analyze the impact of the COVID-19 lockdown on the academic performance of medical students at Gandaki medical college of Pokhara, Nepal. Methods: It was a descriptive study of the first and second-year medical students of Gandaki Medical College. The Likert scale was used to measure the effect of the COVID-19 lockdown on academic performance and to evaluate online education. A census sampling technique was used to collect the data. Results: A total of 171 participants answered the questionnaire with a response rate of 87%. The data showed that covid-19 lockdown affected the academic performance of most participants of 98.2% with varying degrees. The mean evaluation score for online theory education was 4.7±2.06 while for the practical lessons was 2.06±1.4. Conclusions: COVID-19 pandemic lockdown affected the academic performance of most participants to varying degrees. The academic performance of medical students with the online teaching method is effective during COVID-19 lockdown.

Objective: Pediatric burn injuries are common injuries that are traumatic for the child and their families. Although many families report high amounts of distress soon after injury, most are resilient and do not continue to experience prolonged psychosocial problems. The aim was to identify factors associated with parent resilience after pediatric burn injury. Method: Fifty-seven parents of young children (< 5 years old) enrolled in a longitudinal assessment study. Baseline evaluations were conducted within 1 week of injury and included a medical chart review and parent self-report measures of resilience, social support, family functioning, and coping. Follow-up measurement of parent traumatic stress was measured 3 months after injury. We examined baseline resilience, positive emotionality, social support, family functioning, and problem-solving coping behaviors for relationships to traumatic stress. Results: Parent resilience at baseline was associated with lower rates of parent traumatic stress symptoms at follow-up. Lower rates of traumatic stress were more common in parents of older children with more trait-level resilience, more social support, and more planning problem-solving behaviors at baseline. Conclusions: Baseline resilience characteristics are associated with less traumatic stress for parents several months after the injury. Findings can be used to develop screening strategies and interventions that address planning and problem-solving and emphasize social support. Public Significance Statement Many children are injured every year, but only some families go on to have long lasting emotional concerns. This article aimed to explore family resilience after their young child experiences an unintentional burn injury. Findings that parents with more resilience, more social support, and more planning problem-solving behaviors at the time of injury experience better mental health outcomes can inform assessment and intervention strategies. Keywords: injuries, trauma, child, preschool, parents This article was published Online First May 12, 2022., In young children, pediatric burn injuries are among the top 10 leading causes of unintentional injury treated in United States emergency departments (National Electronic Injury Surveillance System All Injury Program, [...]

Immature teratoma is one of the rare malignant germ cell tumours presented in pregnancy. Here, we present 26-year-old pregnant women who had an incidental finding of left adnexal mass in an anomaly scan at 19 weeks of pregnancy. Laparotomy with peritoneal fluid cytology, left salpingo-oophorectomy and omental biopsy at 20 weeks of pregnancy revealed immature teratoma stage 1A, grade 2 in the histopathology report. However, she followed up with the metastatic mass in the pouch of Douglas at 30 weeks of pregnancy in magnetic resonance imaging despite being counselled for possible chemotherapy and surveillance. A baby with a good Apgar score and grade 3 immature teratoma in the metastatic mass was revealed following the exploratory laparotomy and cesarean section at 36 weeks of pregnancy. Fertility-sparing surgery with chemotherapy during pregnancy for high-grade tumours may result in a good prognosis.

Introduction: Cervical cancer is one of the leading causes of morbidity and mortality among women globally as well as in Nepal. It is attributable to persistent infection by high-risk human papillomavirus, especially human papillomavirus-16 and human papillomavirus-18. The aim of this study was to find out the knowledge of cervical cancer screening and prevention by human papillomavirus deoxyribonucleic acid and human papillomavirus vaccination among women attending a tertiary care centre. Methods: A descriptive cross-sectional study was conducted in patients attending the outpatient Department of Gynaecology in a tertiary care centre from 18 March to 30 April 2023. After calculating sample size and taking a convenience sampling a survey questionnaire on knowledge of Cervical Cancer Screening and Prevention by Human Papillomavirus Deoxyribonucleic Acid and Human Papillomavirus Vaccination was collected. The point estimate was calculated at a 95% confidence interval. Results: Among 508 women, 42 (8.25%) (5.86-10.64, 95% Confidence Interval) had knowledge of cervical cancer screening and prevention by human papillomavirus deoxyribonucleic acid and human papillomavirus vaccination. According to the questionnaires with a total sample of 508, 164 (32.28%) know about cervical cancer, 15 (2.95%) know about HPV infection, 14 (2.76%) know about HPV infection causes cervical cancer, and 21 (4.13%) know about HPV transmitted through multiple sex partners. Conclusions: The knowledge of cervical cancer screening and prevention by human papillomavirus deoxyribonucleic acid and human papillomavirus vaccination among women is very low. This study recommends having a health education and awareness programme on it to increase knowledge.

Hydrology and meteorological data from relatively undisturbed watersheds aid in identifying effects on ecosystem services, tracking hydroclimatic trends, and reducing model uncertainties. Sustainable forest, water, and infrastructure management depends on assessing the impacts of extreme events and land use change on flooding, droughts, and biogeochemical processes. For example, global climate models predict more frequent high-intensity storms and longer dry periods for the southeastern USA. We summarized 17 years (2005–2021) of hydrometeorological data recorded in the 52 km2, third-order Turkey Creek watershed at the Santee Experimental Forest (SEF), Southeastern Coastal Plain, USA. This is a non-tidal headwater system of the Charleston Harbor estuary. The study period included a wide range of weather conditions; annual precipitation (P) and potential evapotranspiration (PET) ranged from 994 mm and 1212 mm in 2007 to 2243 mm and 1063 in 2015, respectively. The annual runoff coefficient (ROC) varied from 0.09 in 2007 (with water table (WT) as deep as 2.4 m below surface) to 0.52 in 2015 (with frequently ponded WT conditions), with an average of 0.22. Although the average P (1470 mm) was 11% higher than the historic 1964–1976 average (1320 mm), no significant (α= 0.05) trend was found in the annual P (p = 0.11), ROC (p = 0.17) or runoff (p = 0.27). Runoff occurred on 76.4% of all days in the study period, exceeding 20 mm/day for 1.25% of all days, mostly due to intense storms in the summer and lower ET demand in the winter. No-flow conditions were common during most of the summer growing season. WT recharge occurred during water-surplus conditions, and storm-event base flow contributed 23–47% of the total runoff as estimated using a hydrograph separation method. Storm-event peak discharge in the Turkey Creek was dominated by shallow subsurface runoff and was correlated with 48 h precipitation totals. Estimated precipitation intensity–duration–frequency and flood frequency relationships were found to be larger than those found by NOAA for the 1893–2002 period (for durations ≥ 3 h), and by USGS regional frequencies (for ≥10-year return intervals), respectively, for the same location. We recommend an integrated analysis of these data together with available water quality data to (1) assess the impacts of rising tides on the hydroperiod and biogeochemical processes in riparian forests of the estuary headwaters, (2) validate rainfall–runoff models including watershed scale models to assess land use and climate change on hydrology and water quality, and (3) inform watershed restoration goals, strategies, and infrastructure design in coastal watersheds.

Background: Hepatitis E virus (HEV) causes acute jaundice and poses an important public health problem in low- and middle-income countries. Limited surveillance capacity and suboptimal access to diagnostics leads to under-reporting of HEV infections in affected countries, including Nepal. Serum antibodies against HEV are indicative of past infection. We analyzed existing samples from a nationally representative serosurvey to describe the geospatial distribution and factors associated with HEV seroprevalence in Nepal, as a proxy for infection. Methodology/Principle findings: A nationally representative cross-sectional serosurvey of 3,922 individuals ≥2 years old from 975 households spread across 65 wards throughout Nepal was conducted between November 2021 and January 2022. Bio-banked samples were tested for anti-HEV IgG. Seroprevalence and its 95% confidence interval were estimated by age, sex, ecological region, municipality type, and other waterborne-disease related risk factors. Bayesian geostatistical models were fitted to observed seroprevalence data and used to generate high-resolution maps of seroprevalence across Nepal. Available samples from 3,707 participants were tested for anti-HEV IgG, and 3,703 were used for final analysis. We found 20.8% (95% CI: 19.5–22.2) of participants had evidence of prior HEV infection. HEV seroprevalence increased with age, and was higher in males (23.5%, 95% CI: 21.5–25.5) than in females (18.6%, 95% CI: 16.9–20.3). Seroprevalence in hilly (28.9%, 95% CI: 26.6–31.2) and mountain (24.6%, 95% CI: 18.8–30.5) regions were significantly higher than in terai (14.2%, 95% CI: 12.7–15.8). While there was no significant difference between urban and rural populations, the predicted seroprevalence was highest in Kathmandu, the capital of Nepal, reaching seroprevalence of 50% in some selected area. No statistically significant differences were found for wealth quintile, water source, and toilet facility. Conclusions: This study provides population-based serologic evidence that HEV is endemic in Nepal, with the greatest risk of infection in Kathmandu. Author summary: Hepatitis E virus spreads through fecal to oral transmission, primarily via contaminated water. The virus can impair liver function and causes frequent outbreaks of acute jaundice in Nepal. Diagnostic tests are often not accessible, meaning many cases of hepatitis E go undetected and it is difficult to know how many people are affected or where to target interventions to protect those most at risk. However, infections can be detected retrospectively by looking for long-lasting antibodies produced by the body in response to the virus. We looked for these antibodies in blood specimens collected from a population representative sample of individuals across Nepal and found that, overall, around 1 in 5 people had likely been infected previously. Risk of past infection varied across the three ecological regions of Nepal and was higher in Hilly and Mountain regions than in the southern Terai. We fitted a geospatial model to our data to map the predicted risk across the country and found it to be highest in Kathmandu, with up to half the population previously infected. This research demonstrates the scale of hepatitis E virus infections in Nepal and identified parts of the Hilly region–particularly Kathmandu–as areas where people are most at risk. [ABSTRACT FROM AUTHOR]

Purpose: To systematically evaluate evidence from published systematic reviews for the effectiveness of rehabilitation interventions in adults with burn injury. Materials and methods: A comprehensive literature review conducted using medical and health science electronic databases up to 31 July 2022. Two independent reviewers selected studies, extracted data, and assessed methodological study quality using A Measurement Tool to Assess Systematic Reviews (AMSTAR-2), and the certainty of evidence for reported outcomes using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool. Results: Twenty-one systematic reviews evaluated five categories of interventions: physical, psychological, technology-aided modalities, educational and occupational programs, complementary and alternative medicine. Outcomes included fitness level, hand function, oedema, pain, pruritus, psychological state, quality of life, range of motion, return to work, strength, scar characteristics, level of impairment and burn knowledge. The methodological quality was rated as "critically low" for all reviews. Quality of evidence for the effectiveness of evaluated interventions ranged from "moderate to very low." Conclusions: Beneficial effects of inhaled aromatherapy and extracorporeal shockwave therapy on pain reduction; inhaled or massage aromatherapy, music therapy on anxiety were reported. Safety of interventions was not evaluated, due to the lack of adverse event reporting in primary studies and the included reviews. IMPLICATIONS FOR REHABILITATION: Burn injury is a leading cause of severe morbidity, and long-term disability, with significant health and economic burden. There is emerging evidence to support the use of complementary and alternative medicine interventions (such as aromatherapy and music therapy) for alleviating anxiety. Extracorporeal shockwave therapy with comprehensive rehabilitation therapy has positive effects on pain reduction. These interventions may be considered as adjunctive tools to enhance burn rehabilitation care and improve patient outcomes. However, further robust studies are required to strengthen the evidence, explore adverse effects and associated cost efficiency. [ABSTRACT FROM AUTHOR]

The development of computational models for studying mental disorders is on the rise. However, their psychometric properties remain understudied, posing a risk of undermining their use in empirical research and clinical translation. Here we investigated test-retest reliability (with a 2-week interval) of a computational assay probing advice-taking under volatility with a Hierarchical Gaussian Filter (HGF) model. In a sample of 39 healthy participants, we found the computational measures to have largely poor reliability (intra-class correlation coefficient or ICC < 0.5), on par with the behavioral measures of task performance. Further analysis revealed that reliability was substantially impacted by intrinsic measurement noise (indicated by parameter recovery analysis) and to a smaller extent by practice effects. However, a large portion of within-subject variance remained unexplained and may be attributable to state-like fluctuations. Despite the poor test-retest reliability, we found the assay to have face validity at the group level. Overall, our work highlights that the different sources of variance affecting test-retest reliability need to be studied in greater detail. A better understanding of these sources would facilitate the design of more psychometrically sound assays, which would improve the quality of future research and increase the probability of clinical translation. [ABSTRACT FROM AUTHOR]

Forests are recognized for sustaining good water chemistry within landscapes. This study focuses on the water chemistry parameters and their hydrological predictability and seasonality (as a component of predictability) in watersheds of varying scales, with and without human (forest management) activities on them, using Colwell indicators for data collected during 2011–2019. The research was conducted in three forested watersheds located at the US Forest Service Santee Experimental Forest in South Carolina USA. The analysis revealed statistically significant (α = 0.05) differences between seasons for stream flow, water table elevation (WTE), and all water chemistry indicators in the examined watersheds for the post-Hurricane Joaquin period (2015–2019), compared to the 2011–2014 period. WTE and flow were identified as having the greatest influence on nitrogen concentrations. During extreme precipitations events, such as hurricanes or tropical storms, increases in WTE and flow led to a decrease in the concentrations of total dissolved nitrogen (TDN), NH4-N, and NO3-N+NO2-N, likely due to dilution. Colwell indicators demonstrated higher predictability (P) for most hydrologic and water chemistry indicators in the 2011–2014 period compared to 2015–2019, indicating an increase in the seasonality component compared to constancy (C), with a larger decrease in C/P for 2015–2019 compared to 2011–2014. The analysis further highlighted the influence of extreme hydrometeorological events on the changing predictability of hydrology and water chemistry indicators in forested streams. The results demonstrate the influence of hurricanes on hydrological behavior in forested watersheds and, thus, the seasonality and predictability of water chemistry variables within and emanating out of the watershed, potentially influencing the downstream ecosystem. The findings of this study can inform forest watershed management in response to natural or anthropogenic disturbances. [ABSTRACT FROM AUTHOR]