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Planning adaptation strategies in response to climate change (CC) can be a daunting task, especially in regions such as the Koshi Basin in the Himalayas, where CC impacts are still uncertain. This paper recommends targeting adaptation strategies by focusing on changes in variability between the past and future climates at smaller scales. The Soil and Water Assessment Tool (SWAT) and the Indicators of Hydrologic Alteration (IHA) are used for analysis. The results show: (a) higher maximum precipitation during monsoon and post-monsoon, and lower maximum precipitation during winter; (b) increase in precipitation and flows in the Trans-mountain region during all seasons, except for flows during monsoon; (c) increase in post-monsoon precipitation and routed flow volumes; (d) decrease in precipitation during winter and routed flow volumes in all the regions, except the Trans-mountain region; and (e) increase in frequency of high peak flows and decrease in baseflows.Editor Z.W. Kundzewicz Associate editor S. Kanae; [ABSTRACT FROM AUTHOR]

Aims: This study was done to analyze the cases of obstetric hysterectomy and maternal complications and survival after that. Methods: A retrospective study was carried out from the review of records of the near miss, maternal mortality, cesarean audit and operation theater record of the Department of Obstetrics and Gynaecology, Tribhuvan University Teaching Hospital (TUTH), Kathmandu from 2057-2071 BS. Results: Fourteen maternal survival resulted following total of 19 obstetric hysterectomy, subtotal hysterectomy being the procedure of choice in 11 cases, emergency peripartum hysterectomy (EPH) being performed in abundance (18/19) in comparison to an elective peripartum hysterectomy, which was undertaken in a single case of placenta percreta, and inclusive of latter were four cases of morbid placental adhesion, a placenta increta and two placenta accreta. Eight out of 19 cases had vaginal delivery and rest had cesarean section. Among seven cases of cesarean hysterectomy 3 were done for placenta previa with accreta one case each done for abruptio placentae and placenta accreta and two cases were done for extra placental causes. Among four cases of emergency peripartum hysterectomy (EPH), which were relaparotomy followed by hysterectomy, three cases were done for complication of cesarean section and one done for uterine atonicity. Four cases of spontaneous vaginal deliveries needed peripartum hysterectomy two of them were complicated by morbid placental adhesion placenta increta (1), placental percreta (1), two cases were vaginal birth after cesarean (VBAC). Seven cases of uterine rupture had undergone peripartum hysterectomy. Conclusions: Obstetric hysterectomy is a lifesaving surgical procedure for maternal survival whenever necessary and mandates a quick decision making process, however in consideration of younger age and low parity or nulliparity, the best obstetric governance and services must foresee not to let mothers meet such situation necessitating organ removal and to enjoy potential reproductive life cycle. [ABSTRACT FROM AUTHOR]

Selenium (Se) deficiency is associated with the development of Keshan disease, a cardiomyopathy associated with massive cardiac immune cell infiltration that can lead to heart failure (HF). The purpose of this study was to determine whether high Se diet can attenuate systolic overload-induced cardiopulmonary inflammation and HF. Briefly, transverse aortic constriction (TAC)-induced cardiopulmonary oxidative stress, inflammation, left ventricular (LV) dysfunction, and pulmonary remodeling were determined in male mice fed with either high Se diet or normal Se diet. High Se diet had no detectable effect on LV structure and function in mice under control conditions, but high Se diet significantly protected mice from TAC-induced LV hypertrophy, dysfunction, increase of lung weight, and right ventricular hypertrophy. As compared with mice treated with normal Se diet, high Se diet also reduced TAC-induced LV cardiomyocyte hypertrophy, fibrosis, leukocyte infiltration, pulmonary inflammation, pulmonary fibrosis, and pulmonary micro-vessel muscularization. In addition, high Se diet significantly ameliorated TAC-induced accumulation and activation of pulmonary F4/80 + macrophages, and activation of dendritic cells. Interestingly, high Se diet also significantly attenuated TAC-induced activation of pulmonary CD4 + and CD8 + T cells. Moreover, we found that TAC caused a significant increase in cardiac and pulmonary ROS production, increases of 4-hydroxynonenal (4-HNE) and 3-nitrotyrosine (3-NT), as well as a compensatory increases of LV glutathione peroxidase 1 (GPX1) and 4 (GPX4) in mice fed with normal Se diet. Above changes were diminished in mice fed with high Se diet. Collectively, these data demonstrated that high Se diet significantly attenuated systolic pressure overload-induced cardiac oxidative stress, inflammation, HF development, and consequent pulmonary inflammation and remodeling., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Frailty is a multidimensional syndrome associated with a decline in reserve capacity across multiple organ systems involving physical, psychological, and social aspects. Weakness is the earliest indicator of the frailty process. Multi-morbidity is the state of presence of two or more chronic diseases. Frailty and chronic diseases are interlinked as frail individuals are more prone to develop chronic diseases and multi-morbid individuals may present with frailty. They share common risk factors, pathogenesis, progression, and outcomes. Significant risk factors include obesity, smoking, aging, sedentary, and stressful lifestyle. Pathophysiological mechanisms involve high levels of circulating inflammatory cytokines as seen in individuals with frailty and chronic diseases such as hypertension, cardiovascular diseases, type 2 diabetes mellitus, chronic kidney disease, and anemia. Hence, frailty and chronic diseases go hand in hand and it is of utmost importance to identify them and intervene during early stages. Screening frailty and treating multi-morbidity incorporate both pharmacological and majorly non- pharmacological measures, such as physical activities, nutrition, pro-active care, minimizing polypharmacy and addressing reversible medical conditions. The purpose of this mini-review is to highlight the interrelation of frailty and chronic diseases through the discussion of their predictors and outcomes and how timely interventions are essential to prevent the progression of one to the other., Competing Interests: None., (© 2024 The Author(s). Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd.)

Obesity and exercise intolerance greatly reduce the life quality of older people. Prolyl hydroxylase domain-containing protein 2 (PHD2) is an important enzyme in modulating hypoxia-inducible factor-alpha (HIF) protein. Using vascular endothelial cell-specific PHD2 gene knockout (PHD2 ECKO) mice, we investigated the role of endothelial PHD2 in aging-related obesity and exercise capacity. Briefly, PHD2 ECKO mice were obtained by crossing PHD2-floxed mice with VE-Cadherin (Cdh5)-Cre transgenic mice. The effect of PHD2 ECKO on obesity and exercise capacity in PHD2 ECKO mice and control PHD2 f/f mice were determined in young mice (6 to 7 months) and aged mice (16-18 months). We found that aged PHD2 ECKO mice, but not young mice, exhibited a lean phenotype, characterized by lower fat mass, and its ratio to lean weight, body weight, or tibial length, while their food uptake was not reduced compared with controls. Moreover, as compared with aged control mice, aged PHD2 ECKO mice exhibited increased oxygen consumption at rest and during exercise, and the maximum rate of oxygen consumption (VO 2 max) during exercise. Furthermore, as compared with corresponding control mice, both young and aged PHD2 ECKO mice demonstrated improved glucose tolerance and lower insulin resistance. Together, these data demonstrate that inhibition of vascular endothelial PHD2 signaling significantly attenuates aging-related obesity, exercise intolerance, and glucose intolerance., (© 2024. The Author(s).)

Objectives: The objective of the study was to investigate factors associated with subjective aging among older patients visiting a geriatric medicine outpatient department in Northern-India., Methods: The study is a cross-sectional study. Patients were categorized into three groups: whether they felt younger, equal, or older than their peers of same age. Factors such as fall, incontinence, anorexia, hand grip strength, cognition, depression, vision, hearing, cardiopulmonary function and immunization were assessed. Multinominal logistic regression was used to investigate the associated factors of subjective aging., Results: We assessed 184 older patients with a median age of 66.5 years (IQR 63.0 -78.8). Chronological age and hand grip strength were the significant factors associated with subjective aging. With one year increase in age, odds of feeling older than peers of same age decreased by 8.9% (OR, 0.911; 95% CI, 0.831-0.999, p = 0.047). With one kilogram increase in hand grip strength, odds of feeling younger than peers of same age increased by 7.3% (OR, 1.073; 95% CI, 1.01-1.14, p = 0.032)., Conclusion: Chronological age and hand grip strength are the factors associated with subjective aging in Northern-Indian older adults. Further longitudinal multi-center studies are needed to confirm our findings., (Copyright: © 2024 Hylonome Publications.)

Objective: Rheumatic Heart Disease (RHD) remains a significant public health problem with high morbidity and mortality in children and young adults from lower-middle income countries like Nepal. However, a nation-wide database of the disease is lacking for designing effective future prevention and control programmes and strategies. The aim of our study is to estimate the prevalence of RHD in school-attending Nepalese children., Methods: We performed a cross-sectional descriptive analysis of a nationally representative database of Nepal Heart Foundation (NHF) national RHD screening programme which included school-attending Nepalese children between five and sixteen years of age. The screening was conducted between May 2015 and March 2020 in 236 schools, representing all seven provinces, across all three ecological zones of Nepal. Transthoracic two-dimensional echocardiography was performed in all eligible children with more than grade one murmur on cardiac auscultation. We estimated the prevalence of RHD among school-attending children as the number of RHD cases per 1000 school-attending children with a 95% confidence interval., Results: The database included a total of 107,340 children who were screened clinically, of whom 10,600 (9·9%) underwent transthoracic two-dimensional echocardiography. The overall prevalence of RHD was 2.22 cases per 1000 school-attending children (95% CI:1·94 - 2·50). The highest prevalence was observed among children living in the southern Terai ecological zone (2·89 per 1000, 95% CI (2·32-3·46)) of Nepal. Among the provinces, Karnali had the highest prevalence of RHD (3·45 per 1000, 95% CI (2·42-4·48)). Among the districts screened, Kalikot had the highest RHD prevalence (5.47 per 1000, 95% CI (3.02-7.92))., Conclusion: Primordial, primary and secondary prevention programmes should pay special attention to southern Terai zone, particularly the under-privileged children from remote districts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Background: Inflammation contributes to heart failure (HF) development, the progression from left ventricular failure to pulmonary remodeling, and the consequent right ventricular hypertrophy and failure. NK1.1 plays a critical role in Natural killer (NK) and NK T (NKT) cells, but the role of NK1.1 in HF development and progression is unknown., Methods: We studied the effects of NK1.1 inhibition on transverse aortic constriction (TAC)-induced cardiopulmonary inflammation, HF development, and HF progression in immunocompetent male mice of C57BL/6J background., Results: We found that NK1.1 + cell-derived interferon gamma + (IFN-γ + ) was significantly increased in pulmonary tissues after HF. In addition, anti-NK1.1 antibodies simultaneously abolished both NK1.1 + cells, including the NK1.1 + NK and NK1.1 + NKT cells in peripheral blood, spleen, and lung tissues, but had no effect on cardiopulmonary structure and function under control conditions. However, systemic inhibition of NK1.1 signaling by anti-NK1.1 antibodies significantly rescued mice from TAC-induced left ventricular inflammation, fibrosis, and failure. Inhibition of NK1.1 signaling also significantly attenuated TAC-induced pulmonary leukocyte infiltration, fibrosis, vessel remodeling, and consequent right ventricular hypertrophy. Moreover, inhibition of NK1.1 signaling significantly reduced TAC-induced pulmonary macrophage and dendritic cell infiltration and activation., Conclusions: Our data suggest that inhibition of NK1.1 signaling is effective in attenuating systolic overload-induced cardiac fibrosis, dysfunction, and consequent pulmonary remodeling in immunocompetent mice through modulating the cardiopulmonary inflammatory response., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 He, Xu, Pan, Bhattarai, Liu, Zeng, Chen, Hall and Chen.)

Consumption of mad honey can lead to intoxication. The exact incidence of mad honey-induced intoxication is unknown. Typically, the patients present with dizziness, nausea, syncope, and sinus bradycardia., Case Presentation: The authors reported the case of a middle-aged male patient who presented with blurring of vision, passage of loose stools, vomiting, and profuse sweating after ingestion of honey. He also had a history of loss of consciousness. On presentation, he was hypotensive and tachypneic with cold, clammy extremities. His ECG showed sinus bradycardia. The authors made a diagnosis of mad honey intoxication with suspected anaphylaxis. The authors treated him with intravenous normal saline, epinephrine, and atropine. He again developed hypotension and bradycardia in a few hours, for which hydrocortisone was administered, following which his heart rate was normalized in 2 h. Overall, the recovery time in our patient was 8 h. The patient was counseled to avoid consuming mad honey and did well on his monthly follow-up., Discussion: Our patient had signs and symptoms suggesting intoxication following ingestion of mad honey with suspicion of anaphylaxis. Similar to other reported cases, the patient had sinus bradycardia and hypotension. Epinephrine and atropine were administered to treat hypotension and bradycardia, respectively. Also, refractory hypotension was managed by intravenous hydrocortisone. Usually, atropine and saline infusion are sufficient to manage these cases, and simultaneous use of epinephrine and atropine should be avoided unless indicated., Conclusion: Our case highlighted the approach to diagnosing and treating mad honey intoxication with suspected anaphylaxis., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Delayed reaction following mass hornet envenomation is associated with various clinical manifestations., Case Presentation: The authors present a case of a 24-year-old male from eastern Nepal, who presented following mass envenomation by hornet stings. He had progressive yellowish discoloration of skin and sclera, myalgia, fever, and dizziness. He had passage of tea-coloured urine followed by anuria. Laboratory investigations suggested acute kidney injury, rhabdomyolysis, and acute liver injury. The authors managed the patient with supportive measures and haemodialysis. There was complete recovery of liver and renal function in the patient., Discussion: The findings in this patient were similar to other cases reported in the literature. These patients must be managed supportively, with few requiring renal replacement therapy. Most of these patients recover completely. In low-middle-income countries like Nepal, delay in seeking care and delay in reaching care is associated with severe clinical manifestations. Delayed presentation can lead to renal shutdown and mortality; hence, early intervention is simple, and, crucial., Conclusion: This case highlights the occurrence of delayed reaction following mass envenomation by hornets. Also, the authors show an approach to managing such patients, similar to managing any other case with acute kidney injury. In these cases, an early simple intervention can prevent mortality. It is crucial to train healthcare workers regarding toxin induced acute kidney injury and the importance of early identification and intervention., Competing Interests: The author(s) have no conflict of interest to declare., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

IL-12α plays an important role in modulating inflammatory response, fibroblast proliferation and angiogenesis through modulating macrophage polarization or T cell function, but its effect on cardiorespiratory fitness is not clear. Here, we studied the effect of IL-12α on cardiac inflammation, hypertrophy, dysfunction, and lung remodeling in IL-12α gene knockout (KO) mice in response to chronic systolic pressure overload produced by transverse aortic constriction (TAC). Our results showed that IL-12α KO significantly ameliorated TAC-induced left ventricular (LV) failure, as evidenced by a smaller decrease of LV ejection fraction. IL-12α KO also exhibited significantly attenuated TAC-induced increase of LV weight, left atrial weight, lung weight, right ventricular weight, and the ratios of them in comparison to body weight or tibial length. In addition, IL-12α KO showed significantly attenuated TAC-induced LV leukocyte infiltration, fibrosis, cardiomyocyte hypertrophy, and lung inflammation and remodeling (such as lung fibrosis and vessel muscularization). Moreover, IL-12α KO displayed significantly attenuated TAC-induced activation of CD4 + T cells and CD8 + T cells in the lung. Furthermore, IL-12α KO showed significantly suppressed accumulation and activation of pulmonary macrophages and dendritic cells. Taken together, these findings indicate that inhibition of IL-12α is effective in attenuating systolic overload-induced cardiac inflammation, heart failure development, promoting transition from LV failure to lung remodeling and right ventricular hypertrophy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bhattarai, He, Xu, Liu, Pan, Sun, Chen and Chen.)

Blackeye peas ( Vigna unguiculata L. Walp.) are mainly used as a vegetable throughout the world, however they may contain significant concentrations of quercetin, myricetin, cyanidin, and delphinidin for potential use as a functional vegetable. Thirty-eight blackeye pea genotypes were selected from the core collection in the USDA, ARS, Plant Genetic Resources Conservation Unit's cold storage at 4 °C during 2016. Information regarding concentrations of quercetin, myricetin, cyanidin, delphindin, and correlations among these as well as additional seed traits including seed coat color, seed pattern color, seed pattern, seed texture, and years in storage would add value to the blackeye pea genotypes for use as a functional vegetable. Using high performance liquid chromatography (HPLC), the red seeded accession originating from Mozambique, PI 367927 produced the highest quercetin (469.53 µg/g) and myricetin (212.23 µg/g) concentrations. The black seeded genotype, PI 353236, originating from India, produced the highest cyanidin (1,388.82 µg/g) concentration. However, PI 353236 and the brown seeded genotype, PI 353352 from India produced the highest concentrations of delphinidin (1,343.27 and 1,353.94 µg/g), respectively. Several correlations were observed and interestingly only delphinidin showed a significant negative correlation ( r  = -0.293*) with years in cold storage indicating that delphinidin declined in the seeds stored the longest (from 4-45 years) at 4 °C. Principal component analysis (PCA) explained how the flavonols, anthocyanidins, and the additional seed traits contributed to the variation of the blackeye pea genotypes. The cluster analysis showed six clusters representing low to high phytochemical concentrations. The genetic parameters including σ 2 g, σ 2 p, GCV, PCV, h 2 h , and GG indicate that improvement in these phytochemical traits is possible through selection. The genotypic and phenotypic correlations showed that improving one phytochemical significantly improved the other except for cyanidin with delphinidin. These results can be used by scientists to develop blackeye pea cultivars with high flavonol and anthocyanidin concentrations.

Background: Acute diarrhea (AD) can have significant impacts on military troop readiness. Medical providers must understand current trends of enteropathogen antimicrobial resistance (AMR) in service members (SMs) to inform proper, timely treatment options. However, little is known of enteric pathogen profiles across the Military Health System (MHS). The primary objectives of this study were to identify gaps in enteric pathogen surveillance within the MHS, describe the epidemiology of AMR in enteric pathogens, and identify trends across the MHS both within the Continental United States (CONUS) and outside of the Continental United States (OCONUS)., Methods: Health Level 7 (HL7)-formatted laboratory data were queried for all specimens where Salmonella, Shigella, and Campylobacter species, as well as Shiga toxin-producing Escherichia coli (E. coli) (STEC) were isolated and certified between 1 January 2009 - 31 December 2019. Antibiotic susceptibility testing (AST) results were queried and summarized where available. Descriptive statistics were calculated for each organism by specimen source, year, and susceptibility testing availability., Results: Among a total of 13,852 enteric bacterial isolates, 11,877 (86%) were submitted from CONUS locations. Out of 1479 Shigella spp. and 6755 Salmonella spp. isolates, 1221 (83%) and 5019 (74%), respectively, reported any susceptibility results through the MHS. Overall, only 15% of STEC and 4% of Campylobacter spp. specimens had AST results available. Comparing AST reporting at CONUS versus OCONUS locations, AST was reported for 1175 (83%) and 46 (78%) of Shigella isolates at CONUS and OCONUS locations, respectively, and for 4591 (76%) and 428 (63%) of Salmonella isolates at CONUS and OCONUS locations, respectively., Conclusions: This study revealed inconsistent enteropathogen AST conducted across the MHS, with differing trends between CONUS and OCONUS locations. Additional work is needed to assess pathogen-specific gaps in testing and reporting to develop optimal surveillance that supports the health of the force., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Although both salinity and alkalinity result from accumulation of soluble salts in soil, high pH and ionic imbalance make alkaline stress more harmful to plants. This study aimed to provide molecular insights into the alkalinity tolerance using a recombinant inbred line (RIL) population developed from a cross between Cocodrie and Dular with contrasting response to alkalinity stress. Forty-six additive QTLs for nine morpho-physiological traits were mapped on to a linkage map of 4679 SNPs under alkalinity stress at the seedling stage and seven major-effect QTLs were for alkalinity tolerance scoring, Na + and K + concentrations and Na + :K + ratio. The candidate genes were identified based on the comparison of the impacts of variants of genes present in five QTL intervals using the whole genome sequences of both parents. Differential expression of no apical meristem protein, cysteine protease precursor, retrotransposon protein, OsWAK28 , MYB transcription factor, protein kinase, ubiquitin-carboxyl protein, and NAD binding protein genes in parents indicated their role in response to alkali stress. Our study suggests that the genetic basis of tolerance to alkalinity stress is most likely different from that of salinity stress. Introgression and validation of the QTLs and genes can be useful for improving alkalinity tolerance in rice at the seedling stage and advancing understanding of the molecular genetic basis of alkalinity stress adaptation.

Background: Immune-checkpoint inhibitors (ICI) have revolutionized the treatment of metastatic melanoma. Ipilimumab and Ipilimumab-Nivolumab combination therapies were approved by the United States Food and Drug Administration in 2011 and 2015, respectively. We aimed to evaluate potential changes in the survival of patients with metastatic melanoma following the approval of these agents., Methods: We extracted data from the Surveillance, Epidemiology, and End Results (SEER) database (Nov 2021 submission). All patients aged 20 and above who were diagnosed with 'distant' melanoma (per 'combined summary stage') from 2007 through 2018 were included in the study. This time period was further sub-categorized into 2007-2010 (pre-ICI era), 2011-2014 (single-agent ICI era), and 2015-2018 (combination ICI era) based on the approval timeline of ICI., Results: The median overall survival (OS) was 8, 10, and 14 months in the pre-ICI, single-agent ICI, and combination ICI eras respectively (log-rank test, χ² = 189.03, p < 0.001). On Cox-proportional hazard analysis, patients diagnosed in the single-agent and combination ICI eras had a significantly lower risk of dying [HR 0.82 (95% CI 0.78-0.87) and 0.67 (0.64-0.71), respectively] compared to patients diagnosed in the pre-ICI era. Patients who were of the male gender, aged ≥ 65 years, and those receiving chemotherapy and/or radiotherapy were at a significantly higher risk of dying. Married individuals had a significantly lower risk of dying compared to patients who were divorced, separated, or widowed at the time of diagnosis. There was no significant difference in survival demonstrated among non-Hispanic blacks versus non-Hispanic whites., Conclusion: Survival of patients with metastatic melanoma has improved in the era of immune checkpoint inhibitors. It implies that the survival of patients reported in trials can be correlated at a population level as well. Future analysis from the SEER database is needed when new data becomes available to see if there is a further increase in OS., Competing Interests: Conflicts of interest The authors report no potential conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Despite being one of the proven clean-energy technologies, hydroelectricity is losing attention in global research. Hydroelectricity is extremely important for countries possessing the required water resources, already heavily reliant on it and those lacking the financial capacity to invest in other expensive energy technologies. This study assessed the possible impact of climate change (CC) on hydro-energy generation in the Nepalese Himalaya (possessing eight peaks out of 14 over 8000 m) with a tremendous hydropower potential (∼50,000 MW). A planned 1200 MW storage type Budhigandaki Hydroelectricity Project is taken as a case. We estimated the energy generation for the baseline as well as 10 CC scenarios considering RCPs 4.5 and 8.5 at monthly, seasonal, and annual temporal scales for the mid-century. Results show that energy generation is highly dependent on the reservoir operating rule. The average annual energy generation is expected to vary within -5 to +12% of the base case in the mid-century, with significant variations across the months. We also infer that designing hydro-projects based on ensembled climate values could lead to a "rosy" but less probable and risky picture of energy generation in the future. Therefore, assessment of a wide spectrum of plausible CC scenarios are recommended. Storage type projects with provision of flexible operating rules considering finer temporal resolution and allocation to competing users (in case of multipurpose projects) supported by appropriate policies are desirable for climate resiliency. Complementing the existing energy generation mix with other technologies in areas where hydroelectricity is expected to undergo adverse impacts of CC is warranted for attaining future energy security and environmental safeguarding. Possibility of additional energy due to CC is a strong motivation for this region to focus on hydroelectricity development in the future., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Issues of environmental degradation, finite quantity and uneven spatial distribution of fuels in nature, and growing demand accentuated by volatility of oil prices have led to the global clean renewable energy transition (RET). With an objective of examining the current knowledge-stock on RET, we reviewed 248 journal publications pooled from three databases (ScienceDirect, Web of Science and Scopus) using a Systematic Literature Review method. This study does not focus on the specifications of a particular energy technology or regress relations among a limited set of variables. Rather, the key contribution is the critical assessment of the factors that encourage and those that hinder the transition process to provide a wider perspective through seven broad lenses: technological, investment, market, environmental, government and institutional, policy and social. Research, development and implementation of technology is a direct outcome of policy investment. Developed countries are leading the RET research while the global south is far behind. Most of the studies were found to be donor-driven which faced a serious risk of being counter-welcomed in different settings of the world without compromising the objectives of the transition. A strong international collaboration among the rich and poor countries is urgently felt necessary to foster mutual benefits. Research, planning and implementation of the RET would be highly effective and sustainable through a participatory bottom-up approach promoting local technology instead of imposed expensive imported ones. The need for "demand-pull" and "technology-push" policy instruments is stringent for successful transition. We conclude that there is a unanimous agreement among all the studies on the future prospects of renewable energy in the electricity sector; however, some skepticism still exists regarding other high energy demanding areas. Our review recommends updating existing and designing new robust policy mixes to guide the modality and pace of the RET, adhering to local specificities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The COVID-19 vaccination campaign is going on in Nepal through different phases of immunisation. It has been observed that people are misusing antipyretics and analgesics with the fear of adverse events following immunisation. The possibility of antipyretics and analgesics blunting the antibody response of the human body can be a potential cause for lower immune response and thus a reason for lower efficacy of the vaccine. Prophylactic use of over-the-counter analgesics and antipyretics is to be discouraged until the data for or against its use is available., Keywords: antipyretics; COVID-19 vaccine; drug misuse; vaccine immunogenicity.

Mediators of cardiac injury in preeclampsia are not well understood. Preeclamptic women have decreased cardiac global longitudinal strain (GLS), a sensitive measure of systolic function that indicates fibrosis and tissue injury. GLS is worse in preeclampsia compared to gestational hypertension, despite comparable blood pressure, suggesting that placental factors may be involved. We previously showed that Activin A, a pro-fibrotic factor produced in excess by the placenta in preeclampsia, predicts impaired GLS postpartum. Here, we hypothesized that chronic excess levels of Activin A during pregnancy induces cardiac dysfunction. Rats were assigned to sham or activin A infusion (1.25-6 µg/day) on a gestational day (GD) 14 ( n = 6-10/group). All animals underwent blood pressure measurement and comprehensive echocardiography followed by euthanasia and the collection of tissue samples on GD 19. Increased circulating activin A (sham: 0.59 ± 0.05 ng/mL, 6 µg/day: 2.8 ± 0.41 ng/mL, p < 0.01) was associated with impaired GLS (Sham: -22.1 ± 0.8%, 6 µg/day: -14.7 ± 1.14%, p < 0.01). Activin A infusion (6 µg/day) increased beta-myosin heavy chain expression in heart tissue, indicating cardiac injury. In summary, our findings indicate that increasing levels of activin A during pregnancy induces cardiac dysfunction and supports the concept that activin A may serve as a possible mediator of PE-induced cardiac dysfunction.

SARS-CoV-2 infection associated respiratory disease- COVID-19 has evolved into a pandemic but, being a new form of virus, pathogenesis of disease causation is not fully understood and drugs and vaccines against this virus are still being tested so that no effective drugs or vaccines have been advised by regulatory authority. In this context, the Ministry of AYUSH, Government of India has recommended ' Ayush Kwath ' to improve the immunity and combat the infection. Our objective of this literature review is to review the role of immunity in pathogenesis of COVID-19 and role of Ayush Kwath against the virus and regulation of immunity. Current review was conducted using a search of available literature on COVID-19 and immunity, Vyadhikshamatwa , Ayurveda and COVID-19, Rasayana , Coronavirus, SARS-CoV-2, immunomodulatory effects of medicinal plants; Tulsi /Holy Basil/ Ocimum sanctum , Dalchini /Cinnamon/ Cinnamomum zeylanicum , Sunthi /Ginger/ Zingiber officinale and Marich /Black Pepper/ Piper nigrum . Ayurveda, being an ancient science have both medicinal and cultural values and had stimulated our kitchen and influenced what we ate in different seasons and the remedies we used for common ailments. Herbs such as Tulsi, Marich, Sunthi, Dalchini are the most commonly used and easily available drugs in home. Thus, Ayush Kwath due to its immune-modulatory, antiviral, anti-oxidant, anti-inflammatory, anti-platelet, anti-atherosclerotic, hepato-protective, reno-protective properties; seems to be effective in immuno-regulation for controlling viral infections like COVID-19. Further pre-clinical and clinical trials need to be done for the evaluation of safety and efficacy of this polyherbal formulation., Competing Interests: None., (© 2020 The Authors.)

Every internet search query made out of curiosity by anyone who observed something in nature, as well as every photo uploaded to the internet, constitutes a data point of potential use to scientists. Researchers have now begun to exploit the vast online data accumulated through passive crowdsourcing for studies in ecology and epidemiology. Here, we demonstrate the usefulness of iParasitology, i.e. the use of internet data for tests of parasitological hypotheses, using hairworms (phylum Nematomorpha) as examples. These large worms are easily noticeable by people in general, and thus likely to generate interest on the internet. First, we show that internet search queries (collated with Google Trends) and photos uploaded to the internet (specifically, to the iNaturalist platform) point to parts of North America with many sightings of hairworms by the public, but few to no records in the scientific literature. Second, we demonstrate that internet searches predict seasonal peaks in hairworm abundance that accurately match scientific data. Finally, photos uploaded to the internet by non-scientists can provide reliable data on the host taxa that hairworms most frequently parasitize, and also identify hosts that appear to have been neglected by scientific studies. Our findings suggest that for any parasite group likely to be noticeable by non-scientists, information accumulating through internet search activity, photo uploads, social media or any other format available online, represents a valuable source of data that can complement traditional scientific data sources in parasitology.

While vital to platelet and leukocyte adhesion, the role of integrin affinity modulation in adherent cells remains controversial. In endothelial cells, atheroprone hemodynamics and oxidized lipoproteins drive an increase in the high affinity conformation of α5β1 integrins in endothelial cells in vitro, and α5β1 integrin inhibitors reduce proinflammatory endothelial activation to these stimuli in vitro and in vivo. However, the importance of α5β1 integrin affinity modulation to endothelial phenotype remains unknown. We now show that endothelial cells (talin1 L325R) unable to induce high affinity integrins initially adhere and spread but show significant defects in nascent adhesion formation. In contrast, overall focal adhesion number, area, and composition in stably adherent cells are similar between talin1 wildtype and talin1 L325R endothelial cells. However, talin1 L325R endothelial cells fail to induce high affinity α5β1 integrins, fibronectin deposition, and proinflammatory responses to atheroprone hemodynamics and oxidized lipoproteins. Inducing the high affinity conformation of α5β1 integrins in talin1 L325R endothelial cells suggest that NF-κB activation and maximal fibronectin deposition require both integrin activation and other integrin-independent signaling. In endothelial-specific talin1 L325R mice, atheroprone hemodynamics fail to promote inflammation and macrophage recruitment, demonstrating a vital role for integrin activation in regulating endothelial phenotype., Competing Interests: Declaration of Competing Interest The authors declare no conflicts., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background Alteration in hemodynamic shear stress at atheroprone sites promotes endothelial paracellular pore formation and permeability. The molecular mechanism remains unknown. Methods and Results We show that Nck (noncatalytic region of tyrosine kinase) deletion significantly ameliorates disturbed flow-induced permeability, and selective isoform depletion suggests distinct signaling mechanisms. Only Nck1 deletion significantly reduces disturbed flow-induced paracellular pore formation and permeability, whereas Nck2 depletion has no significant effects. Additionally, Nck1 re-expression, but not Nck2, restores disturbed flow-induced permeability in Nck1/2 knockout cells, confirming the noncompensating roles. In vivo, using the partial carotid ligation model of disturbed flow, Nck1 knockout prevented the increase in vascular permeability, as assessed by Evans blue and fluorescein isothiocyanate dextran extravasations and leakage of plasma fibrinogen into the vessel wall. Domain swap experiments mixing SH2 (phosphotyrosine binding) and SH3 (proline-rich binding) domains between Nck1 and Nck2 showed a dispensable role for SH2 domains but a critical role for the Nck1 SH3 domains in rescuing disturbed flow-induced endothelial permeability. Consistent with this, both Nck1 and Nck2 bind to platelet endothelial adhesion molecule-1 (SH2 dependent) in response to shear stress, but only Nck1 ablation interferes with shear stress-induced PAK2 (p21-activated kinase) membrane translocation and activation. A single point mutation into individual Nck1 SH3 domains suggests a role for the first domain of Nck1 in PAK recruitment to platelet endothelial cell adhesion molecule-1 and activation in response to shear stress. Conclusions This work provides the first evidence that Nck1 but not the highly similar Nck2 plays a distinct role in disturbed flow-induced vascular permeability by selective p21-activated kinase activation.

miRNAs are key regulators of various biological processes. Dysregulation of miRNA is linked to many diseases. Development of miRNA inhibitor has implication in disease therapy and study of miRNA function. The biogenesis pathway of miRNA involves the processing of pre-miRNA into mature miRNA by Dicer enzyme. We previously reported a proximity enabled approach that employs bifunctional small molecules to regulate miRNA maturation through inhibiting the enzymatic activity of Dicer. By conjugating to an RNA targeting unit, an RNase inhibitor could be delivered to the cleavage site of specific pre-miRNA to deactivate the complexed Dicer enzyme. Herein, we expanded this bifunctional strategy by showing that antisense oligonucleotides (ASOs), including morpholinos and γPNAs, could be readily used as the RNA recognition unit to generate bifunctional small molecule-oligonucleotide hybrids as miRNA inhibitors. A systematic comparison revealed that the potency of these hybrids is mainly determined by the RNA binding of the targeting ASO molecules. Since the lengths of the ASO molecules used in this approach were much shorter than commonly used anti-miRNA ASOs, this may provide benefits to the specificity and cellular delivery of these hybrids. We expect that this approach could be complementary to traditional ASO and small molecule based miRNA inhibition and contribute to the study of miRNA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Drought is a major constraint in some rice-growing areas of the United States. Its impact is most severe at the reproductive stage resulting in low grain yield. Therefore, assessment of genetic and phenotypic variation for drought tolerance in US rice germplasm is necessary to accelerate the breeding effort. Evaluation of 205 US rice genotypes for drought tolerance at the reproductive stage revealed tolerant response in rice genotypes Bengal, Jupiter, Cypress, Jazzman, Caffey, and Trenasse. Harvest index and fresh shoot weight were identified as important traits to explain the majority of variability among the genotypes under drought tolerance. Genotyping with 80 SSR markers indicated a low level of genetic diversity in US germplasm. Population structure analysis grouped the genotypes into eight clusters. The genotypes from California, Louisiana, and Arkansas formed distinct subgroups. Texas genotypes were similar to those from Louisiana and Arkansas. Marker-trait association analysis showed significant association of RM570 and RM351 with grain yield, spikelet fertility, and harvest index whereas shoot dry weight showed association with RM302 and RM461. The drought-tolerant genotypes identified in this study and the SSR markers associated with drought tolerance attributes will be helpful for development of improved drought-tolerant rice varieties through marker assisted selection.

miR-155 plays key promoting roles in several cancers and emerges as an important anticancer therapeutic target. However, the discovery of small molecules that target RNAs is challenging. Peptidomimetics have been shown to be a rich source for discovering novel ligands to regulate cellular proteins. However, the potential of using peptidomimetics for RNA targeting is relatively unexplored. To this end, we designed and synthesized members of a novel 320 000 compound macrocyclic peptidomimetic library. An affinity-based screening protocol led to the identification of a pre-miR-155 binder that inhibits oncogenic miR-155 maturation in vitro and in cell and induces cancer cell apoptosis. The results of this investigation demonstrate that macrocyclic peptidomimetics could serve as a new scaffold for RNA targeting.