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Oxidative stress is one of the major causes of different metabolic disorders, including diabetes, cardiovascular diseases, neurodegenerative diseases and cancers. Some metabolic disorders like diabetes mellitus leads to secondary complications after micro and macrovascular complications. Some of the most prevalent neurodegenerative diseases, like cognitive impairment and Alzheimer's disease, are found in chronic diabetic patients. The present study is designed to understand the mechanism of interconnection between diabetes mellitus and cognitive deficit using the alloxan model of diabetes-induced cognitive deficit in the rat model. The alloxan monohydrate produces reactive oxygen species, producing superoxide free radicals, hydrogen peroxide and hydroxyl radicals. The hydroxyl radicals ultimately cause the death of beta cells, causing diabetes. Hence, the correlation of oxidative stress and neurodegeneration in cognitive impairment is the trigger for this study. In the present study, we investigate the ameliorative effect of vildagliptin (VLD) and its conjugated nanoparticles against alloxan-associated brain damage due to oxidative stress. The gold (Au), selenium (Se) nanoparticles, and bimetallic (Se@Au) nanocomposites of VLD are synthesized and assessed for improvement in their brain availability. The in-vitro antioxidant evaluation of the VLD and nanoparticles is done using DPPH, ABTS, and FRAP assay. The memory-related neurobehavioral studies, in-vivo antioxidant studies, in-vivo biochemical studies, and histopathological examinations are evaluated in rat brains. The VLD and its nanoformulations exhibited in-vitro and in-vivo antioxidant properties significantly (p < 0.01). They reduced the activity of AChE and nitrite in the alloxan diabetic rats. The bimetallic Se@Au VLDNCs displayed a more protective effect than VLD, VLD-AuNPs, and VLD-SeNPs., 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 © 2024 Elsevier Inc. All rights reserved.)

Introduction: STAT1a is an essential signal transduction protein involved in the interferon pathway, playing a vital role in IFN-alpha/beta and gamma signaling. Limited information is available about the STAT protein in fish, particularly in Indian major carps (IMC). This study aimed to identify and characterize the STAT1a protein in Labeo rohita (LrSTAT1a)., Methods: The full-length CDS of LrSTAT1a transcript was identified and sequenced. Phylogenetic analyses were performed based on the nucleotide sequences. The in-vivo immune stimulant poly I: C was used to treat various tissues, and the expression of LrSTAT1a was determined using quantitative real-time polymerase chain reaction (qRT-PCR). A 3D model of the STAT1a protein was generated using close structure homologs available in the database and checked using molecular dynamics (MD) simulations., Results: The full-length CDS of Labeo rohita STAT1a ( LrSTAT1a ) transcript consisted of 3238 bp that encoded a polypeptide of 721 amino acids sequence was identified. Phylogenetic analyses were performed based on the nucleotide sequences. Based on our findings, other vertebrates share a high degree of conservation with STAT1a . Additionally, we report that the in vivo immune stimulant poly I: C treatment of various tissues resulted in the expression of LrSTAT1a as determined by quantitative real-time polymerase chain reaction (qRT-PCR). In the current investigation, treatment with poly I: C dramatically increased the expression of LrSTAT1a in nearly every organ and tissue, with the brain, muscle, kidney, and intestine showing the highest levels of expression compared to the control. We made a 3D model of the STAT1a protein by using close structure homologs that were already available in the database. The model was then checked using molecular dynamics (MD) simulations. Consistent with previous research, the MD study highlighted the significance of the STAT1a protein, which is responsible for Src homology 2 (SH2) recognition. An important H-bonding that successfully retains SH2 inside the STAT1a binding cavity was determined to be formed by the conserved residues SER107, GLN530, SER583, LYS584, MET103, and ALA106., Discussion: This study provides molecular insights into the STAT1a protein in Rohu ( Labeo rohita ) and highlights the potential role of STAT1a in the innate immune response in fish. The high degree of conservation of STAT1a among other vertebrates suggests its crucial role in the immune response. The in-vivo immune stimulation results indicate that STAT1a is involved in the immune response in various tissues, with the brain, muscle, kidney, and intestine being the most responsive. The 3D model and MD study provide further evidence of the significance of STAT1a in the immune response, specifically in SH2 recognition. Further research is necessary to understand the specific mechanisms involved in the IFN pathway and the role of STAT1a in the immune response of IMC., 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 © 2024 Das, Panda, Pradhan, Raut, Kumari and Meena.)

Purpose: To identify the incidence, risk factors, demographics, and clinical profile of dupilumab-induced ocular surface disease (DIOSD) in patients with atopic dermatitis (AD), propose a standardised treatment protocol (STP) and evaluate the response., Methods: Prospective case series of AD patients treated in the Dermatology Department, Royal Victoria Infirmary, Newcastle upon Tyne, UK developing ocular symptoms after commencing Dupilumab between September 2018 and February 2020. A standard history and examination protocol were used including subjective symptom severity grading and Ocular Surface Disease Index (OSDI) questionnaire on each visit. Standard treatment was prescribed, and response evaluated., Results: 32 of 113 included patients (28.31%) developed DIOSD, of which 20 (62.5%) were referred to the Cornea Service. Median age was 38.0 years (IQR 26.8; range 19-74). Male to female ratio was 1:1. Average time to onset of ocular symptoms from starting dupilumab was 9.2 weeks (IQR 8.8; range 0.1-40). 90% patients had bilateral conjunctival inflammation and blepharitis at presentation. Significant improvement in the subjective severity scale and the median OSDI score (from 34.0 to 10.2) was noted in response to topical eye treatment. Dupilumab was discontinued in none., Conclusions: DIOSD is not uncommon although, with timely referral and appropriate topical treatment better clinical outcome and patient satisfaction can be achieved without the need to discontinue Dupilumab. Prior allergic conjunctivitis did not affect the incidence or severity of DIOSD. Further prospective studies with longer follow-up and more focus on possible disease mechanism such as goblet cell related changes and immune response are needed., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Due to COVID-19, pharmacists have been exposed to a variety of dangers that have an impact on their mental health. The study highlights that impact of COVID-19 and work led to burnout among them. Thus, it is necessary to offer mental health services., Aims: To assess the impact of COVID-19 on the work of pharmacy professionals and ascertain the extent of the influence of burnout on mental health among pharmacists working as frontline health providers in Nepal., Methods: Pharmacists from Province 2, 3, and 5 in Nepal participated in a self-administered questionnaire that assessed mental health and wellbeing and burnout using 16-item OLBI. Data was collected from January 2023-March 2023. Independent sample t -test, one-way ANOVA, Pearson's correlation, and linear regression were employed to identify any significant connections between burnout and mental health and wellbeing., Results: Out of 243 participants , COVID-19 pandemic and work was found to have a negative impact on the mental health and wellbeing of a 33.7% of pharmacists. Participants reported having financial issues in 41.6% of cases and 9.5% considered leaving the profession and were concerned about the provision of service quality and making mistakes at work. A strong and meaningful positive relationship and linear regression were observed between exhaustion, disengagement, burnout, mental health and wellbeing. Pharmacists working part-time (p < 0.050) in hospital settings experienced burnout as a result of insufficient training, extended working hours, and stress both on and off the job., Conclusions: Pharmacists are to prioritize a healthy work-life balance, which includes avoiding prolonged shifts >8 h, regular physical exercise and promote open communication among colleagues to address workplace concerns., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Uma Langkulsen reports financial support was provided by Faculty of Public Health, 10.13039/501100005790Thammasat University., (© 2024 The Authors.)

Background A thorough knowledge of the root and canal morphology and their possible variations are essential for successful endodontic treatment. Methods like staining and clearing techniques, cross sectional method can provide precise information on root canal systems, however, these methods are invasive. Cone-beam computed tomography (CBCT) is the 3-dimensional scans of the maxillofacial skeleton that best visualizes canal morphology and helps in identifying additional canals and roots in vivo. Objective To investigate the root canal configuration of mandibular anterior teeth using Conebeam computed tomography. Method A total of 2910 CBCT images, comprising 970 central incisors, lateral incisors, and canines each from 485 patients were assessed. The following assessments were made: (1) The number of roots and root canals (2) Canal configuration according to Vertucci's classification (3) Bilateral occurrences for variations. Also, the gender and age of patients were noted. Result The study revealed mandibular anterior teeth predominantly had 1 root with Type I (79.79%, 77.11%, 91.34%) canal configuration followed by type III (20.2%, 22.67%, 5.15%) in central, lateral and canine respectively. Almost 90% incisors had symmetry in the canal configurations. No statistical correlation was found between the gender and root canal configurations. Type III canal configurations in canines were present more in elder age group. Conclusion Clinicians must be aware that each tooth may display a different number of roots and types of canal configurations. During endodontic treatment, presuming lower anterior teeth with single root and single canal may lead to missed canals and consequently, treatment failure.

The incidence of neurodegenerative diseases is increasing exponentially worldwide. Parkinson's disease (PD) is a neurodegenerative disease caused by factors like oxidative stress, gene mutation, mitochondrial dysfunction, neurotoxins, activation of microglial inflammatory mediators, deposition of Lewy's bodies, and α- synuclein proteins in the neurons leading to neuroinflammation and neurodegeneration in the substantia nigra. Hence the development of efficacious neuro-therapy is in demand which can prevent neurodegeneration and protect the nigrostriatal pathway. One of the approaches for managing PD is reducing oxidative stress due to aging and other co-morbid diseased conditions. The phytomolecules are reported as safe and efficacious antioxidants as they contain different secondary metabolites. However, the limitations of low solubility restricted permeability through the blood-brain barrier, and low bioavailability limits their clinical evaluation and application. This review discusses the therapeutic efficacy of phytomolecules in PD and different nanotechnological approaches to improve their brain permeability., 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 Elsevier B.V. All rights reserved.)

Background Graphic health warning labels (HWLs) on tobacco product packaging have been identified by the World Health Organization (WHO) as a cost-effective policy intervention to warn consumers about the health risks of tobacco. Compliance with HWLs shields young individuals from tobacco marketing influences and exposes users to health warnings. Assessing compliance with health warning labels would provide insights into the state of law implementation. The study assessed health warning labels on tobacco packages as per the Cigarettes and Other Tobacco Products (COTPA) (Packaging and Labelling) Amendment Rules of 2020, specifically assessing their availability around educational institutions in Bhubaneswar, Odisha, India. Materials and methods From August 2022 to January 2023, a protocol was employed to collect information on the sale of tobacco products around educational institutions including packages of cigarettes, beedis, and smokeless tobacco (SLT) from Bhubaneswar City. Using multistage random sampling 18 schools were selected in Bhubaneswar City. Areas within 100 yards (91.44 meters) of each school were mapped using a map tool. All prospective tobacco vendors within 100 yards of each school were included in the study. The data on compliance with HWLs were summarized using descriptive statistics. The health warnings compliance assessment of the tobacco products available with the vendors was conducted using three major indicators, including analysis of the font content, size and element of the graphics, and textual health warnings. In addition, the surface area occupied by these warnings was measured using a calibrated ruler. Results Within 100 yards of 18 schools in Bhubaneswar city, 57 vendors were found selling tobacco. About 48 distinct brands and 791 unbranded tobacco products were identified from 2135 packets collected from 57 vendors. Out of the 48 branded product packets examined, 25 brands were for smoking (cigarettes, bidis), while 23 were for SLT products such as khaini, gutkha, and pan masala containing tobacco. Only six brands out of 17 cigarette packs complied with HWL provisions. None of the eight unique bidi packs and 302 unbranded bidi packs were compliant with any HWL compliance indicators. Other compliance-related issues included incomplete health warning labels, out-of-rotation pictorial health warnings, distorted printing (blurry, heavy tint, and faded), and split warnings. Conclusion Tobacco products were sold within 100 yards of educational institutions in clear violation of the COTPA Section 6 provisions. Furthermore, the tobacco products sold were also not in compliance with the health warning label laws under section 7 of COTPA. There is an urgent need for strict enforcement of the provisions relating to the ban on sale within 100 yards of educational institutions and health warning label rules in Bhubaneshwar., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Satpathy et al.)

In this paper, we formulate a geometric nonlinear theory of the mechanics of accreting-ablating bodies. This is a generalization of the theory of accretion mechanics of Sozio & Yavari (Sozio & Yavari 2019 J. Nonlinear Sci. 29 , 1813-1863 (doi:10.1007/s00332-019-09531-w)). More specifically, we are interested in large deformation analysis of bodies that undergo a continuous and simultaneous accretion and ablation on their boundaries while under external loads. In this formulation, the natural configuration of an accreting-ablating body is a time-dependent Riemannian [Formula: see text]-manifold with a metric that is an unknown a priori and is determined after solving the accretion-ablation initial-boundary-value problem. In addition to the time of attachment map, we introduce a time of detachment map that along with the time of attachment map, and the accretion and ablation velocities, describes the time-dependent reference configuration of the body. The kinematics, material manifold, material metric, constitutive equations and the balance laws are discussed in detail. As a concrete example and application of the geometric theory, we analyse a thick hollow circular cylinder made of an arbitrary incompressible isotropic material that is under a finite time-dependent extension while undergoing continuous ablation on its inner cylinder boundary and accretion on its outer cylinder boundary. The state of deformation and stress during the accretion-ablation process, and the residual stretch and stress after the completion of the accretion-ablation process, are computed. This article is part of the theme issue 'Foundational issues, analysis and geometry in continuum mechanics'.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder affecting a major class of silver citizens. The disorder shares a mutual relationship on account of its cellular and molecular pathophysiology with type-II diabetes mellitus (DM). Chronic DM increases the risk for AD. Emerging evidence recommended that resistance in insulin production develops cognitive dysfunction, which generally leads to AD. Repurposing of antidiabetic drugs can be effective in preventing and treatment of the neurodegenerative disorder. Limitations of antidiabetic drugs restrict the repurposing of the drugs for other disorders. Therefore, nanotechnological intervention plays a significant role in the treatment of neurological disorders. In this review, we discuss the common cellular and molecular pathophysiologies between AD and type-II DM, the relevance of in vivo models of type II DM in the study of AD, and the repurposing of antidiabetic drugs and the nanodelivery systems of antidiabetic drugs against AD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Diabetes mellitus is the most chronic metabolic ailment characterized by insulin deficiency leading to aberrant cognitive dysfunction in later stages. Hesperidin is a bioflavonoid, having different pharmacological activities, but its poor water solubility and short plasma half-life restrict its applications in the clinical field. So, the hesperidin was conjugated with gold, selenium, and core-shell bimetallic nanoparticles of gold and selenium. Different spectroscopic methods characterized the synthesized monometallic and bimetallic nanoparticles. The rats were injected with streptozotocin to induce cognitive dysfunction, followed by administering HSP, HSP-Au NPs, HSP-Se NPs, and Se@Au-HSP NPs daily for 21 days. Then, the neurobehavioral studies, oxidative stress parameters, AChE and nitrite levels, the content of amyloid-β42, and inflammatory mediators were accessed to evaluate the effect of the nanoparticles against the STZ rat model. The results showed a significant increase in oxidative stress, AChE activity, amyloid-β42, nitrite levels, and neuroinflammation by upregulating the inflammatory cytokines in the streptozotocin-administered rat brain. The HSP, HSP-Au NPs, HSP-Se NPs, and Se@Au-HSP NPs effectively reversed all these effects of streptozotocin. However, the bimetallic nanoparticle Se@Au-HSP NPs revealed better neuroprotective action than HSP-Au NPs and HSP-Se NPs. Hesperidin-conjugated bimetallic nanoparticles improved learning and memory in the STZ rat model and may be an alternative approach for neurodegenerative diseases, including Alzheimer's disease., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Numerous strategies for enhancing seed germination and growth have been employed over the decades. Despite these advancements, there continues to be a demand for more effective techniques, driven by the growing global population. Recently, various forms of non-thermal atmospheric pressure plasma have garnered attention as environmentally friendly, safe, and cost-effective methods to enhance the agricultural and food sectors. This study explores the remarkable impact of non-thermal plasma (NTP) treatment on cucumber (Cucumis sativus L.) seed germination., Methods: A cost-effective, custom-designed power supply operating at line frequency was used for treating seeds, with exposure times ranging from 1 to 7 min. Various germination parameters, including water contact angle measurements, mass loss, water imbibition rate, and seedling length, were evaluated to assess the impact of plasma treatment on seed germination., Results: Cucumber seeds exposed to NTP treatment for 3 min and 5 min durations showed significant germination improvements, notably a 57.9 ± 4.25 % higher final germination percentage, 14.5 ± 3.75 % reduced mean germination time, and a remarkable 90.6 ± 4.64 % increase in germination index compared to the control. These results suggest that NTP treatment enhanced seed coat permeability, triggered essential biochemical processes, and expedited water absorption and nutrient assimilation, ultimately fostering faster and more synchronized germination., Conclusions: Our findings underscore the potential of NTP as an innovative approach to improving seed germination in agricultural practices., Competing Interests: 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., (© 2023 The Author(s).)

Nanotechnology has emerged in different fields of biomedical application, including lifestyle diseases like diabetes, hypertension, and chronic kidney disease, neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease, and different types of cancers. Metal nanoparticles are one of the most used drug delivery systems due to the benefits of their enhanced physicochemical properties as compared to bulk metals. Neurodegenerative diseases are the second most cause affecting mortality worldwide after cancer. Hence, they require the most specific and targeted drug delivery systems for maximum therapeutic benefits. Metal nanoparticles are the preferred drug delivery system, possessing greater blood-brain barrier permeability, biocompatibility, and enhanced bioavailability. But some metal nanoparticles exhibit neurotoxic activity owing to their shape, size, surface charge, or surface modification. This review article has discussed the pathophysiology of AD. The neuroprotective mechanism of gold, silver, selenium, ruthenium, cerium oxide, zinc oxide, and iron oxide nanoparticles are discussed. Again, the neurotoxic mechanisms of gold, iron oxide, titanium dioxide, and cobalt oxide are also included. The neuroprotective and neurotoxic effects of nanoparticles targeted for treating AD are discussed elaborately. The review also focusses on the biocompatibility of metal nanoparticles for targeting the brain in treating AD. The clinical trials and the requirement to develop new drug delivery systems are critically analyzed. This review can show a path for the researchers involved in the brain-targeted drug delivery for AD., Competing Interests: The authors have no conflict of interest to report., (© 2023 – The authors. Published by IOS Press.)

Background/aims: The objective of this multicentre, multinational, prospective study was to assess the level of basic understanding that individuals with keratoconus possessed about their condition., Methods: We recruited 200 active keratoconus patients who were under regular review, and cornea specialists established a standard of 'minimal keratoconus knowledge' (MKK) that included an understanding of the definition, risk factors, symptoms and treatment options for the condition. We collected data from each participant regarding their clinical characteristics, highest level of education, (para)medical background and experiences with keratoconus within their social circle, and calculated the percentage of MKK attained by each patient., Results: Our findings revealed that none of the participants met the MKK standard, with the average MKK score being 34.6% and ranging from 0.0% to 94.4%. Furthermore, our study showed that patients with a university degree, previous surgical intervention for keratoconus or affected parents had a higher MKK. However, age, gender, disease severity, paramedical knowledge, disease duration and best-corrected visual acuity did not significantly affect the MKK score., Conclusions: Our study demonstrates a concerning lack of basic disease knowledge among keratoconus patients in three different countries. The level of knowledge exhibited by our sample was only one-third of what cornea specialists would typically anticipate from patients. This highlights the need for greater education and awareness campaigns surrounding keratoconus. Further research is needed to determine the most efficient approaches for enhancing MKK and subsequently improving the management and treatment of keratoconus., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Gastric cancer is one of the most common cancers and a leading cause of death worldwide. Most cases of gastric cancer are diagnosed at an advanced stage when no definitive treatment is available leading to an overall declined survival rate. In this study, we aimed to investigate the survival rate of gastric cancer patients admitted to our tertiary care center and determined the relationship between sociodemographic and clinicopathological characteristics with mortality. Methodology Gastric cancer patients treated between January 2019 and December 2020 were included in this retrospective study. The clinicopathological and demographic data of 275 gastric cancer patients were analyzed. The Kaplan-Meier method was used to calculate the overall survival of gastric cancer patients. The Kaplan-Meier log-rank test was used to calculate the difference. Results The mean survival of gastric cancer patients was 20.10 months (95% confidence interval = 19.20-21.03). Deaths were higher among stage III (42.6%) and stage IV (36.1%) patients compared to stage I (1.6%) and stage II (19.7%) patients. Mortality was significantly higher (70.5%) in patients without surgery. Conclusions The mean survival in our study setting is lower and is associated with the pathological stage of the disease, surgical intervention, and patients presenting with other gastrointestinal symptoms. A lower survival rate can be attributed to late diagnosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Pradhan et al.)

The unique properties of nanomaterials have the potential application in different fields of biomedical application along with the management of environmental pollutants. This research work involved the isolation of hesperidin from the orange peel and the preparation of hesperidin gold nanoparticles by the chemical reduction method. The high substrate specificity and lower band gap enable the excitation of gold nanoparticles in visible light. Hence gold nanoparticles are chosen nowadays for the management and removal of organic pollutants. The efficacy of hesperidin gold nanoparticles was evaluated by the photocatalytic activity on organic dyes and pollutants like methyl orange, methylene blue, bromocresol green, and 4 - nitro phenol with sodium borohydride as reducing agent and the antioxidant study by scavenging of free radicals of DPPH, ABTS, and hydroxyl free radicals of hydrogen peroxide. The kinetics of photocatalytic degradation of organic dyes and 4 - nitro phenol was found to follow the first order with rate constants of 10 × 10 -3 , 37 × 10 -3 , 23 × 10 -3 and 49 × 10 -3 min -1 for methyl orange, methylene blue, bromocresol green and 4 - nitro phenol respectively. The hesperidin gold nanoparticles showed significant antioxidant activity as compared to ascorbic acid as standard. The flavonoid conjugated gold nanoparticles can be an efficient antioxidant and photocatalyst for the management of different diseases and wastewater treatment respectively., 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.)

Introduction: Endothelial cell density (ECD) changes long after penetrating keratoplasty (PKP) of organ-cultured corneas have been little studied. We aim to calculate the point when ECD decline stabilises following PKP with organ culture stored corneas., Methods: This is an observational study of first-ever PKPs and first-ever re-grafts, performed over 17 years under a single surgeon. ECDs were acquired at 3 and 6 months, 1 year post-graft and annually thereafter by specular microscopy. Time-dependent ECD data was fitted to a log-biexponential model., Results: We studied 465 first-ever grafts and 128 re-grafts. Mean recipient age was 59 years (range 0-96 years; SD 22). Median follow-up was 5.7 (range 0.2-17.1) years. Probability of ED at 5 years in first grafts and re-grafts was 4.4% (2.6-7.1%) and 14.8% (8.3-23.2%). In first grafts, ECD loss reached 0.6% per annum at 7.9 (6.2-9.6) years post-operatively. The half-lives of ECD loss during the immediate post-operative period for first grafts, re-grafts, dystrophies, ectasias, and previous ocular surgery are 20.1 (14.9-30.9), 12.8 (6.9-79.4), 19.5 (13.1-37.7), 26.2 (16.2-68), and 11.6 (6.7-41.3) months, respectively. The half-life during this rapid phase of ECD loss has an inverse correlation with graft survival at 10 years (r = - 0.89, p = 0.02)., Conclusions: Rate of endothelial decompensation is higher in first grafts than re-grafts. ECD decline stabilises 7.9 years post-operatively in first grafts but then becomes lower than the physiological loss expected. Further work is needed to verify whether organ-cultured grafts reach physiological levels of ECD loss faster than hypothermically stored grafts., (© 2022. The Author(s).)

Alzheimer's disease (AD) is a common neurodegenerative disorder. Aluminium chloride induces AD like pathology in rats. Renin angiotensin system plays a significant role in the pathogenesis and occurrence of Alzheimer's disease. In the present study we evaluated and compared the effect of Captopril and Perindopril against aluminium chloride induced amyloidogenesis and cognitive dysfunction in rats. Wistar rats of both sex were divided randomly into four groups i.e. Group I was served as normal control and treated with normal saline, Group II was administered with AlCl 3 (100 mg/kg, p. o.) and Group III and IV received Captopril (30 mg/kg, p. o.) and Perindopril (5 mg/kg, p. o.) respectively 1hr prior to administration of AlCl 3 . All the doses were given once daily for 42 days. The evaluation of memory function was carried out in Y-maze (spontaneous alternation), radial arm maze (number of correct responses) and elevated plus maze (transfer latency). After behavioral studies, estimation of antioxidant status (brain and serum), amyloid-β content (brain) and histopathology of brain hippocampus region was done. Administration of AlCl 3 for 42 days impaired cognitive dysfunction. Captopril and Perindopril prevented AlCl 3 induced cognitive dysfunction by improving spontaneous alternation behavior, number of correct responses and reducing transfer latency. They also increase the antioxidant status, reduce the Aβ42 content in the brain and reverse the histopathological changes caused by AlCl 3 in hippocampal region. Both Captopril and Perindopril protects against aluminium chloride induced amyloidogenesis and AD like pathology. Captopril is found to be more effective than Perindopril., Competing Interests: The authors declare no conflict of interest., (© 2022 Published by Elsevier Ltd.)

Background: Suicide is a growing public health problem globally. Suicide accounts for 70% of violent deaths among women in low and middle income countries. In Nepal suicide is the single leading cause of death among women of reproductive age. The aim of this scoping review is to explore and understand the various contexts related to vulnerability of Nepalese woman towards suicide and deliberate self-harm., Methods: A scoping review based on Arksey and O'Malley's methodological framework including a combination of peer-reviewed publications and grey literature was conducted. The National Library of Medicine's PubMed and Google Scholar search engines were used during July 2019 applying a Boolean search strategy., Results: Suicide incidence was found to be higher among younger age group and married women, with poisoning as the most common means of suicide. Psychosocial and economic factors such as abuse, interpersonal conflicts, marital disputes, relationship problems, adjustment problems, unpaid loans and financial losses; and mental health conditions such as mood disorder, adjustment disorder and substance abuse disorder were found to be contributing factors for suicide and deliberate self-harm among women in Nepal., Conclusion: Socio-cultural and economic factors shape family and marital relationships which impacts psycho-social and mental wellbeing of women in Nepal inciting suicidal attempts and deliberate self-harm. However, very few studies were found that explore the context of poverty, social exclusion, gender inequality, education, traditional/cultural and patriarchal system in which suicide among women in Nepal occurs., (© 2021. The Author(s).)

Flavonoids have achieved widespread importance in pharmaceutical, food, and cosmetics industries. Furthermore, modification of these naturally occurring flavonoids to structurally diverse compounds through whole cell biotransformation with enhanced biological activities has numerous biotechnological applications. The present study investigated the biotransformation potential of Streptomyces species isolated from a high-altitude-soil sample towards selected flavonoid molecules. The biotransformed metabolites were confirmed by comparing the HPLC chromatogram with authentic compounds and LC-MS/MS analysis. Of these isolates, Streptomyces species G-18 (Accession number: MW663767.1) catalyzed isoflavone molecules daidzein and genistein to produce hydroxylated products at 24 h of reaction condition in a whole cell system. The hydroxylation of daidzein (4',7-dihydroxyisoflavone) was confirmed at 3'-position of the B ring to produce 3',4',7-trihydroxyisoflavone. In addition, Streptomyces species G-14 (Accession number: MW663770.1) and Streptomyces species S4L (Accession number: MW663769.1) also revealed the transformation of daidzein (4',7-dihydroxyisoflavone) to hydroxy daidzein at a distinct position than that of G-18 isolates, whereas thee Streptomyces species S4L reaction mixture with naringenin as a substrate also revealed the hydroxylated product. Our results demonstrated that microorganisms isolated from different ecological niches have broad application., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Lasata Shrestha et al.)

Slope stability assessment is essential for safe and sustainable development widely applied in mining, civil, and environmental engineering projects around the world. This study aimed to conduct a stability analysis of a selected Himalayan road cut slope from two different sections, named sections (A) and (B). The strength reduction factor (SRF) based on the finite element method was used to simulate the slope sections using Phase2 software. A mesh pattern of six node triangle elements was used during the numerical simulation. The Mohr-Coulomb parameters and other inputs used in the numerical modelling of the investigated slope were estimated by different geotechnical tests, namely, the direct shear test, density analysis test, rock hardness test, and Brazilian test. The results indicated that the critical SRF of the completely weathered slope profile section (A), with a relatively low overall angle, was found to be 1.25, which is approximately 50% lower than the value obtained in the moderately to highly weathered profile section (B), equal to 2.53. These results are in agreement with other published studies, which revealed that the geometry of a slope influences the weathering grade, which in turn destabilizes the slope. The results of this study will help in engineering slope design considering the influence of weathering., (© 2020 The Author(s).)

Background: The Bergenia species are perennial herbs native to central Asia, and one of the most promising medicinal plants of the family Saxifragaceae which are popularly known as 'Pashanbheda'. The aim of this study was to evaluate antioxidant and α-amylase, α-glucosidase, lipase, tyrosinase, elastase, and cholinesterases inhibition potential of Bergenia pacumbis of Nepali origin collected from the Karnali region of Nepal., Methods: The sequential crude extracts were made in hexane, ethyl acetate, methanol, and water. Antioxidant activities were analyzed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. The α-amylase, α-glucosidase, lipase, tyrosinase, elastase, acetylcholinesterase, and butyrylcholinesterase inhibition were analyzed by the 3,5-Dinitrosalicylic acid (DNSA), p-Nitrophenyl-α-D-glucopyranoside (p-NPG), 4-nitrophenyl butyrate (p-NPB), l-3,4-dihydroxyphenylalanine (L-DOPA), N-Succinyl-Ala-Ala-p-nitroanilide (AAAPVN), acetylthiocholine, and butyrylcholine as a respective substrate. The major metabolites were identified by high performance liquid chromatography with electron spray ionization- quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS) profiling., Results: Our results revealed the great antioxidant ability of crude extract of B. pacumbis in ethyl acetate extract against both DPPH (IC 50  = 30.14 ± 0.14 μg/mL) and ABTS (IC 50  = 17.38 ± 1.12 μg/mL). However, the crude methanol extract of B. pacumbis showed the comparable enzymes inhibitions with standard drugs; α-amylase (IC 50  = 14.03 ± 0.04 μg/mL), α-glucosidase (IC 50  = 0.29 ± 0.00 μg/mL), lipase (IC 50  = 67.26 ± 0.17 μg/mL), tyrosinase (IC 50  = 58.25 ± 1.63 μg/mL), elastase (IC 50  = 74.00 ± 3.03 μg/mL), acetylcholinesterase (IC 50  = 31.52 ± 0.58 μg/mL), and butyrylcholinesterase (IC 50  = 11.69 ± 0.14 μg/mL). On the basis of HPLC-ESI-QTOF-MS profiling of metabolites, we identified major compounds such as Bergenin, Catechin, Arbutin, Gallic acid, Protocatechuic acid, Syringic acid, Hyperoside, Afzelechin, Methyl gallate, Paashaanolactone, Astilbin, Quercetin, Kaempferol-7-O-glucoside, Diosmetin, Phloretin, and Morin in methanol extract which has reported beneficial bioactivities., Conclusion: Our study provides a plethora of scientific evidence that the crude extracts of B. pacumbis from Nepalese origin in different extracting solvents have shown significant potential on inhibiting free radicals as well as enzymes involved in digestion, skin related problems, and neurological disorders compared with the commercially available drugs.

The innate immune system offers the first line of defense against invading microbial pathogens through the recognition of conserved pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs). The host innate immune system through PRRs, the sensors for PAMPs, induces the production of cytokines. Among different families of PRRs, the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), and its mitochondrial adaptor ie, the mitochondrial antiviral-signaling (MAVS) protein, are crucial for RLR-triggered interferon (IFN) antiviral immunity. Recent studies have shown that the N-terminal caspase recruitment domain (CARD) and transmembrane domain play a pivotal role in oligomerization of black carp MAVS (BcMAVS), crucial for the host innate immune response against viral invasion. In this study, we have used molecular modeling, docking, and molecular dynamics (MD) simulation approaches to shed molecular insights into the oligomerization mechanism of BcMAVS CARD . MD simulation and interaction analysis portrayed that the type-I surface patches of BcMAVS CARD  make the major contribution to the interaction. Moreover, the evidence from surface patches and critical residues involved in the said interaction is found to be similar to that of the human counterpart and requires further investigation for legitimacy. Altogether, our study provided crucial information on oligomerization of BcMAVS CARDs and might be helpful for clarifying the innate immune response against pathogens and downstream signaling in fishes., (© 2019 Wiley Periodicals, Inc.)

Background: In 2009, the Nepal Ministry of Health and Population launched a national program for prevention of postpartum hemorrhage (PPH) during home births that features advance distribution of misoprostol to pregnant women. In the years since, the government has scaled-up the program throughout much of the country. This paper presents findings from the first large-scale assessment of the effectiveness of the advance distribution program., Methods: Data collection was carried out in nine districts and all three ecological zones. To assess knowledge, receipt and use of misoprostol, household interviews were conducted with 2070 women who had given birth within the past 12 months. To assess supply and provision of misoprostol, interviews were conducted with 270 Female Community Health Volunteers (FCHVs) and staff at 99 health facilities., Results: Among recently delivered women, only 15% received information about misoprostol and 13% received misoprostol tablets in advance of delivery. Yet 87% who received advance misoprostol and delivered at home used it for PPH prevention. Among FCHVs, 96% were providing advance misoprostol for PPH prevention; however 81% had experienced at least one misoprostol stock out within the past year. About one-half of FCHVs were providing incomplete information about the use of misoprostol; in addition, many did not discuss side effects, how to recognize PPH or where to go if PPH occurs. Among health facilities, just one-half had sufficient misoprostol stock, while 95% had sufficient oxytocin stock, at the time of this assessment., Conclusions: In Nepal, women who receive advance misoprostol are both willing and able to use the medication for PPH prevention during home births. However the supply and personnel challenges identified raise questions about scalability and impact of the program over the long-term. Further assessment is needed.

Background: Because treatment with third-generation cephalosporins is associated with slow clinical improvement and high relapse burden for enteric fever, whereas the fluoroquinolone gatifloxacin is associated with rapid fever clearance and low relapse burden, we postulated that gatifloxacin would be superior to the cephalosporin ceftriaxone in treating enteric fever., Methods: We did an open-label, randomised, controlled, superiority trial at two hospitals in the Kathmandu valley, Nepal. Eligible participants were children (aged 2-13 years) and adult (aged 14-45 years) with criteria for suspected enteric fever (body temperature ≥38·0°C for ≥4 days without a focus of infection). We randomly assigned eligible patients (1:1) without stratification to 7 days of either oral gatifloxacin (10 mg/kg per day) or intravenous ceftriaxone (60 mg/kg up to 2 g per day for patients aged 2-13 years, or 2 g per day for patients aged ≥14 years). The randomisation list was computer-generated using blocks of four and six. The primary outcome was a composite of treatment failure, defined as the occurrence of at least one of the following: fever clearance time of more than 7 days after treatment initiation; the need for rescue treatment on day 8; microbiological failure (ie, blood cultures positive for Salmonella enterica serotype Typhi, or Paratyphi A, B, or C) on day 8; or relapse or disease-related complications within 28 days of treatment initiation. We did the analyses in the modified intention-to-treat population, and subpopulations with either confirmed blood-culture positivity, or blood-culture negativity. The trial was powered to detect an increase of 20% in the risk of failure. This trial was registered at ClinicalTrials.gov, number NCT01421693, and is now closed., Findings: Between Sept 18, 2011, and July 14, 2014, we screened 725 patients for eligibility. On July 14, 2014, the trial was stopped early by the data safety and monitoring board because S Typhi strains with high-level resistance to ciprofloxacin and gatifloxacin had emerged. At this point, 239 were in the modified intention-to-treat population (120 assigned to gatifloxacin, 119 to ceftriaxone). 18 (15%) patients who received gatifloxacin had treatment failure, compared with 19 (16%) who received ceftriaxone (hazard ratio [HR] 1·04 [95% CI 0·55-1·98]; p=0·91). In the culture-confirmed population, 16 (26%) of 62 patients who received gatifloxacin failed treatment, compared with four (7%) of 54 who received ceftriaxone (HR 0·24 [95% CI 0·08-0·73]; p=0·01). Treatment failure was associated with the emergence of S Typhi exhibiting resistance against fluoroquinolones, requiring the trial to be stopped. By contrast, in patients with a negative blood culture, only two (3%) of 58 who received gatifloxacin failed treatment versus 15 (23%) of 65 who received ceftriaxone (HR 7·50 [95% CI 1·71-32·80]; p=0·01). A similar number of non-serious adverse events occurred in each treatment group, and no serious events were reported., Interpretation: Our results suggest that fluoroquinolones should no longer be used for treatment of enteric fever in Nepal. Additionally, under our study conditions, ceftriaxone was suboptimum in a high proportion of patients with culture-negative enteric fever. Since antimicrobials, specifically fluoroquinolones, are one of the only routinely used control measures for enteric fever, the assessment of novel diagnostics, new treatment options, and use of existing vaccines and development of next-generation vaccines are now a high priority., Funding: Wellcome Trust and Li Ka Shing Foundation., (Copyright © 2016 Arjyal et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.)

Aim: The study was carried to find a relationship between the postextraction stable landmark, the incisive papilla, and the most labial position of the maxillary central incisor teeth, which occurred in Nepalese population., Materials and Methods: Casts of the subjects selected by nonprobability random sampling meeting the inclusion criteria were obtained. Each casts were standardized with respect to the occlusal plane and a photographic technique was used to measure the distance from the tangent of the labial surface of the central incisors to the posterior border of the incisive papilla. The measurements were made using Adobe Photoshop and results were analyzed by using appropriate statistical methods. Most appropriate software (SPSS) for the purpose was used to generate all desired values., Results: The data obtained suggested that the distance from the labial surface of maxillary central incisors to the posterior border of the incisive papilla ranged from 9 to 15.9 mm with a mean of 11.59 mm (SD 1.3). Various other results were also found after evaluation of the arch forms in relation to sex and race., Conclusion: Within the limitations of the study, these results suggested that there is a relationship between the maxillary central incisors and the incisive papilla aiding in the anteroposterior positioning of the anterior tooth. The clinical relevance of the study lies in application of the incisive papilla as a starting point in the preliminary location of maxillary incisors and canines during construction of the denture in absence of preextraction records.

A total of 1,040 birds from 5 common commercial genetic broiler strains were raised and processed to analyze the effect of strain and deboning time on meat quality. The birds were processed at either 6 or 7 wk of age in 4 replications each. Carcasses were deboned at either 2 or 4 h postmortem (PM; n = 52 birds per treatment). Carcass and breast weights were measured on each bird to calculate breast yield. Muscle pH was measured at time of deboning. Fillets deboned at 4 h PM were measured for length, width, and height to evaluate footprint analysis. At 24 h PM, fillets were weighed to calculate drip loss, and color (L*) was also measured. The fillets were then cooked to 76 degrees C, and cook loss was calculated. Fillets were then subjected to shear analysis using the Meullenet-Owens razor shear method where shear energy (N x mm) was calculated to evaluate tenderness. The strains in this study were chosen for differences in yield; therefore, as expected, breast yield was significantly different among strains. Variation in meat quality attributes existed among strains deboned at 2 h PM, but there was no consistent relationship between meat quality and breast yield. However, at 4 h PM, fewer differences among strains existed in meat quality characteristics (tenderness, water holding capacity, and pH). As expected, deboning at 2 h PM resulted in higher shear energy, higher muscle pH, and lower L* value compared with deboning at 4 h PM in all but one strain. However, water-holding capacity was not affected by deboning time at either age interval. Footprint analysis showed that most differences among strains were in heights measured at the fillet midpoint and caudal end. These results suggest that early deboning may affect meat quality of broiler strains differently, resulting in greater variation within the industry.

The Institute of Gas Technology (IGT) conducted a pilot-scale study at a former manufactured gas plant (MGP) site in New Jersey. The objective of the study was to determine the effectiveness of an innovative chemical/biological treatment process (MGP-REM process) to remediate soils contaminated with polynuclear aromatic hydrocarbons (PAHs). In order to identify the benefits of the MGP-REM process, the system was also operated in the conventional bioremediation mode. Results showed that the MGP-REM process can effectively treat PAH-contaminated MGP site soils, and it reduced the toxicity of the soil by a factor of 50, as indicated by the Microtox Toxicity Test. The MGP-REM process was 70% more efficient than conventional bioremediation in the removal of the PAHs from the soils. Air emissions data suggest that minimal air pollution control and monitoring are required for the slurry-phase application of both the MGP-REM process and the conventional biological treatment. Process economics indicate that the MGP-REM process in a slurry-phase mode has an estimated treatment cost of $100/cubic yard for remediation of PAH-contaminated soils.

During 1994, field studies were conducted in the Midwestern Region of Nepal. Two camps were located in the "inner terai," low mountain valleys between the Churia Range and the Mahabarat Lekh. A third camp was in the mountains at Jumla. Visits were made to 2 high mountain sites, Simikot, Humla District, and Rara National Park. The result from all these sampling sites was the recovery of 6 new country records, 5 in the genus Aedes and 1 in the genus Heizmannia. Some mosquitoes in the Nepal checklist had no voucher specimens. Locality data are given for 9 of these. Biodata on another species that is quite rare in Nepal are given.

The ecology of Anopheles mosquitoes in relation to malaria transmission was studied at sprayed and unsprayed villages and two unsprayed cattle sheds in the inner terai of Sindhuli District, Central Region, and at two unsprayed villages and one cattle shed in Kanchanpur, Far Western Region of Nepal, from August 1987 to August 1989. Anopheles maculatus was the most abundant of 26 anopheline species collected in Sindhuli District; however, An. fluviatilis was collected most frequently at human bait and was infected most frequently with malaria sporozoites. Residual house spray controlled the indoor resting abundance of the endophilic resting species and protected the population from malaria during midsummer, but had less effect on exophilic resting species and those abundant after and before spray application during the fall and spring, respectively. Malaria at the unsprayed village was detected predominantly in adults of both sexes, perhaps because young children retired early and frequently slept indoors under bed nets during the early evening period of elevated anopheline host-seeking activity. Malaria transmission was verified by the collection of sporozoite infected An. fluviatilis and An. maculatus during spring at cattle sheds in the forested Churia Hills and during the summer monsoon season within the unsprayed village. An. culicifacies was the most abundant of 12 anopheline species collected in Kanchanpur District. Few females of all species were collected at human bait positioned in or out of houses or had human positive blood meals; none were infected with sporozoites. Malaria incidence was higher in the study village positioned along the forest-rice field ecotone than in the cleared rice growing area.

Thirteen mosquito species of the genera Aedes, Culex, Mimoyia and Uranotaenia are reported from Nepal for the first time. Taking into account taxonomic changes, 70 species of culicine (i.e., non-anopheline) mosquitoes are now known from Nepal.