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BACKGROUND AND OBJECTIVE: This study examined the potential influence of pre-pandemic psychological resilience on use of approach or avoidant coping styles and strategies to manage stress during the COVID-19 pandemic. We hypothesized that higher resilience would be associated with more approach coping and less avoidant coping. DESIGN AND METHODS: Longitudinal cohort data were from the Nurses Health Study II, including 13,143 female current and former healthcare professionals with pre-pandemic lifetime trauma. Pre-pandemic resilience was assessed between 2018-2019 and current coping during the outbreak of the pandemic in the United States (May-August 2020). Multiple linear regression model results identified associations between continuous pre-pandemic resilience scores and use of approach and avoidant coping styles, as well as individual coping strategies, adjusting for relevant covariates. RESULTS: Greater resilience was associated with higher use of approach coping (ß = 0.06, 95% CI 0.05, 0.08) and lower use of avoidant coping styles (ß = -0.39, 95% CI -0.41, -0.38). Higher pre-pandemic resilience was also associated with use of eight (distraction [ß = -0.18, 95% CI -0.20, -0.16], substance use [ß = -0.15, 95% CI -0.17, -0.13], behavioral disengagement [ß = -0.29, 95% CI -0.30, -0.27], self-blame [ß = -0.44, 95% CI -0.45, -0.42], emotional support (ß = 0.03, 95% CI 0.01, 0.05), positive reframing [ß = 0.13, 95% CI 0.12, 0.15], humor [ß = 0.03, 95% CI 0.01, 0.05] and religion [ß = 0.06, 95% CI 0.04, 0.08]) of the nine coping strategies in expected directions. CONCLUSION: Findings have important implications for intervention or even prevention efforts to support vulnerable groups, such as women with prior trauma histories, during this and other immensely stressful times. Supporting or building psychological resilience following trauma may promote effective coping in times of future stress.

All nitrogen-fixing root nodule symbioses of angiosperms-legume and actinorhizal symbioses-possess a common ancestor. Molecular processes for the induction of root nodules are modulated by phytohormones, as is the case of the first nodulation-related transcription factor NODULE INCEPTION (NIN), whose expression can be induced by exogenous cytokinin in legumes. The process of actinorhizal nodule organogenesis is less well understood. To study the changes exerted by phytohormones on the expression of the orthologs of CYCLOPS, NIN, and NF-YA1 in the actinorhizal host Datisca glomerata, an axenic hydroponic system was established and used to examine the transcriptional responses (RT-qPCR) in roots treated with the synthetic cytokinin 6-Benzylaminopurine (BAP), the natural auxin Phenylacetic acid (PAA), and the synthetic auxin 1-Naphthaleneacetic acid (NAA). The model legume Lotus japonicus was used as positive control. Molecular readouts for auxins and cytokinin were established: DgSAUR1 for PAA, DgGH3.1. for NAA, and DgARR9 for BAP. L. japonicus NIN was induced by BAP, PAA, and NAA in a dosage- and time-dependent manner. While expression of D. glomerata NIN2 could not be induced in roots, D. glomerata NIN1 was induced by PAA; this induction was abolished in the presence of exogenous BAP. Furthermore, the induction of DgNIN1 expression by PAA required ethylene and gibberellic acid. This study suggests that while cytokinin signaling is central for cortex-induced nodules of L. japonicus, it acts antagonistically to the induction of nodule primordia of D. glomerata by PAA in the root pericycle.

Female Genital Mutilation (FGM) has become a global health concern. It is a deeply entrenched harmful practice involving partial or total removal of the external female genitalia for non-medical reasons. To inform effective policymaking and raise awareness about FGM's health risks, understanding socioeconomic and demographic factors influencing the timing of girls' circumcision is crucial. This study employed semi-parametric survival models to examine the association between residential status and time-to-circumcision of girls in Ethiopia. The data used in this study was the 2016 Ethiopian Demographic and Health Survey (EDHS) report, which was conducted by the Central Statistical Agency (CSA). The analysis revealed that residential status (rural vs urban, HR = 1.73: 1.35-2.70), religion (Muslim vs Christian, HR = 1.51: 1.38-2.70), mother's educational level (none vs higher, HR = 5.25: 2.23-12.36 or primary vs higher HR = 4.12: 1.25-9.68), father's educational level (none vs higher, HR = 1.65: 1.12-2.43), and mother's age (15-24 years vs 35 +, HR = 1.89: 1.21-2.95 or 24-34 years vs 35 +, HR = 1.55: 1.18-2.02) are significant risk factors for age at circumcision. Mother's age and family wealth index were time dependent risk factors. Effective interventions to reduce FGM prevalence would need to address multiple aspects simultaneously, including improving access to education (especially for girls and women), targeting both urban and rural areas with awareness campaigns, and considering culturally sensitive approaches that take into account religious and traditional beliefs while promoting the health and rights of girls and women.

IntroductionAntimicrobial resistance (AMR) is a significant problem in developing, low- and middle-income countries like Nepal. Community engagement can be an important means to address the problem. Knowledge, attitude, practice, and adherence of women regarding antibiotics and AMR was studied.MethodsThis baseline study was conducted in two urban municipalities of Lalitpur district as preparation for a larger intervention study (Mahalaxmi municipality will be the intervention and Godawari the comparison/control area). The study population was women belonging to the mother's groups of 45 female community health volunteers (FCHVs) from each municipality. The study was done from September 2023 to January 2024. A total of 1207 individuals (580 in Mahalaxmi and 627 in Godawari) were involved. Data on demographics, knowledge, attitude, practice, and adherence was collected using a pre-validated structured questionnaire.ResultsThe average age, educational status, monthly income, occupation, presence of respiratory disease, chronic diseases and communicable diseases were found to be not different among the two municipalities. Work experience, presence of respiratory disease and of health worker in the household was different in the baseline survey among the two locations. Knowledge was higher in Mahalaxmi municipality, but adherence was higher in Godawari municipality (p ConclusionAt baseline the two study sites were broadly comparable in terms of participants' demographic characteristics. There was higher knowledge and lower adherence in Mahalaxmi municipality. An educational intervention to improve KAP and adherence is required and will be conducted.

The ability of Mycobacterium tuberculosis (Mtb) to persist in its host may enable an evolutionary advantage for drug resistant variants to emerge. A potential strategy to prevent persistence and gain drug efficacy is to directly target the activity of enzymes that are crucial for persistence. We present a method for expedited discovery and structure-based design of lead compounds by targeting the hypoxia-associated enzyme L-alanine dehydrogenase (AlaDH). Biochemical and structural analyses of AlaDH confirmed binding of nucleoside derivatives and showed a site adjacent to the nucleoside binding pocket that can confer specificity to putative inhibitors. Using a combination of dye-ligand affinity chromatography, enzyme kinetics and protein crystallographic studies, we show the development and validation of drug prototypes. Crystal structures of AlaDH-inhibitor complexes with variations at the N6 position of the adenyl-moiety of the inhibitor provide insight into the molecular basis for the specificity of these compounds. We describe a drug-designing pipeline that aims to block Mtb to proliferate upon re-oxygenation by specifically blocking NAD accessibility to AlaDH. The collective approach to drug discovery was further evaluated through in silico analyses providing additional insight into an efficient drug development strategy that can be further assessed with the incorporation of in vivo studies.

During the COVID-19 pandemic, Nepal rapidly expanded its PCR testing capacity, essential for effective outbreak response. However, many laboratories faced overwhelming test volumes, resulting in delays that may have hindered containment efforts. This study aims to determine whether these challenges stemmed from capacity limitations and/or imbalanced sample distribution due to inadequate coordination. In this retro-perspective simulation of SARS-CoV-2 testing in Nepal during 2021, we evaluate the impact of coordinated sample transfers on reducing laboratory stress and wait times during demand peaks. Our findings reveal that centralized coordination and strategic partnerships for sample transfers significantly enhance diagnostic network performance, even under high demand. These insights offer valuable guidance for policymakers on implementing effective coordination strategies to strengthen diagnostic networks for future pandemics.

Liver cancer is one of the most prevalent malignant diseases in humans and the second leading cause of cancer-related mortality globally. Angiopteris helferiana was mentioned as a possible anticancer herb according to ethnomedicinal applications. However, the molecular docking and chemical profiling of the bioactive phytoconstituents accountable for the reported anticancer action still require research. The present study aims the phytochemical profiling and bioactivity evaluation of A. helferiana. The study design with in-vitro and in-silico technique of the LC-MS followed by a study of the ligand-protein interaction using the molecular docking method, and investigates the cytotoxic activity by MTT assay of A. helferiana bioactive compounds on HepG2 cell lines. LC-MS results detected seventeen phytoconstituents in A. helferiana extract belonging to variable chemical classes with most prevailing compounds such as Vicenin 1, Schafroside, Violanthin, Coumarin, Quercetin, Angiopterioside, and Corosolic acid. The finding concluded that Quercetin showed significant binding energy of -8.8 kcal/mol and then Schafroside also possesses the binding energy of -8.1 kcal/mol against the human PPAR-δ receptor (PDBID: 1I7G). The extract showed the moderate cytotoxic activity having IC50 value of 236.93 μg/mL. Our finding suggests that these bioactive compounds could be developed as promising anticancer agent, but further in-vivo study require to validate the finding along with isolation of individual phytoconstituents.

BackgroundRetroareolar region refers to the region within two centimeters from the nipple and/or involves the nipple-areolar complex on mammogram. In this study, we graded asymmetric retroareolar density on mammography and determined the underlying cause.ObjectivesTo identify and grade retroareolar densities and evaluate characteristics of lesion using ultrasonography and histopathology.MethodsMammograms with asymmetric retroareolar density done in our tertiary care hospital were included. Retroareolar density was categorized into three grades based on morphological appearance in mammography. Sonography was performed in all patients and tissue diagnosis was obtained for suspicious lesions.ResultsOf the 100 patients included in the study, most of the patients with mammographic grade 1, grade 2 and 3 retroareolar asymmetry had normal sonography, pathologically proven mastitis and invasive ductal carcinoma, respectively. Presenting indication usually was diagnostic (n = 87), lump being most common. Benign (58%) diagnosis was more often present, with equal number of normal studies and malignancies (21%). Frequently pathologically proven malignant lesions (n = 17) had grade 3 asymmetry and none were grade 1. Invasive ductal carcinoma was the most common malignancy while mastitis the most common benign disease.ConclusionsGrade I retroareolar asymmetric density on mammography was normal or had a benign etiology while grade 2 or 3 asymmetric density had underlying pathology, often malignancy.ContributionGrading retroareolar density in mammogram may improve the evaluation of retroareolar region and increase emphasis on higher grades.

[This corrects the article DOI: 10.1371/journal.pone.0263759.].

BackgroundNepal is one of the high prevalent countries for tobacco use in Southeast Asia regions. Tobacco related cancer share the major burden since a decade, however, population-based estimates is still lacking. This study provides results from population-based cancer registries on tobacco-related cancer (TRCs) burden in Nepal.MethodsThe data were collected by population-based cancer registry conducted in nine districts by Nepal Health Research Council. The districts were categorized in urban, semi-urban and rural regions on the basis of geographical locations and facilities available in the regions. Analysis was done to identify tobacco-associated cancer incidence, mortality and patterns along with cumulative risk of having cancer before the age of 75 years.ResultsTobacco-related cancer was 35.3% in men and 17.3% in women. We found that every one in 36 men and one in 65 women developed tobacco-related cancer before age 75 in Nepal. Cancer of lung, mouth, esophagus and larynx were among the five most common tobacco-related cancers in both men and women. The incidence of tobacco-associated cancers was higher in urban region with age adjusted rate 33.6 and 17.0 per 100,000 population for men and women respectively compared to semi-urban and rural regions. Tobacco-associated cancer mortality was significantly higher compared to incidence.ConclusionThe prevalence of tobacco-related cancer found high in Nepal despite of enforcement of tobacco control policy and strategies including WHO framework convention on tobacco control. Concerned authorities should focus towards monitoring of implemented tobacco control policy and strategies.

Both diabetes mellitus (DM) and hypertension (HTN) have been on the rise in recent decades all over the world more remarkably in developing countries like India. We intend to measure the prevalence of DM and HTN in the Indian population and to compare the trends and various correlates of these diseases in NFHS (National Family Health Survey)-4 and 5. Data of NFHS-4 and 5 were accessed from dhs program website. All statistical analyses were done in SAS (version 9.4). Mixed effects survey logistic regression models were used for estimating odds ratio (OR).p-values 50 years (11.9%) in males as per NFHS-5. Similarly, the highest prevalence of HTN was seen in the age group of45-49 years (31.2%) in females and > 50 years (41.4%) in males as per NFHS-5. The OR (95% CI) of prevalence of DM, HTN and both the diseases in age group >50 years was 14.46 (13.14-15.7), 16.65 (15.78-17.6), 79.5 (64.76-97.73) respectively when compared to reference age group15-19 years. Highest odds for having both DM, HTN concurrently was in age >50 years with aOR(95% CI) 65.32 (52.26-72.63) in NFHS 4 and 35.57 (97.47-45.53) in NFHS 5.Rise in prevalence of DM, HTN and concurrent presence is noted with an apparent increase in cases.

IntroductionNasopharyngeal carcinoma (NPC) shows geographic and ethnic variation with specific etiopathogenesis. This study characterized the distribution of NPC patients stratified by ethnicity, geography, and histology in a tertiary-level cancer center in Nepal.MethodsA descriptive retrospective study was designed to analyze NPC cases from different regions among patients visiting the hospital from 2016 to 2021. Demographic and clinical information was obtained from medical records. Ethical approval was granted by the Nepal Health Research Council (NHRC). Data analyses and visualization were carried out with R software.ResultsDuring the six-year period, a total of 65 individuals were diagnosed with NPC, comprising 42 males and 23 females. Patient median age was 43 years (range 11-85 years). A bimodal age distribution of cases was observed with peaks in patients aged 30-39 years and 50-59 years. Of the NPC patients studied, 29 were from Koshi Province, with 7 cases from Ilam district and 6 cases from Morang district. There were 18 patients in Bagmati Province, and Kathmandu district had the highest number of cases within this region, with 8 patients. The highest proportion of cases were observed among patients of Janajati ethnicity (60%), including Rai, Limbu, and Sherpa people. Histologically, undifferentiated non-keratinizing NPC was the most commonly observed subtype, accounting for 43.1% of cases, followed by 20% differentiated non-keratinizing NPC and 4.6% keratinizing NPC across the entire sample population. The majority of patients (75.3%) were diagnosed at an advanced stage (stage III or IV) with none diagnosed at stage I.ConclusionsIn our study, most cases of NPC occurred in patients from provinces in eastern Nepal (Koshi province), and of the Janajati ethnic community. The most common histological subtype was undifferentiated non-keratinizing carcinoma. Further epidemiological studies could address differences in prevalence and the challenge of late presentation of NPC patients in Nepal.

The gut microbiome is increasingly being appreciated as a master regulator of animal health. However, avian gut microbiome studies commonly focus on birds of economic importance and the gut microbiomes of raptors remain underexplored. Here we examine the gut microbiota of 29 captive falcons-raptors of historic importance-in the context of avian evolution by sequencing the V4 region of the 16S rRNA gene. Our results reveal that evolutionary histories and diet are significantly associated with avian gut microbiota in general, whereas diet plays a major role in shaping the falcon gut microbiota. Multiple analyses revealed that gut microbial diversity, composition, and relative abundance of key diet-discriminating bacterial genera in the falcon gut closely resemble those of carnivorous raptors rather than those of their closest phylogenetic relatives. Furthermore, the falcon microbiota is dominated by Firmicutes and contains Salmonella at appreciable levels. Salmonella presence was associated with altered functional capacity of the falcon gut microbiota as its abundance is associated with depletion of multiple predicted metabolic pathways involved in protein mass buildup, muscle maintenance, and enrichment of antimicrobial compound degradation, thus increasing the pathogenic potential of the falcon gut. Our results point to the necessity of screening for Salmonella and other human pathogens in captive birds to safeguard both the health of falcons and individuals who come in contact with these birds.

During the COVID-19 pandemic, Nepal rapidly expanded its PCR testing capacity, essential for effective outbreak response. However, many laboratories faced overwhelming test volumes, resulting in delays that may have hindered containment efforts. This study aims to determine whether these challenges stemmed from capacity limitations and/or imbalanced sample distribution due to inadequate coordination. In this retro-perspective simulation of SARS-CoV-2 testing in Nepal during 2021, we evaluate the impact of coordinated sample transfers on reducing laboratory stress and wait times during demand peaks. Our findings reveal that centralized coordination and strategic partnerships for sample transfers significantly enhance diagnostic network performance, even under high demand. These insights offer valuable guidance for policymakers on implementing effective coordination strategies to strengthen diagnostic networks for future pandemics. [ABSTRACT FROM AUTHOR]

BackgroundWomen's birthing experience is a sensitive indicator of the quality of childbirth care and can impact the physical and mental health of both women and their neonates. Negligible evidence exists on Indian women's birth experiences and-to the best of authors' knowledge-no questionnaire has been tested in India for measuring women's birthing experiences. This study aimed to test the construct validity and reliability of the Kannada-translated Revised Childbirth Experience Questionnaire.MethodologyA cross-sectional survey was carried out among postnatal women (n = 251, up to six months postpartum, with a live healthy neonate) who had given birth at a public or private health facility using the Kannada-translated CEQ2 in two districts of Karnataka. Data were collected at participants' homes after seeking written informed consent. Model fit was determined by Confirmatory Factor Analyses.ResultsThe 4-factor model of the CEQ2 showed good fit after deletion of one item (item 8, subcategory "participation") with CMIN = 1.33; SRMR = 0.04; GFI = 0.92, CFI = 0.98, TLI = 0.99, RMSEA = 0.037 and p value 0.002). The Cronbach alpha values were acceptable for the four subscales (0.92, 0.93, 0.97, 0.91) as well as for the overall 21-item scale (0.84).ConclusionsThe Kannada-translated CEQ2 is a reliable tool to measure the childbirth experiences among Kannada-speaking women and can serve as a reliable ongoing evaluation of women's birth experiences.

All nitrogen-fixing root nodule symbioses of angiosperms–legume and actinorhizal symbioses–possess a common ancestor. Molecular processes for the induction of root nodules are modulated by phytohormones, as is the case of the first nodulation-related transcription factor NODULE INCEPTION (NIN), whose expression can be induced by exogenous cytokinin in legumes. The process of actinorhizal nodule organogenesis is less well understood. To study the changes exerted by phytohormones on the expression of the orthologs of CYCLOPS, NIN, and NF-YA1 in the actinorhizal host Datisca glomerata, an axenic hydroponic system was established and used to examine the transcriptional responses (RT-qPCR) in roots treated with the synthetic cytokinin 6-Benzylaminopurine (BAP), the natural auxin Phenylacetic acid (PAA), and the synthetic auxin 1-Naphthaleneacetic acid (NAA). The model legume Lotus japonicus was used as positive control. Molecular readouts for auxins and cytokinin were established: DgSAUR1 for PAA, DgGH3.1. for NAA, and DgARR9 for BAP. L. japonicus NIN was induced by BAP, PAA, and NAA in a dosage- and time-dependent manner. While expression of D. glomerata NIN2 could not be induced in roots, D. glomerata NIN1 was induced by PAA; this induction was abolished in the presence of exogenous BAP. Furthermore, the induction of DgNIN1 expression by PAA required ethylene and gibberellic acid. This study suggests that while cytokinin signaling is central for cortex-induced nodules of L. japonicus, it acts antagonistically to the induction of nodule primordia of D. glomerata by PAA in the root pericycle. [ABSTRACT FROM AUTHOR]

Female Genital Mutilation (FGM) has become a global health concern. It is a deeply entrenched harmful practice involving partial or total removal of the external female genitalia for non-medical reasons. To inform effective policymaking and raise awareness about FGM's health risks, understanding socioeconomic and demographic factors influencing the timing of girls' circumcision is crucial. This study employed semi-parametric survival models to examine the association between residential status and time-to-circumcision of girls in Ethiopia. The data used in this study was the 2016 Ethiopian Demographic and Health Survey (EDHS) report, which was conducted by the Central Statistical Agency (CSA). The analysis revealed that residential status (rural vs urban, HR = 1.73: 1.35–2.70), religion (Muslim vs Christian, HR = 1.51: 1.38–2.70), mother's educational level (none vs higher, HR = 5.25: 2.23–12.36 or primary vs higher HR = 4.12: 1.25–9.68), father's educational level (none vs higher, HR = 1.65: 1.12–2.43), and mother's age (15–24 years vs 35 +, HR = 1.89: 1.21–2.95 or 24–34 years vs 35 +, HR = 1.55: 1.18–2.02) are significant risk factors for age at circumcision. Mother's age and family wealth index were time dependent risk factors. Effective interventions to reduce FGM prevalence would need to address multiple aspects simultaneously, including improving access to education (especially for girls and women), targeting both urban and rural areas with awareness campaigns, and considering culturally sensitive approaches that take into account religious and traditional beliefs while promoting the health and rights of girls and women. [ABSTRACT FROM AUTHOR]

Introduction: Antimicrobial resistance (AMR) is a significant problem in developing, low- and middle-income countries like Nepal. Community engagement can be an important means to address the problem. Knowledge, attitude, practice, and adherence of women regarding antibiotics and AMR was studied. Methods: This baseline study was conducted in two urban municipalities of Lalitpur district as preparation for a larger intervention study (Mahalaxmi municipality will be the intervention and Godawari the comparison/control area). The study population was women belonging to the mother's groups of 45 female community health volunteers (FCHVs) from each municipality. The study was done from September 2023 to January 2024. A total of 1207 individuals (580 in Mahalaxmi and 627 in Godawari) were involved. Data on demographics, knowledge, attitude, practice, and adherence was collected using a pre-validated structured questionnaire. Results: The average age, educational status, monthly income, occupation, presence of respiratory disease, chronic diseases and communicable diseases were found to be not different among the two municipalities. Work experience, presence of respiratory disease and of health worker in the household was different in the baseline survey among the two locations. Knowledge was higher in Mahalaxmi municipality, but adherence was higher in Godawari municipality (p <0.0001). No significant difference was seen in attitude and practice scales. Knowledge, attitude, practice and adherence scores among different subgroups of respondents in the two municipalities were found to be significantly different for occupation (p <0.0001), and education (p <0.0001). The attitude scores were also significantly different according to presence/absence of respiratory disease in the household (p = 0.027). Conclusion: At baseline the two study sites were broadly comparable in terms of participants' demographic characteristics. There was higher knowledge and lower adherence in Mahalaxmi municipality. An educational intervention to improve KAP and adherence is required and will be conducted. [ABSTRACT FROM AUTHOR]

Objectives Child dietary diversity is very low across rural communities in Bihar. Based on the experience of behavior change communication (BCC) module roll out in self-help group (SHG) sessions in rural Bihar, this study aims to assess the impact of the intervention on child dietary diversity levels in the beneficiary groups. Methods The study is based on a pre-post study design whereby child dietary diversity is examined for a sample of 300 children (6–23 months old from 60 village organizations) during both pre-intervention as well as post-intervention phase. The latter consists of two types of group viz. a) children whose mothers were directly exposed to BCC module in SHGs sessions and b) those who were non-participants but may have indirect exposure through spillovers of BCC activities. Econometric analysis including logistic regression as well as propensity score matching techniques are applied for estimating the changes in dietary diversity in the post-intervention phase. Results During the pre-intervention phase, 19% of the children (6–23 months) had adequate dietary diversity (eating from at least 4 out of 7 different food groups) and this increased to 49% among the exposed group and to 28% among the non-exposed group in the post-intervention phase. The exposed group have an odds ratio of 3.81 (95% CI: 2.03, 7.15) for consuming diverse diet when compared to the pre-intervention group. The propensity score matching analysis finds a 33% average treatment effect on the treated (ATT) for the group participating in BCC sessions at SHG events. Conclusion BCC roll out among SHG members is an effective mode to increase dietary diversity among infants and young children. The impact on child dietary diversity was significantly higher among mothers directly exposed to BCC modules. The BCC module also improved knowledge and awareness levels on complementary feeding and child dietary diversity.

The Upper Cretaceous (Maastrichtian) Lameta Formation is well-known for its osteological and oological remains of sauropods from the eastern and western parts of the Narmada Valley, central India. The newly documented ninety-two titanosaur clutches from Dhar District (Madhya Pradesh State, central India) add further to this extensive data. Previously parataxonomy of these titanosaur clutches was carried out with a few brief reports on palaeobiological and taphonomic aspects. The quantitative data collected from the new clutches (this study) opens avenues to additionally understand more about titanosaur palaeobiology and to qualitatively understand preservation and taphonomical aspects of their egg clutches. Herein, we document 256 eggs and three clutch patterns (viz. circular, combination, linear) that are assignable to six oospecies. The high oospecies diversity points to a possible high diversity in titanosaur taxa in the Indian sub-continent though it is not reflected in titanosaurid body fossils. All the macro- and micro-structures helped in understanding egg deformation and preservation from a taphonomic point of view. Additionally, a pathologic egg documented from the study area helped in understanding the reproductive biology of titanosaurs, such as the possibility of segmented oviduct and sequential laying of eggs by titanosaurs. In addition, we made an attempt to infer aspects such as egg burial, absence of parental care, colonial nesting behavior. All the egg clutches were observed within sandy limestone and calcareous sandstone lithologies that occur in scattered outcrops with rocks showing floating siliciclastic grains in a micritic groundmass. Further, the presence of ferruginous sandstone in the Jamniapura and Padlya regions (Dhar District, central India) is indicative of a possible alluvial/fluvial setting. The presence of grainy intraclastic fabric, alveolar-septal fabrics, brecciation and shrinkage cracks observed in the clutch-bearing rocks are indicative of a low energy-low gradient palustrine depositional condition in a fluvial/alluvial setting. Finally, we envisage that a few egg clutches of this area were laid close to lake/pond margins while most were laid away from the lake/pond margins, and thus, were hatched.

Adoption of conservation agriculture (CA) is very slow due to weed infestations. The application of herbicides is the only viable option to deal with problem of weed management to adhere with basic principles of CA. A field experiment was carried out for three years to evaluate the expediency of different herbicides and their sequential applications under CA. In this study, seven treatments comprised of either alone or sequential application of pre-emergence (PE) and post-emergence (PoE) herbicides, hand weeding and weedy check were tested in soybean. Result indicated that sequential application of glyphosate at 1 kg ai ha-1 + pendimethalin at 1 kg ai ha-1as PE followed by PoE application of imazethapyr at 100 g ai ha-1 at 30 days after sowing (DAS) proved to be the best economical option in terms of plant growth parameters, crop biomass, seed yield, weed index and carbon and nutrient recycling. Pearson's correlation coefficients matrix revealed that grain yield was significantly (P

Cell-based strategies for the treatment of ischemic diseases are at the forefront of tissue engineering and regenerative medicine. Cell therapies purportedly can play a key role in the neovascularization of ischemic tissue; however, low survival and poor cell engraftment with the host vasculature following implantation limits their potential to treat ischemic diseases. To overcome these limitations, we previously developed a growth factor sequestering hyaluronic acid (HyA)-based hydrogel that enhanced transplanted mouse cardiosphere-derived cell survival and formation of vasculature that anastomosed with host vessels. In this work, we examined the mechanism by which HyA hydrogels presenting transforming growth factor beta-1 (TGF-β1) promoted proliferation of more clinically relevant human cardiosphere-derived cells (hCDC), and their formation of vascular-like networks in vitro. We observed hCDC proliferation and enhanced formation of vascular-like networks occurred in the presence of TGF-β1. Furthermore, production of nitric oxide (NO), VEGF, and a host of angiogenic factors were increased in the presence of TGF-β1. This response was dependent on the co-activity of CD105 (Endoglin) with the TGF-βR2 receptor, demonstrating its role in the process of angiogenic differentiation and vascular organization of hCDC. These results demonstrated that hCDC form vascular-like networks in vitro, and that the induction of vascular networks by hCDC within growth factor sequestering HyA hydrogels was mediated by TGF-β1/CD105 signaling.

Liver cancer is one of the most prevalent malignant diseases in humans and the second leading cause of cancer-related mortality globally. Angiopteris helferiana was mentioned as a possible anticancer herb according to ethnomedicinal applications. However, the molecular docking and chemical profiling of the bioactive phytoconstituents accountable for the reported anticancer action still require research. The present study aims the phytochemical profiling and bioactivity evaluation of A. helferiana. The study design with in-vitro and in-silico technique of the LC-MS followed by a study of the ligand–protein interaction using the molecular docking method, and investigates the cytotoxic activity by MTT assay of A. helferiana bioactive compounds on HepG2 cell lines. LC-MS results detected seventeen phytoconstituents in A. helferiana extract belonging to variable chemical classes with most prevailing compounds such as Vicenin 1, Schafroside, Violanthin, Coumarin, Quercetin, Angiopterioside, and Corosolic acid. The finding concluded that Quercetin showed significant binding energy of -8.8 kcal/mol and then Schafroside also possesses the binding energy of -8.1 kcal/mol against the human PPAR-δ receptor (PDBID: 1I7G). The extract showed the moderate cytotoxic activity having IC50 value of 236.93 μg/mL. Our finding suggests that these bioactive compounds could be developed as promising anticancer agent, but further in-vivo study require to validate the finding along with isolation of individual phytoconstituents. [ABSTRACT FROM AUTHOR]

Background: Retroareolar region refers to the region within two centimeters from the nipple and/or involves the nipple-areolar complex on mammogram. In this study, we graded asymmetric retroareolar density on mammography and determined the underlying cause. Objectives: To identify and grade retroareolar densities and evaluate characteristics of lesion using ultrasonography and histopathology. Methods: Mammograms with asymmetric retroareolar density done in our tertiary care hospital were included. Retroareolar density was categorized into three grades based on morphological appearance in mammography. Sonography was performed in all patients and tissue diagnosis was obtained for suspicious lesions. Results: Of the 100 patients included in the study, most of the patients with mammographic grade 1, grade 2 and 3 retroareolar asymmetry had normal sonography, pathologically proven mastitis and invasive ductal carcinoma, respectively. Presenting indication usually was diagnostic (n = 87), lump being most common. Benign (58%) diagnosis was more often present, with equal number of normal studies and malignancies (21%). Frequently pathologically proven malignant lesions (n = 17) had grade 3 asymmetry and none were grade 1. Invasive ductal carcinoma was the most common malignancy while mastitis the most common benign disease. Conclusions: Grade I retroareolar asymmetric density on mammography was normal or had a benign etiology while grade 2 or 3 asymmetric density had underlying pathology, often malignancy. Contribution: Grading retroareolar density in mammogram may improve the evaluation of retroareolar region and increase emphasis on higher grades. [ABSTRACT FROM AUTHOR]

BackgroundPeople with drug-resistant tuberculosis (DR-TB) are known to suffer from many mental-health disorders. This study aims to describe the proportion of patients diagnosed with psychiatric comorbidities, the different psychiatric diagnoses made, and treatment outcomes among DR-TB patients with or without psychiatric comorbidity and initiated on DR-TB treatment between January 2012 and March 2019 at Médecins Sans Frontières independent clinic in Mumbai, India.MethodsThis is a retrospective study using routinely collected clinical data. DR-TB care included individualised treatment, psychosocial support, and integrated psychiatric care.ResultsDuring the study period, 341 DR-TB patients were enrolled, with a median age of 25 years (IQR:20.0-36.5 years), 185 (54.2%) females, 143 (41.9%) with PreXDR-TB, and 140 (41.0%) with XDR-TB. All 341 patients were screened by a counsellor, 119 (34.9%) were referred for psychiatric evaluation, and 102 (29.9% of 341) were diagnosed with a psychiatric comorbidity. Among 102 diagnosed with a psychiatric comorbidity, 48 (47.0%) were diagnosed at baseline, and 86 (84.3%), or 25.2% of all 341 patients enrolled, were treated with psychotropic drugs. Depressive disorders were diagnosed in 49 (48.0%), mixed anxiety and depression in 24 (23.5%), neurocognitive disorders and anxiety in five (4.9%), and medication induced psychosis in two (2.0%). No anti-TB drugs were significantly associated with psychiatric comorbidities developed during treatment. Of 102 DR-TB patients with a psychiatric comorbidity, 75.5% (77) had successful DR-TB treatment outcomes, compared to 61.1% (146/239) not diagnosed with a psychiatric comorbidity (p = 0.014).ConclusionIn our setting, among people started on DR-TB treatment, and with a complex TB resistance profile, about one in three patients experienced a psychiatric comorbidity, of which half developed this comorbidity during treatment. With comprehensive psychiatric care integrated into DR-TB care delivery, treatment outcomes were at least as good among those with psychiatric comorbidities compared to those without such comorbidities.

The variability of clinical course and prognosis of COVID-19 highlights the necessity of patient sub-group risk stratification based on clinical data. In this study, clinical data from a cohort of Indian COVID-19 hospitalized patients is used to develop risk stratification and mortality prediction models. We analyzed a set of 70 clinical parameters including physiological and hematological for developing machine learning models to identify biomarkers. We also compared the Indian and Wuhan cohort, and analyzed the role of steroids. A bootstrap averaged ensemble of Bayesian networks was also learned to construct an explainable model for discovering actionable influences on mortality and days to outcome. We discovered blood parameters, diabetes, co-morbidity and SpO2 levels as important risk stratification features, whereas mortality prediction is dependent only on blood parameters. XGboost and logistic regression model yielded the best performance on risk stratification and mortality prediction, respectively (AUC score 0.83, AUC score 0.92). Blood coagulation parameters (ferritin, D-Dimer and INR), immune and inflammation parameters IL6, LDH and Neutrophil (%) are common features for both risk and mortality prediction. Compared with Wuhan patients, Indian patients with extreme blood parameters indicated higher survival rate. Analyses of medications suggest that a higher proportion of survivors and mild patients who were administered steroids had extreme neutrophil and lymphocyte percentages. The ensemble averaged Bayesian network structure revealed serum ferritin to be the most important predictor for mortality and Vitamin D to influence severity independent of days to outcome. The findings are important for effective triage during strains on healthcare infrastructure.

Background High dietary salt intake is recognized as a risk factor for several non-communicable diseases (NCDs), in particular cardiovascular diseases (CVDs), including heart attack and stroke. Accurate measurement of population level salt intake is essential for setting targeted goals and plans for salt reduction strategies. We used a spot urine sample to estimate the mean population salt intake in Nepal and evaluated the association of salt intake with excess weight, hypertension, raised blood sugar and hypercholesterolemia, and a number of socio-demographic characteristics. Methods A population-based cross-sectional study was carried out from February to May 2019 using a WHO STEPwise approach to surveillance. Spot urine was collected from 4361 participants aged 15–69 years for the analysis of salt intake. We then used the INTERSALT equation to calculate population salt intake. Student’s ‘t’ test, one-way ANOVA and multivariable linear regression were used to assess the association between salt intake and a number of factors. Statistical significance was accepted at P < .05. Results The average (±SD) age of participants was 40 (14.1) years. Mean salt intake, derived from spot urine samples, was estimated to be 9.1g/d. A total of 70.8% of the population consumed more than the WHO’s recommended amount of 5g salt per day, with almost one third of the population (29%) consuming more than 10g of salt per day. Higher salt intake was significantly associated with male gender (β for male = 0.98g; 95%CI:0.87,1.1) and younger age groups (β25–39 years = 0.08; 95%CI:-0.08,0.23) and higher BMI (β = 0.19; 95%CI:0.18,0.21). Participants who were hypertensive and had raised blood cholesterol consumed less salt than people who had normal blood pressure and cholesterol levels (PConclusions Salt consumption in Nepal is high, with a total of 70.8% of the population having a mean salt intake >5g/d, well above the World Health Organization recommendation. High salt intake was found to be associated with sex, age group, education, province, BMI, and raised cholesterol level of participants These findings build a strong case for action to reduce salt consumption in Nepal in order to achieve the global target of 30% reduction in population salt intake by 2025.

Iron and steel industries are the major contributors to persistent organic pollutants (POPs). The microbial community present at such sites has the potential to remediate these contaminants. The present study highlights the metabolic potential of the resident bacterial community of PAHs and PCB contaminated soil nearby Bhilai steel plant, Chhattisgarh (India). The GC-MS/MS analysis of soil samples MGB-2 (sludge) and MGB-3 (dry soil) resulted in identification of different classes of POPs including PAHs {benzo[a]anthracene (nd; 17.69%), fluorene (15.89%, nd), pyrene (nd; 18.7%), benzo(b)fluoranthene (3.03%, nd), benzo(k)fluoranthene (11.29%; nd), perylene (5.23%; nd)} and PCBs (PCB-15, PCB-95, and PCB-136). Whole-genome metagenomic analysis by Oxford Nanopore GridION Technology revealed predominance of domain bacteria (97.4%; 97.5%) followed by eukaryote (1.4%; 1.5%), archaea (1.2%; 0.9%) and virus (0.02%; 0.04%) in MGB-2 and MGB-3 respectively. Proteobacteria (44.3%; 50.0%) to be the prominent phylum followed by Actinobacteria (22.1%; 19.5%) in MBG-2 and MBG-3, respectively. However, Eukaryota microbial communities showed a predominance of phylum Ascomycota (20.5%; 23.6%), Streptophyta (18.5%, 17.0%) and unclassified (derived from Eukaryota) (12.1%; 12.2%) in MGB-2 and MGB-3. The sample MGB-3 was richer in macronutrients (C, N, P), supporting high microbial diversity than MGB-2. The presence of reads for biphenyl degradation, dioxin degradation, PAH degradation pathways can be further correlated with the presence of PCB and PAH as detected in the MGB-2 and MGB-3 samples. Further, taxonomic vis-à-vis functional analysis identified Burkholderia, Bradyrhizobium, Mycobacterium, and Rhodopseudomonas as the keystone degrader of PAH and PCB. Overall, our results revealed the importance of metagenomic and physicochemical analysis of the contaminated site, which improves the understanding of metabolic potential and adaptation of bacteria growing under POP contaminated environments.

Background Nepal has implemented the social health security program in certain health facilities to improve access to quality health services. The aim of the study is to understand the utilization pattern of social health security schemes and community’s perception of the social health security program. Method A descriptive cross-sectional mixed-method study was conducted among 300 households of Illam district who had enrolled in the social health security scheme. A multi-stage random sampling method was used. A semi-structured questionnaire was used to collect quantitative data whereas focus group discussions (FGDs) were conducted for qualitative data. Descriptive analysis, bivariate and multivariate analysis was done. FGDs were transcribed and thematic analysis was done. Findings The utilization rate of social health security scheme was 88.7%. Factors associated with the utilization of program included: presence of under-five children and chronic illness in households, sex and age group. Focus group discussion revealed that people were aware of social health insurance and pleased with program implemented by government. However, the hospitals under the social health insurance were not able to meet their expectations. Conclusion Although the utilization of social health security scheme was high, people were dissatisfied with the service provided by the hospital under the social health security scheme. Therefore, the social health insurance board should closely monitor the hospitals and develop a feedback mechanism from the users.

BackgroundUnused medicines can be stored by many people at their places of residence and houses for later use. This study evaluated knowledge, and attitudes regarding unused and expired medicines and explored medicine storage and disposal practices among selected households in the Kathmandu valley, Nepal.MethodA cross-sectional study with a two-stage cluster survey design was done using a semi-structured questionnaire from April to October 2021. The sample size (total number of households) after adjusting for design effect and non-response rate was 210 and the study population was the household heads. Simple random sampling was done to select clusters during the first stage and systematic random sampling to select households during the second stage. Descriptive statistics and t-test/one-way ANOVA were used to compare the respondents' average knowledge scores. Practice variables were presented using frequency distribution.ResultsAround half the respondents were from the Kathmandu district, nearly 20% were from Bhaktapur and 30% were from Lalitpur. Nearly two-thirds were male and about 25% had a bachelor's degree. Nearly 90% of respondents agreed that storage of excess medicines at home may promote self-medication. Similarly, 97.6% of respondents agreed there is a lack of adequate information on the safe disposal of unused medicines. The majority [125 (59.5%)] of participants always checked the expiry date of medicines. The safe methods of medicine disposal were not known by 137 (65.2%) participants. Throwing in a dustbin was the preferred method of expired medicine disposal.ConclusionThe level of knowledge and practice of disposing of unused and expired medicines requires improvement. Educational interventions may help improve awareness further. Creating a chart summarizing disposal procedures of common medicines is important. Similar studies in other regions are required.

BackgroundArtificial intelligence (AI) algorithms have been applied to diagnose temporomandibular disorders (TMDs). However, studies have used different patient selection criteria, disease subtypes, input data, and outcome measures. Resultantly, the performance of the AI models varies.ObjectiveThis study aimed to systematically summarize the current literature on the application of AI technologies for diagnosis of different TMD subtypes, evaluate the quality of these studies, and assess the diagnostic accuracy of existing AI models.Materials and methodsThe study protocol was carried out based on the preferred reporting items for systematic review and meta-analysis protocols (PRISMA). The PubMed, Embase, and Web of Science databases were searched to find relevant articles from database inception to June 2022. Studies that used AI algorithms to diagnose at least one subtype of TMD and those that assessed the performance of AI algorithms were included. We excluded studies on orofacial pain that were not directly related to the TMD, such as studies on atypical facial pain and neuropathic pain, editorials, book chapters, and excerpts without detailed empirical data. The risk of bias was assessed using the QUADAS-2 tool. We used Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) to provide certainty of evidence.ResultsA total of 17 articles for automated diagnosis of masticatory muscle disorders, TMJ osteoarthrosis, internal derangement, and disc perforation were included; they were retrospective studies, case-control studies, cohort studies, and a pilot study. Seven studies were subjected to a meta-analysis for diagnostic accuracy. According to the GRADE, the certainty of evidence was very low. The performance of the AI models had accuracy and specificity ranging from 84% to 99.9% and 73% to 100%, respectively. The pooled accuracy was 0.91 (95% CI 0.76-0.99), I2 = 97% (95% CI 0.96-0.98), p < 0.001.ConclusionsVarious AI algorithms developed for diagnosing TMDs may provide additional clinical expertise to increase diagnostic accuracy. However, it should be noted that a high risk of bias was present in the included studies. Also, certainty of evidence was very low. Future research of higher quality is strongly recommended.

Plant growth promoting rhizobacterium (PGPR) designated as ZNP-4, isolated from the rhizosphere of Ziziphus nummularia, was identified as Enterobacter cloacae following 16S rRNA sequence analysis. The isolated strain exhibited various plant growth promoting (PGP) traits. The 1-aminocyclopropane-1-carboxylic acid deaminase (ACCD) activity was evaluated under diverse physiological conditions that could be useful for minimizing the abiotic stress-induced inhibitory effects on wheat plants. The strain showed resistance to salt (NaCl) and metal (ZnSO4) stress. The effect of E. cloacae ZNP-4 on the augmentation of plant growth was studied under salinity stress of 150 mM (T1 treatment) & 200 mM (T2 treatment) NaCl. The inoculation of strain ZNP-4 significantly improved the various growth parameters of wheat plant such as shoot length (41%), root length (31%), fresh weight (28%), dry weight (29%), photosynthetic pigments chlorophyll a (62%) and chlorophyll b (34%). Additionally, the strain was found to be efficient for minimizing the imposed Zn stress in terms of improving plant growth, biomass and photosynthetic pigments in pots containing different levels of metal stress of 150 mg kg-1 (treatment T1) and 250 mg kg-1 (treatment T2). Isolate ZNP-4 also improved the proline content and decreased malondialdehyde (MDA) level under both salinity and metal stress, therefore maintaining the membrane integrity. Furthermore, bacterial inoculation increased the activities of antioxidative enzymes such as superoxide dismutase (SOD), catalase (CAT), and peroxidase (POX). The positive effects of PGPR occurred concurrently with the decrease in abiotic stress-induced reactive oxygen species (ROS) molecules such as hydrogen peroxide (H2O2) and superoxide (O2-) contents. Overall, the observed results indicate that use of bacteria with such beneficial traits could be used as bio-fertilizers for many crops growing under stress conditions.

Vitamin D plays an important role in proliferation and differentiation of cells and deficiency of vitamin D disturbs angiogenic balance. Previous studies in animal models have reported an association between serum levels of vitamin D and balance between pro- and anti-angiogenic factors. There is insufficient evidence about the effect of vitamin D on mediators of angiogenesis in patients with CKD. We investigated the effect of cholecalciferol supplementation on serum levels of angiogenic markers in non-diabetic patients with CKD stage 3-4. In this secondary analysis on stored samples of our previously published randomized, double-blind, placebo-controlled trial, stable patients of either sex, aged 18-70 years, with non-diabetic CKD stage 3-4 and vitamin D deficiency (serum 25-hydroxyvitamin D ≤20 ng/ml) were randomized to receive either two directly observed oral doses of cholecalciferol (300,000 IU) or matching placebo at baseline and 8 weeks. The primary outcome was change in brachial artery flow-mediated dilatation at 16 weeks. Changes in levels of serum angiogenesis markers (angiopoietin-1, angiopoietin-2, VEGF-A, VEGEF-R, and Tie-2) between groups over 16 weeks were compared. A total 120 patients were enrolled. Supplementation with cholecalciferol led to significant improvement in FMD. Serum 25(OH)D levels were similar in both groups at baseline (13.21±4.78 ng/ml and 13.40±4.42 ng/ml; p = 0.888). At 16 weeks, the serum 25(OH)D levels increased in the cholecalciferol group but not in the placebo group (between-group difference in mean change:23.40 ng/ml; 95% CI, 19.76 to 27.06; p

The actinorhizal plant Datisca glomerata (Datiscaceae, Cucurbitales) establishes a root nodule symbiosis with actinobacteria from the earliest branching symbiotic Frankia clade. A subfamily of a gene family encoding nodule-specific defensin-like cysteine-rich peptides is highly expressed in D. glomerata nodules. Phylogenetic analysis of the defensin domain showed that these defensin-like peptides share a common evolutionary origin with nodule-specific defensins from actinorhizal Fagales and with nodule-specific cysteine-rich peptides (NCRs) from legumes. In this study, the family member with the highest expression levels, DgDef1, was characterized. Promoter-GUS studies on transgenic hairy roots showed expression in the early stage of differentiation of infected cells, and transient expression in the nodule apex. DgDef1 contains an N-terminal signal peptide and a C-terminal acidic domain which are likely involved in subcellular targeting and do not affect peptide activity. In vitro studies with E. coli and Sinorhizobium meliloti 1021 showed that the defensin domain of DgDef1 has a cytotoxic effect, leading to membrane disruption with 50% lethality for S. meliloti 1021 at 20.8 μM. Analysis of the S. meliloti 1021 transcriptome showed that, at sublethal concentrations, DgDef1 induced the expression of terminal quinol oxidases, which are associated with the oxidative stress response and are also expressed during symbiosis. Overall, the changes induced by DgDef1 are reminiscent of those of some legume NCRs, suggesting that nodule-specific defensin-like peptides were part of the original root nodule toolkit and were subsequently lost in most symbiotic legumes, while being maintained in the actinorhizal lineages.

Myostatin (MSTN) is a negative regulator of skeletal muscle growth, thus it was hypothesized that immunization of hens against MSTN would enhance post-hatch growth and muscle mass via suppression of MSTN activity by anti-MSTN IgY in fertilized eggs. This study investigated the effects of immunization of hens against chicken MSTN (chMSTN) or a MSTN fragment (Myo2) on the growth and muscle mass of offspring. In Experiment 1, hens mixed with roosters were divided into two groups and hens in the Control and chMSTN groups were immunized with 0 and 0.5 mg of chMSTN, respectively. In Experiment 2, hens in the chMSTN group were divided into chMSTN and Myo2 groups while the Control group remained the same. The Control and chMSTN groups were immunized in the same way as Experiment 1. The Myo2 group was immunized against MSTN peptide fragment (Myo2) conjugated to KLH. Eggs collected from each group were incubated, and chicks were reared to examine growth and carcass parameters. ELISA showed the production of IgYs against chMSTN and Myo2 and the presence of these antibodies in egg yolk. IgY from the chMSTN and Myo2 groups showed binding affinity to chMSTN, Myo2, and commercial MSTN in Western blot analysis but did not show MSTN-inhibitory capacity in a reporter gene assay. In Experiment 1, no difference was observed in the body weight and carcass parameters of offspring between the Control and chMSTN groups. In Experiment 2, the body weight of chicks from the Myo2 group was significantly lower than that of the Control or chMSTN groups. The dressing percentage and breast muscle mass of the chMSTN and Myo2 groups were significantly lower than those of the Control group, and the breast muscle mass of Myo2 was significantly lower than that of the chMSTN. In summary, in contrast to our hypothesis, maternal immunization of hens did not increase but decreased the body weight and muscle mass of offspring.

The ability of Mycobacterium tuberculosis (Mtb) to persist in its host may enable an evolutionary advantage for drug resistant variants to emerge. A potential strategy to prevent persistence and gain drug efficacy is to directly target the activity of enzymes that are crucial for persistence. We present a method for expedited discovery and structure-based design of lead compounds by targeting the hypoxia-associated enzyme L-alanine dehydrogenase (AlaDH). Biochemical and structural analyses of AlaDH confirmed binding of nucleoside derivatives and showed a site adjacent to the nucleoside binding pocket that can confer specificity to putative inhibitors. Using a combination of dye-ligand affinity chromatography, enzyme kinetics and protein crystallographic studies, we show the development and validation of drug prototypes. Crystal structures of AlaDH-inhibitor complexes with variations at the N6 position of the adenyl-moiety of the inhibitor provide insight into the molecular basis for the specificity of these compounds. We describe a drug-designing pipeline that aims to block Mtb to proliferate upon re-oxygenation by specifically blocking NAD accessibility to AlaDH. The collective approach to drug discovery was further evaluated through in silico analyses providing additional insight into an efficient drug development strategy that can be further assessed with the incorporation of in vivo studies.

The rapid emergence of coronavirus disease 2019 (COVID-19) as a global pandemic affecting millions of individuals globally has necessitated sensitive and high-throughput approaches for the diagnosis, surveillance, and determining the genetic epidemiology of SARS-CoV-2. In the present study, we used the COVIDSeq protocol, which involves multiplex-PCR, barcoding, and sequencing of samples for high-throughput detection and deciphering the genetic epidemiology of SARS-CoV-2. We used the approach on 752 clinical samples in duplicates, amounting to a total of 1536 samples which could be sequenced on a single S4 sequencing flow cell on NovaSeq 6000. Our analysis suggests a high concordance between technical duplicates and a high concordance of detection of SARS-CoV-2 between the COVIDSeq as well as RT-PCR approaches. An in-depth analysis revealed a total of six samples in which COVIDSeq detected SARS-CoV-2 in high confidence which were negative in RT-PCR. Additionally, the assay could detect SARS-CoV-2 in 21 samples and 16 samples which were classified inconclusive and pan-sarbeco positive respectively suggesting that COVIDSeq could be used as a confirmatory test. The sequencing approach also enabled insights into the evolution and genetic epidemiology of the SARS-CoV-2 samples. The samples were classified into a total of 3 clades. This study reports two lineages B.1.112 and B.1.99 for the first time in India. This study also revealed 1,143 unique single nucleotide variants and added a total of 73 novel variants identified for the first time. To the best of our knowledge, this is the first report of the COVIDSeq approach for detection and genetic epidemiology of SARS-CoV-2. Our analysis suggests that COVIDSeq could be a potential high sensitivity assay for the detection of SARS-CoV-2, with an additional advantage of enabling the genetic epidemiology of SARS-CoV-2.

The Indian Middle Palaeolithic has been recognized as crucial evidence for understanding the complex behavioural dynamics of hominins and is also seen as a behavioural marker of early Homo sapiens in the region. Recent research has pushed back the timeline of the Middle Palaeolithic to the Middle Pleistocene epoch, indicating a potential in-situ emergence from the earlier Late Acheulian culture. The long-lasting Middle Palaeolithic culture in India evolve over multiple glacial-interglacial cycle, showing signs of behavioural resilience to bigger climatic upheaval like ~74 ka Toba super-eruption. This has added to the complexity of our understanding of the Middle Palaeolithic in the region and emphasizes the need for further research. This study focuses upon the investigation of Middle Palaeolithic artefacts found in the Retlapalle area within the upper Gundlakamma river basin, Andhra Pradesh. The dating of the artefact-bearing layer was carried out using the p-IR-IRSL method, which revealed a burial age of 139±17 thousand years. The Retlapalle assemblage is characterized by a diverse range of Levallois core reductions, various retouched artefacts, with a dominance of pointed tools, and a few blade components. The study provides a valuable addition to the existing body of data concerning Palaeolithic sites dating back to the Middle Pleistocene, a period that remains relatively underexplored. [ABSTRACT FROM AUTHOR]

Both diabetes mellitus (DM) and hypertension (HTN) have been on the rise in recent decades all over the world more remarkably in developing countries like India. We intend to measure the prevalence of DM and HTN in the Indian population and to compare the trends and various correlates of these diseases in NFHS (National Family Health Survey)-4 and 5. Data of NFHS-4 and 5 were accessed from dhs program website. All statistical analyses were done in SAS (version 9.4). Mixed effects survey logistic regression models were used for estimating odds ratio (OR).p-values <0.05 were considered significant.1,637,762 individual case entries were evaluated. Both the diseases showed an increasing trend as per the advancing age in both sexes. The highest prevalence of DM is seen in the age group of 45–49 years (7.8%) in females and > 50 years (11.9%) in males as per NFHS-5. Similarly, the highest prevalence of HTN was seen in the age group of45–49 years (31.2%) in females and > 50 years (41.4%) in males as per NFHS-5. The OR (95% CI) of prevalence of DM, HTN and both the diseases in age group >50 years was 14.46 (13.14–15.7), 16.65 (15.78–17.6), 79.5 (64.76–97.73) respectively when compared to reference age group15-19 years. Highest odds for having both DM, HTN concurrently was in age >50 years with aOR(95% CI) 65.32 (52.26–72.63) in NFHS 4 and 35.57 (97.47–45.53) in NFHS 5.Rise in prevalence of DM, HTN and concurrent presence is noted with an apparent increase in cases. [ABSTRACT FROM AUTHOR]

BackgroundAntibodies are important in the control of blood stage Plasmodium falciparum infection. It is unclear which antibody responses are responsible for, or even associated with protection, partly due to confounding by heterogeneous exposure. Assessment of response to partially effective antimalarial therapy, which requires the host to assist in clearing parasites, offers an opportunity to measure protection independent of exposure.MethodsA cohort of children aged 1-10 years in Kampala, Uganda were treated with amodiaquine+sulfadoxine-pyrimethamine for uncomplicated malaria. Serum samples from the time of malaria diagnosis and 14 days later were analyzed for total IgG to 8 P. falciparum antigens using a quantitative indirect ELISA. Associations between antibody levels and risk of treatment failure were estimated using Cox proportional hazard regression.ResultsHigher levels of antibodies to apical membrane antigen 1 (AMA-1), but to none of the other 7 antigens were significantly associated with protection against treatment failure (HR 0.57 per 10-fold increase in antibody level, CI 0.41-0.79, p = 0.001). Protection increased consistently across the entire range of antibody levels.ConclusionsMeasurement of antibody levels to AMA-1 at the time of malaria may offer a quantitative biomarker of blood stage immunity to P. falciparum, a tool which is currently lacking.