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Background People 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. Methods This is a retrospective study using routinely collected clinical data. DR-TB care included individualised treatment, psychosocial support, and integrated psychiatric care. Results During 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). Conclusion In 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.

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 (P2 value of 0.53, 0.99, 0.95 and 0.98, respectively. The fitted stepwise multiple regression model also revealed that N and P uptake in grain, weed density at 20 DAS and K uptake in weed were actual predictor for grain yield. We concluded that, effective and economical weed control under CA in soybean can be achieved through sequential application of glyphosate along with pendimethalin at 1 kg ai ha-1 each PE followed by PoE use of imazethapyr at 100 g ai ha-1 at 30 DAS.

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.

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 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.

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.

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

Background Artificial 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. Objective This 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 methods The 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. Results A 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. Conclusions Various 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.

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.

Background Unused 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. Method A 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. Results Around 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. Conclusion The 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.

Drug repurposing has the potential to bring existing de-risked drugs for effective intervention in an ongoing pandemic—COVID-19 that has infected over 131 million, with 2.8 million people succumbing to the illness globally (as of April 04, 2021). We have used a novel `gene signature’-based drug repositioning strategy by applying widely accepted gene ranking algorithms to prioritize the FDA approved or under trial drugs. We mined publically available RNA sequencing (RNA-Seq) data using CLC Genomics Workbench 20 (QIAGEN) and identified 283 differentially expressed genes (FDR1) after a meta-analysis of three independent studies which were based on severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection in primary human airway epithelial cells. Ingenuity Pathway Analysis (IPA) revealed that SARS-CoV-2 activated key canonical pathways and gene networks that intricately regulate general anti-viral as well as specific inflammatory pathways. Drug database, extracted from the Metacore and IPA, identified 15 drug targets (with information on COVID-19 pathogenesis) with 46 existing drugs as potential-novel candidates for repurposing for COVID-19 treatment. We found 35 novel drugs that inhibit targets (ALPL, CXCL8, and IL6) already in clinical trials for COVID-19. Also, we found 6 existing drugs against 4 potential anti-COVID-19 targets (CCL20, CSF3, CXCL1, CXCL10) that might have novel anti-COVID-19 indications. Finally, these drug targets were computationally prioritized based on gene ranking algorithms, which revealed CXCL10 as the common and strongest candidate with 2 existing drugs. Furthermore, the list of 283 SARS-CoV-2-associated proteins could be valuable not only as anti-COVID-19 targets but also useful for COVID-19 biomarker development.

Background A key component of the WHO End TB Strategy is quality of care, for which case fatality is a critical marker. Half of India’s nearly 3 million TB patients are treated in the highly unregulated private sector, yet little is known about the outcomes of these patients. Using a retrospective cohort design, we estimated the case fatality ratio (CFR) and rate of recurrent TB among patients managed in the private healthcare sector in Patna, India. Methods World Health Partners’ Private Provider Interface Agencies (PPIA) pilot project in Patna has treated 89,906 private sector TB patients since 2013. A random sample of 4,000 patients treated from 2014 to 2016 were surveyed in 2018 for case fatality and recurrent TB. CFR is defined as the proportion of patients who die during the period of interest. Treatment CFRs, post-treatment CFRs and rates of recurrent TB were estimated. Predictors for fatality and recurrence were identified using Cox proportional hazards modelling. Survey non-response was adjusted for using inverse probability selection weighting. Results The survey response rate was 56.0%. The weighted average follow-up times were 8.7 months in the treatment phase and 26.4 months in the post-treatment phase. Unobserved patients were more likely to have less than one month of treatment adherence (32.0% vs. 13.5%) and were more likely to live in rural Patna (21.9% vs. 15.0%). The adjusted treatment phase CFR was 7.27% (5.97%, 8.49%) and at 24 months post-treatment was 3.32% (2.36%, 4.42%). The adjusted 24 month post-treatment phase recurrent TB rate was 3.56% (2.54%, 4.79%). Conclusions Our cohort study provides critical estimates of TB patient outcomes in the Indian private sector, and accounts for selection bias. Patients in the private sector in Patna experienced a moderate treatment CFR but rates of recurrent TB and post-treatment fatality were low.