Unearthing the Fossorial Tadpoles of the Indian Dancing Frog Family Micrixalidae

Tadpoles of the monotypic Indian dancing frog family Micrixalidae have remained obscure for over 125 years. Here we report the discovery of the elusive tadpoles of Micrixalus herrei from the sand beds of a forested stream in southern Western Ghats, and confirm their identity through DNA barcoding. These actively burrowing tadpoles lead an entirely fossorial life from eggs to late metamorphic stages. We describe their internal and external morphological characters while highlighting the following features: eel-like appearance, extensively muscularized body and tail, reduced tail fins, skin-covered eyes, delayed development of eye pigmentation in early pre-metamorphic stages (Gosner stages 25–29), prominent tubular sinistral spiracle, large transverse processes on vertebrae II and III, ankylosed ribs on transverse processes of vertebra II, notochord terminating before the atlantal cotyle-occipital condyle junction, absence of keratodonts, serrated well-formed jaw sheaths, and extensive calcified endolymphatic sacs reaching sacrum posteriorly. The tadpole gut contains mostly fine sediments and sand. We discuss the eel-like morphology and feeding habits of M. herrei in the context of convergence with other well-known fossorial tadpoles. This discovery builds the knowledge base for further comparative analyses and conservation of Micrixalus, an ancient and endemic lineage of Indian frogs

An integrative approach to infer systematic relationships and define species groups in the shrub frog genus Raorchestes, with description of five new species from the Western Ghats, India

The genus Raorchestes is a large radiation of Old World tree frogs for which the Western Ghats in Peninsular India is the major center for origin and diversification. Extensive studies on this group during the past two decades have resolved long-standing taxonomic confusions and uncovered several new species, resulting in a four-fold increase in the number of known Raorchestes frogs from this region. Our ongoing research has revealed another five new species in the genus, formally described as Raorchestes drutaahu sp. nov., Raorchestes kakkayamensis sp. nov., Raorchestes keirasabinae sp. nov., Raorchestes sanjappai sp. nov., and Raorchestes vellikkannan sp. nov., all from the State of Kerala in southern Western Ghats. Based on new collections, we also provide insights on the taxonomic identity of three previously known taxa. Furthermore, since attempts for an up-to-date comprehensive study of this taxonomically challenging genus using multiple integrative taxonomic approaches have been lacking, here we review the systematic affinities of all known Raorchestes species and define 16 species groups based on evidence from multi-gene (2,327 bp) phylogenetic analyses, several morphological characters (including eye colouration and pattern), and acoustic parameters (temporal and spectral properties, as well as calling height). The results of our study present novel insights to facilitate a better working taxonomy for this rather speciose and morphologically conserved radiation of shrub frogs. This will further enable proper field identification, provide momentum for multi-disciplinary studies, as well as assist conservation of one of the most colourful and acoustically diverse frog groups of the Western Ghats biodiversity hotspot

In silico targeting enterotoxin from Staphylococcus aureus with selected flavonoids: Hope for the discovery of natural anti-mastitis agents

Staphylococcus aureus is a facultative anaerobe and catalase-positive bacterium responsible for various skin infections and life-threatening problems, including bacteremia and pneumonia. This bacterium produces a bunch of superantigens in the blood called enterotoxin. This toxin is responsible for food poisoning and toxic shock syndrome. Moreover, Bovine mastitis is also associated with S. aureus. Further, S. aureus related to drug resistance makes the infection more dreadful. Now a day, various natural compounds such as phytochemicals are gaining importance as they are effective against many diseases, including S. aureus infections. The present study used molecular docking of three ligands, i.e., Kaempferol, Apigenin, and Quercetin, with enterotoxin A from S. aureus. The docking study revealed that the binding energy of ligands with receptors was -6.6 to -6.9 Kcal/mol. Kaempferol had the highest binding affinity of -6.9 Kcal/mol, suggesting it has a potential against S. aureus. Therefore, in the current research, we have tried to identify occurring compounds that might be used to develop an effective anti-S.aureus agent. The findings are encouraging and will aid researchers in creating new mastitis-fighting medications based on natural phytochemicals

Effect of Phacoemulsification on Intraocular Pressure in Eyes with Functioning Tube Shunts

Purpose: To evaluate the effect of phacoemulsification on intraocular pressure (IOP) in eyes with functioning tube shunts. Methods: This was a retrospective chart review of primary open-angle glaucoma (POAG) patients with a functioning tube who underwent phacoemulsification and had ≥24 months of follow-up. The primary end point was defined as surgical failure (IOP > 21 mmHg) at month 24, progression to no light perception (NLP) vision, glaucoma reoperation, or implant removal. Surgical failure defined as IOP >18 and >15 mmHg, changes in visual acuity (VA), IOP, and number of medications were assessed. Results: Twenty-seven eyes of 27 patients with moderate or severe POAG were included. The mean age of the patients was 64.2 ± 10.8 years. The interval between the tube shunt and phacoemulsification was 28.8 ± 25.0 months. At the end of the study, four (14.8%) eyes met the failure criteria; the average time to failure was 9.3 ± 3.8 months. The causes of failure were high IOP in two (50.0%) and glaucoma reoperation in two (50.0%) eyes; however, no eyes progressed to NLP vision. Surgical failure defined as IOP >18 and >15 mmHg showed an increasing failure rate (18.5% and 48.5%, respectively). The mean IOP and medications number remained stable at month 24 compared to baseline (P = 0.131 and P = 0.302, respectively). Initially, VA showed improvement, with the greatest improvement at 6 months (P = 0.001), but at 24 months the improvement was no longer significant (P = 0.430). Conclusion: Phacoemulsification in patients with functioning tubes did not change the mean IOP in most of the patients (86.2%); the number of medications also did not increase

Effect of Phacoemulsification on Intraocular Pressure in Eyes With Functioning Tube Shunts

Purpose: To evaluate the effect of phacoemulsification on intraocular pressure (IOP) in eyes with functioning tube shunts. Methods: This was a retrospective chart review of primary open-angle glaucoma (POAG) patients with a functioning tube who underwent phacoemulsification and had ≥24 months of follow-up. The primary end point was defined as surgical failure (IOP \u3e 21 mmHg) at month 24, progression to no light perception (NLP) vision, glaucoma reoperation, or implant removal. Surgical failure defined as IOP \u3e18 and \u3e15 mmHg, changes in visual acuity (VA), IOP, and number of medications were assessed. Results: Twenty-seven eyes of 27 patients with moderate or severe POAG were included. The mean age of the patients was 64.2 ± 10.8 years. The interval between the tube shunt and phacoemulsification was 28.8 ± 25.0 months. At the end of the study, four (14.8%) eyes met the failure criteria; the average time to failure was 9.3 ± 3.8 months. The causes of failure were high IOP in two (50.0%) and glaucoma reoperation in two (50.0%) eyes; however, no eyes progressed to NLP vision. Surgical failure defined as IOP \u3e18 and \u3e15 mmHg showed an increasing failure rate (18.5% and 48.5%, respectively). The mean IOP and medications number remained stable at month 24 compared to baseline (P = 0.131 and P = 0.302, respectively). Initially, VA showed improvement, with the greatest improvement at 6 months (P = 0.001), but at 24 months the improvement was no longer significant (P = 0.430). Conclusion: Phacoemulsification in patients with functioning tubes did not change the mean IOP in most of the patients (86.2%); the number of medications also did not increase

Bronchiectasis in India:results from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India Registry

BACKGROUND: Bronchiectasis is a common but neglected chronic lung disease. Most epidemiological data are limited to cohorts from Europe and the USA, with few data from low-income and middle-income countries. We therefore aimed to describe the characteristics, severity of disease, microbiology, and treatment of patients with bronchiectasis in India. METHODS: The Indian bronchiectasis registry is a multicentre, prospective, observational cohort study. Adult patients ( 6518 years) with CT-confirmed bronchiectasis were enrolled from 31 centres across India. Patients with bronchiectasis due to cystic fibrosis or traction bronchiectasis associated with another respiratory disorder were excluded. Data were collected at baseline (recruitment) with follow-up visits taking place once per year. Comprehensive clinical data were collected through the European Multicentre Bronchiectasis Audit and Research Collaboration registry platform. Underlying aetiology of bronchiectasis, as well as treatment and risk factors for bronchiectasis were analysed in the Indian bronchiectasis registry. Comparisons of demographics were made with published European and US registries, and quality of care was benchmarked against the 2017 European Respiratory Society guidelines. FINDINGS: From June 1, 2015, to Sept 1, 2017, 2195 patients were enrolled. Marked differences were observed between India, Europe, and the USA. Patients in India were younger (median age 56 years [IQR 41-66] vs the European and US registries; p<0\ub70001]) and more likely to be men (1249 [56\ub79%] of 2195). Previous tuberculosis (780 [35\ub75%] of 2195) was the most frequent underlying cause of bronchiectasis and Pseudomonas aeruginosa was the most common organism in sputum culture (301 [13\ub77%]) in India. Risk factors for exacerbations included being of the male sex (adjusted incidence rate ratio 1\ub717, 95% CI 1\ub703-1\ub732; p=0\ub7015), P aeruginosa infection (1\ub729, 1\ub710-1\ub750; p=0\ub7001), a history of pulmonary tuberculosis (1\ub720, 1\ub707-1\ub734; p=0\ub7002), modified Medical Research Council Dyspnoea score (1\ub732, 1\ub725-1\ub739; p<0\ub70001), daily sputum production (1\ub716, 1\ub703-1\ub730; p=0\ub7013), and radiological severity of disease (1\ub703, 1\ub701-1\ub704; p<0\ub70001). Low adherence to guideline-recommended care was observed; only 388 patients were tested for allergic bronchopulmonary aspergillosis and 82 patients had been tested for immunoglobulins. INTERPRETATION: Patients with bronchiectasis in India have more severe disease and have distinct characteristics from those reported in other countries. This study provides a benchmark to improve quality of care for patients with bronchiectasis in India. FUNDING: EU/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium, European Respiratory Society, and the British Lung Foundation

Global, regional, and national sex-specific burden and control of the HIV epidemic, 1990-2019, for 204 countries and territories: the Global Burden of Diseases Study 2019

Background: The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic. Methods: To estimate age-specific and sex-specific trends in 48 of 204 countries, we extended the Estimation and Projection Package Age-Sex Model to also implement the spectrum paediatric model. We used this model in cases where age and sex specific HIV-seroprevalence surveys and antenatal care-clinic sentinel surveillance data were available. For the remaining 156 of 204 locations, we developed a cohort-incidence bias adjustment to derive incidence as a function of cause-of-death data from vital registration systems. The incidence was input to a custom Spectrum model. To assess progress, we measured the percentage change in incident cases and deaths between 2010 and 2019 (threshold >75% decline), the ratio of incident cases to number of people living with HIV (incidence-to-prevalence ratio threshold <0·03), and the ratio of incident cases to deaths (incidence-to-mortality ratio threshold <1·0). Findings: In 2019, there were 36·8 million (95% uncertainty interval [UI] 35·1–38·9) people living with HIV worldwide. There were 0·84 males (95% UI 0·78–0·91) per female living with HIV in 2019, 0·99 male infections (0·91–1·10) for every female infection, and 1·02 male deaths (0·95–1·10) per female death. Global progress in incident cases and deaths between 2010 and 2019 was driven by sub-Saharan Africa (with a 28·52% decrease in incident cases, 95% UI 19·58–35·43, and a 39·66% decrease in deaths, 36·49–42·36). Elsewhere, the incidence remained stable or increased, whereas deaths generally decreased. In 2019, the global incidence-to-prevalence ratio was 0·05 (95% UI 0·05–0·06) and the global incidence-to-mortality ratio was 1·94 (1·76–2·12). No regions met suggested thresholds for progress. Interpretation: Sub-Saharan Africa had both the highest HIV burden and the greatest progress between 1990 and 2019. The number of incident cases and deaths in males and females approached parity in 2019, although there remained more females with HIV than males with HIV. Globally, the HIV epidemic is far from the UNAIDS benchmarks on progress metrics. Funding: The Bill & Melinda Gates Foundation, the National Institute of Mental Health of the US National Institutes of Health (NIH), and the National Institute on Aging of the NIH

Assessing performance of the Healthcare Access and Quality Index, overall and by select age groups, for 204 countries and territories, 1990-2019: a systematic analysis from the Global Burden of Disease Study 2019

Background: Health-care needs change throughout the life course. It is thus crucial to assess whether health systems provide access to quality health care for all ages. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019), we measured the Healthcare Access and Quality (HAQ) Index overall and for select age groups in 204 locations from 1990 to 2019. Methods: We distinguished the overall HAQ Index (ages 0–74 years) from scores for select age groups: the young (ages 0–14 years), working (ages 15–64 years), and post-working (ages 65–74 years) groups. For GBD 2019, HAQ Index construction methods were updated to use the arithmetic mean of scaled mortality-to-incidence ratios (MIRs) and risk-standardised death rates (RSDRs) for 32 causes of death that should not occur in the presence of timely, quality health care. Across locations and years, MIRs and RSDRs were scaled from 0 (worst) to 100 (best) separately, putting the HAQ Index on a different relative scale for each age group. We estimated absolute convergence for each group on the basis of whether the HAQ Index grew faster in absolute terms between 1990 and 2019 in countries with lower 1990 HAQ Index scores than countries with higher 1990 HAQ Index scores and by Socio-demographic Index (SDI) quintile. SDI is a summary metric of overall development. Findings: Between 1990 and 2019, the HAQ Index increased overall (by 19·6 points, 95% uncertainty interval 17·9–21·3), as well as among the young (22·5, 19·9–24·7), working (17·2, 15·2–19·1), and post-working (15·1, 13·2–17·0) age groups. Large differences in HAQ Index scores were present across SDI levels in 2019, with the overall index ranging from 30·7 (28·6–33·0) on average in low-SDI countries to 83·4 (82·4–84·3) on average in high-SDI countries. Similarly large ranges between low-SDI and high-SDI countries, respectively, were estimated in the HAQ Index for the young (40·4–89·0), working (33·8–82·8), and post-working (30·4–79·1) groups. Absolute convergence in HAQ Index was estimated in the young group only. In contrast, divergence was estimated among the working and post-working groups, driven by slow progress in low-SDI countries. Interpretation: Although major gaps remain across levels of social and economic development, convergence in the young group is an encouraging sign of reduced disparities in health-care access and quality. However, divergence in the working and post-working groups indicates that health-care access and quality is lagging at lower levels of social and economic development. To meet the needs of ageing populations, health systems need to improve health-care access and quality for working-age adults and older populations while continuing to realise gains among the young. Funding: Bill & Melinda Gates Foundation

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND: Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. METHODS: We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. FINDINGS: Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. INTERPRETATION: As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed