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Phytoplankton have a high potential for CO 2 capture and conversion. Besides being a vital food source at the base of oceanic and freshwater food webs, microalgae provide a critical platform for producing chemicals and consumer products. Enhanced nutrient levels, elevated CO 2 , and rising temperatures increase the frequency of algal blooms, which often have negative effects such as fish mortalities, loss of flora and fauna, and the production of algal toxins. Harmful algal blooms (HABs) produce toxins that pose major challenges to water quality, ecosystem function, human health, tourism, and the food web. These toxins have complex chemical structures and possess a wide range of biological properties with potential applications as new therapeutics. This review presents a balanced and comprehensive assessment of the roles of algal blooms in generating fixed carbon for the food chain, sequestering carbon, and their unique secondary metabolites. The structural complexity of these metabolites has had an unprecedented impact on structure elucidation technologies and total synthesis, which are highlighted throughout this review. In addition, the influence of biogeochemical environmental perturbations on algal blooms and their influence on biospheric environments is discussed. Lastly, we summarize work on management strategies and technologies for the control and treatment of HABs.

Background: Reliable and recent data of human rabies deaths and animal bites are not available in India, where a third of global cases occur. Since there is a global target of eliminating dog-mediated human rabies by 2030, understanding whether the country is on track is essential. We aimed to estimate the animal-bite burden and the number of human rabies deaths in India., Methods: We conducted a community-based nationwide cross-sectional survey with a multistage cluster-sampling design from March 2, 2022 to Aug 26, 2023, covering 60 districts in 15 Indian states. The head of the household or an adult family member was interviewed to collect information about animal-bite history in family members, receipt of anti-rabies vaccination (ARV), and death following animal bite in the family. Annual animal-bite incidence along with 95% CIs were estimated after applying the sampling weights and adjusting for clustering. We estimated annual human rabies deaths using a decision-tree probability model with parameters from the community survey and laboratory data on rabies positivity among suspected rabid dogs., Findings: Of the 337 808 individuals residing in the 78 807 households surveyed, 2052 gave a history of animal bite, mostly (1576 [76·8%]) due to dogs in the past 1 year. The weighted and adjusted annual incidence of animal bite was 6·6 (95% CI 5·7-7·6) per 1000 population, translating into 9·1 million bites nationally. Annual dog-bite incidence was 5·6 (4·8-6·6) per 1000. Among people who had been bitten by a dog, 323 (20·5%) did not receive ARV, and 1043 (66·2%) received at least three doses. Nearly half (615 [49·1%]) of the 1253 individuals who received one dose did not complete their full course of vaccination. We estimated 5726 (95% uncertainty interval 3967-7350) human rabies deaths occurring annually in India., Interpretation: Although there was a substantial decline in human rabies deaths over the past two decades, to eliminate dog-mediated human rabies by 2030, India needs to fast-track its actions by adopting a focused one-health approach. Integrating human and animal surveillance, ensuring timely administration of full course of post-exposure prophylaxis, and accelerating dog vaccination across the country are crucial steps towards this goal., Funding: Indian Council of Medical Research., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Sponges are recognized as promising sources for novel bioactive metabolites. Among them are terpenoid metabolites that constitute key biochemical defense mechanisms in several sponge taxa. Despite their significance, the genetic basis for terpenoid biosynthesis in sponges remains poorly understood. Dictyoceratida comprise demosponges well-known for their bioactive terpenoids. In this study, we explored the currently available genomic data for insights into the metabolic pathways of dictyoceratid terpenoids. We first identified prenyltransferase (PT) and terpene cyclase (TC) enzymes essential for the terpenoid biosynthetic processes in the terrestrial realm by analyzing available transcriptomic and genomic data of Dictyoceratida sponges and 10 other sponge species. All Dictyoceratida sponges displayed various PTs involved in either sesqui- or diterpene, steroid and carotenoid production. Additionally, it was possible to identify a potential candidate for a dictyoceratid sesterterpene PT. However, analogs of common terrestrial TCs were absent, suggesting the existence of a distinct or convergently evolved sponge-specific TC. Our study aims to contribute to the foundational understanding of terpene biosynthesis in sponges, unveiling the currently evident genetic components for terpenoid production in species not previously studied. Simultaneously, it aims to identify the known and unknown factors, as a starting point for biochemical and genetic investigations in sponge terpenoid production., (© 2024 The Author(s). Chemistry & Biodiversity published by Wiley-VHCA AG.)

Retinoblastoma (RB) is an intraocular malignancy initiated by loss of RB1 function and/or dysregulation of MYCN oncogene. RB is primarily treated with chemotherapy; however, systemic toxicity and long-term adverse effects remain a significant challenge necessitating the identification of specific molecular targets. Aurora kinase A (AURKA), a critical cell cycle regulator, contributes to cancer pathogenesis, especially in RB1-deficient and MYCN-dysregulated tumors. The current immunohistochemistry study in patient specimens (n = 67) indicated that AURKA is overexpressed in RB, and this elevated expression correlates with one or more histopathologic high-risk factors, such as tumor involvement of the optic nerve, choroid, sclera, and/or anterior segment. More specifically, AURKA is ubiquitously expressed in most advanced-stage RB tumors that show a suboptimal response to chemotherapy. shRNA-mediated depletion/pharmacologic inhibition studies in cell lines, patient-derived cells, in vivo xenografts, and enucleated patient specimens confirmed that RB cells are highly sensitive to a lack of functional AURKA. In addition, AURKA and N-myc proto-oncogene protein (MYCN) associate with each other to regulate their levels in RB cells. Overall, these results demonstrate a previously unknown up-regulation of AURKA in RB, facilitated by its crosstalk with MYCN. The elevated levels of this kinase may indicate unfavorable prognosis in tumors refractory to chemotherapy. This study provides a rationale and confirms that therapeutic targeting of elevated AURKA in RB could be a potential treatment approach., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Stroke is a major cause of adult disability, prompting the exploration of innovative rehabilitation methods. Virtual rehabilitation (VR), leveraging technological advances, has gained popularity as a treatment for stroke recovery., Methodology: The authors conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) published in English within the last decade, adhering to the PRISMA guidelines. The authors searched databases such as Medline/PubMed, and the Cochrane Library using specific search keywords and Medical Subject Headings (MeSH). The methodological quality was assessed using the PEDro scale, focusing on RCTs involving adult stroke patients undergoing VR rehabilitation, with outcomes related to motor function and quality of life., Results: The authors included 15 studies in our meta-analysis. VR rehabilitation offers several advantages over traditional therapy, such as enhanced feedback and increased patient motivation. Engaging VR environments helps improve focus during treatment, potentially boosting recovery from post-stroke impairments. VR therapies significantly benefit motor function, which can improve activities of daily living and overall quality of life., Conclusion: VR has demonstrated efficacy in improving motor function and quality of life for stroke survivors. Future research should explore patient variability and refine intervention methods. Incorporating VR into rehabilitation programs could optimize stroke recovery outcomes., Competing Interests: All authors do not have any conflict of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The southern coast of Africa is one of the few places in the world where water temperatures are predicted to cool in the future. This endemism-rich coastline is home to two sister species of kelps of the genus Ecklonia maxima and Ecklonia radiata, each associated with specific thermal niches, and occuring primarily on opposite sides of the southern tip of Africa. Historical distribution records indicate that E. maxima has recently shifted its distribution ~ 70 km eastward, to sites where only E. radiata was previously reported. The contact of sister species with contrasting thermal affinities and the occurrence of mixed morphologies raised the hypothesis that hybridization might be occurring in this contact zone. Here we describe the genetic structure of the genus Ecklonia along the southern coast of Africa and investigate potential hybridization and cryptic diversity using a combination of nuclear microsatellites and mitochondrial markers. We found that both species have geographically discrete genetic clusters, consistent with expected phylogeographic breaks along this coastline. In addition, depth-isolated populations were found to harbor unique genetic diversity, including a third Ecklonia lineage. Mito-nuclear discordance and high genetic divergence in the contact zones suggest multiple hybridization events between Ecklonia species. Discordance between morphological and molecular identification suggests the potential influence of abiotic factors leading to convergent phenotypes in the contact zones. Our results highlight an example of cryptic diversity and hybridization driven by contact between two closely related keystone species with contrasting thermal affinities., (© 2024. The Author(s).)

Aortic valve stenosis is a disease characterized by thickening and narrowing of the aortic valve (AV), most commonly due to calcification, which leads to left ventricular outflow obstruction called calcific aortic valve disease (CAVD). CAVD presents as a progressive clinical syndrome with cardiorespiratory symptoms, often with rapid deterioration. The modern-day pathophysiology of CAVD involves a complex interplay of genetic factors, chronic inflammation, lipid deposition, and valve calcification, with early CAVD stages resembling atherosclerosis. Various imaging modalities have been used to evaluate CAVD, with a recent trend of using advanced imaging to measure numerous AV parameters, such as peak jet velocity. Significant improvements in mortality have been achieved with transcatheter AV repair, but numerous therapeutics and modalities are being researched to delay the progression of CAVD. This article aims to provide a comprehensive review of CAVD, explore recent developments, and provide insights into future treatments with various novel modalities., Competing Interests: The authors have no conflicts of interest to report.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The chemical diversity of annelids, particularly those belonging to the class Sipuncula, remains largely unexplored. However, as part of a Marine Biodiscovery program in Ireland, the peanut worm Phascolosoma granulatum emerged as a promising source of unique metabolites. The purification of the MeOH/CH 2 Cl 2 extract of this species led to the isolation of six new linear guanidine amides, named phascolosomines A-F ( 1 - 6 ). NMR analysis allowed for the elucidation of their structures, all of which feature a terminal guanidine, central amide linkage, and a terminal isobutyl group. Notably, these guanidine amides were present in unusually high concentrations, comprising ∼3% of the dry mass of the organism. The primary concentration of the phascolosomines in the viscera is similar to that previously identified in linear amides from sipunculid worms and marine fireworms. The compounds from sipunculid worms have been hypothesized to be toxins, while those from fireworms are reported to be defensive irritants. However, screening of the newly isolated compounds for inhibitory bioactivity showed no significant inhibition in any of the assays conducted.

Background: Adolescents are exposed to various psycho-physiological stressors due to rapid changes in their bodies along with increased academic pressure, peer pressure, and pressures from other sources of society. Group health education sessions in schools could have a positive outcome in not only the way they perceive stress but also tackle it efficiently., Objective: The objective of the study was to assess the effectiveness of group health education intervention on "perceived stress" among the high school children of Kolar., Materials and Methods: An open-label cluster randomized controlled trial was conducted among high school students (8th, 9th, and 10th standard) in selected English Medium Schools of Kolar Taluk. The study was conducted in three phases spanning 5 months of duration. Phase I included baseline data collection wherein "perceived stress" level was captured using the Perceived Stress Scale (PSS) 10 questionnaire. Phase II was the interventional phase in the form of group health education sessions. Phase III was end-line assessment., Results: Before the intervention, 6.2%, 92.4%, and 1.5% of the students had mild, moderate, and severe stress, respectively, in the intervention group. After the intervention in the intervention group, about 57.9% had mild stress, 42.1% had moderate stress, and none had severe stress. The difference in difference analysis (DID) showed that the mean PSS scores in the intervention group changed by -8.84 while in the control group by 0.40., Conclusion: Group health education delivered was effective in reducing the perceived stress levels among high school children and it is a feasible and acceptable intervention for stress in school-going adolescent children., (Copyright © 2024 Copyright: © 2024 Indian Journal of Public Health.)

Due to the lower LUMO energy level at the β-position of α,β-unsaturated-β-trifluoromethyl enone than that of its non-fluorinated counterpart, there is a challenge to activate the sp 2 C-H bond of aromatic rings. Herein, we have reported iridium(III)-catalyzed β-trifluoromethyl enone carbonyl-directed regioselective aromatic C(sp 2 )-H olefination with acrylates under oxidative conditions. Furthermore, coupling with natural product-derived acrylates, scale-up and product diversification have also been performed.

Introduction: India launched the COVID-19 vaccination drive on 16th January 2021 by vaccinating the adult population above 18 years of age. This was followed by the introduction of an additional precaution dose. As on 18th October 2022, 1,02,66,96,808 (1.02 Billion) first dose and 94, 95, 39,516 (949 Million) second doses of COVID-19 vaccine were administered. However, when compared to the uptake of the primary doses, the precaution dose uptake lagged behind with only 21,75, 12,721 (217 million) doses administered. Even though, the uptake of the primary doses remained optimal, irrespective of different interventions by the Government of India, the uptake of the precaution dose remained poor. In this context, the Ministry of Health & Family Welfare wanted to understand the facilitators and Barriers for precaution dose uptake among adults so that future immunization campaigns could address these issues., Methods: An exploratory qualitative study was conducted to assess the facilitators and barriers for COVID-19 precaution dose uptake at community level across 6 different states in India. From each of the states, two districts with the highest and lowest rates of COVID-19 vaccine precaution dose uptake were selected. In each of these districts, 2 block Primary Healthcare Centres (PHCs), one with high and one with low uptake were identified. Within these block PHCs, a PHC field area with high and low precaution dose uptakes was identified. From the identified sites a minimum of four IDIs, four FGDs were conducted among the community members. KIIs of the State Immunization Officers, District Immunisation Officers, PHC Medical Officers, healthcare workers like Accredited Social Health Activist/Auxiliary Nurse Midwife were also conducted. The data was audio recorded and it was transcribed, translated and analysed using framework approach., Results: It was observed that rise in COVID-19 cases prompted the community to take the precaution dose, this along with the cost of hospitalization and the number of productive days being lost as a result of being infected resulted in vaccine uptake. The fear of non-availability of COVID-19 vaccines latter on also prompted people for vaccine uptake. While the barriers were, poor accessibility to vaccination centers, long hours of travel, poor road connectivity and lack of transportation facilities. However, the most prominent barriers observed across all study sites was that a sense of pandemic fatigue and complacency had developed both among the providers as well as the beneficiaries. Other barriers include differences in vaccination schedules and longer duration between the primary doses of some vaccines. Media was identified to be both a barrier and facilitator for Covid-19 Precaution dose uptake. Even though media played an important role in disseminating information in the beginning of the campaign, it was soon followed by the circulation of both misinformation and disinformation., Discussion: The study identified that dissemination of accurate information and community involvement at each stage of planning and implementation are crucial for the success of any campaign. Efforts should be constantly made to address and re-invent strategies that will be most suitable for the needs of the community. Therefore, in order to ensure successful vaccination campaigns, it is crucial that along with political will it is also important to have a decentralized approach with inter-sectoral coordination with different stakeholders such as healthcare workers, community members and the different departments such as the local self-governments, education department, law & order department etc. These lessons learnt from COVID-19 vaccination campaigns must not be forgotten and must be applied in future vaccination campaigns and while framing public health policies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Godbole, Diwan, Das, Reddy, Kalyanasundaram, Rajendran, Biswas, Mamulwar, Tiwari, Majumder, Mishra, Muthusamy, Memeenao, Gupta, Gupta, George, Kadale, Trushna, Saha, Alam, Kathiresan, Phukan, Sane, Bhowmik, Yadav, Krishnamurthy, Gogoi, Padhye, Kant, Ghosh, Kharat and Kulkarni.)

Premature ventricular contractions (PVC) are a type of ventricular arrhythmias, occurring as a result of formation or reentry of an abnormal impulse in the ventricular myocardium or in the Purkinje system. PVC occurs commonly in healthy individuals and is observed in 1%-4% of the population. Several lifestyle factors like stress levels, caffeine, drugs, alcohol, nicotine, sleep, and physical exercise have been implicated in increasing the risk. Caffeine and drugs precipitate heightened cardiac stimulation, precipitating PVCs. Excessive alcohol and nicotine disturb the electrical pathways resulting in PVCs. Higher rates of PVCs have been associated with obesity. Individuals with insomnia and increased stress levels are also at an increased risk due to an imbalance in the autonomic system. Exercise is known to induce PVCs, including in healthy, asymptomatic individuals. Modification of these factors can decrease PVC risk. This article aims to provide a comprehensive review of the effects of lifestyle factors on PVC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Conductive hydrogels are promising materials with mixed ionic-electronic conduction to interface living tissue (ionic signal transmission) with medical devices (electronic signal transmission). The hydrogel form factor also uniquely bridges the wet/soft biological environment with the dry/hard environment of electronics. The synthesis of hydrogels for bioelectronics requires scalable, biocompatible fillers with high electronic conductivity and compatibility with common aqueous hydrogel formulations/resins. Despite significant advances in the processing of carbon nanomaterials, fillers that satisfy all these requirements are lacking. Herein, intrinsically dispersible acid-crystalized PEDOT:PSS nanoparticles (ncrys-PEDOT X ) are reported which are processed through a facile and scalable nonsolvent induced phase separation method from commercial PEDOT:PSS without complex instrumentation. The particles feature conductivities of up to 410 S cm -1 , and when compared to other common conductive fillers, display remarkable dispersibility, enabling homogeneous incorporation at relatively high loadings within diverse aqueous biomaterial solutions without additives or surfactants. The aqueous dispersibility of the ncrys-PEDOT X particles also allows simple incorporation into resins designed for microstereolithography without sonication or surfactant optimization; complex biomedical structures with fine features (< 150 µm) are printed with up to 10% particle loading . The ncrys-PEDOT X particles overcome the challenges of traditional conductive fillers, providing a scalable, biocompatible, plug-and-play platform for soft organic bioelectronic materials., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

In our continuing efforts to describe the biological and chemical diversity of sponges from Kimbe Bay, Papua New Guinea, the known 30-norlanostane saponin sarasinoside C 1 ( 1 ) was identified along with six new analogues named sarasinosides C 4 , C 5 , C 6 , C 7 , C 8 , and C 9 ( 2 - 7 ) from the sponge Melophlus sarasinorum . The structures of the new compounds were elucidated by analysis of 1D and 2D NMR and HRMS data, as well as comparison with literature data. All new compounds are characterized by the same tetraose moiety, β-d-Xyl p -(1→6)-β-d-GlcNAc p -(1→2)-[β-d-GalNAc p -(1→4)]-β-d-Xyl p , as described previously for sarasinoside C 1 , but differed in their aglycone moieties. When comparing NMR data of sarasinoside C 8 with those of known analogues, a misassignment was identified in the configuration of the C-8/C-9 diol for the previously described sarasinoside R ( 8 ), and it has been corrected here using a combination of ROESY analysis and molecular modeling.

Species of Ulva have a wide range of commercial applications and are increasingly being recognized as promising candidates for integrated aquaculture. In South Africa, Ulva has been commercially cultivated in integrated seaweed-abalone aquaculture farms since 2002, with more than 2000 tonnes of biomass cultivated per annum in land-based paddle raceways. However, the identity of the species of Ulva grown on these farms remains uncertain. We therefore characterized samples of Ulva cultivated in five integrated multi-trophic aquaculture farms (IMTA) across a wide geographical range and compared them with foliose Ulva specimens from neighboring seashores. The molecular markers employed for this study were the chloroplast-encoded Ribulose-1,5-bisphosphate carboxylase oxygenase (rbcL), the Internal Transcribed Spacer (ITS) of the nuclear, and the chloroplast elongation factor tufA. All currently cultivated specimens of Ulva were molecularly resolved as a single species, U. lacinulata. The same species has been cultivated for over a decade, although a few specimens of two other species were also present in early South African IMTA systems. The name Ulva uncialis is adopted for the Ulva "Species A" by Fort et al. (2021), Molecular Ecology Resources, 22, 86) significantly extending the distribution range for this species. A comparison with wild Ulva on seashores close to the farms resulted in five new distribution records for South Africa (U. lacinulata, U. ohnoi, U. australis, U. stenophylloides, and U. aragoënsis), the first report of a foliose form of U. compressa in the region, and one new distribution record for Namibia (U. australis). This study reiterates the need for DNA confirmation, especially when identifying morphologically simple macroalgae with potential commercial applications., (© 2023 The Authors. Journal of Phycology published by Wiley Periodicals LLC on behalf of Phycological Society of America.)

Purpose: To compare the outcomes of the Aurolab aqueous drainage implant (AADI) placed in eyes with refractory primary congenital glaucoma (PCG) versus aphakic glaucoma (APG)., Design: Retrospective comparative interventional case series., Methods: Case files of consecutive eyes with PCG or APG that underwent AADI surgery between January 2013 and December 2016 and had a minimum 4 years follow-up were extracted from a computerised database. Failure was defined as intraocular pressure (IOP)>21 mm Hg or reduced<20% below baseline on two consecutive follow-up visits after 3 months, IOP≤5 mm Hg on two consecutive follow-up visits after 3 months, reoperation for glaucoma or a complication, or loss of light perception., Results: Eighty-nine eyes underwent AADI placement, including 42 eyes (47%) with PCG and 47 eyes (53%) with APG. Both groups were comparable at baseline. At 1 year, the APG group had lower mean IOP (13.6±8.1 mm Hg vs 17.6±7.5 mm Hg, p=0.02) with use of fewer IOP-lowering medications (0.8±1.0 vs 1.5±1.0, p=0.01) than the PCG group. The cumulative failure rate at 4 years was 57% (95% CI 43% to 72%) in PCG versus 40% (95% CI 28% to 56%) in the APG eyes (p=0.11). Eyes with PCG had greater tube-related complications (48% vs 38%, p=0.07) and number of reoperations (40% vs 32%, p=0.02) compared with eyes with APG., Conclusions: Eyes with APG had relatively better outcomes after AADI placement compared with PCG during 4 years of follow-up. Reoperations accounted for more than 70% of the failures., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

TLR7 agonists have significant therapeutic potential in a variety of oncology and autoimmune applications. We recently reported a potent TLR7 selective agonist 1 that could be delivered by antibody-drug conjugate (ADC) technology to elicit potent anticancer activity. Herein we report synthetic chemistry and structure-activity relationship studies to develop TLR7 agonists with improved potency for next-generation ADC efforts. We found that the addition of hydrophobic acyl tails to parent compound 1 generally resulted in retained or improved TLR7 agonist activity without sacrificing the permeability or the selectivity over TLR8. In contrast, the addition of a simple alkyl tail at the same position resulted in a dramatic loss in potency. Molecular modeling was performed to provide a rationale for this dramatic loss in potency. We ultimately identified compounds 17b , 16b , and 16d as highly potent TLR7 agonists that potently induced the activation of mouse macrophages and hPBMCs at low-nanomolar concentrations., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

Subcutaneous entomophthoromycosis is an infection caused by saprophytic, ubiquitous and highly opportunistic fungal pathogens. Individuals with immune disorders are frequently susceptible to these infections. Entomophthoromycosis is a rare fungal infection that primarily affects children andmen, and is known to cause infection in healthy individuals. Diagnosis of the disease is by demonstration of fungal elements using special stains, and the disease responds well to oral antifungal agents. Long-term antifungal agents reduce the need for surgical intervention when the disease presents as a mass. We report a case of an immunocompetent nursing mother in her 20s who presented with a soft tissue mass in her right arm. It was diagnosed as subcutaneous entomophthoromycosis and treated with long-term fluconazole. The lesion showed a significant reduction in size following treatment for 2 months. Subcutaneous fungal infection presenting as a mass-forming lesion in extremities may mimic a neoplasm. Fungal infection should be ruled out in inflammatory cell-rich lesions seen on histopathological examination., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Pancytopenia due to systemic lupus erythematosus (SLE) is rarely reported, and among those reported, it is mostly due to immunologically mediated cell destruction. Pancytopenia due to bone marrow fibrosis secondary to SLE is an extremely rare entity. Myelofibrosis secondary to SLE per se is reported only in 21 cases in the literature. Ours probably is the 22nd case report on SLE with myelofibrosis. Primary presentation of SLE with bleeding manifestation is also a rare phenomenon. Partial to complete regression of myelofibrosis is noted following treatment in secondary myelofibrosis caused by SLE. We report a case of a woman in her late 40s who presented to us with bleeding manifestations of petechial rash and menorrhagia, which on further evaluation showed pancytopenia due to myelofibrosis secondary to SLE. Our case underlines multiple features like primary bleeding manifestation and regression of myelofibrosis following treatment which is rarely reported in association with SLE., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To identify the genes and pathways responsible for treatment resistance (TR) in retinoblastoma (RB) by analyzing serum small extracellular vesicles (sEVs) of patients with TR active RB (TR-RB) and completely regressed RB (CR-RB)., Methods: Serum-derived sEVs were characterized by transmission electron microscopy and nanoparticle tracking analysis. sEV transcriptome profiles of two TR-RB and one CR-RB with good response (>20 years tumor free) were compared to their age-matched controls (n = 3). Gene expression data were analyzed by the R Bioconductor package. The CD9 protein and mRNA expression of CD9, CD63, and CD81 were studied in five RB tumors and two control retinae by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction., Results: The isolated serum sEVs were round shaped and within the expected size (30-150 nm), and they had zeta potentials ranging from -10.8 to 15.9 mV. The mean ± SD concentrations of sEVs for two adults and four children were 1.1 × 1012 ± 0.1 and 5.8 × 1011 ± 1.7 particles/mL. Based on log2 fold change of ±2 and P < 0.05 criteria, there were 492 dysregulated genes in TR-RB and 184 in CR-RB. KAT2B, VWA1, CX3CL1, MLYCD, NR2F2, USP46-AS1, miR6724-4, and LINC01257 genes were specifically dysregulated in TR-RB. Negative regulation of apoptotic signaling, cell growth, and proton transport genes were greater than fivefold expressed only in TR-RB. CD9, CD63, and CD81 mRNA levels were high in RB tumors versus control retina, with increased and variable CD9 immunoreactivity in the invasive areas of the tumor., Conclusions: Serum sEVs could serve as a potential liquid biopsy source for understanding TR mechanisms in RB.

Background: Oral cancers are often detected at late stages, and patients usually had a 50% chance of a 5-year survival rate. Oral cancer usually has an early precancerous stage before its actual malignant transformation. Although there are various approaches to diagnose the early stages of cancer, there is one less explored, cost-effective, and simple technique known as the crystallization test. The aim of the study was to evaluate the crystallization patterns in tobacco users, oral potentially malignant disorders (OPMDs), and oral malignancies., Materials and Methods: Fifteen patients with oral malignancies, 15 patients with oral potentially malignant disorders, 15 tobacco users, and 15 healthy individuals participated in the crystallization test. Single blood drop was used to perform this test and the obtained crystal patterns were analyzed., Results: This test had a sensitivity of 93.3%, 80.0%, and 20.0% for oral malignancies, oral Potentially Malignant Disorders (PMDs), and tobacco users, respectively. Chi-square analysis revealed a highly significant transverse form between OPMDs and oral malignancies (P < 0.05)., Conclusion: Crystallization test was found to be a sensitive, reliable, economical, and less invasive procedure for screening of oral PMDs and oral malignancies under strictly maintained physical conditions.

Pyridine is a crucial heterocyclic scaffold that is widely found in organic chemistry, medicines, natural products, and functional materials. In spite of the discovery of several methods for the synthesis of functionalized pyridines or their integration into an organic molecule, new methodologies for the direct functionalization of pyridine scaffolds have been developed during the past two decades. In addition, transition-metal-catalyzed C-H functionalization and rare earth metal-catalyzed reactions have flourished over the past two decades in the development of functionalized organic molecules of concern. In this review, we discuss recent achievements in the transition-metal and rare earth metal-catalyzed C-H bond functionalization of pyridine and look into the mechanisms involved., (Copyright © 2023, Sindhe et al.)

Background: Acute encephalitis syndrome (AES) is a major public health concern in India, and the Japanese Encephalitis (JE) virus is the most common cause of viral encephalitis in Asia affecting children under the age of 15 years. In India, despite the introduction of the JE vaccine (SA-14-14-2) in the immunization programme, JE continues to account for 15-20% of AES cases to date. This study evaluates the immunogenicity of live attenuated SA-14-14-2 JE vaccine in terms of persistence of the humoral response after two doses., Methods: A cross-sectional study was conducted among 266 children belonging to one of the JE endemic regions of Uttar Pradesh, India. Blood samples were taken from children (2-10 years) and grouped according to the duration (in years) after two doses of the vaccine (5 groups with a class interval of 2 years). Informed written consent was obtained from the parents/guardians. All the samples collected were tested for the presence of anti-JEV-specific IgG antibodies by enzyme-linked immunosorbent assay (ELISA) and further confirmed by micro neutralization test (MNT) and immunofluorescence assays., Results: Of the 266 samples tested by ELISA for anti-JEV-specific IgG antibodies, 260 (97.74%) were negative and 6 (2.26%) were equivocal. The geometric mean immune status ratio across the five groups, 0-2 years (n = 59), 2-4 years (n = 73), 4-6 years (n = 65), 6-8 years (n = 48) and 8-10 years (n = 21) post-two doses of SA-14-14-2 JE vaccine was 1.143, 1.059, 1.138, 1.075 and 1.130, respectively, and the geometric mean titre obtained from MNT across the five groups was 10.77, 8.400, 8.453, 9.517 and 9.674, respectively., Conclusion: The study showed a decreasing trend of anti-JEV specific IgG antibody titres across the five groups based on the duration following two doses of SA-14-14-2 vaccine. The results emphasize the significance of booster doses of vaccine for children living in endemic areas., (© International Society of Travel Medicine 2022. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Tumor cells reprogram their metabolism, including glucose, glutamine, nucleotide, lipid, and amino acids to meet their enhanced energy demands, redox balance, and requirement of biosynthetic substrates for uncontrolled cell proliferation. Altered lipid metabolism in cancer provides lipids for rapid membrane biogenesis, generates the energy required for unrestricted cell proliferation, and some of the lipids act as signaling pathway mediators. In this review, we focus on the role of lipid metabolism in embryonal neoplasms with MYCN dysregulation. We specifically review lipid metabolic reactions in neuroblastoma, retinoblastoma, medulloblastoma, Wilms tumor, and rhabdomyosarcoma and the possibility of targeting lipid metabolism. Additionally, the regulation of lipid metabolism by the MYCN oncogene is discussed.

Context: Exclusive breastfeeding (EBF) provides protection to the child from risk of obesity, overweight, type II diabetes and helps in enhancing brain development, learning capabilities and also reduces gastrointestinal infections. Breast problems, societal barriers, insufficient support, poor knowledge, mode of delivery and community beliefs are associated., Aim: To determine the survival and prevalence of exclusive breast-feeding practice and their associated factors., Settings and Design: An ambispective community-based observational study was conducted., Materials and Methods: A sample of 441 mothers was estimated with a prevalence of EBF of 54.9% based on the National Family Health Survey 2015-16., Study Procedure: The selected mothers with an infant less than one year of age and those with infants less than six months were interviewed retrospectively and prospectively and information on the duration of EBF, demography and factors associated were collected., Statistical Analysis Used: The data were analysed using IBM SPSS, version 22. The Chi-square test and binary logistic regression were used to determine the associated factors for EBF. A P value of <0.05 was considered significant., Results: EBF survival rate was good till three months and decreased drastically after five months. EBF practice in the present study was 69.4%. Birth order, maternal age, birth weight, paternal education and religion were significantly associated with EBF., Conclusion: Primary health care providers in the community should also consider the cultural factors and educate the mothers on the practice of EBF to reduce morbidity and mortality and promote better health for a healthy, strong, younger population., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Family Medicine and Primary Care.)

Background: Recent studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reveal that Omicron variant BA.1 and sub-lineages have revived the concern over resistance to antiviral drugs and vaccine-induced immunity. The present study aims to analyze the clinical profile and genome characterization of the SARS-CoV-2 variant in eastern Uttar Pradesh (UP), North India., Methods: Whole-genome sequencing (WGS) was conducted for 146 SARS-CoV-2 samples obtained from individuals who tested coronavirus disease 2019 (COVID-19) positive between the period of 1 January 2022 and 24 February 2022, from three districts of eastern UP. The details regarding clinical and hospitalized status were captured through telephonic interviews after obtaining verbal informed consent. A maximum-likelihood phylogenetic tree was created for evolutionary analysis using MEGA7., Results: The mean age of study participants was 33.9 ± 13.1 years, with 73.5% accounting for male patients. Of the 98 cases contacted by telephone, 30 (30.6%) had a travel history (domestic/international), 16 (16.3%) reported having been infected with COVID-19 in past, 79 (80.6%) had symptoms, and seven had at least one comorbidity. Most of the sequences belonged to the Omicron variant, with BA.1 (6.2%), BA.1.1 (2.7%), BA.1.1.1 (0.7%), BA.1.1.7 (5.5%), BA.1.17.2 (0.7%), BA.1.18 (0.7%), BA.2 (30.8%), BA.2.10 (50.7%), BA.2.12 (0.7%), and B.1.617.2 (1.3%) lineages. BA.1 and BA.1.1 strains possess signature spike mutations S:A67V, S:T95I, S:R346K, S:S371L, S:G446S, S:G496S, S:T547K, S:N856K, and S:L981F, and BA.2 contains S:V213G, S:T376A, and S:D405N. Notably, ins214EPE (S1- N-Terminal domain) mutation was found in a significant number of Omicron BA.1 and sub-lineages. The overall Omicron BA.2 lineage was observed in 79.5% of women and 83.2% of men., Conclusion: The current study showed a predominance of the Omicron BA.2 variant outcompeting the BA.1 over a period in eastern UP. Most of the cases had a breakthrough infection following the recommended two doses of vaccine with four in five cases being symptomatic. There is a need to further explore the immune evasion properties of the Omicron variant., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zaman, Shete, Mishra, Kumar, Reddy, Sahay, Yadav, Majumdar, Pandey, Dwivedi, Deval, Singh, Behera, Kumar, Patil, Kumar, Dudhmal, Joshi, Shukla, Gawande, Kavathekar, Kumar, Kumar, Kumar, Singh, Kumar, Tiwari, Verma, Yadav and Kant.)

To analyze the patterns of failure and factors affecting recurrence and overall survival in mucoepidermoid carcinoma of the salivary gland. The hospital records were retrospectively analyzed from October 2010 to January 2016. Patients diagnosed as mucoepidermoid carcinoma of the salivary gland were eligible for analysis. All patients received surgery as the primary treatment modality with or without post operative radiotherapy. Statistical analysis for factors affecting recurrence was done by cox regression analysis and p value less than 0.05 was considered significant. A total of 116 patients were diagnosed to have malignant salivary gland tumors of which 69 were mucoepidermoid carcinomas (69.5%). The median age was 43 years (8-75 years). Majority of the tumors occurred in major salivary glands gland (77%). 51% patients were females. Most common stage was stage II (36%) followed by stage I (27.5%), stage IV (20.3%) and stage III (16%). High grade carcinomas comprised 34.8%, intermediate grade 30.4% and low grade 34.8%. 36 patients (52.2%) received adjuvant radiotherapy (60 Gy in 30 fractions). At a median follow up of 42 months (8-70 months), 8 (11.6%) patients died (7 cancer related and 1 noncancer related). The locoregional recurrence rate was 4.3% whereas the distant metastasis rate was 11.6%. Most common site of distant metastasis was lung. The mean disease free survival time was 61.4 months and the mean overall survival was 62 months. On univariate analysis, age < 50 years, node positive, presence of PNI, high grade, presence of LVI and local recurrence were significant factors for distant metastasis ( p  < 0.05). On multivariate analysis, high grade, presence of LVI and local recurrence were significant factors for distant metastasis ( p  < 0.05). Mucoepidermoid carcinomas of salivary gland have good long term local control and overall survival. Majority of the recurrences are distant metastasis. High grade, LVI and local recurrence are significant risk factors for distant relapse., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Association of Otolaryngologists of India 2020.)

The present study employed nanoparticle tracking analysis, transmission electron microscopy, immunoblotting, RNA sequencing, and quantitative real-time PCR validation to characterize serum-derived small extracellular vesicles (sEVs) from RB patients and age-matched controls. Bioinformatics methods were used to analyze functions, and regulatory interactions between coding and non-coding (nc) sEVs RNAs. The results revealed that the isolated sEVs are round-shaped with a size < 150 nm, 5.3 × 1011 ± 8.1 particles/mL, and zeta potential of 11.1 to −15.8 mV, and expressed exosome markers CD9, CD81, and TSG101. A total of 6514 differentially expressed (DE) mRNAs, 123 DE miRNAs, and 3634 DE lncRNAs were detected. Both miRNA-mRNA and lncRNA-miRNA-mRNA network analysis revealed that the cell cycle-specific genes including CDKNI1A, CCND1, c-MYC, and HIF1A are regulated by hub ncRNAs MALAT1, AFAP1-AS1, miR145, 101, and 16-5p. Protein-protein interaction network analysis showed that eye-related DE mRNAs are involved in rod cell differentiation, cone cell development, and retinol metabolism. In conclusion, our study provides a comprehensive overview of the RB sEV RNAs and regulatory interactions between them.

Introduction: The Maternal and Child Health (MCH) Pipeline Training Program, promotes development of a diverse health workforce by training undergraduate students from underrepresented minorities. We aimed to evaluate the success of this program based on three domains: (1) demographic characteristics, (2) academic and career development, and (3) attitudes towards the field of MCH and the training programs among graduates., Methods: Three domains of success were determined through a collaborative effort between current program directors and the funding agency project officers. The survey with questions related to the three domains was distributed via an online platform to graduates from seven sites (one former site and six current sites). Data were analyzed and presented utilizing descriptive statistics., Results: The survey was distributed to 550 graduates, 162 responded (37% response rate). Demographically, 78% were female, 54% were Black/African American, 22% were Latinx and 83% did not report any disability. Eighty percent of respondents applied to graduate/professional schools, 67% received admission. Graduates often continued to work in MCH fields (70%). Majority felt confident and knowledgeable in the field (89%) and agreed the faculty were supportive at their training sites (90%)., Conclusion: The study highlights successes in recruiting from underrepresented minorities, particularly Black/African Americans and first-time college goers in the family into the MCH Pipeline Training Programs. Programs were successful in furthering academic and career development for most trainees. Attitudes towards MCH and the training programs were overwhelmingly positive. Continued support of these programs is critical in addressing health disparities and achieving health equity., (© 2022. The Author(s).)

Purpose: Presently, there are six undergraduate HRSA-funded MCH pipeline training programs (MCHPTP) in the nation and they have gained significant momentum since inception by recruiting, training and mentoring undergraduate students in a comprehensive MCH-focused approach. This article describes the outcomes from the 6 training programs; and primarily Baylor College of Medicine-Texas Southern University (BCM-TSU's) collaborative strategy focusing on the MCH research training and outcomes, which align with HRSA's MCH bureau's missions., Description: Each MCHPTP offers trainees interdisciplinary MCH research experiences through intra/inter-institutional collaborations and partnerships, but BCM-TSU's MCHPTP was the only one with the primary focus to be research. As a case study, the BCM-TSU Program developed an innovative research curriculum integrated with MCH Foundations Course that comprised 2 hour weekly meetings. Students were split into collaborative research groups of 4-5 students, with multidisciplinary peer-mentors, clinical fellows and MCH research faculty from institutions at the world-renowned Texas Medical Center., Assessment: Since the inception of the MCH mentorship programs, all six MCHPTPs have enrolled up to 1890 trainees and/or interns. BCM-TSU Program trainees are defined as undergraduate students in their 1st or 2nd year of college while research interns are upper classmen in their 3rd or 4th year of college. The case study showed that BCM-TSU Program trainees demonstrated outstanding accomplishments in the area of research through primary and co-authorships of 13 peer-reviewed journal publications by 78 trainees, over a period of 3 years, in addition to dozens of presentations at local, regional and national conferences., Conclusions: The research productivity of students in the six MCHPTPs is strongly indicative of the success of integrating MCH research mentoring into MCH didactic training. The development of a diverse and robust MCH mentorship program promotes and strengthens research activities in areas of high priority such as addressing health disparities in MCH morbidity and mortality in the U.S., (© 2022. The Author(s).)

Purpose: The HRSA-funded maternal and child health pipeline training programs (MCHPTPs) are a response to the critical need to diversify the MCH workforce, as a strategy to reduce health disparities in MCH populations. These MCHPTPs support students from undergraduate to graduate education and ultimately into the MCH workforce., Description: The models and components of training across the six MCHPTPs funded in 2016-2021 are summarized, to examine the design and delivery of undergraduate pipeline training and the insights gained across programs., Assessment: Strategies that emerged across training programs were organized into three themes: recruitment, support for student persistence (in education), and pipeline-to-workforce intentionality. Support for student persistence included financial support, mentoring, creating opportunity for students to develop a sense of belonging, and the use of research as a tool to promote learning and competitiveness for graduate education. Finally, the link to Maternal and Child Health Bureau (MCHB) long-term training and other MCHB opportunities for professional development contributed significant nuance to the pipeline-to-workforce objectives of these programs., Conclusions: The MCHPTPs not only increase the diversity of the MCH workforce, they also actively prepare the next generation of MCH leaders. The intentional connection of undergraduates to the infrastructure and continuum of MCH training, underscores the comprehensive impact of this funding., (© 2022. The Author(s).)

Introduction: Efforts to recruit and retain diverse Maternal and Child Health (MCH) professionals are of paramount public health significance. Culturally congruent mentorship strategies are key to supporting a successful transition from undergraduate to graduate studies., Methods: This mixed-method study evaluated a culturally congruent mentorship training used by one of the MCH Pipeline Training programs and described mentorship practices and lessons learned from the six MCH Pipeline programs. A retrospective pre-test post-test survey assessed mentorship competency skills following a mentoring workshop. All MCH Pipeline program leaders completed a questionnaire to elicit responses about mentoring training practices, mentor evaluation strategies, and lessons learned., Results: Maternal and Child Health Pipeline Training Programs supported 1890 undergraduate scholars at universities and institutions nationally. Scholars at six MCH Pipeline Programs participated in MCH education and mentored experiential leadership opportunities in clinical practice, research, and public health education. Qualitative program-level mentor survey themes indicated the importance of creating a reflective space and building mentorship teams. Mean mentor self-assessed improvement in mentor competencies was 14.4 points, 95% CI [10.5, 18.3], p < .001 following completion of a mentoring training workshop implemented by one of the MCH Pipeline programs., Discussion: The Health Resources and Services Administration's Maternal and Child Health Bureau recognized the need to support the development of the next generation of diverse MCH leaders. Pipeline programs that included mentoring workshops and building culturally congruent mentorship teams are two strategies to increase and retain diverse scholars in graduate school and leaders in the public health workforce., (© 2022. The Author(s).)

Background: Falls in elderly persons are one of the leading causes of death. Falls are responsible for 10-15% of all emergency department visits among elderly. The study was conducted to determine the prevalence of falls in rural areas and to assess the various socio-demographic factors associated with falls., Methodology: It was a community-based, cross-sectional study conducted in Rural Health Training Centre (RHTC), Devarayanasamudra, Department of Community Medicine, among the elderly persons aged ≥ 60 years. The total sample size was 511, calculated using a previous study using OpenEpi software. The data were collected using a pretested semi-structured questionnaire. The period prevalence of falls was assessed by asking for history of falls in the past 12 months. Chi-square and regression analysis were performed with statistically significant P value defined as less than 0.05., Results: Out of 511 elderly persons aged ≥60 years, females accounted for about 54.8% and most of them were of 60-69 years age-group. The majority of the study subjects were illiterates (77.3%), and most of them were married (77.2%). The prevalence of falls in elderly persons was 46.8%. The elderly aged ≥70 years, females, chronic diseases, and use of walking aid were observed to have a statistically significant association with falls (p < 0.005)., Conclusion: Elderly falls are very common. The primary healthcare providers in rural areas play an important role in prevention of falls in elderly. Caregivers, along with elderly, should be given more detailed health education related to fall prevention., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Background: Contribution to antibiotic resistance can happen at two interfaces - doctor prescribing antibiotics inadvertently or patient's usage of antibiotics inadvertently. This study was conducted among diabetic inpatients in a rural tertiary health center in Kolar, South India, to assess the various practices related to antibiotic use and to explore the possible reasons for these practices with regard to antibiotic use., Materials and Methods: An exploratory sequential mixed-methods study was conducted with an initial cross-sectional quantitative study followed by qualitative in-depth interviews during August-September 2019. A pretested semi-structured questionnaire was used to capture the sociodemographic, disease-, and treatment-related characteristics and practices related to antibiotic use. An open-ended interview guide was used to conduct in-depth interviews. The practices to antibiotic use were reported using frequency (percentage). Manual descriptive content analyses were done by two investigators separately to identify codes under the broad topic "reasons for adopted practices with regard to antibiotic use.", Results: Of the 152 diabetic inpatients interviewed, 20 (13.2%) felt that antibiotics are safe drugs and can be used commonly. Among these inpatients, seven (4.6%) knew that antibiotics can kill bacteria and four (2.6%) perceived 'antibiotic resistance' as a big problem in India. The practice of checking the expiry date before using antibiotics was seen in 21 (13.8%) and 44 (29%) of them finished the full course of antibiotics. A total of six codes were identified under the broad theme of "reasons for adopted practices with regard to antibiotic use" among diabetic inpatients., Conclusions: Less than one-third of them completed the antibiotic course given by the doctor, and almost everyone was ready for over-the-counter purchase of antibiotics offered by the pharmacist. The reasons for such practices were mostly attributed to the "partial drug purchases" and "incomplete advice by the doctor." There is an urgent need to plan and deliver an interventional package to enhance the knowledge and inculcate good antibiotic usage practices among these high-risk populations., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Education and Health Promotion.)