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Introduction: Primary healthcare is broadly acknowledged as the cornerstone of any strategy aimed at achieving Universal Health Coverage (UHC). This study aims to evaluate the costs, work patterns and efficiency of comprehensive primary healthcare (CPHC) in India., Methods and Analysis: We will use a top-down microcosting approach to estimate the economic cost of services delivered at the primary healthcare facilities in India. A multistage stratified random sampling approach will be applied to select the primary healthcare facilities -Ayushman Arogya Mandirs (AAMs), formerly Health and Wellness Centres (HWCs). First, states will be selected based on key supply-side and demand-side healthcare indicators. Second, two districts will be chosen in each state based on advanced functionality criteria of AAMs. Finally, AAM-subhealth centres (SHCs) and AAM-primary health centres (PHCs) will be randomly selected within each district, implying a total of 48 SHCs and 24 PHCs. Data on both quantity and prices of capital (such as space, building, equipment and furniture) and recurrent resources (including salaries, medicines, consumables, stationery and overheads) used for delivering primary healthcare services during the period from April 2022 to March 2023 will be collected. All costs will be reported in current India Rupees (₹) and US Dollar (USD) ($) at an exchange rate of $1 = ₹86. A time and motion study will be undertaken to collect data from a total of 48 Community Health Officers (CHOs) and 48 auxiliary nurse midwives (ANMs) over a period of 6 days. This will be complemented by interviews to ascertain time spent on various services and activities. The data will be analysed to derive the annual cost of delivering CPHC services at an AAM, unit cost of individual services as a part of the 12 CPHC packages, as well as time spent by the healthcare workers (CHO and ANM) on various activities and services. Finally, a data envelopment analysis will be used to assess the level of technical efficiency in delivering primary healthcare services. The evidence on cost generated through the study will be useful for decisions related to better planning of healthcare services by aligning the work pattern to desired goals, efficient resource allocation, as well as future research on cost-effectiveness and benefit incidence over health accounts of primary healthcare services., Ethics and Dissemination: The study has been approved by the Institute Ethics Committee of the Post Graduate Institute of Medical Education and Research, Chandigarh, India vide IEC no: PGI/IEC/2023/EIC000588. The study results will be published in peer-reviewed journals and presented to the policymakers at the national level. Furthermore, the cost estimates generated by the study will be integrated into the National Health System Cost Database for India, providing information to policymakers and researchers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

The microtubule-associated protein tau is implicated in neurodegenerative diseases characterized by amyloid formation. Mutations associated with frontotemporal dementia increase tau aggregation propensity and disrupt its endogenous microtubule-binding activity. However, the structural relationship between aggregation propensity and biological activity remains unclear. We employed a multi-disciplinary approach, including computational modeling, NMR, cross-linking mass spectrometry, and cell models to engineer tau sequences that modulate its structural ensemble. Our findings show that substitutions near the conserved 'PGGG' β-turn motif informed by tau isoform context reduce tau aggregation in vitro and cells and can even counteract aggregation induced by turn destabilizing disease-associated proline-to-serine mutations. Engineered tau sequences maintain microtubule binding and explain why 3R isoforms exhibit reduced pathogenesis compared to 4R. We propose a simple mechanism to reduce the formation of pathogenic species while preserving biological function, thus offering insights for therapeutic strategies aimed at reducing tau protein misfolding in neurodegenerative diseases.

This paper presents an adaption of the finite-element based beam-to-beam contact interactions into a finite volume numerical framework. A previous work of the same authors, where a cell-centred based finite volume implementation of geometrically exact nonlinear Simo-Reissner beams was developed, is used as an underlying mathematical model. An implicit contact procedure is developed for both point-to-point and line-to-line beam frictionless contact interactions, and is implemented using the cell-centred finite volume method. To enforce the contact constraint, both penalty method and augmented-Lagrangian based techniques are used. A total of six numerical benchmark cases for point and line beam-to-beam contact interactions based on the finite element method are used to verify the numerical results, accuracy and robustness of the developed contact procedure., (© The Author(s) 2024.)

Neurons deploy diverse adaptive strategies to ensure survival and neurotransmission amid cellular stress. When these adaptive pathways are overwhelmed, functional impairment or neurodegeneration follows. Here we show that stressed neurons actively induce a state of transmissive dormancy as a protective measure. Extending observations of neurotrauma in C. elegans and mice, human dopaminergic neurons capable of surviving severe cellular challenges both decrease spontaneous activity and modulate dopamine homeostasis through the transcriptional regulator Yin Yang 1 (YY1). To bolster stress resilience and mitigate dopamine toxicity, YY1 increases expression of the vesicular monoamine transporter 2, vMAT2, while coordinately inhibiting dopamine synthesis through stabilization of a guanine quadruplex in intron 10 of tyrosine hydroxylase, TH. This dopaminergic stress response has the potential to cause circuit inactivation, yet safeguards neurons by minimizing the toxic accumulation of cytosolic dopamine and inducing a state of neuronal dormancy. In essence, neurons appear to actively prioritize viability over functionality., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Study Design: Retrospective comparative study., Objective: To compare the accuracy of intra-operative navigation-assisted percutaneous pedicle screw insertion between bone fixed and skin fixed dynamic reference frame (DRF) in Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF)., Methods: Between October 2018 and September 2022, patients who underwent MIS-TLIF were included in this study with DRF fixed either on bone (group B) or skin (group S). Pedicle screws were inserted under the guidance of intra-operative Cone bean Computed tomography (cbCT) based navigation. Accuracy of pedicle screw placement was immediately checked by a final intra-operative cbCT Spin., Results: Among 170 patients, group B included 91 patients and group S included 79 patients. Out of total 680 screws, 364 screws (group B) and 316 screws (group S) were placed. Patient's demographic data and distribution of screws showed no statistically significant difference. The accuracy showed no significant difference between both the groups (94.5% in group B and 94.3% in group S)., Conclusion: Skin fixed DRF can serve as an alternate way for placement and avoids extra incision with similar accuracy in pedicle screw insertions with bone fixed DRF using intra-operative CT guided navigation in MIS TLIF., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Conservative and surgical approach timeline in post-operative spondylodiscitis (POS) following lumbar disc herniation (LDH) surgery is ill defined, and patients have a protracted recovery phase with social, psychological, and financial implications., Material and Methods: Retrospective analysis of patients operated by transforaminal lumbar interbody fusion (TLIF) in POS was done. Confirmed clinico-radiological diagnosed POS cases, not responding within three to four weeks were included. Normalisation of CRP and radiological stable reconstruction was assessed for objective clearance of POS and bony union., Results: Ninety-five patients were included in the study with minimum follow-up period of two years. The mean age was 51.63±13.63 years. There were organisms cultured in 55 patients (57.89%). The ODI improvement of the patients was noted to improve from 88.71±5.3 to 20.80±9.7 (8 weeks) and was incremental at 2 years follow-up (10.12±6.41) and maintained further at final follow-up at 9±4.3. Bony union achieved in all with stable reconstruction. The resumption of activities of daily living (ADL) was quick (15.90±8.20 days) and job (3.67±1.31 months) was achieved in all the patients. In poor outcomes, two patients didn't respond, and one patient died due to uncontrolled infection., Conclusion: Early diagnosis and intervention is the key to effective management of POS. Utilisation of aggressive TLIF yields faster ADL resumption., Competing Interests: The authors declare no potential conflict of interest., (© 2024 Malaysian Orthopaedic Association (MOA). All Rights Reserved.)

Purpose: To determine the ability of the photopic negative response (PhNR) of the uniform field electroretinogram (UF-ERG) to identify early glaucomatous changes in comparison to the checkerboard and bar stimuli of the pattern electroretinogram (PERG)., Methods: Forty-nine glaucoma patients were classified into two groups: glaucoma-suspect (23 eyes) and early to moderate glaucoma (30 eyes), based on their clinical examination and the results of standard automated perimetry. Thirty patients (30 eyes) with intraocular pressures (IOP) of 21 mmHg or less, with no history of reported high IOP, were included as controls. PERG and UF-ERG recordings were obtained on a Diagnosys D-341 Attaché-Envoy System. Visual field testing was done only for glaucoma-suspect and glaucoma patients., Results: All three tests (PERG bar stimulus, PERG checkerboard stimulus and PhNR) displayed significantly prolonged peak times for glaucoma and glaucoma-suspect patients, with delays ranging from 7.8 to 14.8%, depending on the test. The PERG bar stimulus also showed a significantly lower N95 amplitude for both glaucoma groups (with reductions of 26.0% and 33.0% for glaucoma-suspect and glaucoma groups, respectively). The PERG checkerboard N95 amplitude component had high sensitivity for detecting glaucoma patients but a low specificity (97% and 37%, respectively; AUC = 0.61). Overall, the PhNR peak time showed the highest sensitivity and specificity (77% and 90%, respectively; AUC = 0.87)., Conclusions: PERG bar stimuli and the PhNR of the UF-ERG can be used in the clinical setting to detect glaucoma-related changes in glaucoma-suspect and glaucoma patients. However, our data confirm that the PhNR peak time has the best combined sensitivity and specificity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Protein fibril self-assembly is a universal transition implicated in neurodegenerative diseases. Although fibril structure/growth are well characterized, fibril nucleation is poorly understood. Here, we use a computational-experimental approach to resolve fibril nucleation. We show that monomer hairpin content quantified from molecular dynamics simulations is predictive of experimental fibril formation kinetics across a tau motif mutant library. Hairpin trimers are predicted to be fibril transition states; one hairpin spontaneously converts into the cross-beta conformation, templating subsequent fibril growth. We designed a disulfide-linked dimer mimicking the transition state that catalyzes fibril formation, measured by ThT fluorescence and TEM, of wild-type motif - which does not normally fibrillize. A dimer compatible with extended conformations but not the transition-state fails to nucleate fibril at any concentration. Tau repeat domain simulations show how long-range interactions sequester this motif in a mutation-dependent manner. This work implies that different fibril morphologies could arise from disease-dependent hairpin seeding from different loci., (© 2024. The Author(s).)

Pesticides are chemical substances of natural or synthetic origin that are used to eradicate pests and insects. These are indispensable in the agricultural processes for better crop production. Pesticide use aims to promote crop yield and protect the crops from diseases and damage. Pesticides must be handled carefully and disposed of appropriately because they are dangerous to people and other species by default. Environmental pollution occurs when pesticide contamination spreads away from the intended plants. Older pesticides such as lindane and dichlorodiphenyltrichloroethane (DDT) may remain in water and soil for a longer time. These accumulate in various parts of the food chain and cause damage to the ecosystem. Biological techniques in the management of pest control such as importation, augmentation, and conservation, and the accompanying procedures are more efficient, less expensive, and ecologically sound than other ways. This review mainly focuses on the consequences on the targeted and non-targeted organisms including the health and well-being of humans by the use of pesticides and their toxicity. The side effects that occur when a pesticide's LD 50 exceeds the accepted limit through oral or skin penetration due to their binding to various receptors such as estrogen receptors, GABA, EGFR, and others. These pesticide classes include carbamates, pyrethroids, organochlorides, organophosphorus, and others. The current study seeks to highlight the urgent requirement for a novel agricultural concept that includes a major reduction in the use of chemical pesticides., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Root-knot and cyst nematodes are two groups of plant parasitic nematodes that cause the majority of crop losses in agriculture. As a result, these nematodes are the focus of most nematode effector research. Root-knot and cyst nematode effectors are defined as secreted molecules, typically proteins, with crucial roles in nematode parasitism. There are likely hundreds of secreted effector molecules exuded through the nematode stylet into the plant. The current research has shown that nematode effectors can target a variety of host proteins and have impacts that include the suppression of plant immune responses and the manipulation of host hormone signaling. The discovery of effectors that localize to the nucleus indicates that the nematodes can directly modulate host gene expression for cellular reprogramming during feeding site formation. In addition, plant peptide mimicry by some nematode effectors highlights the sophisticated strategies the nematodes employ to manipulate host processes. Here we describe research on the interactions between nematode effectors and host proteins that will provide insights into the molecular mechanisms underpinning plant-nematode interactions. By identifying the host proteins and pathways that are targeted by root-knot and cyst nematode effectors, scientists can gain a better understanding of how nematodes establish feeding sites and subvert plant immune responses. Such information will be invaluable for future engineering of nematode-resistant crops, ultimately fostering advancements in agricultural practices and crop protection. [Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 "No Rights Reserved" license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2024., Competing Interests: The author(s) declare no conflict of interest.

Background: Gender-based violence (GBV) is a global public health concern. India's socio-cultural and regional diversity poses challenges for obtaining accurate and comprehensive indicators of gender-based violence. This study aimed to explore the prevalence and predictors of GBV among adolescents. This was a community-based cross-sectional study conducted among adolescents aged 10 to 19 years in six districts of Madhya Pradesh, the central part of India, from December 2017 to 2019., Methods and Material: GBV was assessed using a validated questionnaire adapted from a nationwide survey. Data were analyzed using SPSS (version 16.0). Logistic regression analysis was performed to identify factors associated with GBV., Results: The study revealed that 10.4% of adolescents were victims of GBV. The multi-variable logistic regression showed that girls were at higher risk (odds ratio = 5.7) of facing GBV. Other significant factors associated with GBV included older adolescents (15-19 years old), those belonging to scheduled caste/tribal areas, those whose mothers were literate, those who had a boyfriend/girlfriend, and those who justified wife beating., Conclusion: GBV is a serious public health problem among adolescents, with one in every 10 adolescents experiencing GBV. It is essential to instil awareness of gender-equal norms from early childhood and within households. Implementing violence prevention policies and strategies in educational and work institutions, as well as at the community level, is crucial., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Community Medicine.)

Introduction: Digital health innovations are modern solutions for the management and treatment of diseases, particularly non-communicable diseases. This study was conducted to assess the feasibility of the management of diabetes and hypertension through patient-generated health data (PGHD)., Methods: A mobile application (One Health) was used for the entry of data on blood pressure, blood glucose, physical activity, and dietary intake for six months by the patients. Frequency of application download, monthly data entry, and change in control of blood pressure and glycemic markers during six months of application use were used to assess the feasibility and impact of the application for the management of hypertension and type 2 diabetes mellitus (T2DM)., Results: A higher proportion of patients entered data generated non-invasively (blood pressure) as compared to data generated via invasive techniques (glycemic control measures). The frequency of monthly data entry remained unchanged during One Health use. At the end of six months, control of hypertension and glycemic control was achieved in 53.3% and 33.9% of patients, respectively. Furthermore, there was a significant reduction of mean diastolic blood pressure (0.60 (±2.31); p=0.03) and glycosylated hemoglobin (0.657 (±1.808); p=0.04)., Discussion: The acceptability of One Health appears to be associated with the frequency of data entry. The entry of health data by patients was sufficient to effect positive change in health indicators. Although mobile applications enable the monitoring and management of chronic health conditions, additional research shall help in optimizing interventions to be adopted as acceptable tools of patient management., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, S et al.)

The microtubule-associated protein tau is implicated in neurodegenerative diseases characterized by amyloid formation. Mutations associated with frontotemporal dementia increase tau aggregation propensity and disrupt its endogenous microtubule-binding activity. The structural relationship between aggregation propensity and biological activity remains unclear. We employed a multi-disciplinary approach, including computational modeling, NMR, cross-linking mass spectrometry, and cell models to design tau sequences that stabilize its structural ensemble. Our findings reveal that substitutions near the conserved 'PGGG' beta-turn motif can modulate local conformation, more stably engaging in interactions with the 306 VQIVYK 311 amyloid motif to decrease aggregation in vitro and in cells. Designed tau sequences maintain microtubule binding and explain why 3R isoforms of tau exhibit reduced pathogenesis over 4R isoforms. We propose a simple mechanism to reduce the formation of pathogenic species while preserving biological function, offering insights for therapeutic strategies aimed at reducing protein misfolding in neurodegenerative diseases.

A specific reagent/aptamer-free easy redox strategy between silver(I) moieties present in a citrate-stabilized colloidal silver nanoparticle (NP) system and arsenite ions is described that enables plasmonic change of AgNPs for the selective quantification of arsenite ions in the range of 0 to 30 μM with a low limit of quantification value of 50 nM (5.3 ppb).

Seed thermoinhibition protects emerging seedlings from thermodamage by preventing seed germination at elevated temperatures. It had remained unknown how a seed fine-tunes its germination in response to temperature. Recently, Piskurewicz et al. demonstrated that endosperm phyB senses increased temperature, thereby facilitating PIF3-mediated abscisic acid (ABA) accumulation to inhibit germination and embryo elongation., Competing Interests: Declaration of interests None declared by authors., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Arteriovenous malformations (AVMs) are developmental defects in the vascular system with abnormal connections between arteries and veins. A minority of AVMs are characterized by aggressive growth and continue to proliferate despite maximal surgical and interventional therapy. We report our outcomes with the use of thalidomide as the only UK specialist center adopting this novel approach for the management of AVMs refractory to conventional therapy., Methods: This was a retrospective case series which included only complex and proliferative AVM lesions (Schobinger grade III and IV). All patients prescribed thalidomide on a compassionate basis between September 2006 and August 2022 after attempts at embolosclerotherapy without satisfactory response were reviewed., Results: Eleven patients were included in our study. The median total duration of thalidomide use was 10 months. Two thirds of patients with pain (six of nine) reported an improvement, three quarters reported a reduction in swelling (six of eight) and all who presented with bleeding reported improvement in overall volume or frequency (four of four). Over the study period, 45% achieved a non-proliferative state with no further target vessel demonstrable on angiography. Mild, tolerable side effects such as fatigue were common (73%). There was only one major adverse reaction (neutropenia) necessitating cessation of therapy., Conclusions: We can conclude that thalidomide is able to reduce the symptom burden for patients with complex and proliferative AVMs that were refractory to established treatment modalities. Adverse effects are common, but the benefit achieved from taking thalidomide in otherwise treatment resistant cases outweighs the risks, most of which are manageable.

Competing Interests: Competing interests: None declared.

Plants, being sessile, are frequently exposed to environmental perturbations, affecting their sustenance and survival. In response, distinct inherent mechanisms emerged during plant evolution to deal with environmental stresses. Among various organelles, chloroplast plays an indispensable role in plant cells. Besides providing the site for photosynthesis and biosynthesis of many important primary and secondary metabolites, including hormones, chloroplasts also act as environmental sensors. Any environmental perturbation directly influences the photosynthetic electron transport chain, leading to excess accumulation of reactive oxygen species (ROS), causing oxidative damages to biomolecules in the vicinity. To prevent excess ROS accumulation and the consequent oxidative damages, the chloroplast activates retrograde signaling (RS) pathways to reprogramme nuclear gene expression, defining plant's response to stress. Based on levels and site of ROS accumulation, distinct biomolecules are oxidized, generating specific derivatives that act as genuine signaling molecules, triggering specific RS pathways to instigate distinctive responses, including growth inhibition, acclimation, and programmed cell death. Though various RS pathways independently modulate nuclear gene expression, they also implicate the defense hormone salicylic acid (SA) and oxylipins, including 12-oxo-phytodienoic acid (OPDA) and jasmonic acid (JA), by promoting their biosynthesis and utilizing them for intra- and intercellular communications. Several studies reported the involvement of both hormones in individual RS pathways, but the precise dissection of their activation and participation in a given RS pathway remains an enigma. The present review describes the current understanding of how SA and JA intertwine in ROS-triggered RS pathways. We have also emphasized the future perspectives for elucidating stress specificity and spatiotemporal accumulation of respective hormones in a given RS pathway., (© 2023 Scandinavian Plant Physiology Society.)

In osteoarthritis (OA), a disease characterized by progressive articular cartilage degradation and calcification, the articular chondrocyte phenotype changes and this correlates with actin cytoskeleton alterations suggesting that it regulates gene expression essential for proper phenotype. This study reports that OA is associated with the loss of adseverin, an actin capping and severing protein. Adseverin deletion (Adseverin -/- ) in mice compromised articular chondrocyte function, by reducing F-actin and aggrecan expression and increasing apoptosis, Indian hedgehog, Runx2, MMP13, and collagen type X expression, and cell proliferation. This led to stiffer cartilage and decreased hyaline and increased calcified cartilage thickness. Together, these changes predisposed the articular cartilage to enhanced OA severity in Adseverin -/- mice who underwent surgical induction of OA. Adseverin -/- chondrocyte RNA sequencing and in vitro studies together suggests that adseverin modulates cell viability and prevents mineralization. Thus, adseverin maintains articular chondrocyte phenotype and cartilage tissue homeostasis by preventing progression to hypertrophic differentiation in vivo. Adseverin may be chondroprotective and a potential therapeutic target.

Background: Anemia is associated with impaired physical performance and adverse perioperative outcomes. Iron-deficiency anemia is increasingly treated with intravenous iron before elective surgery. We explored the relationship between exercise capacity, anemia, and total hemoglobin mass (tHb-mass) and the response to intravenous iron in anemic patients prior to surgery., Methods: A prospective clinical study was undertaken in patients having routine cardiopulmonary exercise testing (CPET) with a hemoglobin concentration ([Hb]) < 130 g . l -1 and iron deficiency/depletion. Patients underwent CPET and tHb-mass measurements before and a minimum of 14 days after receiving intravenous (i.v.) Ferric derisomaltose (Monofer®) at the baseline visit. Comparative analysis of hematological and CPET variables was performed pre and post-iron treatment., Results: Twenty-six subjects were recruited, of whom 6 withdrew prior to study completion. The remaining 20 (9 [45%] male; mean ± SD age 68 ± 10 years) were assessed 25 ± 7 days between baseline and the final visit. Following i.v. iron, increases were seen in [Hb] (mean ± SD) from 109 ± 14 to 116 ± 12 g l -1 (mean rise 6.4% or 7.3 g l -1 , p =  < 0.0001, 95% CI 4.5-10.1); tHb-mass from 497 ± 134 to 546 ± 139 g (mean rise 9.3% or 49 g, p =  < 0.0001, 95% CI 29.4-69.2). Oxygen consumption at anerobic threshold ([Formula: see text] O 2 AT ) did not change (9.1 ± 1.7 to 9.8 ± 2.5 ml kg -1  min -1 , p = 0.09, 95% CI - 0.13 - 1.3). Peak oxygen consumption ([Formula: see text] O 2 peak ) increased from 15.2 ± 4.1 to 16 ± 4.4 ml . kg .-1  min -1 , p = 0.02, 95% CI 0.2-1.8) and peak work rate increased from 93 [67-112] watts to 96 [68-122] watts (p = 0.02, 95% CI 1.3-10.8)., Conclusion: Preoperative administration of intravenous iron to iron-deficient/deplete anemic patients is associated with increases in [Hb], tHb-mass, peak oxygen consumption, and peak work rate. Further appropriately powered prospective studies are required to ascertain whether improvements in tHb-mass and performance in turn lead to reductions in perioperative morbidity., Trial Registration: ClinicalTrials.gov identifier: NCT 033 46213., (© 2023. The Author(s).)

Amyloid deposition of the microtubule-associated protein tau is associated with neurodegenerative diseases. In frontotemporal dementia with abnormal tau (FTD-tau), missense mutations in tau enhance its aggregation propensity. Here we describe the structural mechanism for how an FTD-tau S320F mutation drives spontaneous aggregation, integrating data from in vitro, in silico and cellular experiments. We find that S320F stabilizes a local hydrophobic cluster which allosterically exposes the 306 VQIVYK 311 amyloid motif; identify a suppressor mutation that destabilizes S320F-based hydrophobic clustering reversing the phenotype in vitro and in cells; and computationally engineer spontaneously aggregating tau sequences through optimizing nonpolar clusters surrounding the S320 position. We uncover a mechanism for regulating tau aggregation which balances local nonpolar contacts with long-range interactions that sequester amyloid motifs. Understanding this process may permit control of tau aggregation into structural polymorphs to aid the design of reagents targeting disease-specific tau conformations., (© 2023. The Author(s).)

Purpose: To assess the radiological morphometric parameters of OLIF surgical technique in lower lumbar spine among normal and in patients with adult degenerative spine (levoscoliosis and dextroscoliosis)., Method: Standing AP radiographs and MRI in supine position were taken. Patients were divided into 3 groups based on Cobbs' angle into normal, levo and dextro scoliosis. Moros classification was used to calculate bare window (BW), vascular window (VW), Psoas window (PW), psoas major height (pmh) and width (pmw) at lower lumbar levels and measurements were done on PACS., Results: Seventy five patients (25 in each group) were assessed. BW has trend from L2-L3 > L3-L4 > L4-L5 in dextro and levoscoliosis. PW has trend from L3-L4 > L2-L3 > L4-L5 in levoscoliosis and normal group. VW has trend from L4-L5 > L3-L4 > L2-L3 in dextro and levoscoliosis; pmw has trend from L4-L5 > L3-L4 > L2-L3 in Levo and dextroscoliosis; pmh has trend from L4-L5 > L3-L4 > L2-L3 in levoscoliosis and normal group., Conclusion: BW was noted to be highest at L3-4, lowest at L4-5 in normal group. VW was constant, BW showed a reverse trend with PW across all the levels. Though levoscoliosis group of patients had significantly higher BW, psoas retraction issues are to be kept in mind in view of anatomically taught psoas., (© 2022. The Author(s), under exclusive licence to Scoliosis Research Society.)

Background: COVID-19 vaccination of the healthcare workers (HCWs) is a key priority in the fight against the SARS-CoV-2 pandemic. India launched its COVID-19 vaccination program in January 2021. We aimed to understand the trends in willingness to receive COVID-19 vaccines and its associated factors among HCWs in India., Methods: Using a repeated cross-sectional survey design, we collected information from HCWs in three critical time points: before ( n = 937, October 2020), during ( n = 1346, January 2021); and after ( n = 812, May 2021) the introduction of COVID-19 vaccines in India. The third survey coincided with the peak of the second wave of COVID-19 pandemic in India., Findings: Of the study participants, 43.7, 60.2, and 73.2% were willing to receive COVID-19 vaccines during the first, second and third rounds of surveys, respectively. In multivariable logistic regression analysis, participants who trusted the health care system were more likely to report willingness to receive a COVID-19 vaccine; medical trust emerged as a significant factor in all the three rounds of surveys (First survey-aOR: 2.24, 95% CI: 1.67-2.99; Second survey-aOR: 3.38, 95% CI: 2.64-4.33; Third survey-aOR: 2.54, 95% CI: 1.65-3.91). Having confidence in domestic vaccines (Second survey-aOR: 2.21, 95% CI: 1.61-3.02; Third survey-aOR: 2.05, 95% CI: 1.24-3.37); and high perceived risk of contracting COVID-19 (Second survey-aOR: 1.48, 95% CI: 1.13-1.93; Third survey-aOR: 2.02, 95% CI: 1.31-3.13) were found to be associated with willingness to receive vaccines. Among socio-demographic characteristics, being married (aOR: 1.71, 95% CI: 1.08-2.71) and having high socio-economic status (aOR: 3.01, 95% CI: 1.65-5.51) emerged as significant factors associated with willingness to receive COVID-19 vaccines in the third round of the surveys., Interpretation: Willingness to receive COVID-19 vaccine increased with time, as the severity of the pandemic increased. To increase COVID-19 acceptance and coverage among HCWs, it is important to instill confidence in domestic vaccines and assist in accurate assessment of risk toward contracting COVID-19 infection., 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 Padhi, Chakrapani, Gupta, Sharma, Patro, Kar, Singh, Pala, Sankhe, Modi, Bali, Rustagi, Jain, Vij, Satapathy, Goel, Rajagopal, Kiran and Aggarwal.)

Background: India's flagship program on adolescent health - Rashtriya Kishor Swasthya Karyakram (RKSK) emphasises the importance of strengthening Adolescent Friendly Health Clinics (AFHCs) under its facility-based approach for improving the health of adolescents. AFHCs are intended to provide targeted intervention in six domains - nutrition, injuries & violence (including gender-based violence), mental health, sexual & reproductive health, substance abuse and noncommunicable diseases., Objective: The current study was conducted to assess the determinants of awareness and utilisation of AFHC services in districts with RKSK services in Madhya Pradesh., Subjects: In total, 1605 adolescents (both males and females) within the age group of 10-19 years were included in the study., Methods: Multistage stratified random sampling was employed to enrol participants from three districts of Madhya Pradesh, where AFHC services have been launched., Results: The mean age of the participants was 15.07 ± 2.32 years. Only 153 (9.5%) adolescents were aware of AFHC services. On multivariate logistic regression, awareness of AFHC was seen to be associated with being aware of RKSK, being a part of the peer educator-led peer group, having had adolescent health days organised in the village and belonging from one of the financially better off districts. Utilisation rate of AFHC services was lower still - at 2.74%., Conclusion: Both awareness and utilisation of AFHC services remain very low among adolescents. There is a pressing need to focus on awareness generation campaigns - via mass media, but more importantly, through community health workers and peer educators - in order to sensitise target beneficiaries about the available services., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Purpose: To evaluate the effect of tobacco smoking on trabeculectomy outcomes., Methods: Charts of patients with glaucoma who underwent trabeculectomy performed by a single surgeon between 2007 and 2016 were retrospectively reviewed. Charts were screened for a documented history of smoking status before surgery. Demographic and clinical preoperative variables were recorded. Based on smoking history, subjects were divided into two groups: smokers and nonsmokers. Any bleb-related interventions (e.g., 5-flourouracil injections ± laser suture lysis) or bleb revision performed during the postoperative period were noted. Success was defined as an intraocular pressure >5 mmHg and <21 mm Hg without (complete success) or with (qualified success) the use of ocular hypotensive medications. Failure was identified as a violation of the criteria mentioned above., Results: A total of 98 eyes from 83 subjects were included. The mean age of the subjects was 70.7 ± 11.09 years, and 53% (44/83) were female. The most common diagnosis was primary open-angle glaucoma in 47 cases (47.9%). The smokers Group included 30 eyes from 30 subjects. When compared with nonsmokers, smokers had a significantly worse preoperative best-corrected visual acuity (p=0.038), greater central corneal thickness (p=0.047), and higher preoperative intraocular pressure (p=0.011). The success rate of trabeculectomy surgery at 1 year was 56.7% in the smokers Group compared with 79.4% in the Group nonsmokers (p=0.020). Smoking presented an odds ratio for failure of 2.95 (95% confidence interval, 1.6-7.84)., Conclusion: Smokers demonstrated a significantly lower success rate 1 year after trabeculectomy compared with nonsmokers and a higher requirement for bleb-related interventions.

This article presents a novel total Lagrangian cell-centered finite volume formulation of geometrically exact beams with arbitrary initial curvatures undergoing large displacements and finite rotations. The choice of rotation parameterization, the mathematical formulation of the beam kinematics, conjugate strain measures, and the linearization of the strong form of governing equations are described. The finite volume based discretization of the computational domain and the governing equations for each computational volume are presented. The discretized integral form of the equilibrium equations is solved using a block-coupled Newton-Raphson solution procedure. The efficacy of the proposed methodology is presented by comparing the simulated numerical results with classic benchmark test cases available in the literature. The objectivity of strain measures for the current formulation and mesh convergence studies for both initially straight and curved beam configurations are also discussed., Competing Interests: The authors declare that they have no conflict of interest., (© 2022 The Authors. International Journal for Numerical Methods in Engineering published by John Wiley & Sons Ltd.)

Databases contain millions of reactions for compound synthesis, rendering selection of reactions for forward synthetic design of small molecule screening libraries, such as DNA-encoded libraries (DELs), a big data challenge. To support reaction space navigation, we developed the computational workflow Reaction Navigator. Reaction files from a large chemistry database were processed using the open-source KNIME Analytics Platform. Initial processing steps included a customizable filtering cascade that removed reactions with a high probability to be incompatible with DEL, as they would e.g. damage the genetic barcode, to arrive at a comprehensive list of transformations for DEL design with applicability potential. These reactions were displayed and clustered by user-defined molecular reaction descriptors which are independent of reaction core substitution patterns. Thanks to clustering, these can be searched manually to identify reactions for DEL synthesis according to desired reaction criteria, such as ring formation or sp 3 content. The workflow was initially applied for mapping chemical reaction space for aromatic aldehydes as an exemplary functional group often used in DEL synthesis. Exemplary reactions have been successfully translated to DNA-tagged substrates and can be applied to library synthesis. The versatility of the Reaction Navigator was then shown by mapping reaction space for different reaction conditions, for amines as a second set of starting materials, and for data from a second database., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Vaccine hesitancy is of considerable concern as it threatens the great potential of a vaccine against COVID-19. This study aims to determine factors associated with community health workers' willingness to participate in clinical trials of COVID-19 vaccine, and their vaccination intention, in India., Methods: A cross-sectional study was conducted among 377 community health workers using self-administered anonymous questionnaire during the lockdown periods in India. Participant's socio-demographics, willingness-to-participate in COVID-19 vaccine trials, intention to accept COVID-19 vaccine were recorded in a Likert scale. Data were analysed descriptively, and a multivariate logistic regression model was used to investigate factors associated with willingness to participate and accept the vaccine., Results: Among 377 CHWs, 70 (19%) intended to participate in COVID-19 vaccine trial, 151 (40%) responded positively regarding their intention to get vaccinated. Those with knowledge on development of COVID-19 vaccine [aOR 3.05 (95% CI: 1.18-7.88), p = 0.021], and men [aOR 3.69 (95% CI: 1.51-8.97), p = 0.004] were more willing to participate in clinical-trial, while an undergraduate degree, and trust in domestic vaccines were identified as deterrents for the same. Perceiving COVID-19 as risk [aOR 2.31 (95% CI: 1.24-4.31), p = 0.009], and male gender [aOR 2.39 (95% CI: 1.17-4.88), p = 0.017] were factors associated with intention to get vaccinated. Respondents who had knowledge about COVID-19 virus were less likely to uptake the hypothetical vaccine [aOR 0.32 (95% CI: 0.12-0.88), p = 0.027]., Conclusions: Increasing knowledge regarding COVID-19 is not enough to improve vaccine acceptance rates. Targeted interventions addressing socio-demographic determinants related to COVID-19 vaccination should help improve acceptance., Competing Interests: The authors declare they have no competing interests., (© 2022 The Author(s).)

Regulated cell death (RCD) is an ordered and tightly orchestrated set of changes/signaling events in both gene expression and protein activity and is responsible for normal development as well as maintenance of tissue homeostasis. Aberrant activation of this pathway results in cell death by various mechanisms including apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death. Such pathological changes in neurons alone or in combination have been observed in the pathogenesis of various neurodegenerative diseases including Alzheimer's disease (AD). Pathological hallmarks of AD focus primarily on the accumulation of two main protein markers: amyloid β peptides and abnormally phosphorylated tau proteins. These protein aggregates result in the formation of A-β plaques and neuro-fibrillary tangles (NFTs) and induce neuroinflammation and neurodegeneration over years to decades leading to a multitude of cognitive and behavioral deficits. Autopsy findings of AD reveal massive neuronal death manifested in the form of cortical volume shrinkage, reduction in sizes of gyri to up to 50% and an increase in the sizes of sulci. Multiple forms of cell death have been recorded in neurons from different studies conducted so far. However, understanding the mechanism/s of neuronal cell death in AD patients remains a mystery as the trigger that results in aberrant activation of RCD is unknown and because of the limited availability of dying neurons. This review attempts to elucidate the process of Regulated cell death, how it gets unregulated in response to different intra and extracellular stressors, various forms of unregulated cell death, their interplay and their role in pathogenesis of Alzheimer's Disease in both human and experimental models of AD. Further we plan to explore the correlation of both amyloid-beta and Tau with neuronal loss as seen in AD., 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 Goel, Chakrabarti, Goel, Bhutani, Chopra and Bali.)

Pest attacks on plants can substantially change plants' volatile organic compounds (VOCs) emission profiles. Comparison of VOC emission profiles between non-infected/non-infested and infected/infested plants, as well as resistant and susceptible plant cultivars, may provide cues for a deeper understanding of plant-pest interactions and associated resistance. Furthermore, the identification of biomarkers-specific biogenic VOCs-associated with the resistance can serve as a non-destructive and rapid tool for phenotyping applications. This research aims to compare the VOCs emission profiles under diverse conditions to identify constitutive (also referred to as green VOCs) and induced (resulting from biotic/abiotic stress) VOCs released in potatoes and wheat. In the first study, wild potato Solanum bulbocastanum (accession# 22; SB22) was inoculated with Meloidogyne chitwoodi race 1 (Mc1), and Mc1 pathotype Roza (SB22 is resistant to Mc1 and susceptible to pathotype Roza), and VOCs emission profiles were collected using gas chromatography-flame ionization detection (GC-FID) at different time points. Similarly, in the second study, the VOCs emission profiles of resistant ('Hollis') and susceptible ('Alturas') wheat cultivars infested with Hessian fly insects were evaluated using the GC-FID system. In both studies, in addition to variable plant responses (susceptibility to pests), control treatments (non-inoculated or non-infested) were used to compare the VOCs emission profiles resulting from differences in stress conditions. The common VOC peaks (constitutive VOCs) between control and infected/infested samples, and unique VOC peaks (induced VOCs) presented only in infected/infested samples were analyzed. In the potato-nematode study, the highest unique peak was found two days after inoculation (DAI) for SB22 inoculated with Mc1 (resistance response). The most common VOC peaks in SB22 inoculated with both Mc1 and Roza were found at 5 and 10 DAI. In the wheat-insect study, only the Hollis showed unique VOC peaks. Interestingly, both cultivars released the same common VOCs between control and infected samples, with only a difference in VOC average peak intensity at 22.4 min retention time where the average intensity was 4.3 times higher in the infested samples of Hollis than infested samples of Alturas. These studies demonstrate the potential of plant VOCs to serve as a rapid phenotyping tool to assess resistance levels in different crops.

Introduction: Targeting the huge burden of adolescent anemia, the Weekly Iron and Folic acid Supplementation (WIFS) was launched by the Government of India. Few studies have been done to assess the effective functioning of the program since its inception. The present study was done to assess the knowledge WIFS among adolescents of Madhya Pradesh and the associated factors., Materials and Methods: A cross-sectional study was done in a total of six districts (3 districts where the national adolescent program was implemented and 3 districts where it was not) of Madhya Pradesh. Multistage stratified random sampling technique was used for the enrollment of 3213 adolescent boys and girls, and a prestructured and validated tool was used to collect paperless data. Ethical approval and consent from the participants were obtained. Statistical analysis was performed using SPSS v21., Results: It was observed that the knowledge of WIFS was more among adolescent girls (29.3%) as compared to adolescent boys (14.1%). More of the adolescent girls received Iron and folic acid tablets as compared to adolescent boys (60.8% girls vs. 24.1% boys). Mostly, the adolescents got Iron tablets from school followed by Anganwadi and PHC/CHC. Girls, rural location, literacy, below poverty line status, knowledge of anemia, adolescents who got iron and albendazole tablets, and adequate consumption of iron tablets (>4) were associated with higher knowledge of WIFS., Conclusion: The knowledge of WIFS was found to be less in adolescent boys. There is a hint of the fact that effective execution of the program among its beneficiaries leads to an automatic increased knowledge of the program, at least among the beneficiaries. Thus, an indirect but significant indirect finding is that the nationwide WIFS program needs to be put to greater focus among the adolescent boys, apart from its major focus on the female gender among most age groups., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Education and Health Promotion.)

Background: Responding to the fast transmission rates and increasing fatality rates, countries across the world expedited the development and deployment of the vaccine for coronavirus disease 2019 (COVID-19). Evaluation of individuals' willingness to pay (WTP) would provide pertinent information regarding future demand and financing preferences, which shall help to devise the effective payment strategy for COVID-19 vaccination., Methods: A nationwide, cross-sectional, and self-administered online survey using a structured questionnaire was conducted to identify the sociodemographic determinants of willingness and extent to pay for COVID-19 vaccine in India. A non-probability convenience sampling followed by snowball sampling was employed to recruit participants ( n = 3,341). The likelihood of sociodemographic determinants to predict willingness and extent to pay was modeled using the multivariate binary logistic regression analysis., Results: Out of 3,341 participants, 68% ( n = 2,271) were willingness to pay for COVID-19 vaccine. Results showed significantly higher odds for willingness to pay among participants who were single [adjusted odds ratio (aOR) = 1.394, p < 0.01] and having a family size of 4 members (aOR = 1.346, p < 0.01). The adjusted odds ratio sizably increased from 1.396 for participants whose monthly income was between INR 10,000 and 20,000/month to 2.240 for participants whose monthly income was above INR 50,000/month. Further, out of 2,271 of those participants who were willingness to pay for COVID-19 vaccine, majority ( n = 1,246, 54.9%) of participants were willingness to pay below 50% of COVID-19 vaccine cost. This study found that those who are single (aOR = 0.688, p < 0.01), having an income between INR 20,000 and 50,000/month (aOR = 0.686, p < 0.05), and those who belonged to socially disadvantaged category (aOR = 0.450, p < 0.01) were estimated to have significantly lower odds of willingness to pay more than 50% of COVID-19 vaccine cost., Conclusion: This study observed that majority of those participants who willingness to pay for COVID-19 vaccine were willingness to pay only up to 50% of COVID-19 vaccine and income was observed as a precursor predictor of the willingness and extent to pay for COVID-19 vaccine. The understanding on the willingness and extent to pay for COVID-19 vaccine and its sociodemographic determinants will be helpful for making the strategic decisions related to the financing of COVID vaccine in India., 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 Kiran, Junaid, Sharma, Jain, Vij, Satapathy, Chakrapani, Patro, Kar, Singh, Pala, Bali, Rustagi, Goel, Sankhe, Modi, Gupta, Aggarwal, Rajagopal and Padhi.)

Objective: To gain better insight into the extent of secondary bacterial and fungal infections in hospitalized patients in India, and to assess how these alter the course of coronavirus disease 2019 (COVID-19) so that control measures can be suggested., Methods: In this retrospective, multicentre study, the data of all patients who tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on reverse transcriptase polymerase chain reaction (RT-PCR), admitted to hospital between March 2020 and July 2021, were accessed from the electronic health records of a network of 10 hospitals across five states in North India., Results: Of 19,852 patients testing positive for SARS-CoV-2 on RT-PCR and admitted to the study hospitals during the study period, 1940 (9.8%) patients developed secondary infections (SIs). Patients with SIs were, on average, 8 years older than patients without SIs (median age 62.6 vs 54.3 years; P <0.001). The risk of SIs was significantly ( P <0.001) associated with age, severity of disease at admission, diabetes, admission to the intensive care unit (ICU), and ventilator use. The most common site of infection was urine (41.7%), followed by blood (30.8%) and sputum/bronchoalveolar lavage/endotracheal fluid (24.8%); the least common was pus/wound discharge (2.6%). Gram-negative bacilli (GNB) were the most common organisms (63.2%), followed by Gram-positive cocci (GPC) (19.6%) and fungi (17.3%). Most patients with SIs were on multiple antimicrobials. The most commonly used antibiotics against GNB were beta-lactam/beta-lactamase inhibitors (76.9%), carbapenems (57.7%), cephalosporins (53.9%), and antibiotics against carbapenem-resistant Enterobacteriaceae (47.1%). Empirical use of antibiotics against GPC was seen in 58.9% of patients with SIs, and empirical use of antifungals was observed in 56.9% of patients with SIs. The average length of hospital stay for patients with SIs was almost twice as long as that of patients without SIs (median 13 vs 7 days). Overall mortality among patients with SIs (40.3%) was more than eight times higher than that among patients without SIs (4.6%). Only 1.2% of patients with SIs with mild COVID-19 at admission died, compared with 17.5% of those with moderate COVID-19 at admission and 58.5% of those with severe COVID-19 at admission ( P <0.001). The mortality rate was highest in patients with bloodstream infections (49.8%), followed by those with hospital-acquired pneumonia (47.9%), urinary tract infections (29.4%), and skin and soft tissue infections (29.4%). The mortality rate in patients with diabetes with SIs was 45.2%, compared with 34.3% in those without diabetes ( P <0.001)., Conclusions: SIs complicate the course of patients hospitalized with COVID-19. These patients tend to have a much longer hospital stay, a higher requirement for oxygen and ICU care, and a significantly higher mortality rate compared with those without SIs. The groups most vulnerable to SIs are patients with more severe COVID-19, elderly patients and patients with diabetes. Judicious empirical use of combination antimicrobials in these groups of vulnerable patients can save lives. It is desirable to have region- or country-specific guidelines for appropriate use of antibiotics and antifungals to prevent their overuse., (© 2022 The Author(s).)

Background: Despite the success of adult vaccination against COVID-19, providing vaccines to children remains a challenge for policymakers globally. As parents are primary decision-makers for their children, we aimed to assess parents' perceptions and intentions regarding COVID-19 vaccination in India., Methods: A cross-sectional web-based study was designed, parents or caregivers ( N = 770) were recruited through snowball sampling using Google form. Cross-tabulation was performed by parents' intention to vaccinate their children against COVID-19 virus with sociodemographic characteristics and their risk perception toward COVID-19, trust in the healthcare system, and their history of vaccine hesitancy behavior. Multivariable logistic regression analysis was performed to compute the predictors of child vaccination intention among Indian parents., Results: Seven hundred and seventy parents across the country have completed the survey. Of the 770 participants, 258 (33.5%) have shown intent to vaccinate their children. The stated likelihood of child vaccination was greater among parents who had a bachelor's degree or higher education (aOR: 1.98, 95% CI: 1.15-3.51); as well as among parents who intended to vaccinate themselves (aOR: 2.35, 95% CI: 1.30-4.67). Parental concerns centered around vaccine safety and side effects., Conclusion: Indian parents reported high knowledge of the COVID-19 virus and were aware of the development of a vaccine. However, about one-third of parents intended to vaccinate their children, and about half of them were not sure whether to vaccinate their children or not against the COVID-19 virus. The study highlighted the need for health promotion strategies that promote vaccine uptake among parents., 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 Padhi, Satapathy, Rajagopal, Rustagi, Vij, Jain, Chakrapani, Patro, Kar, Singh, Pala, Sankhe, Modi, Bali, Kiran, Goel, Aggarwal and Gupta.)

For thousands of years, lipid based Ayurvedic formulations have been made in India, and the craft has survived down the millennia up to the present time. Some of these deliciously potent phytonutrient preparations are very popular and have sustained the test of time pertaining to their efficacy. Recent researches on the role of phytonutrients in promoting cardio-pulmonary, brain and immune health substantially buttress the philosophy underlying the use of lipids in preparing these emulsions, since a large number of these bioactives are lipophilic. Being lipoidic, they are absorbed through the lacteals in the small intestine, and are then transported through the thoracic duct directly to the heart, bypassing the liver. The formulations utilizing ghee (clarified butter) or sesame oil as the carrier lipid, either while frying the myrobalams or as Anupana (adjuvant), have special significance in modulating bodily immunity, since the immune system is housed in lymphatics which are lipid rich. Amla and lipid based Ayurvedic rasayans (rejuvenating formulations) are a popular and highly palatable group of phytonutraceutical preparations. This group of polyherbal adaptogenic formulations is classified separately from other formulations in Ayurvedic therapeutics. Several of these health-promoting rasayans are suitable to be consumed by all age-groups in the recommended season and dose. Current research on endothelial and immune cell receptor mediated uptake of lipoidic molecules, together with the knowledge of lipid absorption pathways, lends credence to the usefulness of rasayans in targeting the cardio-pulmonary and immune systems. An attempt has been made in this paper to elucidate the mechanisms underpinning the complex interplay between lipid delivered hydrophobic phyto-molecules, systemic lymphatics and the Immune system., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Meloidogyne chitwoodi is a major threat to potato production in the Pacific Northwest region of the United States. Infected tubers are rendered unmarketable; hence, growers' profitability is adversely affected. Breeding for nematode resistance is a long-term process and phenotyping the segregating populations for nematode resistance is the most time-consuming and laborious part of the process. Using DNA-based markers closely linked to the nematode resistance trait for marker-assisted selection (MAS) could enhance breeding efficiency and accuracy. In the present study, a pool of phenotyped progenies segregating for nematode resistance and susceptibility were fingerprinted using a 21 K single-nucleotide polymorphism (SNP) array. Eight candidate SNPs located on potato Chromosome 11, segregating with the nematode resistance trait, were identified and used as landmarks for discovery of other marker types such as simple sequence repeat (SSR) and insertion-deletion (INDEL) markers. Subsequently, a total of eight SNPs, 30 SSRs, and four INDELS located on scaffold 11 of Solanum bulbocastanum were used to design primers; markers were validated in a panel of resistant and susceptible clones. Two SNPs (SB&#95;MC1Chr11-PotVar0066518 and SB&#95;MC1Chr11-PotVar0064140), five SSRs (SB&#95;MC1Chr11-SSR04, SB&#95;MC1Chr11-SSR08, SB&#95;MC1Chr11-SSR10, SB&#95;MC1Chr11-SSR13, and SB&#95;MC1Chr11-SSR20), and one INDEL (SB&#95;MC1Chr11-INDEL4) markers showed polymorphism between the resistant and susceptible clones in the test panel and in other segregating progenies. These markers are robust, highly reproducible, and easy to use for MAS of nematode-resistant potato clones to enhance the breeding program., Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01285-w., Competing Interests: Conflicts of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature B.V. 2022.)

Protein assembly into β-sheet-rich amyloid structures is a general biophysical phenomenon that has significant biological consequences, most notable for their prominent association with neurodegenerative diseases, including Alzheimer's, Huntington's, or Parkinson's diseases. The assembly of amyloid structures is driven by short sequences called amyloid motifs. In many neurodegenerative diseases, intrinsically disordered proteins (IDPs) self-assemble through amyloid motifs, but these motifs are present in all proteins, including folded globular proteins. Importantly, mechanistic knowledge is lacking for how IDPs, which do not adopt a stable tertiary structure, mask these amyloidogenic motifs to mitigate or slow the formation of β-sheet-rich amyloid structures that cause disease. Our recent work has shown that local structural elements can modify the aggregation propensity of amyloid motifs in the intrinsically disordered microtubule-associated protein tau by adopting metastable β-hairpin-like structures that shield the amyloid motif, and disease-causing mutations change the conformation, thus increase aggregation propensity (Chen, Nat Commun 10:2493, 2019). Here we describe a protocol that correlates experimentally determined aggregation propensities for peptides measured by the Thioflavin T (ThT) fluorescence aggregation assay with their conformational ensembles derived from Groningen machine chemical simulations (GROMACS). Integration of experiment and simulation will help uncover structural rules behind changes in conformation that modulate protein aggregation. We anticipate that our general protocol will help identify key interactions in local structures that engage amyloid-forming motifs in IDPs which influence aggregation behavior., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Students act as messengers in delivering effective messages for better uptake of health-promoting behavior. Understanding their knowledge about coronavirus disease 2019 (COVID-19), intentions to use the COVID-19 vaccine, and its associated factors will help develop promising strategies in vaccine promotion concerning the current COVID-19 pandemic. Methods: A cross-sectional online survey was carried out among students in the healthcare and non-healthcare sectors to assess their intentions to get vaccinated against the COVID-19. A non-probability snowball sampling technique was used to recruit study participants ( N = 655) through social media platforms and emails. Study participants were recruited across the country, including six major geographical regions (Eastern, Western, Northern, Southern, North-east, and Central) in India between November 2020 and January 2021 before the introduction of the COVID-19 vaccine. Descriptive statistics were used to present the sociodemographic, and vaccine-related behaviors of the study participants. Key determinants that likely predict vaccine acceptance among students were modeled using logistic regression analysis. For each analysis, p < 0.05 was considered significant. Results: A total of 655 students were recruited, 323 from healthcare and 332 from non-healthcare sectors, to assess their intentions to receive the COVID-19 vaccine. Of the 655 students, 63.8% expressed intentions to receive the COVID-19 vaccine. The acceptance was higher among non-healthcare students (54.07 vs. 45.93%). At the time of the study, 27.8% of the students indicated that they had been exposed to a confirmed COVID-19 patient. A vast majority (93.4%) of the students knew about the COVID-19 virus, and most (89.3%) of them were aware of the development of a COVID-19 vaccine. The history of vaccine hesitancy was found to be low (17.1%). Only one-third (33.4%) of the students showed concern about contracting COVID-19. Trust in the healthcare system [adjusted odds ratio (aOR): 4.13; (95% CI: 2.83-6.04), p < 0.00] and trust in domestic vaccines [aOR: 1.46; (95% CI: 1.02-2.08), p < 0.05] emerged as the significant predictors of student's intention to get vaccinated. Higher acceptance for vaccine was observed among students in the non-healthcare [aOR: 1.982; 95% CI: 1.334-2.946, p < 0.00]. Conclusion: This study shows that the Indian college students had relatively high levels of positive intentions to receive COVID-19 vaccines, although about one-third were not sure or unwilling to receive the vaccine, highlighting possible vaccine hesitancy. Informational campaigns and other strategies to address vaccine hesitancy are needed to promote uptake of COVID-19 vaccines., 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 © 2021 Jain, Vij, Satapathy, Chakrapani, Patro, Kar, Singh, Pala, Sankhe, Modi, Bali, Rustagi, Rajagopal, Kiran, Goel, Aggarwal, Gupta and Padhi.)

Introduction: Uncrossmatched ABO-compatible red blood cells (RBCs) are generally recommended in patients with life-threatening massive bleeding. There is little data regarding RBC transfusion when patients are transfused against clinically significant alloantibodies because compatible RBCs are not immediately available., Methods/patients: All patients reviewed in this study ( n = 6,109) required emergency blood transfusion and were treated at the Charité - Universitätsmedizin Berlin between 2001 and 2015. Primary uncrossmatched O Rh(D)-positive or -negative RBC units were immediately transfused prior to complete regulatory serological testing including determination of ABO group, Rhesus antigens, antibody screening, and crossmatching., Results: Without any significant change in the protocol of emergency transfusion of RBCs, a total of 63,373 RBC units were transfused in 6,109 patients. Antibody screening was positive in 413 patients (6.8%), and 19 of these patients received RBC units against clinically significant alloantibodies. None of these patients appeared to have developed significant hemolysis, and only one patient with anti-D seems to have developed signs of insignificant hemolysis following the transfusion of three Rh(D)-positive units. One patient who had anti-Jk a received unselected units and did not develop a hemolytic transfusion reaction., Conclusion: Transfusion of uncrossmatched ABO-compatible RBCs against alloantibodies is highly safe in patients with life-threatening hemorrhage., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 by The Author(s). Published by S. Karger AG, Basel.)

The COVID-19 pandemic taught us many lessons, most critically that its human and economic toll would have been significantly smaller if countries had in place strong layers of defence that would have either prevented the spillover of the SARS-CoV-2 into a human population in the first place, or, failing that, contained the outbreak to avert its global spread. Further, the brunt of COVID-19 impacts on some countries considered 'most prepared' for pandemics underscored the need for an integrated approach to ensure resilience to future epidemics. Consequently, as countries plan ahead to prevent future pandemics, they should give priority to investments that transform their systems, particularly in the precrises phase, to preparedness and response through a multilayered defence. We propose a three-layered approach for post-COVID-19 investments in public health functions and service delivery, particularly at the community and precrises levels. This framework highlights the interventions that enable countries to better prevent, detect and contain epidemic threats, and that strengthen the efficient use of limited resources towards high-impact precrises systems., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The Coronavirus disease 2019 (COVID-19) pandemic created havoc within a few weeks of its outbreak affecting over 100 countries. The rapid increase in the established cases urged for the prevention and control of COVID-19 belligerently on both national and worldwide fronts to prevent the healthcare systems from collapsing. For the sake of successfully preventing and restricting a fatal pandemic outbreak such as COVID-19, it requires the apex health institutions to have a uniform, urgent, flexible and effective policy response framework ensuring strict adherence too. In this regard, the Apex Institutes of National Importance in India (INIs) have released a series of documents on COVID-19 prevention and management., Methods: Documents regarding COVID-19 preparedness and management were retrieved from the official websites of the INIs in India. The general population and healthcare workers' guidelines, standard operating procedures (SOPs) on COVID-19 prevention and management, action and response plans were included in the study. The full text of each document was analysed in detail and themes and subthemes were derived through content analysis., Results: A total of 68 documents was included in the study. Five major themes and 12 subthemes were formulated after content analysis. A major similarity was found across all INIs on screening and testing and infection prevention control measures. The INIs formulated guidelines adhering to the World Health Organization, Indian Council of Medical Research and Ministry of Health and Family Welfare Recommendations., Conclusion: Common measures like quarantine, social distancing, travel bans and mass gathering restrictions were adopted to prevent the spread of COVID-19 during the initial period. The INIs have developed policies and standard operating protocols on COVID-19 management based on the Government of India guidelines. Better understanding of these guidelines will help in effective implementation of the nationwide pandemic management., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Family Medicine and Primary Care.)

The development of methyl transverse relaxation optimized spectroscopy has greatly facilitated the study of macromolecular assemblies by solution NMR spectroscopy. However, limited sample solubility and stability has hindered application of this technique to ongoing studies of complexes formed on membranes by the neuronal SNAREs that mediate neurotransmitter release and synaptotagmin-1, the Ca 2+ sensor that triggers release. Since the 1 H NMR signal of a t Bu group attached to a large protein or complex can be observed with high sensitivity if the group retains high mobility, we have explored the use of this strategy to analyze presynaptic complexes involved in neurotransmitter release. For this purpose, we attached t Bu groups at single cysteines of fragments of synaptotagmin-1, complexin-1 and the neuronal SNAREs by reaction with 5-(tert-butyldisulfaneyl)-2-nitrobenzoic acid (BDSNB), t Bu iodoacetamide or t Bu acrylate. The t Bu resonances of the tagged proteins were generally sharp and intense, although t Bu groups attached with BDSNB had a tendency to exhibit somewhat broader resonances that likely result because of the shorter linkage between the t Bu and the tagged cysteine. Incorporation of the tagged proteins into complexes on nanodiscs led to severe broadening of the t Bu resonances in some cases. However, sharp t Bu resonances could readily be observed for some complexes of more than 200 kDa at low micromolar concentrations. Our results show that tagging of proteins with t Bu groups provides a powerful approach to study large biomolecular assemblies of limited stability and/or solubility that may be applicable even at nanomolar concentrations., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Meloidogyne chitwoodi is one of the most devastating pests of potato in the U.S. Pacific Northwest (PNW). Nematode-infected tubers develop external as well as internal defects, making the potato tubers unmarketable, and resulting in economic losses. Draft genome assemblies of three M. chitwoodi genotypes-race 1, race 2 and race 1 pathotype Roza-were generated using Illumina and PacBio Sequel RS II sequencing. The final assemblies consist of 30, 39, and 38 polished contigs for race 1, race 2 and race 1 pathotype Roza, respectively, with average N 50 of 2.37 Mb and average assembled genome size of approximately 47.41 Mb. On average, 10,508 genes were annotated for each genome. Benchmarking universal single-copy ortholog (BUSCO) analysis indicated that 69.80% of the BUSCOs were complete whereas 68.80, 0.93, and 12.67% were single copy, duplicated, and fragmented, respectively. These highly contiguous genomes will enrich resources to study potato-nematode interactions and enhance breeding efforts to develop nematode-resistant potato varieties for the PNW.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Potato production is negatively affected by root-knot nematodes (Meloidogyne spp.). There are no commercially available potato cultivars that are resistant to root-knot nematodes. To reduce the reliance on chemical controls, genetic engineering for nematode resistance in potato shows promise. Genetically modified potatoes that silence a parasitism gene or that express toxic protease inhibitors display reduced nematode infections. Modifying potato immune responses may also offer new opportunities for nematode resistance in potato. Plant defense elicitors, including those secreted by modified bacteria, enhanced resistance against root-knot nematodes in potato. The use of transgenic bacteria as delivery vehicles of defense-related molecules presents several possibilities for sophisticated nematode management and because this does not involve transgenic plants, it may garner greater public acceptance., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Anemia and poor menstrual hygiene practices have a considerable impact on all aspects of an adolescent girl's life. There is a dire need for evidence on the burden and its association to provide actionable preventive measures., Objective: The objective of this study is to explore the magnitude and association between poor Menstrual Hygiene Management (MHM) practices and anemia., Materials and Methods: A cross-sectional study conducted among 393 adolescent girls of the urban slum of Bhopal (June 2017-July 2018). Hemoglobin (Hb) was determined by a portable Hb meter (HemoCue). Logistic regression analysis was done to find out if there is any association between poor MHM practices and anemia., Results: The present study found the prevalence of anemia as 38.7% among which 65.1%, 31.5%, and 3.2% were suffering from mild, moderate, and severe forms of anemia, respectively, and 87.3% were practicing poor MHM. Logistic regression found that the MHM, bleeding during menstruation, religion, educational status, and nutritional status of adolescents were significant factors associated with anemia., Conclusion: The study concluded that there is a significant association between poor MHM and anemia. Concerted convergent actions focusing on the provision of awareness regarding MHM and sanitary facilities to maintain proper menstrual hygiene are needed to reduce the burden of anemia., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Indian Journal of Community Medicine.)

Competing Interests: There are no conflicts of interest.

The Hsp40/Hsp70 chaperone families combine versatile folding capacity with high substrate specificity, which is mainly facilitated by Hsp40s. The structure and function of many Hsp40s remain poorly understood, particularly oligomeric Hsp40s that suppress protein aggregation. Here, we used a combination of biochemical and structural approaches to shed light on the domain interactions of the Hsp40 DnaJB8, and how they may influence recruitment of partner Hsp70s. We identify an interaction between the J-Domain (JD) and C-terminal domain (CTD) of DnaJB8 that sequesters the JD surface, preventing Hsp70 interaction. We propose a model for DnaJB8-Hsp70 recruitment, whereby the JD-CTD interaction of DnaJB8 acts as a reversible switch that can control the binding of Hsp70. These findings suggest that the evolutionarily conserved CTD of DnaJB8 is a regulatory element of chaperone activity in the proteostasis network.

Background: In a country with a high demand for contraception such as India, one of the most common methods is surgical sterilization, which is delivered by two approaches namely the camp approach and the fixed day static approach. The quality of services for sterilization in India for both the approaches has remained questionable., Objectives: This paper seeks to determine the quality of sterilization services at fixed day static centers of Madhya Pradesh., Methods: It was a descriptive observational study done between September 2017-December 2017 in 10 districts of Madhya Pradesh. One District Hospital and 2 Community Health Centers were randomly chosen from each district. The study was carried out using a prestructured, pretested, and prevalidated tool which used the Ona Platform., Results: Two of the facilities conducted more than 30 operations on the day of the visit. In only 18.3% of the cases was the patient informed about all contraception options. The duration between the start of surgery and the signing of consent was less than 2 h in 42% of the patients. The surgical protocol for proper surgical wear was not followed in most cases., Conclusion: The quality of care of sterilization services was found to be substandard in the fixed day static centers. The guidelines for the sterilization services were not being followed, and follow up of the patients was also neglected. Better training of the staff with strict and timely supervision is required for the better quality provision at the fixed day static centers., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Family Medicine and Primary Care.)