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The present study aims to analyse the research domains, gender gap, and labour market perspectives of doctoral research in LIS in India. Sodhganga, a digital repository of Indian thesis and dissertations, was used for extracting doctoral thesis information and Jarvelin & Vakkari classification system was used for categorising the doctoral research topics. A total of 808 doctoral dissertations awarded between 2016 and 2020 were analysed using IBM SPSS and Tableau. The study's findings revealed that the growth of doctoral research in LIS is on rising trends with 150 PhD awarded in LIS every year. Information seeking (33.8%), library and information service activities (30.7%), and scientific & professional communication (16.5%) were found to be the preferred research themes among doctoral students during the study period. Furthermore, it is revealed that there is a gender gap in the number of PhDs conferred, with more men than women receiving these degrees. LIS professionals with a doctorate have the highest employment rate, at 96.2%, and most are in government jobs. Besides, only 40 percent of doctoral candidates reported receiving an incentive after the doctoral degree. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: This study aimed to assess the oral health and the prevalence of pre‐existing oral colonization with respiratory pathogens in dependent elderly, and whether these factors influence pneumonia development. Materials and Methods: Participants residing in a long‐term care facility received bedside oral examinations, and information on their oral health (caries status, calculus index and debris index) was obtained. Samples from the tongue and teeth were collected at baseline and at time of pneumonia development. Sputum was collected at the time of pneumonia diagnosis. Samples were assessed for Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pneumoniae by polymerase chain reaction. Results: This was a 1‐year longitudinal study of 60 dependent elderly (mean age: 64.2 ± 14.1 years). Seventeen patients (28.3%) developed pneumonia. The mean Decayed, Missing and Filled Teeth and Simplified Oral Hygiene Index were 22.8 ± 9.2 and 4.0 ± 1.0, respectively. At baseline, 48.3% were orally colonized with ≥1 respiratory pathogens. The presence of H. influenzae (P = .002) and P. aeruginosa (P = .049) in the sputum was significantly associated with their colonization on the tongue at baseline. In the bivariate analyses, pneumonia development was associated with naso‐gastric feeding tube (P = .0001), H. influenzae (P = .015) and P. aeruginosa (P = .003) tongue colonization at baseline and calculus index (P = .002). Multivariate analyses revealed that calculus index (P = .09) and the presence of tracheostomy (P = .037) were associated with pneumonia. Conclusions: The calculus amount and tongue colonization with respiratory pathogens are risk factors for pneumonia development. Oral hygiene measures to remove tongue biofilm and calculus may reduce pneumonia development. [ABSTRACT FROM AUTHOR]

Background & objectives: District-Level Household Survey-4 (DLHS-4) indicated that during 2012-2013, only 56 per cent of children aged 12-23 months in Tamil Nadu were fully vaccinated, which were lesser than those reported in earlier national surveys. We, therefore, conducted cluster surveys to estimate coverage of childhood vaccination in the State, and also to identify the factors associated with low coverage. Methods: Cross-sectional surveys were conducted in 15 strata [municipal corporation non-slum (n=1), municipal corporation slum (n=1), hilly (n=1), rural (n=6) and urban (n=6)]. From each stratum, 30 clusters were selected using probability proportional to the population size linear systematic sampling; seven children aged 12-23 months were selected from each cluster and their mothers/care-takers were interviewed to collect information about vaccination status of the child. A child was considered fully vaccinated if he/she received bacillus Calmette-Guérin (BCG), three doses of pentavalent, three doses of oral polio vaccine and one dose of measles vaccine, and appropriately vaccinated if all vaccine doses were given at right age and with right interval. Further, coverage of fully vaccinated children (FVC) as per vaccination cards or mothers' recall, validated coverage of FVC (V-FVC) among those having cards, and coverage of appropriately vaccinated children (AVC) were estimated using survey data analysis module with appropriate sampling weights. Results: A total of 3150 children were surveyed, of them 2528 (80.3%) had vaccination card. The weighted coverage of FVC, V-FVC and AVC in the State was 79.9 per cent [95% confidence interval (CI): 78.2-81.5], 78.8 per cent (95% CI: 76.9-80.5) and 69.7 per cent (95% CI: 67.7-71.7), respectively. The coverage of individual vaccine ranged between 84 per cent (measles) and 99.8 per cent (BCG). About 12 per cent V-FVC were not vaccinated as per the vaccination schedule. Interpretation & conclusions: The coverage of FVC in Tamil Nadu was high, with about 80 per cent children completing primary vaccination. Efforts to increase vaccination coverage in the State need to focus on educating vaccinators about the need to adhere to the national vaccination schedule and strengthening supervision to ensure that children are vaccinated appropriately. [ABSTRACT FROM AUTHOR]

Background & objectives: Japanese encephalitis (JE) is an important aetiology of acute encephalitis syndrome in Gorakhpur division, Uttar Pradesh, India. Two doses of JE vaccine (first during 9-12 months and second during 16-24 months of age) are administered under the Universal Immunization Programme. We conducted surveys to estimate the coverage of JE vaccine and magnitude of missed opportunity for vaccination (MoV) for JE in Gorakhpur division. Methods: To estimate the JE vaccine coverage, cluster surveys were conducted in four districts of Gorakhpur division by selecting 30 clusters by probability proportional to size method in each district, seven children aged 25-36 months were selected from each cluster and their mothers were interviewed about JE vaccination. To estimate the magnitude of MoV, exit surveys were conducted in vaccination clinics in selected health facilities, mothers were interviewed about the vaccination status of their children and vaccines administered to the child on the day of interview. Results: A total of 840 children were surveyed, 210 from each district. The coverages of one and two doses of JE vaccine in Gorakhpur division were 75 per cent [95% confidence interval (CI): 71.0-78.9] and 42.3 per cent (95% CI: 37.8-46.8), respectively. Facility-based exit survey indicated that 32.7 per cent of the eligible children missed JE vaccine. Interpretation & conclusions: The survey results showed that three of the four children aged 25-36 months in Gorakhpur division had received at least one dose of JE vaccine. The coverage of second dose of JE vaccine, however, was low. Failure to administer vaccination simultaneously was the most common reason for MoV for JE vaccine. Training vaccinators about correct vaccination schedule and removing their misconception about administering vaccines simultaneously would substantially improve JE vaccine coverage in Gorakhpur. [ABSTRACT FROM AUTHOR]

Imidazoles are a category of azole antifungals that encompass compounds such as ketoconazole, miconazole, esomeprazole, and clotrimazole. In contrast, the triazoles group, which includes fluconazole, voriconazole, and itraconazole, also plays a significant role. The rise of antibiotic resistance in fungal pathogens has evolved into a substantial global public health concern. In this study, two newly synthesized imidazo[1,2-a]pyridine derivative (Probe I and Probe II) molecules were investigated for its antimicrobial potency against of a panel of bacterial (Gram-positive and Gram-negative bacteria) and fungal pathogens. Among the different types of pathogens, we found that Probe II showed excellent antifungal activity against fungal pathogens, based on the preliminary screening the potent molecule further investigated against multidrug-resistance Candida sp. (n = 10) and compared with commercial molecules. In addition, in-silico molecular docking, its dynamics, absorption, distribution, metabolism, excretion and toxicity (ADMET) were analyzed. In this study, the small molecule (Probe II) displayed potent activity only against the Candida spp. including several multidrug-resistant Candida spp. Probe II exhibited minimum inhibitory concentration ranges from 4 to 16 µg/mL and minimum fungicidal concentration in the range 4‒32 µg/mL as the lowest concentration enough to eliminate the Candida spp. The selected molecules inhibit the formation of yeast to mold as well as ergosterol formation by the computational simulation against Sterol 14-alpha demethylase (CYP51) and inhibition of ergosterol biosynthesis by in-vitro model show that the Probe II completely inhibits the formation of ergosterol in yeast cells at 2× MIC. The ADMET analysis Probe II could be moderately toxic to the human being, though the in-vitro toxicity studies will help to understand the real-time toxic level. The novel compound Probe II, which was synthesized during the study, shows promise for development into a new generation of drug treatments aimed at addressing the emerging drug resistance in Candida sp., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Single-voxel proton magnetic resonance spectroscopy (SV 1 H-MRS) is an in vivo noninvasive imaging technique used to detect neurotransmitters and metabolites. It enables repeated measurements in living participants to build explanatory neurochemical models of psychiatric symptoms and testing of therapeutic approaches. Given the tight link among glutamate, gamma-amino butyric acid (GABA), glutathione and glutamine within the cellular machinery, MRS investigations of neurocognitive and psychiatric disorders must quantify a network of metabolites simultaneously to capture the pathophysiological states of interest. Metabolite-selective sequences typically provide improved metabolite isolation and spectral modelling simplification for a single metabolite at a time. Non-metabolite-selective sequences provide information on all detectable human brain metabolites, but feature many signal overlaps and require complicated spectral modelling. Although there are short-echo time (TE) MRS sequences that do not use spectral editing and are optimised to target either glutamate, GABA or glutathione, these approaches usually imply a precision tradeoff for the remaining two metabolites. Given the interest in assessing psychiatric and neurocognitive diseases that involve excitation-inhibition imbalances along with oxidative stress, there is a need to survey the literature on the quantification precision of current metabolite-selective MRS techniques. In this review, we locate and describe 17 studies that report on the quality of simultaneously acquired MRS metabolite data in the human brain. We note several factors that influence the data quality for single-shot acquisition of multiple metabolites of interest using metabolite-selective MRS: (1) internal in vivo references; (2) brain regions of interests; (3) field strength of scanner; and/or (4) optimised acquisition parameters. We also highlight the strengths and weaknesses of various SV spectroscopy techniques that were able to quantify in vivo glutamate, GABA and glutathione simultaneously. The insights from this review will assist in the development of new MRS pulse sequences for simultaneous, selective measurements of these metabolites and simplified spectral modelling., (© 2023 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Polymorphism is common in both in vitro and in vivo amyloid fibrils formed by the same peptide/protein. However, the differences in their self-assembled structures at the amino acid level remain poorly understood. In this study, we utilized isotope-edited vibrational circular dichroism (VCD) on a well-known amyloidogenic peptide fragment (N 22 FGAIL 27 ) of human islet amyloid polypeptide (IAPf) to investigate the structural polymorphism. Two individual isotope-labeled IAPf peptides were used, with a 13 C label on the carbonyl group of phenylalanine (IAPf-F) and glycine (IAPf-G). We compared the amyloid-like nanofibril of IAPf induced by solvent casting (fibril B) with our previous report on the same IAPf peptide fibril but with a different fibril morphology (fibril A) formed in an aqueous buffer solution. Fibril B consisted of entangled, laterally fused amyloid-like nanofibrils with a relatively shorter diameter (15-50 nm) and longer length (several microns), while fibril A displayed nanofibrils with a higher diameter (30-60 nm) and shorter length (500 nm-2 μm). The isotope-edited VCD analysis indicated that fibrils B consisted of anti-parallel β-sheet arrangements with glycine residues in the registry and phenylalanine residues out of the registry, which was significantly different from fibrils A, where a mixture of parallel β-sheet and turn structure with the registry at phenylalanine and glycine residues was observed. The VCD analysis, therefore, suggests that polymorphism in amyloid-like fibrils can be attributed to the difference in the packing/arrangement of the individual β-strands in the β-sheet and the difference in the amino acid registry. Our findings provide insights into the structural aspects of fibril polymorphism related to various amyloid diseases and may aid in designing amyloid fibril inhibitors for therapeutic purposes.

Tuberculosis is the disease which is caused due to the contagion of Mycobacterium tuberculosis. The multidrug resistance Mycobacterium tuberculosis is the main hassle in the treatment of this worldwide health threats. Pantothenate synthase is a legitimate goal for rational drug designing against Mycobacterium tuberculosis. The enzyme is most active in the presence of magnesium or manganese. Marine algal cell wall is rich in sulfated polysaccharides such as fucoidans (brown algae), κ-carrageenans (red algae), and ulvan (green algae) with various favorable biological activities such as anticoagulant, antiviral, antioxidative, anticancer, and immunomodulating activities. In this study, we have modeled binding modes of selected known anti-tubercular compounds and different solvent extract against pantothenate synthase using advanced docking program AutoDock 4.2 tool. In our current study, in silico experiments were carried out to determine if fucoidan, κ-carrageenan, and ulvan sulfated polysaccharides could be a potential target against PANc (pantothenate synthetase), with the goal of identifying potential inhibitors as anti-TB leads targeting PANc for further wet lab validation. Two bioactive compounds were docked to the Mtb pantothenate synthetase protein binding site, with docking scores ranging from - 5.57 to - 2.73. κ-carrageenan had the best pose and docking score, with a Ligand fit score of - 5.815. Ulvan did not dock with the protein. The molecular dynamics simulations were conducted with substrate and ligand bounded fucoidan and κ-carrageenan for 150 ns and the protein Mtb pantothenate synthetase showed a stable conformation in the simulation, with tight amino acid contributions binding to the ligand molecule. RMSD characterizes the conformation and stability of protein ligand complexes, with higher fluctuations indicating low stability and minimal low-level fluctuations indicating equilibration and stability. The graph for RMSF shows significant peaks due to fluctuations in active site regions and other peaks indicating the adaptation of the ligand molecule to the protein binding pocket. From the molecular dynamics study, it is clear that the compounds are having good binding affinity in the active site. The root mean square deviation, root mean square fluctuations, and radius of gyration are supportive evidences which helped us to conclude that the compounds κ-carrageenan and fucoidan are suitable lead molecules for inhibiting pantothenate synthetase. Based on these evidences, the natural compounds from seaweeds can be tested clinically either alone or in combinations against the protein, which could facilitate the designing or the synthesis of new lead molecules as drugs against the tuberculosis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The WNT signaling pathway is a central regulator of bone development and regeneration. Functional alterations of WNT ligands and inhibitors are associated with a variety of bone diseases that affect bone fragility and result in a high medical and socioeconomic burden. Hence, this cellular pathway has emerged as a novel target for bone-protective therapies, e.g. in osteoporosis. Here, we investigated glycosaminoglycan (GAG) recognition by Dickkopf-1 (DKK1), a potent endogenous WNT inhibitor, and the underlying functional implications in order to develop WNT signaling regulators. In a multidisciplinary approach we applied in silico structure-based de novo design strategies and molecular dynamics simulations combined with synthetic chemistry and surface plasmon resonance spectroscopy to Rationally Engineer oligomeric Glycosaminoglycan derivatives ( RE GAG) with improved neutralizing properties for DKK1. In vitro and in vivo assays show that the GAG modification to obtain RE GAG translated into increased WNT pathway activity and improved bone regeneration in a mouse calvaria defect model with critical size bone lesions. Importantly, the developed RE GAG outperformed polymeric high-sulfated hyaluronan (sHA3) in enhancing bone healing up to 50% due to their improved DKK1 binding properties. Thus, rationally engineered GAG variants may represent an innovative strategy to develop novel therapeutic approaches for regenerative medicine., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lorenz Hofbauer reports a relationship with Alexion that includes: funding grants. Lorenz Hofbauer reports a relationship with Ascendis Pharma, Inc. that includes: funding grants. Lorenz Hofbauer reports a relationship with Takeda Pharmaceutical Co Ltd that includes: funding grants. Lorenz Hofbauer reports a relationship with UCB Inc that includes: funding grants. Lorenz Hofbauer reports a relationship with Amgen Inc that includes: consulting or advisory. Lorenz Hofbauer reports a relationship with Pharmacosmos, Inc. that includes: consulting or advisory. Lorenz Hofbauer reports a relationship with UCB Inc that includes: consulting or advisory., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

High-income nations have established that early diagnosis and preventive treatment reduces early deaths in sickle cell disease (SCD). However, in low-/middle-income countries where SCD is common, attrition from clinical care is common. Reasons for poor retention in care are multi-factorial and poorly understood. The objective of this study was to identify factors that influence caregiver decision-making around chronic health care needs of a child with SCD. We conducted an exploratory sequential mixed methods study of caregivers of children diagnosed with SCD during a newborn screening program in Liberia. Caregivers completed questionnaires and semi-structured interviews designed to identify drivers of health decision-making. Interviews were digitally recorded, transcribed, coded, and analyzed using semi-structured thematic analysis to identify themes. Data integration occurred by using quantitative results to expand and clarify the qualitative themes. Twenty-six caregivers participated in the study. The mean age of the child at the interview was 43.7 months. Five themes influencing health decisions were identified: grief, the importance of support networks, stigma, perceived benefits, and the burden of chronic disease. The five themes crossed multiple domains of a socioecological model and identified complex interactions between family, community, social and cultural norms, and organizational structures. This study highlights the importance of community awareness of SCD and appropriate health communication by healthcare workers. Healthcare decision-making is multifactorial and complex. These results provide a framework for improving retention in care. In a low-resource country such as Liberia, much can be done by leveraging existing resources and cultural practices., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Dr. Tubman and Dr. Franklin receive travel support from the American Society of Hematology Consortium for Newborn Screening in Africa (CONSA). CONSA has no role in the study design, writing, or reviewing of this manuscript., (Copyright: © 2023 Udhayashankar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Adult mammals are incapable of multitissue regeneration, and augmentation of this potential may shift current therapeutic paradigms. We found that a common co-receptor of interleukin 6 (IL-6) cytokines, glycoprotein 130 (gp130), serves as a major nexus integrating various context-specific signaling inputs to either promote regenerative outcomes or aggravate disease progression. Via genetic and pharmacological experiments in vitro and in vivo, we demonstrated that a signaling tyrosine 814 (Y814) within gp130 serves as a major cellular stress sensor. Mice with constitutively inactivated Y814 (F814) were resistant to surgically induced osteoarthritis as reflected by reduced loss of proteoglycans, reduced synovitis, and synovial fibrosis. The F814 mice also exhibited enhanced regenerative, not reparative, responses after wounding in the skin. In addition, pharmacological modulation of gp130 Y814 upstream of the SRC and MAPK circuit by a small molecule, R805, elicited a protective effect on tissues after injury. Topical administration of R805 on mouse skin wounds resulted in enhanced hair follicle neogenesis and dermal regeneration. Intra-articular administration of R805 to rats after medial meniscal tear and to canines after arthroscopic meniscal release markedly mitigated the appearance of osteoarthritis. Single-cell sequencing data demonstrated that genetic and pharmacological modulation of Y814 resulted in attenuation of inflammatory gene signature as visualized by the anti-inflammatory macrophage and nonpathological fibroblast subpopulations in the skin and joint tissue after injury. Together, our study characterized a molecular mechanism that, if manipulated, enhances the intrinsic regenerative capacity of tissues through suppression of a proinflammatory milieu and prevents pathological outcomes in injury and disease.

Schizophrenia and related psychoses are complex neuropsychiatric diseases representing dysconnectivity across multiple scales, through the micro (cellular), meso (brain network), manifest (behavioral), and social (interpersonal) levels. In vivo human neuroimaging, particularly at ultra-high field (UHF), offers unprecedented opportunity to examine multiscale dysconnectivity in psychosis. In this review, we provide an overview of the literature to date on UHF in psychosis, focusing on microscale findings from magnetic resonance spectroscopy (MRS), mesoscale studies on structural and functional magnetic resonance imaging (fMRI), and multiscale studies assessing multiple neuroimaging modalities and relating UHF findings to behavior. We highlight key insights and considerations from multiscale and longitudinal studies and provide recommendations for future research on UHF neuroimaging in psychosis., Competing Interests: LP reports personal fees from Janssen Canada, Otsuka Canada, SPMM Course Limited, UK, Canadian Psychiatric Association; book royalties from Oxford University Press; investigator-initiated educational grants from Janssen Canada, Sunovion and Otsuka Canada in the last 5 years outside the submitted work. KL reports speaker’s honoraria from Otsuka Canada outside this work. The remaining author declares 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 Lavigne, Kanagasabai and Palaniyappan.)

Background: Mosquito coil smoke, along with biomass fuel smoke, are sources of indoor air pollution. Biomass fuel smoke has been studied as a risk factor for poor respiratory outcomes. However, in an Indian context, few studies examine the effect of mosquito coil exposure on poor respiratory outcomes at the community level., Objectives: To estimate the prevalence of the biomass fuel and mosquito coil use and to determine the association between the use of bio-mass fuel and mosquito coil and poor respiratory health., Methods: A cross-sectional survey of 4662 individuals (above the age of 30 years) was conducted using a pre-tested questionnaire. Trained interviewers collected data on current and past use of biomass fuels and mosquito coils, usage practices and respiratory health. We computed proportions for exposure variables namely biomass fuel, mosquito coil use and other covariates. We conducted univariate analysis, followed by multivariate logistic regression., Results: The prevalence of ever use of biomass fuels was high (wood: 97.9%; cow dung cake: 76.0% and crop residue: 54.4%). Current use of wood, cow dung cake and crop residue was prevalent among 75.7, 24.3 and 30.9% respondents, respectively. Almost 70% of respondents had ever used mosquito coils, whereas 54% were current users. Overall, 5.5% respondents had poor respiratory health either due to chronic bronchitis or asthma. In multivariate analysis, use of combination of all three biomass fuel types (adjusted odds ratio [AOR] 1.69, 95% confidence interval [CI]: 1.13-2.54) and use of mosquito coil more than or equal to 5 days per week (AOR 1.43, 95% CI: 1.04-1.99) were associated with poor respiratory health after adjusting for covariates age, gender, smoking, kitchen type and for each other., Conclusions: Use of biomass fuels and mosquito coils was high in the study population and was associated with poor respiratory health. Therefore, mosquito coil smoke should also be considered an important source of indoor air pollution, similar to biomass fuel exposure. Community education about these sources of indoor air pollution and increased coverage of cleaner fuels and alternative mosquito control methods should be the way forward in the rural areas., (© The Author(s) 2021. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Pulmonary rehabilitation is recommended for most patients with chronic obstructive pulmonary disease (COPD). Accordingly, the aim of this study was to explore the feasibility of devising a pulmonary rehabilitation program for patients with COPD in a low resource setting (Jaffna, Sri Lanka) and to observe its effects., Methods: Non-randomized controlled feasibility trial of ambulatory patients with COPD attending the pulmonary outpatient clinic of the Jaffna Teaching Hospital, Northern Province, Sri Lanka. Age-matched patients were allocated alternatively to an intervention group or to a control group. Twice weekly, for six weeks, patients in the intervention group attended pulmonary rehabilitation sessions consisting of supervised stretching, aerobic and strengthening exercises, and patient-education. Before and at the conclusion of the study, all patients performed incremental shuttle walking test (ISWT), 6-min walk test (6MWT) and completed the Medical Research Council (MRC) dyspnea scale, COPD assessment test (CAT), chronic COPD questionnaire (CCQ), and hospital anxiety depression scale (HADS)., Results: 204 patients with COPD (94% males) were identified at screening; 136 (66.7%) were eligible for pulmonary rehabilitation and 96 patients (47%) consented to participate. Of these, 54 patients (53 males) eventually participated in the study (42 patients were discouraged to participate by family members or friends); 40 patients (20 in the rehabilitation group and 20 patients in the control group) completed the study. Baseline characteristics of the intervention group and the control group were similar. 95% of patients in the intervention group adhered to regular home training exercises (self-reported diary). At post assessment, only the intervention group experienced clinically-meaningful improvements in symptoms and exercise capacity., Conclusion: A simple and clinically beneficial pulmonary rehabilitation program for patients with COPD can be effectively implemented in a low resource setting. However, there is a need for educating patients and the local community on the benefits of pulmonary rehabilitation to enhance uptake. Retrospective Trial Registration date and number: 16/04/2021, ISRCTN10069208., (© 2022. The Author(s).)

Laurin-Sandrow syndrome (LSS) is an extremely rare syndrome of mirror hand and leg with less than 20 cases reported in literature. The syndrome has been attributed to a mutation in the MIPOL-1 (mirror-image polydactyly) gene located on locus 14q13.3-q21 coding for CCDC193 (coiled-coli domain containing 193) protein. It is characterised by limb, facial and central nervous system anomalies with the most constant being fibular dimelia with fibular ray duplication, polydactyly with secondary deformities of fixed equinus, knee joint instability and flexion deformity. It is associated less frequently with ulnar dimelia, thumb aplasia/hypoplasia, ulnar ray duplication, symbrachypolydactyly, 'rosette' hands, facial dysmorphism like hypertelorism, broad columella and flat nose, CNS anomalies like aplasia/hypoplasia of corpus callosum, hydrocephalus and muscular dystonia. We report a 2-year-old male child with LSS and perform a literature review to expound on this rare syndrome. Level of Evidence: Level V (Therapeutic).

Background: Rotavirus is the leading cause of severe dehydrating gastroenteritis among children younger than 5 years in low-income and middle-income countries. Two vaccines-Rotavac and Rotasiil-are used in routine immunisation in India. The safety and immunogenicity of these vaccines administered in a mixed regimen is not documented. We therefore aimed to compare the safety and seroresponse of recipients of a mixed regimen versus a single regimen., Methods: We did a multicentre, open-label, randomised, controlled, phase 4, non-inferiority trial at two sites in India. We recruited healthy infants aged 6-8 weeks. Infants with systemic disorders, weight-for-height Z scores of less than minus three SDs, or a history of persistent diarrhoea were excluded. Eligible infants were randomly allocated to six groups in equal numbers to receive either the single vaccine regimen (ie, Rotavac-Rotavac-Rotavac [group 1] or Rotasiil-Rotasiil-Rotasiil [group 2]) or the mixed vaccine regimen (ie, Rotavac-Rotasiil-Rotavac [group 3], Rotasiil-Rotavac-Rotasiil [group 4], Rotavac-Rotasiil-Rotasiil [group 5], or Rotasiil-Rotavac-Rotavac [group 6]). Randomisation was done using an online software by site in blocks of at least 12. The primary outcome was seroresponse to rotavirus vaccine, measured using rotavirus-specific serum IgA antibodies 4 weeks after the third dose. The seroresponse rates were compared between recipients of the four mixed vaccine regimens (consisting of various combinations of Rotavac and Rotasiil) with recipients of the single vaccine regimens (consisting of Rotavac or Rotasiil only for all three doses). The non-inferiority margin was set at 10%. Safety follow-ups were done for the duration of study participation. This trial was registered with the Clinical Trials Registry India, number CTRI/2018/08/015317., Findings: Between March 25, 2019, and Jan 15, 2020, a total of 1979 eligible infants were randomly assigned to receive a single vaccine regimen (n=659; 329 in group 1 and 330 in group 2) or a mixed vaccine regimen (n=1320; 329 each in groups 3 and 4, and 331 each in groups 5 and 6). All eligible participants received the first dose, 1925 (97·3%) of 1979 received the second dose, and 1894 (95·7%) received all three doses of vaccine. 1852 (93·6%) of 1979 participants completed the follow-up. The immunogenicity analysis consisted of 1839 infants (1238 [67·3%] in the mixed vaccine regimen and 601 [32·7%] in the single vaccine regimen; 13 samples were insufficient in quantity) who completed vaccination and provided post-vaccination sera. The seroresponse rate in the mixed vaccine regimen group (33·5% [95% CI 30·9-36·2]) was non-inferior compared with the single vaccine regimen group (29·6% [26·1-33·4]); the seroresponse rate difference was 3·9% (95% CI -0·7 to 8·3). The proportion of participants with any type of solicited adverse events was 90·9% (95% CI 88·4-93·0) in the single vaccine regimen group and 91·1% (89·5-92·6) in the mixed vaccine regimen group. No vaccine-related serious adverse events or intussusception were reported during the study., Interpretation: Rotavac and Rotasiil can be safely used in an interchangeable manner for routine immunisation since the seroresponse was non-inferior in the mixed vaccine regimen compared with the single vaccine regimen. These results allow for flexibility in administering the vaccines, helping to overcome vaccine shortages and supply chain issues, and targeting migrant populations easily., Funding: Ministry of Health and Family Welfare, Government of India., Translation: For the Hindi translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Soil-transmitted helminth (STH) infections are highly prevalent in many developing countries, affecting the poorest and most deprived communities. We conducted school-based surveys among children studying in first to fifth standard in government schools in the Indian States of Chhattisgarh, Telangana, and Tripura to estimate the prevalence and intensity of STH infections during November 2015 and January 2016. We adopted a two-stage cluster sampling design, with a random selection of districts within each agro-climatic zone in the first stage. In the second stage, government primary schools were selected by probability proportional to size method from the selected districts. We collected information about demographic details, water, sanitation, and hygiene (WASH) characteristics and stool samples from the school children. Stool samples were tested using Kato-Katz method. Stool samples from 3,313 school children (Chhattisgarh: 1,442, Telangana: 1,443, and Tripura: 428) were examined. The overall prevalence of any STH infection was 80.2% (95% confidence interval [CI]: 73.3-85.7) in Chhattisgarh, 60.7% (95% CI: 53.8-67.2) in Telangana, and 59.8% (95% CI: 49.0-69.7) in Tripura. Ascaris lumbricoides was the most prevalent STH infection in all three states. Most of the STH infections were of light intensity. Our study findings indicate that STH infections were highly prevalent among the school children in Chhattisgarh, Telangana, and Tripura, indicating the need for strengthening STH control program in these states. The prevalence estimates from the survey would serve as a baseline for documenting the impact of the National Deworming Day programs in these states.

Competing Interests: None

Objective: To assess Liberian health care workers' feelings around safety in returning to work in the setting of the Ebola virus disease outbreak of 2014-2015 after receiving infection prevention and control (IPC) training., Methods: Academic Consortium Combating Ebola in Liberia (ACCEL) training surveys were done at 21 public, Liberian hospitals to understand health care workers' attitudes surrounding Ebola and whether they felt safe while at work based on multiple factors. Logistic regression was used for analysis., Results: We found that health care workers feeling safe at work during the Ebola outbreak was primarily predicted by the number of IPC/Ebola trainings received pre-ACCEL interventions. Health care workers felt increasingly safer and motivated to return to work as trainings approached 3 (OR 8, p-value < 0.001); however, more than 3 trainings resulted in decreased safety and motivation. In addition, health care workers who reported washing their hands before and after patient contact were 3.4 times more likely to understand how to protect themselves from Ebola., Conclusions: These results help to better understand the utility of repeated trainings on health care worker practice attitudes and the importance of IPC policies within hospitals, such as hand hygiene promotion and education, when coordinating humanitarian efforts.

In this work, anion-π interactions between sulfate groups (SO 4 2- ) and protein aromatic amino acids (AAs) (histidine protonated (HisP), histidine neutral (HisN), tyrosine (Tyr), tryptophan (Trp), and phenylalanine (Phe)) in an aqueous environment have been analyzed using quantum chemical (QC) calculations and molecular dynamics (MD) simulations. Sulfates can occur naturally in solution and can be contained in biomolecules playing relevant roles in their biological function. In particular, the presence of sulfate groups in glycosaminoglycans such as heparin and heparan sulfate has been shown to be relevant for protein and cellular communication and, consequently, for tissue regeneration. Therefore, anion-π interactions between sulfate groups and aromatic residues represent a relevant aspect to investigate. QC results show that such an anion-π mode of interaction between SO 4 2- and aromatic AAs is only possible in the presence of water molecules, in the absence of any other cooperative non-covalent interactions. Protonated histidine stands out in terms of its enhancement in the magnitude of interaction strength on solvation. Other AAs such as non-protonated histidine, tyrosine, and phenylalanine can stabilize anion-π interactions on solvation, albeit with weak interaction energy. Tryptophan does not exhibit any anion-π mode of interaction with SO 4 2- . The order of magnitude of the interaction of aromatic AAs with SO 4 2- on microsolvation is HisP > HisN > Tyr > Trp > Phe. Atoms in molecules (AIM) analysis illustrates the significance of water molecules in stabilizing the divalent SO 4 2- anion over the π surface of the aromatic AAs. MD simulation analysis shows that the order of magnitude of the interaction of SO 4 2- with aromatic AAs in macroscopic solvation is HisP > HisN, Tyr, Trp > Phe, which is very much in line with the QC results. Spatial distribution function analysis illustrates that protonated histidine alone is capable of establishing the anion-π interaction with SO 4 2- in the solution phase. This study sheds light on the understanding of anion-π interactions between SO 4 2- and aromatic AAs such as His and Tyr observed in protein crystal structures and the significance of water molecules in stabilizing such interactions, which is not feasible otherwise., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Angiogenesis is an important physiological process playing a crucial role in wound healing and cancer progression. Vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) are key players in angiogenesis. Based on previous findings regarding the modulation of VEGF activity by glycosaminoglycans (GAG), here we explore the interaction of hyaluronan (HA)-based GAG with PDGF and its receptor PDGFR-β by applying molecular modeling and dynamics simulations in combination with surface plasmon resonance (SPR). Computational analysis on the interaction of oligo-hyaluronan derivatives with different sulfation pattern and functionalization shows that these GAG interact with PDGF in relevant regions for receptor recognition, and that high sulfation as well as modification with the TAMRA group convey stronger binding. On the other hand, the studied oligo-hyaluronan derivatives are predicted to scarcely recognize PDGFR-β. SPR results are in line with the computational predictions regarding the binding pattern of HA tetrasaccharide (HA4) derivatives to PDGF and PDGFR-β. Furthermore, our experimental results also show that the complexation of PDGF to PDGFR-β can be modulated by HA4 derivatives. The results found open the path for considering HA4 derivatives as potential candidates to be exploited for modulation of the PDGF/PDGFR-β signaling system in angiogenesis and related disease conditions., (© 2021 Kanagasabai Balamurugan et al., published by De Gruyter, Berlin/Boston.)

Movement of patients in a health care network poses challenges for the control of carbapenemase-producing Enterobacteriaceae (CPE). We aimed to identify intra- and interfacility transmission events and facility type-specific risk factors of CPE in an acute-care hospital (ACH) and its intermediate-term and long-term-care facilities (ILTCFs). Serial cross-sectional studies were conducted in June and July of 2014 to 2016 to screen for CPE. Whole-genome sequencing was done to identify strain relatedness and CPE genes ( bla IMI , bla IMP-1 , bla KPC-2 , bla NDM-1 , and bla OXA-48 ). Multivariable logistic regression models, stratified by facility type, were used to determine independent risk factors. Of 5,357 patients, half (55%) were from the ACH. CPE prevalence was 1.3% in the ACH and 0.7% in ILTCFs ( P  = 0.029). After adjusting for sociodemographics, screening year, and facility type, the odds of CPE colonization increased significantly with a hospital stay of ≥3 weeks (adjusted odds ratio [aOR], 2.67; 95% confidence interval [CI], 1.17 to 6.05), penicillin use (aOR, 3.00; 95% CI, 1.05 to 8.56), proton pump inhibitor use (aOR, 3.20; 95% CI, 1.05 to 9.80), dementia (aOR, 3.42; 95% CI, 1.38 to 8.49), connective tissue disease (aOR, 5.10; 95% CI, 1.19 to 21.81), and prior carbapenem-resistant Enterobacteriaceae (CRE) carriage (aOR, 109.02; 95% CI, 28.47 to 417.44) in the ACH. For ILTCFs, presence of wounds (aOR, 5.30; 95% CI, 1.01 to 27.72), respiratory procedures (aOR, 4.97; 95% CI, 1.09 to 22.71), vancomycin-resistant enterococcus carriage (aOR, 16.42; 95% CI, 1.52 to 177.48), and CRE carriage (aOR, 758.30; 95% CI, 33.86 to 16,982.52) showed significant association. Genomic analysis revealed only possible intra-ACH transmission and no evidence for ACH-to-ILTCF transmission. Although CPE colonization was predominantly in the ACH, risk factors varied between facilities. Targeted screening and precautionary measures are warranted.

Coagulation factor VIIa (FVIIa) consists of a γ-carboxyglutamic acid (GLA) domain, two epidermal growth factor-like (EGF) domains and a protease domain. FVIIa binds three Mg 2+ ions and four Ca 2+ ions in the GLA domain, one Ca 2+ ion in the EGF1 domain and one Ca 2+ ion in the protease domain. Further, FVIIa contains an Na + site in the protease domain. Since Na + and water share the same number of electrons, Na + sites in proteins are difficult to distinguish from waters in X-ray structures. Here, to verify the Na + site in FVIIa, the structure of the FVIIa-soluble tissue factor (TF) complex was solved at 1.8 Å resolution containing Mg 2+ , Ca 2+ and Rb + ions. In this structure, Rb + replaced two Ca 2+ sites in the GLA domain and occupied three non-metal sites in the protease domain. However, Rb + was not detected at the expected Na + site. In kinetic experiments, Na + increased the amidolytic activity of FVIIa towards the synthetic substrate S-2288 (H-D-Ile-Pro-Arg-p-nitroanilide) by ∼20-fold; however, in the presence of Ca 2+ , Na + had a negligible effect. Ca 2+ increased the hydrolytic activity of FVIIa towards S-2288 by ∼60-fold in the absence of Na + and by ∼82-fold in the presence of Na + . In molecular-dynamics simulations, Na + stabilized the two Na + -binding loops (the 184-loop and 220-loop) and the TF-binding region spanning residues 163-180. Ca 2+ stabilized the Ca 2+ -binding loop (the 70-loop) and Na + -binding loops but not the TF-binding region. Na + and Ca 2+ together stabilized both the Na + -binding and Ca 2+ -binding loops and the TF-binding region. Previously, Rb + has been used to define the Na + site in thrombin; however, it was unsuccessful in detecting the Na + site in FVIIa. A conceivable explanation for this observation is provided.

In order to restore the regeneration capacity of large-size vascularized tissue defects, innovative biomaterial concepts are required. Vascular endothelial growth factor (VEGF 165 ) is a key factor of angiogenesis interacting with sulfated glycosaminoglycans (sGAG) within the extracellular matrix. As this interplay mainly controls and directs the biological activity of VEGF 165 , we used chemically modified sGAG derivatives to evaluate the structural requirements of sGAG for controlling and tuning VEGF 165 function and to translate these findings into the design of biomaterials. The in-depth analysis of this interaction by surface plasmon resonance and ELISA studies in combination with molecular modeling stressed the relevance of the substitution position, degree of sulfation, and carbohydrate backbone of GAG. Acrylated hyaluronan (HA-AC)/collagen (coll)-based hydrogels containing cross-linked acrylated, sulfated hyaluronan (sHA-AC) derivatives with different substitution patterns or an acrylated chondroitin sulfate (CS-AC) derivative function as multivalent carbohydrate-based scaffolds for VEGF 165 delivery with multiple tuning capacities. Depending on the substitution pattern of sGAG, the release of biologically active VEGF 165 was retarded in a defined manner compared to pure HA/coll gels, which further controlled the VEGF 165 -induced stimulation of endothelial cell proliferation and extended morphology of cells. This indicates that sGAG can act as modulators of protein interaction profiles of HA/coll hydrogels. In addition, sHA-AC-containing gels with and even without VEGF 165 strongly stimulate endothelial cell proliferation compared to gels containing only CS-AC or HA-AC. Thus, HA/coll-based hydrogels containing cross-linked sHA-AC are biomimetic materials able to directly influence endothelial cells in vitro , which might translate into an improved healing of injured vascularized tissues.

Current antifibrinolytic agents reduce blood loss by inhibiting plasmin active sites (e.g., aprotinin) or by preventing plasminogen/tissue plasminogen activator (tPA) binding to fibrin clots (e.g., ε-aminocaproic acid and tranexamic acid); however, they have adverse side effects. Here, we expressed 60-residue ( NH2 NAE…IEK COOH ) Kunitz domain1 (KD1) mutants of human tissue factor pathway inhibitor type-2 that inhibit plasmin as well as plasminogen activation. A single (KD1-L17R-K COOH ) and a double mutant (KD1-Y11T/L17R- K COOH ) were expressed in Escherichia coli as His-tagged constructs, each with enterokinase cleavage sites. KD1-Y11T/L17R-K COOH was also expressed in Pichia pastoris . KD1-Y11T/L17R-K COOH inhibited plasmin comparably to aprotinin and bound to the kringle domains of plasminogen/plasmin and tPA with K d of ~50 nM and ~35 nM, respectively. Importantly, compared to aprotinin, KD1-L17R-K COOH and KD1-Y11T/L17R-K COOH did not inhibit kallikrein. Moreover, the antifibrinolytic potential of KD1-Y11T/L17R-K COOH was better than that of KD1-L17R-K COOH and similar to that of aprotinin in plasma clot-lysis assays. In thromboelastography experiments, KD1-Y11T/L17R-K COOH was shown to inhibit fibrinolysis in a dose dependent manner and was comparable to aprotinin at a higher concentration. Further, KD1-Y11T/L17R-K COOH did not induce cytotoxicity in primary human endothelial cells or fibroblasts. We conclude that KD1-Y11T/L17R-K COOH is comparable to aprotinin, the most potent known inhibitor of plasmin and can be produced in large amounts using Pichia .

Understanding the dual inhibition mechanism of food derivative peptides targeting the enzymes (Renin and Angiotensin Converting enzyme) in the Renin Angiotensin System. Two peptides RALP and WYT were reported to possess antihypertensive activity targeting both renin and ACE, and we have used molecular docking and molecular dynamics simulation, in order to understand the underlying mechanism. The selected peptides (RALP and WYT) from the series of peptides reported were docked to renin and ACE and two binding modes were selected based on the binding energy, interaction pattern and clusters of docking simulation. The enzyme-peptide complexes for renin and ACE (Renin/RALP 1,2; ACE/RALP 1,2 ; Renin/WYT 1,2 and ACE/WYT 1,2 ) were subjected to molecular dynamics simulation. Our results identified that the peptides inhibiting renin, tends to move out of the binding pockets (S1' S2') which is critical for potent binding and occupies the less important pockets (S4 and S3). This could possibly be the reason for its low potency. Whereas, the same peptides targeting ACE, tends to be intact in the pocket because of the metal ion coordination and there is an ample room to improve on its efficacy. Our results further pave way for the biochemist, medicinal chemist to design dual peptides targeting the RAS effectively. Communicated by Ramaswamy H. Sarma.

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) has spread across countries and healthcare settings, with different clones occupying different ecological niches. It is crucial to understand the comparative epidemiology of MRSA clones between healthcare settings and independent factors associated with colonization of specific clones., Methods: We conducted annual cross-sectional surveillance studies in a network comprising an acute-care hospital and six closely-affiliated intermediate- and long-term care facilities in Singapore between June and July, 2014-2016; 5394 patients contributed 16 045 nasal, axillary and groin samples for culture and MRSA isolates for whole-genome sequencing. Multivariable multilevel multinomial regression models were constructed to assess independent factors associated with MRSA colonization., Results: MRSA clonal complex (CC) 22 was more prevalent in the acute-care hospital (n = 256/493; 51.9%) and intermediate-care facilities (n = 348/634; 54.9%) than in long-term care (n = 88/351; 25.1%) facilities, with clones other than CC22 and CC45 being more prevalent in long-term care facilities (n = 144/351; 41.0%) (p < 0.001). Groin colonization with CC45 was six times that of nasal colonization (aOR 6.21, 95%CI 4.26-9.01). Prior MRSA carriage was associated with increased odds of current MRSA colonization in all settings, with a stronger association with CC22 (aOR 6.45, 95%CI 3.85-10.87) than CC45 (aOR 4.15, 95%CI 2.26-7.58)., Conclusions: Colonization by MRSA clones differed between anatomical sites and across healthcare settings. With CC22 having a predilection for the nares and CC45 the groin, MRSA screening should include both sites. Prior MRSA carriage is a risk factor for colonization with predominant MRSA clones in the acute-care hospital and intermediate- and long-term care facilities. Contact precautions for prior MRSA carriers on admission to any healthcare facility could prevent intra- and inter-institutional MRSA transmission., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)