Publications by authors named "N S Sampath Kumar"

6,107 Publications

  • Page 1 of 1

Impact of opioid maintenance treatment during pregnancy on neonatal birth weight and head circumference.

J Neonatal Perinatal Med 2021 Apr 7. Epub 2021 Apr 7.

Division of Neonatology, Hurley Medical Center, Flint, MI, USA.

Background: Pregnant mothers with opioid dependency commonly receive maintenance treatment of opioid (OMT), either as buprenorphine (BMT) or methadone maintenance treatment (MMT). We investigated, whether OMT adversely affects standardized neonatal anthropometric outcomes and whether BMT is potentially safer than MMT in this regard.

Methods: Retrospective chart review of mother infant dyad, with and without OMT. Infant's absolute and standardized (z-score) anthropometric outcomes at birth were first compared, between OMT and control group (negative meconium drug screen), and then between BMT and MMT group. These outcomes were also compared between infants who did or did not require treatment after birth for neonatal abstinence syndrome (NAS).

Result: A total of 1479 participants with MDS were included [Control = 1251; OMT = 228 (MMT = 181; BMT = 47)]. Both the z-scores of birth weight (BW) and head circumference (HC) was lower in OMT group (p <  0.001). Among the OMT group, GA at delivery was slightly higher in the BMT group (p = 0.05). There was an inverse correlation between maternal dose at the time of delivery and anthropometric z-scores in the BMT group, mainly in female infants (BW: p = 0.006; HC: p = 0.003). Furthermore, In BMT group, infants with lower HC were more likely to require treatment for NAS (p = 0.01).

Conclusion: HC and BW when comparing Z-scores were not different between MMT and BMT. High maternal dosing of buprenorphine is associated with lower BW and HC Z-scores but dose effect is not seen with methadone. In addition, there seems to be an association between NAS severity and HC, especially in the BMT group.
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http://dx.doi.org/10.3233/NPM-200645DOI Listing
April 2021

Time Till Viral Clearance of Severe Acute Respiratory Syndrome Coronavirus 2 Is Similar for Asymptomatic and Non-critically Symptomatic Individuals.

Front Med (Lausanne) 2021 26;8:616927. Epub 2021 Mar 26.

Royal College of Surgeons in Ireland, Manama, Bahrain.

Despite the modeled estimations of the burden of asymptomatic spread, the duration of viral positivity and infectiousness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains understudied. The objective of the present study was to estimate and compare the time till viral clearance of SARS-CoV-2 in asymptomatic and non-critical symptomatic individuals. We studied 184 SARS-CoV-2-positive participants, of whom 145 were asymptomatic. Our analysis uncovered that time till viral negativity is similar for subclinical [median time till viral clearance: 11 days, interquartile range (IQR): 8, 14] and overt infections (median: 11 days, IQR: 9, 14) after controlling for age and sex. This has implications in understanding the period of infectivity for SARS-CoV-2 in order to plan adequate public health measures to control the community spread.
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http://dx.doi.org/10.3389/fmed.2021.616927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032858PMC
March 2021

Development and Evaluation of Active Case Detection Methods to Support Visceral Leishmaniasis Elimination in India.

Front Cell Infect Microbiol 2021 24;11:648903. Epub 2021 Mar 24.

Bihar Technical Support Program, CARE-India Solutions for Sustainable Development, Patna, India.

As India moves toward the elimination of visceral leishmaniasis (VL) as a public health problem, comprehensive timely case detection has become increasingly important, in order to reduce the period of infectivity and control outbreaks. During the 2000s, localized research studies suggested that a large percentage of VL cases were never reported in government data. However, assessments conducted from 2013 to 2015 indicated that 85% or more of confirmed cases were eventually captured and reported in surveillance data, albeit with significant delays before diagnosis. Based on methods developed during these assessments, the CARE India team evolved new strategies for active case detection (ACD), applicable at large scale while being sufficiently effective in reducing time to diagnosis. Active case searches are triggered by the report of a confirmed VL case, and comprise two major search mechanisms: 1) case identification based on the index case's knowledge of other known VL cases and searches in nearby houses (snowballing); and 2) sustained contact over time with a range of private providers, both formal and informal. Simultaneously, house-to-house searches were conducted in 142 villages of 47 blocks during this period. We analyzed data from 5030 VL patients reported in Bihar from January 2018 through July 2019. Of these 3033 were detected passively and 1997 ACD (15 (0.8%) house-to-house and 1982 (99.2%) by light touch ACD methods). We constructed multinomial logistic regression models comparing time intervals to diagnosis (30-59, 60-89 and ≥90 days with <30 days as the referent). ACD and younger age were associated with shorter time to diagnosis, while male sex and HIV infection were associated with longer illness durations. The advantage of ACD over PCD was more marked for longer illness durations: the adjusted odds ratios for having illness durations of 30-59, 60-89 and >=90 days compared to the referent of <30 days for ACD vs PCD were 0.88, 0.56 and 0.42 respectively. These ACD strategies not only reduce time to diagnosis, and thus risk of transmission, but also ensure that there is a double check on the proportion of cases actually getting captured. Such a process can supplement passive case detection efforts that must go on, possibly perpetually, even after elimination as a public health problem is achieved.
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http://dx.doi.org/10.3389/fcimb.2021.648903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024686PMC
March 2021

Primer on the In-home Teleneurologic Examination: A COVID-19 Pandemic Imperative.

Neurol Clin Pract 2021 Apr;11(2):e157-e164

Department of Neurology, Mayo Clinic, Rochester, MN.

It is imperative in the coronavirus disease 2019 (COVID-19) pandemic that we serve our patients by implementing teleneurology visits for those who require neurologic advice but do not need to be seen face to face. The authors propose a thorough, practical, in-home, teleneurologic examination that can be completed without the assistance of an on-the-scene medical professional and can be tailored to the clinical question. We hope to assist trainees and practicing neurologists doing patient video visits for the first time during the COVID-19 pandemic, focusing on what can, rather than what cannot, be easily examined.
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http://dx.doi.org/10.1212/CPJ.0000000000000876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032424PMC
April 2021

Assessment of arsenic exposure in the population of Sabalpur village of Saran District of Bihar with mitigation approach.

Environ Sci Pollut Res Int 2021 Apr 11. Epub 2021 Apr 11.

Mahavir Cancer Sansthan and Research Centre, Phulwarisharif, Patna, Bihar, 801505, India.

Arsenic poisoning through groundwater is the world's greatest normal groundwater catastrophe which got an immense effect on worldwide general wellbeing. India is confronting the outcomes of arsenic poisoning in the zone of Ganga Brahmaputra alluvial plains. In Bihar, out of 38 districts, 18 districts are exceptionally influenced with groundwater arsenic defilement. In the present study, we have assessed the current situation of arsenic exposure in Sabalpur village of Saran district of Bihar after reporting of breast, renal, skin and thyroid cancer cases from this village along with typical symptoms of arsenicosis. Such cancer patients were identified at our institute and were taken for the study. The present investigation deals with the quantification of arsenic in groundwater, hair and nail samples of subjects as well as the survey of entire village to know the overall health status of the village people. A total of n=128 household handpump water samples as well as n=128 human hair and nail samples were collected from over n=520 households. Using the graphite furnace atomic absorption spectrophotometer (GF-AAS), all the samples were analysed. The investigation resulted that the 61% of the analysed samples particularly the groundwater had the arsenic levels more than the permissible limit of WHO (> 10 μg/L) with 244.20 μg/L as the highest arsenic contamination in one of the handpump water sample. The exposure effect of hair sample was worst as 88% of all the collected samples were having high arsenic levels more than the permissible limit (> 0.2 mg/Kg). In case of nail samples, 92% of the samples were having high arsenic concentration more than the permissible limit (> 0.5 mg/Kg). The health survey study revealed high magnitude of disease burden in the exposed population with symptoms such as asthma, anaemia, hepatomegaly, diabetes, cardiac problem, skin fungal infections, breathlessness and mental disability. Few cancer cases of renal, skin, breast and cervix were also found among the exposed population of this village. The percentage of cancer cases in this village was 0.94% that was low, but it would be an aggravated situation in the near future if people will continue drinking arsenic-contaminated water. Therefore, a mitigation intervention was carried out in March 2020 by installing an arsenic filter plant. The health situation in the village in the present scenario is hope to improve in the coming years. However, motivation and awareness among the village population are still required.
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http://dx.doi.org/10.1007/s11356-021-13521-5DOI Listing
April 2021

Restless legs syndrome among subjects having chronic liver disease: A systematic review and meta-analysis.

Sleep Med Rev 2021 Mar 11;58:101463. Epub 2021 Mar 11.

Department of Neurology, John Hopkins University, Baltimore, MD, USA.

Sleep disturbances are commonly reported in patients with chronic liver disease (CLD). Changes in quality of sleep in patients with CLD could be related to multiple factors viz., elevated levels of tryptophan, histamine, and increased turnover of dopamine in caudate-putamen and cingulate cortex. Also, iron metabolism disturbances are reported in patients with CLD. These changes may result in restless legs syndrome (RLS) that worsens sleep-quality. There have been reports suggesting an increased prevalence of RLS among patients with CLD. Literature was searched in PubMed, EMBASE, and Google Scholar. A total of twenty-two relevant articles were found. Out of these, nine studies have assessed the prevalence of RLS among patients with chronic liver disease or cirrhosis in the clinical population. Population prevalence reported from various studies was used to calculate odds ratio. Having included studies using various methods for diagnosis (clinical as well as questionnaires) pooled odds-ratio for the RLS was 8.62. It remains unaffected by study-method, gender, age, and geographical-area. However, studies using clinical diagnosis for RLS had lower odds compared to questionnaire based diagnosis. Studies varied with regards to diagnostic methods, age, gender, etiology, and severity of liver dysfunction. The severity and etiology of CLD and biochemical correlate of CLD were not found to be associated with RLS. Possible pathophysiological mechanisms are discussed for the occurrence of RLS in this population. In conclusion, the prevalence of RLS is higher among patients with CLD, however, the correlates are unknown.
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http://dx.doi.org/10.1016/j.smrv.2021.101463DOI Listing
March 2021

Autoimmune Sclerosing Cholangitis in Children: A Prospective Case-Control Study.

Pediatr Gastroenterol Hepatol Nutr 2021 Mar 8;24(2):154-163. Epub 2021 Mar 8.

Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Purpose: In children overlap of autoimmune hepatitis (AIH) and primary sclerosing cholangitis is labelled as autoimmune sclerosing cholangitis (ASC). The only prospective pediatric study showed a high prevalence of ASC by using endoscopic retrograde cholangiopancreatography. Aims of our study were to find the prevalence of ASC by using magnetic resonance cholangiography (MRC) in AIH and in non-AIH cirrhosis and to compare clinical presentation and outcome of AIH and ASC.

Methods: Prospectively we did MRC in 38 children with AIH (cases) and 19 disease controls (Wilson disease). Multiple biliary strictures with proximal dilatation on MRC were taken as definitive changes of ASC. Detail clinical, laboratory parameters, liver histopathology and treatment outcome were recorded.

Results: The median age of cases was 11.5 (3-18) years, 22 (57.9%) were girls and 28 (73.7%) were diagnosed as type 1 AIH. MRC was done in 11 children (28.9%) at the time of diagnosis and in 27 (71.1%) after a median follow-up of 2.5 (0.3-10) years. Abnormal MRC changes were seen in 14/38 (36.8%) of AIH and 8/19 (42.1%) of controls. However, definite changes of ASC were present in four (10.5%) children in AIH and none in controls. None of the clinical, laboratory, histological parameters and treatment response were significantly different between ASC and AIH groups.

Conclusion: The prevalence of ASC in children with AIH was just 10.5%. We suggest MRC in select group with cholestatic features, inflammatory bowel disease and in those who showed poor response to immunosuppression instead of all children with AIH.
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http://dx.doi.org/10.5223/pghn.2021.24.2.154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007839PMC
March 2021

Molecular insights into a mechanism of resveratrol action using hybrid computational docking/CoMFA and machine learning approach.

J Biomol Struct Dyn 2021 Apr 8:1-15. Epub 2021 Apr 8.

School of Pharmacy, Graphic Era Hill University, Dehradun, Uttarakhand, India.

A phytoalexin, Resveratrol remains a legendary anticancer drug candidate in the archives of scientific literature. Although earlier wet-lab experiments rendering its multiple biological targets, for example, epidermal growth factors, Pro-apoptotic protein p53, sirtuins, and first apoptosis signal (Fas) receptor, Mouse double minute 2 (MDM2) ubiquitin-protein ligase, Estrogen receptor, Quinone reductase, etc. However, notwithstanding some notable successes, identification of an appropriate Resveratrol target(s) has remained a major challenge using physical methods, and hereby limiting its translation into an effective therapeutic(s). Thus, computational insights are much needed to establish proof-of-concept towards potential Resveratrol target(s) with minimum error rate, narrow down the search space, and to assess a more accurate Resveratrol signaling pathway/mechanism at the starting point. Herein, a brute-force technique combining computational receptor-, ligand-based virtual screening, and classification-based machine learning, reveals the precise mechanism of Resveratrol action. Overall, MDM2 ubiquitin-protein ligase (4OGN.pdb) and co-crystallized quinone reductases 2 (4QOH.pdb) were found two suitable drug targets in the case of Resveratrol derivatives. Indeed, carotenoid cleaving oxygenase together with later twos gave gigantic momentum in guiding the rational drug design of Resveratrol derivatives. These molecular modeling insights would be useful for Resveratrol lead optimization into a more precise science.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.1910572DOI Listing
April 2021

Cytotoxic T-lymphocyte elicited vaccine against SARS-CoV-2 employing immunoinformatics framework.

Sci Rep 2021 04 7;11(1):7653. Epub 2021 Apr 7.

Department of Biotechnology, Jawahar Lal Nehru University, Delhi, 110067, India.

Development of effective counteragents against the novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains, requires clear insights and information for understanding the immune responses associated with it. This global pandemic has pushed the healthcare system and restricted the movement of people and succumbing of the available therapeutics utterly warrants the development of a potential vaccine to contest the deadly situation. In the present study, highly efficacious, immunodominant cytotoxic T-lymphocyte (CTL) epitopes were predicted by advanced immunoinformatics assays using the spike glycoprotein of SARS-CoV2, generating a robust and specific immune response with convincing immunological parameters (Antigenicity, TAP affinity, MHC binder) engendering an efficient viral vaccine. The molecular docking studies show strong binding of the CTL construct with MHC-1 and host membrane specific TLR2 receptors. The molecular dynamics simulation in an explicit system confirmed the stable and robust binding of CTL epitope with TLR2. Steep magnitude RMSD variation and compelling residual fluctuations existed in terminal residues and various loops of the β linker segments of TLR2-epitope (residues 105-156 and 239-254) to about 0.4 nm. The reduced R value (3.3 nm) and stagnant SASA analysis (275 nm/S/N after 8 ns and 5 ns) for protein surface and its orientation in the exposed and buried regions suggests more compactness due to the strong binding interaction of the epitope. The CTL vaccine candidate establishes a high capability to elicit the critical immune regulators, like T-cells and memory cells as proven by the in silico immunization assays and can be further corroborated through in vitro and in vivo assays.
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http://dx.doi.org/10.1038/s41598-021-86986-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027208PMC
April 2021

Elicitation of potent serum neutralizing antibody responses in rabbits by immunization with an HIV-1 clade C trimeric Env derived from an Indian elite neutralizer.

PLoS Pathog 2021 Apr 7;17(4):e1008977. Epub 2021 Apr 7.

Translational Health Science & Technology Institute, NCR Biotech Science Cluster, Faridabad, India.

Evaluating the structure-function relationship of viral envelope (Env) evolution and the development of broadly cross-neutralizing antibodies (bnAbs) in natural infection can inform rational immunogen design. In the present study, we examined the magnitude and specificity of autologous neutralizing antibodies induced in rabbits by a novel HIV-1 clade C Env protein (1PGE-THIVC) vis-à-vis those developed in an elite neutralizer from whom the env sequence was obtained that was used to prepare the soluble Env protein. The novel 1PGE-THIVC Env trimer displayed a native like pre-fusion closed conformation in solution as determined by small angle X-ray scattering (SAXS) and negative stain electron microscopy (EM). This closed spike conformation of 1PGE-THIVC Env trimers was correlated with weak or undetectable binding of non-neutralizing monoclonal antibodies (mAbs) compared to neutralizing mAbs. Furthermore, 1PGE-THIVC SOSIP induced potent neutralizing antibodies in rabbits to autologous virus variants. The autologous neutralizing antibody specificity induced in rabbits by 1PGE-THIVC was mapped to the C3/V4 region (T362/P401) of viral Env. This observation agreed with electron microscopy polyclonal epitope mapping (EMPEM) of the Env trimer complexed with IgG Fab prepared from the immunized rabbit sera. Our study demonstrated neutralization of sequence matched and unmatched autologous viruses by serum antibodies induced in rabbits by 1PGE-THIVC and also highlighted a comparable specificity for the 1PGE-THIVC SOSIP trimer with that seen with polyclonal antibodies elicited in the elite neutralizer by negative-stain electron microscopy polyclonal epitope (ns-EMPEM) mapping.
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http://dx.doi.org/10.1371/journal.ppat.1008977DOI Listing
April 2021

Is sickle cell disease a risk factor for severe COVID-19 outcomes in hospitalized patients? A multicenter national retrospective cohort study.

EJHaem 2021 Feb 10. Epub 2021 Feb 10.

National Taskforce for Combating the Coronavirus (COVID-19) Riffa Bahrain.

Introduction: Studies that examine the association between sickle cell disease (SCD) and COVID-19 outcomes are lacking. This study aims to determine whether SCD is a risk factor for severe COVID-19 infection in regard to the requirement of noninvasive ventilation/high flow nasal cannula (NIV/HFNC), mechanical ventilation (MV), or death in hospitalized patients.

Methods: Retrospective cohort study included COVID-19 patients admitted to four COVID-19 treatment facilities in Bahrain between February 24, 2020 and July 31, 2020. All SCD patients with COVID-19 were included and compared to a randomly selected sample of non-SCD patients with COVID-19. Data were collected from the medical records. Multivariate logistic regression models were used to control for confounders and estimate the effect of SCD on the outcomes.

Results: 1792 patients with COVID-19 were included; 38 of whom were diagnosed with SCD as well. In the SCD group, one (2.6%) patient required NIV/HFNC, one (2.6%) required MV, and one (2.6%) death occurred. In comparison, 56 (3.2%) of the non-SCD patients required NIV/HFNC, 47 (2.7%) required MV, and death occurred in 58 (3.3%) patients. Upon adjusting for confounders, SCD had an odds ratio of 1.847 (95% CI: 0.39-8.83; p = 0.442).

Conclusion: Our results indicate that SCD is not a risk factor for worse COVID-19 outcomes in hospitalized patients.
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http://dx.doi.org/10.1002/jha2.170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014602PMC
February 2021

Development of a time of flight spectrometer based on position sensitive multi-wire proportional counters for fission fragment mass distribution studies.

Rev Sci Instrum 2021 Mar;92(3):033309

Inter University Accelerator Centre, P.O. Box 10502, New Delhi 110067, India.

Characteristics and performance of a time of flight (TOF) spectrometer developed for performing fission mass distribution studies are presented. The spectrometer contains two TOF arms based on multi-wire proportional counters (MWPCs). Each arm has two MWPCs to form a start-stop detection system for TOF measurements. The start detector has an active area of 4 × 4 cm. The stop detector is a two-dimensional position sensitive MWPC with an active area of 16 × 11 cm. Salient features of the MWPCs are the use of reduced sub-millimeter wire pitches of 0.635 and 0.317 mm in the electrodes along with the use of gold plated tungsten wires of diameters 10 and 20 µm. A delay line for position electrodes is prepared using chip inductors and capacitors. Ten different configurations of MWPC were investigated for the start detector, which involved the use of three and four electrode geometries, use of different wire pitches, and use of aluminized mylar for timing electrodes. Performance results close to micro-channel plate detectors have been observed with some designs of MWPC, displaying rise times better than 2 ns with an estimated inherent time resolution of ∼100 ps FWHM. A position resolution of ∼1 mm (FWHM) has been observed. Design features of the MWPCs and their test performance results are described in this article.
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http://dx.doi.org/10.1063/5.0029603DOI Listing
March 2021

Anti-NMDA Receptor Encephalitis Associated with Coats-Like Retinal Telangiectasia.

Mov Disord Clin Pract 2021 Apr 25;8(3):483-485. Epub 2021 Feb 25.

Department of Ophthalmology All India Institute of Medical Sciences Rishikesh India.

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http://dx.doi.org/10.1002/mdc3.13152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015915PMC
April 2021

Mucosal Epithelial Jak Kinases in Health and Diseases.

Mediators Inflamm 2021 16;2021:6618924. Epub 2021 Mar 16.

Department of Pharmaceutical Sciences, ILR College of Pharmacy, Texas A&M Health Science Center, Kingsville TX 78363, USA.

Janus kinases (Jaks) are a family of nonreceptor tyrosine kinase that include four different members, ., Jak1, Jak2, Jak3, and Tyk2. Jaks play critical roles in immune cells functions; however, recent studies suggest they also play essential roles in nonimmune cell physiology. This review highlights the significance of epithelial Jaks in understanding the molecular basis of some of the diseases through regulation of epithelial-mesenchymal transition, cell survival, cell growth, development, and differentiation. Growth factors and cytokines produced by the cells of hematopoietic origin use Jak kinases for signal transduction in both immune and nonimmune cells. Among Jaks, Jak3 is widely expressed in both immune cells and in intestinal epithelial cells (IECs) of both humans and mice. Mutations that abrogate Jak3 functions cause an autosomal severe combined immunodeficiency disease (SCID) while activating Jak3 mutations lead to the development of hematologic and epithelial cancers. A selective Jak3 inhibitor CP-690550 (Xeljanz) approved by the FDA for certain chronic inflammatory conditions demonstrates immunosuppressive activity in rheumatoid arthritis, psoriasis, and organ transplant rejection. Here, we also focus on the consequences of Jak3-directed drugs on adverse effects in light of recent discoveries in mucosal epithelial functions of Jak3 with some information on other Jaks. Lastly, we brief on structural implications of Jak3 domains beyond the immune cells. As information about the roles of Jak3 in gastrointestinal functions and associated diseases are only just emerging, in the review, we summarize its implications in gastrointestinal wound repair, inflammatory bowel disease, obesity-associated metabolic syndrome, and epithelial cancers. Lastly, we shed lights on identifying potential novel targets in developing therapeutic interventions of diseases associated with dysfunctional IEC.
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http://dx.doi.org/10.1155/2021/6618924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990561PMC
March 2021

Plasma biomarker profiling of PIMS-TS, COVID-19 and SARS-CoV2 seropositive children - a cross-sectional observational study from southern India.

EBioMedicine 2021 Apr 1;66:103317. Epub 2021 Apr 1.

National Institutes of Health-National Institute for Research in Tuberculosis - International Center for Excellence in Research, Chennai, India; LPD, NIAID, NIH, Bethesda, MD, United States.

Background: SARS-CoV-2 infection in children can present with varied clinical phenotypes and understanding the pathogenesis is essential, to inform about the clinical trajectory and management.

Methods: We performed a multiplex immune assay analysis and compared the plasma biomarkers of Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS), acute COVID-19 infection (COVID-19), SARS-CoV-2 seropositive and control children admitted to a tertiary care children's hospital in Chennai, India. Pro-inflammatory cytokines, chemokines and growth factors were correlated with SARS-CoV-2 clinical phenotypes.

Findings: PIMS-TS children had significantly elevated levels of cytokines, IFNγ, IL-2, TNFα, IL-1α, IFNα, IFNβ, IL-6, IL-15, IL-17A, GM-CSF, IL-10, IL-33 and IL-Ra; elevated chemokines, CCL2, CCL19, CCL20 and CXCL10 and elevated VEGF, Granzyme B and PDL-1 in comparison to COVID-19, seropositive and controls. COVID-19 children had elevated levels of IFNγ, IL-2, TNFα, IL-1α, IFNα, IFNβ, IL-6, IL-17A, IL-10, CCL2, CCL5, CCL11, CXCL10 and VEGF in comparison to seropositive and/or controls. Similarly, seropositive children had elevated levels of IFNγ, IL-2, IL-1α, IFNβ, IL-17A, IL-10, CCL5 and CXCL10 in comparison to control children. Plasma biomarkers in PIMS-TS and COVID-19 children showed a positive correlation with CRP and a negative correlation with the lymphocyte count and sodium levels.

Interpretation: We describe a comprehensive plasma biomarker profile of children with different clinical spectrum of SARS-CoV-2 infection from a low- and middle-income country (LMIC) and observed that PIMS-TS is a distinct and unique immunopathogenic paediatric illness related to SARS-CoV-2 presenting with cytokine storm different from acute COVID-19 infection and other hyperinflammatory conditions.
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http://dx.doi.org/10.1016/j.ebiom.2021.103317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016617PMC
April 2021

Tah1, a key component of R2TP complex that regulates assembly of snoRNP, is involved in de novo generation and maintenance of yeast prion [URE3].

J Mol Biol 2021 Mar 31:166976. Epub 2021 Mar 31.

Council of Scientific and Industrial Research-Institute of Microbial Technology, India; Academy of Scientific & Innovative Research, India. Electronic address:

The cellular chaperone machinery plays key role in the de novo formation and propagation of yeast prions (infectious protein). Though the role of Hsp70s in the prion maintenance is well studied, how Hsp90 chaperone machinery affects yeast prions remains unclear. In the current study, we examined the role of Hsp90 and its co-chaperones on yeast prions [PSI] and [URE3]. We show that the overproduction of Hsp90 co-chaperone Tah1, cures [URE3] which is a prion form of native protein Ure2 in yeast. The Hsp90 co-chaperone Tah1 is involved in the assembly of small nucleolar ribonucleoproteins (snoRNP) and chromatin remodelling complexes. We found that Tah1 deletion improves the frequency of de novo appearance of [URE3]. The Tah1 was found to interact with Hsp70. The lack of Tah1 not only represses antagonizing effect of Ssa1 Hsp70 on [URE3] but also improves the prion strength suggesting role of Tah1 in both fibril growth and replication. We show that the N-terminal tetratricopeptide repeat domain of Tah1 is indispensable for [URE3] curing. Tah1 interacts with Ure2, improves its solubility in [URE3] strains, and affects the kinetics of Ure2 fibrillation in vitro. Its inhibitory role on Ure2 fibrillation is proposed to influence [URE3] propagation. The present study shows a novel role of Tah1 in yeast prion propagation, and that Hsp90 not only promotes its role in ribosomal RNA processing but also in the prion maintenance. SUMMARY: Prions are self-perpetuating infectious proteins. What initiates the misfolding of a protein into its prion form is still not clear. The understanding of cellular factors that facilitate or antagonize prions is crucial to gain insight into the mechanism of prion formation and propagation. In the current study, we reveal that Tah1 is a novel modulator of yeast prion [URE3]. The Hsp90 co-chaperone Tah1, is required for the formation of small nucleolar ribonucleoprotein complex. We show that the absence of Tah1 improves the induction of [URE3] prion. The overexpressed Tah1 cures [URE3], and this function is promoted by Hsp90 chaperones. The current study thus provides a novel cellular factor and the underlying mechanism, involved in the prion formation and propagation.
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http://dx.doi.org/10.1016/j.jmb.2021.166976DOI Listing
March 2021

Repurposing of approved drug molecules for viral infectious diseases: a molecular modelling approach.

J Biomol Struct Dyn 2021 Apr 2:1-17. Epub 2021 Apr 2.

Centre for Molecular Modelling, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.

The identification of new viral drugs has become a task of paramount significance due to the frequent occurrence of viral infections and especially during the current pandemic. Despite the recent advancements, the development of antiviral drugs has not made parallel progress. Reduction of time frame and cost of the drug development process is the major advantage of drug repurposing. Therefore, in this study, a drug repurposing strategy using molecular modelling techniques, i.e. biological activity prediction, virtual screening, and molecular dynamics simulation was employed to find promising repurposing candidates for viral infectious diseases. The biological activities of non-redundant (4171) drug molecules were predicted using PASS analysis, and 1401 drug molecules were selected which showed antiviral activities in the analysis. These drug molecules were subjected to virtual screening against the selected non-structural viral proteins. A series of filters, i.e. top 10 drug molecules based on binding affinity, mean value of binding affinity, visual inspection of protein-drug complexes, and number of H-bond between protein and drug molecules were used to narrow down the drug molecules. Molecular dynamics simulation analysis was carried out to validate the intrinsic atomic interactions and binding conformations of protein-drug complexes. The binding free energies of drug molecules were assessed by employing MMPBSA analysis. Finally, nine drug molecules were prioritized, as promising repurposing candidates with the potential to inhibit the selected non-structural viral proteins.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.1905558DOI Listing
April 2021

Investigation and Modeling of the Electrical Conductivity of Graphene Nanoplatelets-Loaded Doped-Polypyrrole.

Polymers (Basel) 2021 Mar 26;13(7). Epub 2021 Mar 26.

Centre for Nanostructures and Advanced Materials, DSI-CSIR Nanotechnology Innovation Centre, Council for Scientific and Industrial Research, Pretoria 0001, South Africa.

In this study, a hybrid of graphene nanoplatelets with a polypyrrole having 20 wt.% loading of carbon-black (HGPPy.CB20%), has been fabricated. The thermal stability, structural changes, morphology, and the electrical conductivity of the hybrids were investigated using thermogravimetric analyzer, differential scanning calorimeter, X-ray diffraction analyzer, scanning electron microscope, and laboratory electrical conductivity device. The morphology of the hybrid shows well dispersion of graphene nanoplatelets on the surface of the PPy.CB20% and the transformation of the gravel-like PPy.CB20% shape to compact spherical shape. Moreover, the hybrid's electrical conductivity measurements showed percolation threshold at 0.15 wt.% of the graphene nanoplatelets content and the curve is non-linear. The electrical conductivity data were analyzed by comparing different existing models (Weber, Clingerman and Taherian). The results show that Taherian and Clingerman models, which consider the aspect ratio, roundness, wettability, filler electrical conductivity, surface interaction, and volume fractions, closely described the experimental data. From these results, it is evident that Taherian and Clingerman models can be modified for better prediction of the hybrids electrical conductivity measurements. In addition, this study shows that graphene nanoplatelets are essential and have a significant influence on the modification of PPy.CB20% for energy storage applications.
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http://dx.doi.org/10.3390/polym13071034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036337PMC
March 2021

Novel Seleno- and Thio-Urea Containing Dihydropyrrol-2-One Analogues as Antibacterial Agents.

Antibiotics (Basel) 2021 Mar 19;10(3). Epub 2021 Mar 19.

School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia.

The quorum sensing (QS) system in multi-drug-resistant bacteria such as is primarily responsible for the development of antibiotic resistance and is considered an attractive target for antimicrobial drug discovery. In this study, we synthesised a series of novel selenourea and thiourea-containing dihydropyrrol-2-one (DHP) analogues as LasR antagonists. The selenium DHP derivatives displayed significantly better quorum-sensing inhibition (QSI) activities than the corresponding sulphur analogues. The most potent analogue efficiently inhibited the QS system by 81% at 125 µM and 53% at 31 µM. Additionally, all the compounds were screened for their minimum inhibitory concentration (MIC) against the Gram-positive bacterium , and interestingly, only the selenium analogues showed antibacterial activity, with and being the most potent with a MIC of 15.6 µM.
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http://dx.doi.org/10.3390/antibiotics10030321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003518PMC
March 2021

Perspectives on the Health Effects of Hurricanes: A Review and Challenges.

Int J Environ Res Public Health 2021 Mar 9;18(5). Epub 2021 Mar 9.

Division of Environmental Health, Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.

Hurricanes are devastating natural disasters which dramatically modify the physical landscape and alter the socio-physical and biochemical characteristics of the environment, thus exposing the affected communities to new environmental stressors, which persist for weeks to months after the hurricane. This paper has three aims. First, it conceptualizes potential direct and indirect health effects of hurricanes and provides an overview of factors that exacerbate the health effects of hurricanes. Second, it summarizes the literature on the health impact of hurricanes. Finally, it examines the time lag between the hurricane (landfall) and the occurrence of diseases. Two major findings emerge from this paper. Hurricanes are shown to cause and exacerbate multiple diseases, and most adverse health impacts peak within six months following hurricanes. However, chronic diseases, including cardiovascular disease and mental disorders, continue to occur for years following the hurricane impact.
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http://dx.doi.org/10.3390/ijerph18052756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967478PMC
March 2021

Comparison of treatment response assessed by 18F-FDG PET/CT with the histopathological response using tumor regression grading on surgically resected specimen following neoadjuvant chemotherapy in squamous cell carcinoma of esophagus.

Nucl Med Commun 2021 Mar 30. Epub 2021 Mar 30.

Department of Surgical Oncology Department of Medical Oncology, BRA-IRCH Department of Nuclear Medicine Department of Pathology, All India institute of medical sciences, New Delhi, India.

Background: For the response assessment after chemotherapy, gold standard is always the histopathological response. However, metabolic response can also guide further treatment. Herein, this study aimed to evaluate metabolic response assessment to neoadjuvant chemotherapy in squamous cell carcinoma esophagus using PET response criteria in solid tumors (PERCIST) criteria with taking histopathological response by tumor regression grading as the standard method.

Methods: Total fifty-seven patients with squamous cell carcinoma esophagus were enrolled between April 2017 to December 2018 for this prospective study. All patients were undergone for baseline PET scan before going for neoadjuvant chemotherapy. Repeat PET scan was done after neoadjuvant chemotherapy. Operable patients were taken for surgery. Final histological response was assessed by Mandard grading. Three metabolic tools [maximum standardized uptake value (SUVmax), tumor regression grading, PERCIST] were compared.

Results: The mean SULpeak of the primary lesion was 11.7 ± 5.5 (median, 10.2, range 5.5-31.8). The average percentage change (%Δ) in SUVmax was 42.9 ± 26.3. On histopathology, 5 (13.1%) patients showed complete pathological response, whereas grade II, III, IV and V in 8 (21.1%), 12 (31.6%), 10 (26.3%) and 3 (7.8%) respectively. On comparison of PERCIST with Mandard grading, agreement analysis showed that there was moderate agreement (k, 0.48). %ΔSUV peak change showed a strong correlation with %ΔSUVmax (P = 0.01) and percentage tumor to liver ratio change (P = 0.01). On comparison, these metabolic response tools showed a weak agreement (k, 0.28 with tumor to liver ratio, k, 0.38 with SUVmax).

Conclusion: After neoadjuvant chemotherapy, 18F-fluorodeoxyglucose PET/CT can help to assess the response and guide the treatment. However, a larger study is warranted to evaluate their correlation with pathological response.
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http://dx.doi.org/10.1097/MNM.0000000000001413DOI Listing
March 2021

Clinical behaviour and outcome in pediatric glioblastoma: current scenario.

Radiat Oncol J 2021 Mar 30;39(1):72-77. Epub 2021 Mar 30.

Department of Radiodiagnosis, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Pediatric glioblastoma (pGBM) is a rare entity accounting for only approximately 3% of all childhood brain tumors. Treatment guidelines for pGBM have been extrapolated from those in adult glioblastoma. Rarity of pGBM and underrepresentation of pediatric population in major studies precludes from defining the ideal treatment protocol for these patients. Maximum safe resection is performed in most of the cases followed by postoperative radiotherapy in children over 3 years of age. Benefit of temozolomide is unclear in these patients. Here, we present the clinicopathological details and outcome of six pGBM patients treated at our institute in 2018-2019.
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http://dx.doi.org/10.3857/roj.2020.00591DOI Listing
March 2021

Obstetric Anesthesia: A Case Based and Visual Approach.

Authors:
Nishant Kumar

Anesth Analg 2021 Feb;132(2):e18

Department of Anaesthesiology, Lady Hardinge Medical College and Associated Hospitals, Shaheed Bhagat Singh Marg, New Delhi, India,

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http://dx.doi.org/10.1213/ANE.0000000000005310DOI Listing
February 2021

Epidural Technique in Obstetric Anesthesia.

Authors:
Nishant Kumar

Anesth Analg 2021 Mar;132(3):e40

Department of Anaesthesiology, Lady Hardinge Medical College and Associated Hospitals, New Delhi, India,

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http://dx.doi.org/10.1213/ANE.0000000000005359DOI Listing
March 2021

Prevalence and risk factors for chalazion in an older veteran population.

Br J Ophthalmol 2021 Mar 31. Epub 2021 Mar 31.

Bascom Palmer Eye Institute, University of Miami Health System, Miami, Florida, USA

Background: Chalazia are common inflammatory eyelid lesions, but their epidemiology remains understudied. This retrospective case-control study examined the prevalence, risk factors and geographic distribution of chalazia in a large veteran population.

Methods: Data on all individuals seen at a Veterans Affairs (VA) clinic between October 2010 and October 2015 were extracted from the VA health database. Subjects were grouped based on International Classification of Diseases, Ninth Revision (ICD-9) code for chalazion. Univariable logistic regression modelling was used to identify clinical and demographic factors associated with chalazion presence, followed by multivariable modelling to examine which factors predicted risk concomitantly. All cases were mapped across the continental US using geographic information systems modelling to examine how prevalence rates varied geographically.

Results: Overall, 208 720 of 3 453 944 (6.04%) subjects were diagnosed with chalazion during the study period. Prevalence was highest in coastal regions. The mean age of the population was 69.32±13.9 years and most patients were male (93.47%), white (77.13%) and non-Hispanic (93.72%). Factors associated with chalazion risk included smoking (OR=1.12, p<0.0005), conditions of the tear film (blepharitis (OR=4.84, p<0.0005), conjunctivitis (OR=2.78, p<0.0005), dry eye (OR=3.0, p<0.0005)), conditions affecting periocular skin (eyelid dermatitis (OR=2.95, p<0.0005), rosacea (OR=2.50, p<0.0005)), allergic conditions (history of allergies (OR=1.56, p<0.0005)) and systemic disorders (gastritis (OR=1.54, p<0.0005), irritable bowel syndrome (OR=1.45, p<0.0005), depression (OR=1.35, p<0.0005), anxiety (OR=1.31, p<0.0005)). These factors remained associated with chalazion risk when examined concomitantly.

Conclusion: Periocular skin, eyelid margin and tear film abnormalities were most strongly associated with risk for chalazion. The impact of environmental conditions on risk for chalazion represents an area in need of further study.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318420DOI Listing
March 2021

Evaluation of Ethnopharmacologically selected Vitex negundo L. for In Vitro Antimalarial Activity and Secondary Metabolite Profiling.

J Ethnopharmacol 2021 Mar 28:114076. Epub 2021 Mar 28.

Department of Biotechnology, Indira Gandhi National Tribal University, Amarkantak Madhya Pradesh 484 887, India. Electronic address:

Ethanopharmacological Relevance: Limited drugs, rise in drug resistance against frontline anti-malarial drugs, non-availability of efficacious vaccines and high cost of drug development hinders malaria intervention programs. Search for safe, effective and affordable plant based anti-malarial agents, thus becomes crucial and vital in the current scenario. The Vitex negundo L. is medicinal plant possessing a variety of pharmaceutically important compounds. The plant is used traditionally worldwide for the treatment of malaria including India and Malaysia by the indigenous tribes. In vitro studies have reported the anti-malarial use of the plant in traditional medicinal systems.

Aim Of The Study: The aim of the current study is to evaluate the traditionally used medicinal plants for in vitro anti-malarial activity against human malaria parasite Plasmodium falciparum and profiling secondary metabolite using spectroscopic and chromatographic methods. Chemical profiling of active secondary metabolites in the extracts was undertaken using LC-MS.

Materials And Methods: Based on the ethno-botanical data V. negundo L. was selected for in vitro anti-malarial activity against P. falciparum chloroquine-sensitive (3D7) and multidrug resistant (K1) strains using SYBR Green-I based fluorescence assay. Cytotoxicity of extracts was evaluated in VERO cell line using the MTT assay. Secondary metabolites profiling was undertaken using chromatographic and spectroscopic analysis. Liquid chromatography analysis was performed using a C18, 150 X 2.1, 2.6 μm column with gradient mobile phase Solvent A: 95% (HO: ACN), Solvent B: Acetonitrile, Solvent C: Methanol, Solvent D: 5 mM NH in 95:5 (HO: ACN) at a constant flow rate of 0.250 ml/minute. The LC-MS spectra were acquired in both positive and negative ion modes with electrospray ionization (ESI) source.

Results: The anti-malarial active extract of V. negundo L. leaf exhibited potent anti-malarial activity with IC50 values of 7.21 μg/ml and 7.43 μg/ml against 3D7 and K1 strains, respectively with no evidence of significant cytotoxicity against mammalian cell line (VERO) and no toxicity as observed in haemolysis assay. The HPLC-LC-MS analysis of the extract led to identification of 73 compounds. We report for the first time the presence of Sabinene hydrate acetate, 5-Hydroxyoxindole, 2(3,4-dimethoxyphenyl)-6, 7-dimethoxychromen-4-one, Cyclotetracosa-1, 13-diene and 5, 7-Dimethoxyflavanone in the anti-malarial active extract of V. negundo L. leaf. Agnuside, Behenic acid and Globulol are some of the novel compounds with no reports of anti-malarial activity so far and require further evaluation in pure form for the development of potent anti-malarial compounds.

Conclusions: The result report and scientifically validate the traditional use of V. negundo L. for the treatment of malaria providing new avenues for anti-malarial drug development. Several novel and unknown compounds were identified that need to be further characterized for anti-malarial potential.
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http://dx.doi.org/10.1016/j.jep.2021.114076DOI Listing
March 2021

17-a-estradiol late in life extends lifespan in aging UM-HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex.

Aging Cell 2021 Mar 31:e13328. Epub 2021 Mar 31.

Department of Pathology and Geriatrics Center, University of Michigan, Ann Arbor, MI, USA.

In genetically heterogeneous mice produced by the CByB6F1 x C3D2F1 cross, the "non-feminizing" estrogen, 17-α-estradiol (17aE2), extended median male lifespan by 19% (p < 0.0001, log-rank test) and 11% (p = 0.007) when fed at 14.4 ppm starting at 16 and 20 months, respectively. 90th percentile lifespans were extended 7% (p = 0.004, Wang-Allison test) and 5% (p = 0.17). Body weights were reduced about 20% after starting the 17aE2 diets. Four other interventions were tested in males and females: nicotinamide riboside, candesartan cilexetil, geranylgeranylacetone, and MIF098. Despite some data suggesting that nicotinamide riboside would be effective, neither it nor the other three increased lifespans significantly at the doses tested. The 17aE2 results confirm and extend our original reports, with very similar results when started at 16 months compared with mice started at 10 months of age in a prior study. The consistently large lifespan benefit in males, even when treatment is started late in life, may provide information on sex-specific aspects of aging.
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http://dx.doi.org/10.1111/acel.13328DOI Listing
March 2021

Pre-operative and post-operative audiological assessment in cleft lip and palate patients-a prospective study.

J Oral Biol Craniofac Res 2021 Apr-Jun;11(2):321-329. Epub 2021 Mar 17.

SDM Craniofacial and Research Centre, SDM College of Medical Sciences and Hospital, Sattur, Dharwad, 580009, Karnataka, India.

Purpose: To assess association of audiological defects in cleft lip and palate (CLP) following two stage cheiloplasty and palatoplasty using clinical evaluation and otoscopy and effect of the surgical repair at an interval of one year.

Materials And Methods: A pilot research study was performed on sixty CLP patients of 1-6 years of age reporting at Craniofacial & Research Centre, Dharwad, India between October 2016 to October 2018.Subjects were assessed based on history, clinical examination and otoscopy for audiometric defects including Serous otitis media (SOM), retraction pockets, impacted wax pre-palatoplasty and findings were compared with control group. Study group were followed up postoperatively at 1, 3, 6 and 12 months and statistical analysis was carried.

Results: Higher incidence of conductive audiological defects were noted in study group (96.6%) to control group (8.33%). Of the sixty cleft patients subjected to screening otoscopy, 58 subjects had significant findings like serous otitis media(12.07%), retraction pockets(23.14%), impacted wax(62.04%), bulging of tympanic membrane(3.45%) which were clinically unnoticed. Post palatoplasty no changes were noted at 1 and 3 months, however at 6- and 12months significant improvement was noted (55.17%), with three subjects lost to follow up (6.90%) and none presenting with permanent deafness.results.

Conclusion: Cleft anomalies occur in different degrees of severity and configuration with greater incidence of conductive hearing defects of 97%. Positive correlation was noted in cleft palate cases with significant improvement after palatoplasty at an earlier age. However, future long term studies are warranted for long term assessment of Eustachian tube function.conclusion.
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http://dx.doi.org/10.1016/j.jobcr.2021.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994542PMC
March 2021

Sexual health (excluding reproductive health, intimate partner violence and gender-based violence) and COVID-19: a scoping review.

Sex Transm Infect 2021 Mar 29. Epub 2021 Mar 29.

University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.

Objectives: The COVID-19 pandemic has exposed and exacerbated existing socioeconomic and health disparities, including disparities in sexual health and well-being. While there have been several reviews published on COVID-19 and population health disparities generally-including some with attention to HIV-none has focused on sexual health (ie, STI care, female sexual health, sexual behaviour). We have conducted a scoping review focused on sexual health (excluding reproductive health (RH), intimate partner violence (IPV) and gender-based violence (GBV)) in the COVID-19 era, examining sexual behaviours and sexual health outcomes.

Methods: A scoping review, compiling both peer-reviewed and grey literature, focused on sexual health (excluding RH, IPV and GBV) and COVID-19 was conducted on 15 September 2020. Multiple bibliographical databases were searched. Study selection conformed to Joanna Briggs Institute (JBI) Reviewers' Manual 2015 Methodology for JBI Scoping Reviews. We only included English-language original studies.

Results: We found that men who have sex with men may be moving back toward pre-pandemic levels of sexual activity, and that STI and HIV testing rates seem to have decreased. There was minimal focus on outcomes such as the economic impact on sexual health (excluding RH, IPV and GBV) and STI care, especially STI care of marginalised populations. In terms of population groups, there was limited focus on sex workers or on women, especially women's sexual behaviour and mental health. We noticed limited use of qualitative techniques. Very few studies were in low/middle-income countries (LMICs).

Conclusions: Sexual health research is critical during a global infectious disease pandemic and our review of studies suggested notable research gaps. Researchers can focus efforts on LMICs and under-researched topics within sexual health and explore the use of qualitative techniques and interventions where appropriate.
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http://dx.doi.org/10.1136/sextrans-2020-054896DOI Listing
March 2021