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Coma is one of the frequently encountered clinical conditions in any intensive care unit (ICU), which is responsible for considerable morbidity and mortality. Therefore, this study was designed to look at the clinical and EEG profile of Nonconvulsive Status Epilepticus (NCSE) in comatose ICU patients using portable electroencephalography (EEG). In all 102 patients of unresponsive coma (GCS ≤ 8), who remained in poor sensorium despite 48 h of optimum treatment in ICU, were included in the study. All patients underwent 1 h of electroencephalography (EEG) monitoring with a portable EEG machine. All EEGs were screened according to Salzburg Consensus Criteria (SCC) for Nonconvulsive Status Epilepticus (NCSE). Patients with evidence of NCSE were administered parenteral Antiepileptic Drugs (AED). A repeat EEG was done after 24 h of baseline to ascertain the effect of AED. The primary outcome was the recognition of patients with NCSE on the basis of established EEG criteria. The secondary outcome measure was the Glasgow outcome scale (GOS) at the time of discharge. Out of 102 cases enrolled, 12 (11.8%) cases were detected to have NCSE on portable EEG. The mean age of patients with NCSE was 52.2 years. In terms of gender distribution, 2/12 (17%) were female, and 10/12 (83%) were male (M: F = 5:1). Median GCS was 6 (range 3–8). Looking at CNS infections, 4/12 (33.3%) had evidence of some form of CNS infection in the NCSE group, compared to 16/90 (18%) in the group without NCSE. This difference was statistically significant (P-value < 0.05). The EEG recordings of patients with NCSE showed dynamicity with fluctuating rhythms and ictal-EEG patterns associated with spatiotemporal evolution. All twelve cases showed reversal of EEG changes with AED administration. In 5 out of 12, transient improvement in GCS (>2 points) after administration of AED' was noted with good clinical outcomes (GOS 5). In five of these 12 cases, death was the final outcome (GOS 1). NSCE should be considered in the differential diagnosis of all unresponsive comatose ICU patients. In resource-limited settings, where continuous EEG monitoring may not be feasible, bedside portable EEG testing can be used to diagnose patients with NCSE. Treating NCSE reverses epileptiform EEG changes and improves clinical outcomes in a subset of comatose ICU patients. [ABSTRACT FROM AUTHOR]

The etiology of respiratory failure associated with Stevens-Johnson syndrome may be multifactorial, including upper airway involvement, pneumothorax/pneumomediastinum, and direct involvement of the respiratory mucosa. Respiratory failure from direct involvement of the respiratory mucosa is relatively uncommon. We describe a 9-year-old boy who had respiratory failure associated with Mycoplasma pneumoniae-induced Stevens-Johnson syndrome. Bronchoscopic examination of the airways revealed sloughed mucosa, ulcerative lesions, and inspissated secretions indicative of lower airway involvement with Stevens-Johnson syndrome. Although the mainstay of therapy is supportive care with controlled ventilation, rigid bronchoscopy with bronchoalveolar lavage to clear the airways of the debris was an invaluable adjunct to this patient's care. [ABSTRACT FROM AUTHOR]

Aims: The aim of this audit was to assess and improve the completeness and accuracy of the National Joint Registry (NJR) dataset for arthroplasty of the elbow., Methods: It was performed in two phases. In Phase 1, the completeness was assessed by comparing the NJR elbow dataset with the NHS England Hospital Episode Statistics (HES) data between April 2012 and April 2020. In order to assess the accuracy of the data, the components of each arthroplasty recorded in the NJR were compared to the type of arthroplasty which was recorded. In Phase 2, a national collaborative audit was undertaken to evaluate the reasons for unmatched data, add missing arthroplasties, and evaluate the reasons for the recording of inaccurate arthroplasties and correct them., Results: Phase 1 identified 5,539 arthroplasties in HES which did not match an arthroplasty on the NJR, and 448 inaccurate arthroplasties from 254 hospitals. Most mismatched procedures (3,960 procedures; 71%) were radial head arthroplasties (RHAs). In Phase 2, 142 NHS hospitals with 3,640 (66%) mismatched and 314 (69%) inaccurate arthroplasties volunteered to assess their records. A large proportion of the unmatched data (3,000 arthroplasties; 82%) were confirmed as being missing from the NJR. The overall rate of completeness of the NJR elbow dataset improved from 63% to 83% following phase 2, and the completeness of total elbow arthroplasty data improved to 93%. Missing RHAs had the biggest impact on the overall completeness, but through the audit the number of RHAs in the NJR nearly doubled and completeness increased from 35% to 70%. The accuracy of data was 94% and improved to 98% after correcting 212 of the 448 inaccurately recorded arthroplasties., Conclusion: The rate of completeness of the NJR total elbow arthroplasty dataset is currently 93% and the accuracy is 98%. This audit identified challenges of data capture with regard to RHAs. Collaboration with a trauma and orthopaedic trainees through the British Orthopaedic Trainee Association improved the completeness and accuracy of the NJR elbow dataset, which will improve the validity of the reports and of the associated research., Competing Interests: Z. Hamoodi reports research fellowship funding from Royal College of Surgeons, National Joint Registry, and The John Charnley Trust, related to this study. A. Sayers is senior statistician on the HQIP/NJR Lot 2 contract. M. R. Whitehouse is the principal investigator for the HQIP/NJR Lot 2 contract to provide statistical support, analysis and associated services to the NJR, related to this study, and reports multiple grants or contracts from the NIHR and Ceramtec, royalties or licenses from Taylor & Frances, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Heraeus, all of which are unrelated to this study. A. C. Watts reports royalties or licenses and patents planned, issued or pendingfrom Adler, consulting fees from Medartis, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Medartis, Stryker, and Arthrex, all of which are unrelated to this study, and is also a member of the editorial boards of the National Joint Registry and The Bone & Joint Journal., (© 2024 The British Editorial Society of Bone & Joint Surgery.)

Background: Nerve injuries have traditionally been repaired with sutures, and this method is considered the gold standard technique in the management of nerve injuries. However, fibrin glue has recently become a promising tool for repairing nerve injuries and has advantages including ease of usability, atraumatic application technique, and decreased co-optation time of the nerves. This study aims to clinically evaluate the efficacy of nerve repair with fibrin glue compared with the usual suture technique in terms of sensory and motor outcomes., Methods: A total of 80 patients were included in the study; 50 patients underwent primary nerve repair, and 30 patients underwent Oberlin's repair. These subsets were randomly divided into two groups in which the nerves were repaired with microsutures in one group and fibrin glue in the other group., Results: In the comparison of fibrin glue with microsutures, there were no significant differences between the two groups in the 2-point discrimination (2PD) test, Semmes-Weinstein test, motor function, and Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire scores. However, the co-optation times were significantly shorter with fibrin glue than with microsutures., Conclusion: Based on our findings, nerve repair with fibrin glue is as effective as microsutures in terms of sensory and motor recovery and has added advantages of ease of usability and shorter repair times. Therefore, fibrin glue may be an effective alternative to sutures in nerve repair., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institute Ethics Committee, All India Institute of Medical Sciences (AIIMS), Patna issued approval RD/AIIMS/Pat//RAC-125. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Haq et al.)

Background: Extraparenchymal neurocysticercosis (NCC) commonly presents with symptoms of raised intracranial pressure such as headache, nausea, vomiting, or delirium. Intraventricular NCC is frequently associated with obstructive hydrocephalus as well as recurrent inflammatory cascade leading to chronic meningitis., Objective: The aim of this study was to report the novel use and benefit of B cell depleting therapy in a case of treatment-refractory cysticercal meningoencephalitis., Case: In this article, we report about a young male with intraventricular NCC, who had recurrent meningitis (with encephalitis) and kept relapsing despite multiple cerebrospinal fluid diversion procedures, cysticidal therapy, and high-dose steroids. He finally showed clinical and radiological resolution with pulsed rituximab therapy., Conclusion: This off-label use of a monoclonal antibody against CD20 may be considered as a rescue therapy in steroid-refractory immune-mediated cysticercal meningitis., (Copyright © 2024 Copyright: © 2024 Neurology India, Neurological Society of India.)

Purpose: Keratoconjunctivitis sicca (KCS) or dry eye disease (DED) is a multifactorial disease that results in discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. A pilot study was undertaken to determine if there were any major substantial differences in the ocular microbiome in DED patients versus healthy controls., Methods: The bacterial communities residing in the conjunctiva of patients with DED (n = 4) and healthy controls (n = 4) were assessed by 16S ribosomal RNA (rRNA) gene sequencing of the V4-V5 region., Results: The phyla Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes were most dominant and accounted for 97% and 94.5% of all bacterial sequences in patients and controls, respectively. At the genus level, 27 bacterial genera were found with more than two-fold difference between patients and controls. Four of these - Acinetobacter, Corynebacterium, Lactobacillus, and Pseudomonas spp. - dominated the ocular microbiome of all subjects, but were proportionately lower in DED (16.5%) compared to controls (37.7%). Several bacterial genera were found to be unique in DED (34) and controls (24)., Conclusion: This pilot study is an attempt to profile the ocular microbiome in patients with DED that demonstrated a higher concentration of microbial DNA compared to controls, with Firmicutes phyla dominating the bacterial population in patients with DED., Competing Interests: None

The prolyl-tRNA synthetase (PRS) is a validated drug target for febrifugine and its synthetic analog halofuginone (HFG) against multiple apicomplexan parasites including Plasmodium falciparum and Toxoplasma gondii. Here, a novel ATP-mimetic centered on 1-(pyridin-4-yl) pyrrolidin-2-one (PPL) scaffold has been validated to bind to Toxoplasma gondii PRS and kill toxoplasma parasites. PPL series exhibited potent inhibition at the cellular (T. gondii parasites) and enzymatic (TgPRS) levels compared to the human counterparts. Cell-based chemical mutagenesis was employed to determine the mechanism of action via a forward genetic screen. Tg-resistant parasites were analyzed with wild-type strain by RNA-seq to identify mutations in the coding sequence conferring drug resistance by computational analysis of variants. DNA sequencing established two mutations, T477A and T592S, proximal to terminals of the PPL scaffold and not directly in the ATP, tRNA, or L-pro sites, as supported by the structural data from high-resolution crystal structures of drug-bound enzyme complexes. These data provide an avenue for structure-based activity enhancement of this chemical series as anti-infectives., Competing Interests: We have read the journal’s policy and the authors of this manuscript declare the competing interest that BL is an MMV employee., (Copyright: © 2023 Yogavel 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.)

Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes in protein translation machinery that provide the charged tRNAs needed for protein synthesis. Over the past decades, aaRSs have been studied as anti-parasitic, anti-bacterial, and anti-fungal drug targets. This study focused on the cytoplasmic glutamyl-tRNA synthetase (GluRS) from Plasmodium falciparum, which belongs to class Ib in aaRSs. GluRS unlike most other aaRSs requires tRNA to activate its cognate amino acid substrate L-Glutamate (L-Glu), and fails to form an intermediate adenylate complex in the absence of tRNA. The crystal structures of the Apo, ATP, and ADP-bound forms of Plasmodium falciparum glutamyl-tRNA synthetase (PfGluRS) were solved at 2.1 Å, 2.2 Å, and 2.8 Å respectively. The structural comparison of the Apo- and ATP-bound holo-forms of PfGluRS showed considerable conformational changes in the loop regions around the ATP-binding pocket of the enzyme. Biophysical characterization of the PfGluRS showed binding of the enzyme substrates L-Gluand ATP.. The sequence and structural conservation were evident across GluRS compared to other species. The structural dissection of the PfGluRS gives insight into the critical residues involved in the binding of ATP substrate, which can be harvested to develop new antimalarial drugs., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022. Published by Elsevier B.V.)

Background: In 2012, the World Health Organization (WHO) released the Global Plan for Insecticide Resistance Management in malaria vectors to stress the need to address insecticide resistance. In a prospective multi-centric study commissioned by the Indian Council of Medical Research (ICMR), we assessed the insecticide susceptibility status of the primary malaria vectors in India from 2017 through 2019., Methods: The insecticide susceptibility status of the prevalent primary malaria vectors - An. culicifacies, An. fluviatilis, An. stephensi, An. minimus and An. baimaii and secondary malaria vectors - An. aconitus, An. annularis and An. philippinensis/nivepes from 328 villages in 79 districts of 15 states of India were assessed following the WHO method mainly to insecticides used in vector control, organochlorine (DDT), organophosphate (malathion), and other pyrethroids (alpha-cypermethrin, cyfluthrin, lambda-cyhalothrin and permethrin). The study sites were selected as suggested by the National Vector Borne Disease Control Programme., Results: The primary malaria vector An. culicifacies showed resistance to DDT (50/50 districts including two districts of Northeastern India), malathion (27/44 districts), and deltamethrin (17/44 districts). This species was resistant to DDT alone in 19 districts, double resistant to DDT-malathion in 16 districts, double resistant to DDT-deltamethrin in 6 districts, and triple resistant to DDT-malathion-deltamethrin in 9 districts. An. minimus and An. baimaii were susceptible in Northeastern India while An. fluviatilis and the secondary malaria vector An. annularis was resistant to DDT in Jharkhand., Conclusion: In this study we report that among the primary vectors An. culicifacies is predominantly resistant to multiple insecticides. Our data suggest that periodic monitoring of insecticide susceptibility is vital. The national malaria program can take proactive steps for insecticide resistance management to continue its push toward malaria elimination in India., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Background: Malaria infection can result in distinct clinical outcomes from asymptomatic to severe. The association between patho-physiological changes and molecular changes in the host, and their correlation with severity of malaria progression is not fully understood., Methods: In this study, we addressed mass spectrometry-based temporal profiling of serum metabolite levels from mice infected with Plasmodium berhgei (strain ANKA)., Results: We show global perturbations and identify changes in specific metabolites in correlation with disease progression. While metabolome-wide changes were apparent in late-stage malaria, a subset of metabolites exhibited highly correlated changes with disease progression. These metabolites changed early on following infection and either continued or maintained the change as mice developed severe disease. Some of these have the potential to be sentinel metabolites for severe malaria. Moreover, glycolytic metabolites, purine nucleotide precursors, tryptophan and its bioactive derivatives were many fold decreased in late-stage disease. Interestingly, uric acid, a metabolic waste reported to be elevated in severe human malaria, increased with disease progression, and subsequently appears to be detoxified into allantoin. This detoxification mechanism is absent in humans as they lack the enzyme uricase., Conclusions: We have identified candidate marker metabolites that may be of relevance in the context of human malaria., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Amit Sharma reports financial support was provided by Department of Science and Technology. Jyoti Chhibber-Goel reports financial support was provided by Department of Biotechnology. Jyoti Chhibber-Goel reports a relationship with Department of Biotechnology that includes: employment and funding grants. Amit Sharma reports a relationship with Department of Science and Technology that includes: employment and funding grants., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The present study tested whether there is cross-interference between electromagnetic articulography (EMA) and electroglottography (EGG) during the acquisition of kinematic speech data. In experiments 1A and 1B, EMA sensors were calibrated with and without EGG electrodes present in the EMA field. In experiment 2, EMA was used to record lip, tongue, and jaw movements for one male speaker and one female speaker, with and without simultaneous EGG recording. Collectively, the results provide no evidence of signal artifacts in either direction, suggesting that EMA and EGG technology can be combined to reliably assess laryngeal and supralaryngeal motor coordination in speech.

The specificity of each aminoacyl-tRNA synthetase (aaRS) for its cognate amino acid ensures correct tRNA esterification and allows fidelity in protein synthesis. The aaRSs discriminate based on the chemical properties of their amino acid substrates and structural features of the binding pockets. In this study, we characterized aspartyl-(DRS) and asparaginyl-tRNA synthetase (NRS) from Plasmodium falciparum to determine the basis of their specificity towards L-asp and L-asn respectively. The negatively charged L-asp and its analogue L-asn differ only in their side-chain groups i.e., -OH and -NH 2 . Further, the amino acid binding sites are highly conserved within these two enzymes. Analysis of the substrate (L-asp/L-asn) binding sites across species revealed two highly conserved residues in PfDRS (D408 and K372) and PfNRS (E395 and L360) that are involved in recognition of the O δ2 /N δ2 of L-asp/L-asn respectively. These residues were mutated and swapped between the D408→E in PfDRS and the corresponding E395→D in PfNRS. A similar approach was employed for residue number K372→L in PfDRS and L360→K in PfNRS. The mutated PfDRS D408E retained its enzymatic activity during step 1 of aminoacylation reaction towards L-asp and L-asn and esterified tRNA Asp with L-asp like wild type enzyme, while the PfDRS K372L was rendered enzymatically inactive. The correspondingly mutated PfNRS E395D was enzymatically inactive. The mutated PfNRS L360K had an altered specificity and esterified tRNA Asn with non-cognate amino acid L-asp and not L-asn. These data suggest that the residue K372 is crucial for the enzymatic activity of PfDRS while the residue L360 in PfNRS imparts specificity towards L-asn., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Mosquito-borne diseases have a devastating impact on human civilization. A few species of Anopheles mosquitoes are responsible for malaria transmission, and while there has been a reduction in malaria-related deaths worldwide, growing insecticide resistance is a cause for concern. Aedes mosquitoes are known vectors of viral infections, including dengue, yellow fever, chikungunya, and Zika. Aminoacyl-tRNA synthetases (aaRSs) are key players in protein synthesis and are potent anti-infective drug targets. The structure-function activity relationship of aaRSs in mosquitoes (in particular, Anopheles and Aedes spp.) remains unexplored., Methods: We employed computational techniques to identify aaRSs from five different mosquito species (Anopheles culicifacies, Anopheles stephensi, Anopheles gambiae, Anopheles minimus, and Aedes aegypti). The VectorBase database ( https://vectorbase.org/vectorbase/app ) and web-based tools were utilized to predict the subcellular localizations (TargetP-2.0, UniProt, DeepLoc-1.0), physicochemical characteristics (ProtParam), and domain arrangements (PfAM, InterPro) of the aaRSs. Structural models for prolyl (PRS)-, and phenylalanyl (FRS)-tRNA synthetases-were generated using the I-TASSER and Phyre protein modeling servers., Results: Among the vector species, a total of 37 (An. gambiae), 37 (An. culicifacies), 37 (An. stephensi), 37 (An. minimus), and 35 (Ae. aegypti) different aaRSs were characterized within their respective mosquito genomes. Sequence identity amongst the aaRSs from the four Anopheles spp. was > 80% and in Ae. aegypti was > 50%., Conclusions: Structural analysis of two important aminoacyl-tRNA synthetases [prolyl (PRS) and phenylanalyl (FRS)] of Anopheles spp. suggests structural and sequence similarity with potential antimalarial inhibitor [halofuginone (HF) and bicyclic azetidine (BRD1369)] binding sites. This suggests the potential for repurposing of these inhibitors against the studied Anopheles spp. and Ae. aegypti., (© 2021. The Author(s).)

Background: A surveillance system is the foundation for disease prevention and control. Malaria surveillance is crucial for tracking regional and temporal patterns in disease incidence, assisting in recorded details, timely reporting, and frequency of analysis., Objective: In this study, we aim to develop an integrated surveillance graphical app called FeverTracker, which has been designed to assist the community and health care workers in digital surveillance and thereby contribute toward malaria control and elimination., Methods: FeverTracker uses a geographic information system and is linked to a web app with automated data digitization, SMS text messaging, and advisory instructions, thereby allowing immediate notification of individual cases to district and state health authorities in real time., Results: The use of FeverTracker for malaria surveillance is evident, given the archaic paper-based surveillance tools used currently. The use of the app in 19 tribal villages of the Dhalai district in Tripura, India, assisted in the surveillance of 1880 suspected malaria patients and confirmed malaria infection in 93.4% (114/122; Plasmodium falciparum), 4.9% (6/122; P vivax), and 1.6% (2/122; P falciparum/P vivax mixed infection) of cases. Digital tools such as FeverTracker will be critical in integrating disease surveillance, and they offer instant data digitization for downstream processing., Conclusions: The use of this technology in health care and research will strengthen the ongoing efforts to eliminate malaria. Moreover, FeverTracker provides a modifiable template for deployment in other disease systems., (©Ipsita Pal Bhowmick, Dibyajyoti Chutia, Avinash Chouhan, Nilay Nishant, P L N Raju, Kanwar Narain, Harpreet Kaur, Rocky Pebam, Jayanta Debnath, Rabindra Tripura, Kongkona Gogoi, Suman Ch Nag, Aatreyee Nath, Debabrata Tripathy, Jotish Debbarma, Nirapada Das, Ujjwal Sarkar, Rislyn Debbarma, Rajashree Roy, Bishal Debnath, Dipanjan Dasgupta, Suraj Debbarma, Kamal Joy Tripura, Guneram Reang, Amit Sharma, Manju Rahi, Jyoti Chhibber-Goel. Originally published in JMIR Formative Research (https://formative.jmir.org), 10.11.2021.)

The present investigation tested whether there is cross-interference between current electromagnetic articulography (EMA) and cochlear implants (CIs). In an initial experiment, we calibrated EMA sensors with and without a CI present in the EMA field, and measured impedances of all CI electrodes when in and out of the EMA field. In a subsequent experiment, head reference sensor positions were recorded during a speaking task for a normal-hearing talker with and without a CI present in the EMA field. Results revealed minimal interference between the devices, suggesting that EMA is a promising method for assessing speech motor skills in CI users.

Malaria is a parasitic illness caused by the genus Plasmodium from the apicomplexan phylum. Five plasmodial species of P. falciparum (Pf), P. knowlesi, P. malariae, P. ovale, and P. vivax (Pv) are responsible for causing malaria in humans. According to the World Malaria Report 2020, there were 229 million cases and ~ 0.04 million deaths of which 67% were in children below 5 years of age. While more than 3 billion people are at risk of malaria infection globally, antimalarial drugs are their only option for treatment. Antimalarial drug resistance keeps arising periodically and thus threatens the main line of malaria treatment, emphasizing the need to find new alternatives. The availability of whole genomes of P. falciparum and P. vivax has allowed targeting their unexplored plasmodial enzymes for inhibitor development with a focus on multistage targets that are crucial for parasite viability in both the blood and liver stages. Over the past decades, aminoacyl-tRNA synthetases (aaRSs) have been explored as anti-bacterial and anti-fungal drug targets, and more recently (since 2009) aaRSs are also the focus of antimalarial drug targeting. Here, we dissect the structure-based knowledge of the most advanced three aaRSs-lysyl- (KRS), prolyl- (PRS), and phenylalanyl- (FRS) synthetases in terms of development of antimalarial drugs. These examples showcase the promising potential of this family of enzymes to provide druggable targets that stall protein synthesis upon inhibition and thereby kill malaria parasites selectively., (© 2021 The Protein Society.)

Background: At onset of coronavirus disease 2019 (COVID-19) pandemic, hydroxychloroquine (HCQ) was repurposed for treatment of patients based on reports that it had in vitro activity. The aim of this study was to find out if HCQ reduces number of days of hospitalization when given to patients with moderate to severe COVID-19 infections who require hospitalized care., Methods: This was an open-label randomized control trial of HCQ administered 400 mg twice on day 1, then 400 mg once daily from day 2 to day 5 in patients with moderate to severe COVID-19 infection. Assessment was not blinded. Standard of care was given to both arms.Primary outcome was number of days of hospitalization till discharge or death., Result: One hundred ten patients (55 in each arm) were included. Mean age was 58 years. Baseline characteristics were well matched. There was no difference in the primary outcome (13.67 vs 13.89; p = 0.98). Number of deaths were more in HCQ arm (RR: 1.81; 95% CI: 1.13-2.93; p = 0.03). There was no difference in number of days on oxygen or normalization of oxygen saturation, number who needed ventilator, days to ventilator requirement and days on ventilator. Twenty-nine patients in control arm received remdesivir. When adjusted analysis was done after removal of these patients, there was no difference in primary or secondary outcomes. Number of deaths in adjusted analysis were not significant (RR: 1.28; 95% CI: 0.87-1.88; p = 0.37)., Conclusion: HCQ does not change the number of days of hospitalization when compared with control., (© 2021 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.)

We describe the epidemiological characteristics and associated risk factors of those presenting at a large testing centre for SARS-CoV-2 infection. This is a retrospective record review of individuals who underwent SARS-CoV-2 testing by reverse transcription-polymerase chain reaction (RT-PCR) at a high-throughput national-level government facility located in the north of India. Samples collected from 6 April to 31 December 2020 are included in this work and represent four highly populous regions. Additionally, there was a prospective follow-up of 1729 cases through telephone interviews from 25 May 2020 to 20 June 2020. Descriptive analysis has been performed for profiling clinic-epidemiological aspects of suspect cases. Multivariable logistic regression analysis was undertaken to determine risk factors that are associated with SARS-CoV-2 test positivity and symptom status. A total of 125 600 participants' details have been included in this report. The mean (s.d.) age of the participants was 33.1 (±15.3) years and 66% were male. Among these tested, 9515 (7.6%) were positive for COVID-19. A large proportion of positive cases were asymptomatic. In symptomatic positive cases, the commonest symptoms were cough and fever. Increasing age (groups 20-59 and ≥60 years compared to age group less than 5 years), male sex, history of international travel, symptoms for SARS-CoV-2, and participants from Delhi and Madhya Pradesh were positively associated with SARS-CoV-2 test positivity. Having co-morbidity, risk behaviours and intra-familial positivity were associated with a positive odds ratio for exhibiting SARS-CoV-2 symptoms. Intensified testing and isolation of cases, identification of both asymptomatic and symptomatic individuals and additional care of those with co-morbidities and risk behaviours will all be collectively important for disease containment in India. Reasons for differentials in testing between men and women remain an important area for in-depth study. The increased deployment of vaccines is likely to impact the trajectory of COVID-19 in the coming time, and therefore our data will serve as a comparative resource as India experiences the second wave of infection in light of newer variants that are likely to accelerate disease spread.

The global spread of sulfadoxine (Sdx, S) and pyrimethamine (Pyr, P) resistance is attributed to increasing number of mutations in DHPS and DHFR enzymes encoded by malaria parasites. The association between drug resistance mutations and SP efficacy is complex. Here we provide an overview of the geographical spread of SP resistance mutations in Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) encoded dhps and dhfr genes. In addition, we have collated the mutation data and mapped it on to the three-dimensional structures of DHPS and DHFR which have become available. Data from genomic databases and 286 studies were collated to provide a comprehensive landscape of mutational data from 2005 to 2019. Our analyses show that the Pyr-resistant double mutations are widespread in Pf/PvDHFR (P. falciparum ∼61% in Asia and the Middle East, and in the Indian sub-continent; in P. vivax ∼33% globally) with triple mutations prevailing in Africa (∼66%) and South America (∼33%). For PfDHPS, triple mutations dominate South America (∼44%), Asia and the Middle East (∼34%) and the Indian sub-continent (∼27%), while single mutations are widespread in Africa (∼45%). Contrary to the status for P. falciparum, Sdx-resistant single point mutations in PvDHPS dominate globally. Alarmingly, highly resistant quintuple and sextuple mutations are rising in Africa (PfDHFR-DHPS) and Asia (Pf/PvDHFR-DHPS). Structural analyses of DHFR and DHPS proteins in complexes with substrates/drugs have revealed that resistance mutations map proximal to Sdx and Pyr binding sites. Thus new studies can focus on discovery of novel inhibitors that target the non-substrate binding grooves in these two validated malaria parasite drug targets., (Copyright © 2021 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.)