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Affinity-based protein depletion and TiO2 enrichment methods play a crucial role in detection of low-abundant proteins and phosphopeptides enrichment, respectively. Here, we assessed the effectiveness of HSA/IgG (HU2) and Human 7 (HU7) depletion methods and their impact on phosphopeptides coverage through comparative proteome analysis, utilizing in-solution digestion and nano-LC-Orbitrap mass spectrometry (MS). Our results demonstrated that both HU2 and HU7 affinity depletion significantly decreased high-abundant proteins by 1.5-7.8-fold (p < 0.001). A total of 1491 proteins were identified, with 48 proteins showing significant expression in the depleted groups. Notably, cadherin-13, neutrophil defensin 1, APM1, and desmoplakin variant protein were exclusively detected in the HU2/HU7-depleted groups. Furthermore, study on effect of depletion on phosphopeptides revealed an increase in tandem MS spectral counts with notable decrease (â¼50%) in peptide spectrum matching in depleted groups, which was attributed to significant reduction in protein counts. Our post translation modification workflow for phosphoproteomics detected 42 phosphorylated peptides, corresponding to 12 phosphoproteins with unique peptide match ≥2 (high false discovery rates confidence). Among them, 10 phosphorylated proteins are highly expressed in depleted groups. Overall, these findings offer valuable insights in selection of protein depletion methods for comprehensive plasma proteomics analysis.
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OBJECTIVE: Miltefosine stands as the sole oral medication approved for the treatment of leishmaniasis. The appearance of severe ophthalmic toxicities induced by miltefosine in the context of leishmaniasis treatment is a matter of significant concern. The main objective of this study is to present a comprehensive summary of the ophthalmic adverse effects associated with miltefosine when used in the treatment of leishmaniasis. METHODS: A systematic search was performed on PubMed, ScienceDirect, Embase, Scopus, and Google Scholar, covering articles from inception up to June 2023, without language restrictions, to identify relevant studies documenting ocular toxicity following miltefosine treatment for leishmaniasis. RESULTS: A total of eight studies involving 31 leishmaniasis patients who developed ocular toxicities while undergoing miltefosine treatment were included in the analysis. These studies were conducted in various regions, with five originating from India, two from Bangladesh, and one from Nepal. Patients presented a spectrum of ophthalmic complications, including uveitis, keratitis, scleritis, and Mooren's ulcer. Commonly reported symptoms included pain, redness, excessive tearing, partial vision impairment, permanent blindness, light sensitivity, and the appearance of white spots on the eye. On average, patients received miltefosine treatment for a duration of 47 days before experiencing the onset of ocular problems. It is important to note that the risk of ocular toxicities increases with prolonged use of miltefosine. CONCLUSIONS: Therefore, to mitigate the potential for irreversible damage to the eyes, it is imperative that all individuals undergoing miltefosine therapy undergo regular eye examinations.
Subject(s)
Antiprotozoal Agents , Phosphorylcholine , Humans , Antiprotozoal Agents/adverse effects , Antiprotozoal Agents/therapeutic use , Phosphorylcholine/analogs & derivatives , Phosphorylcholine/adverse effects , Phosphorylcholine/therapeutic use , Leishmaniasis/drug therapy , Eye Diseases/chemically inducedABSTRACT
BACKGROUND: In Southeast Asia, treatment is recommended for all patients with post-kala-azar dermal leishmaniasis (PKDL). Adherence to the first-line regimen, twelve weeks of miltefosine (MF), is low and ocular toxicity has been observed with this exposure period. We assessed the safety and efficacy of two shorter-course treatments: liposomal amphotericin B (LAmB) alone and combined with MF. METHODOLOGY/PRINCIPAL FINDINGS: An open-label, phase II, randomized, parallel-arm, non-comparative trial was conducted in patients with parasitologically confirmed PKDL, 6 to ≤60 years. Patients were assigned to 20 mg/kg LAmB (total dose, in five injections over 15 days) alone or combined with allometric MF (3 weeks). The primary endpoint was definitive cure at 12 months, defined as complete resolution of papular and nodular lesions and >80% re-pigmentation of macular lesions. Definitive cure at 24 months was a secondary efficacy endpoint. 118/126 patients completed the trial. Definitive cure at 12 months was observed in 29% (18/63) patients receiving LAmB and 30% (19/63) receiving LAmB/MF (mITT), increasing to 58% and 66%, respectively, at 24 months. Most lesions had resolved/improved at 12 and 24 months for patients receiving LAmB (90%, 83%) and LAmB/MF (85%, 88%) by qualitative assessment. One death, unrelated to study drugs, was reported; no study drug-related serious adverse events were observed. The most frequent adverse drug reactions were MF-related vomiting and nausea, and LAmB-related hypokalaemia and infusion reactions. Most adverse events were mild; no ocular adverse events occurred. CONCLUSIONS/SIGNIFICANCE: Both regimens are suitably safe and efficacious alternatives to long-course MF for PKDL in South Asia. TRIAL REGISTRATION: CTRI/2017/04/008421.
Subject(s)
Amphotericin B , Antiprotozoal Agents , Leishmaniasis, Cutaneous , Leishmaniasis, Visceral , Phosphorylcholine , Humans , Amphotericin B/therapeutic use , Amphotericin B/adverse effects , Amphotericin B/administration & dosage , Phosphorylcholine/analogs & derivatives , Phosphorylcholine/therapeutic use , Phosphorylcholine/administration & dosage , Phosphorylcholine/adverse effects , Bangladesh , Male , Antiprotozoal Agents/therapeutic use , Antiprotozoal Agents/adverse effects , Antiprotozoal Agents/administration & dosage , Adult , Adolescent , Female , Middle Aged , Young Adult , Child , India , Leishmaniasis, Visceral/drug therapy , Treatment Outcome , Leishmaniasis, Cutaneous/drug therapy , Leishmaniasis, Cutaneous/parasitology , Drug Therapy, CombinationABSTRACT
Zwitterionic compounds are an emergent class of energetic materials and have gained synthetic interest of many in the recent years. Due to their better packing efficiencies and strong inter/intramolecular electrostatic interactions, they often ensue superior energetic properties than their salt analogues. A systematic review from the perspective of design, synthesis, and physicochemical properties evaluation of the zwitterionic energetic materials is presented. Depending on the parent ring(s) used for the synthesis and the type of moieties bearing positive and negative charges, different classes of energetic materials, such as primary explosives, secondary explosives, heat resistant explosives, oxidizers, etc., may result. The properties of some of the energetic zwitterionic compounds are also compared with analogous energetic salts. This review will encourage readers to explore the possibility of designing new zwitterionic energetic materials.
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This study explores the dynamic self-assembly and disassembly of hypervalent iodine-based macrocycles (HIMs) guided by secondary bonding interactions. The reversible disassembly and reassembly of HIMs are facilitated through anion binding via the addition of tetrabutylammonium (TBA) salts or removal of the anion by the addition of silver nitrate. The association constants for HIM monomers with TBA(Cl) and TBA(Br) are calculated and show a correlation with the strength of the iodine-anion bond. A unique tetracoordinate hypervalent iodine-based compound was identified as the disassembled monomer. Last, the study reveals the dynamic bonding nature of these macrocycles in solution, allowing for rearrangement and participation in dynamic bonding chemistry.
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INTRODUCTION: Post-kala-azar dermal leishmaniasis (PKDL) arises as a dermal complication following a visceral leishmaniasis (VL) infection. Current treatment options for PKDL are unsatisfactory, and there is a knowledge gap regarding the distribution of antileishmanial compounds within human skin. The present study investigated the skin distribution of miltefosine in PKDL patients, with the aim to improve the understanding of the pharmacokinetics at the skin target site in PKDL. METHODS: Fifty-two PKDL patients underwent treatment with liposomal amphotericin B (20â mg/kg) plus miltefosine (allometric dosing) for 21 days. Plasma concentrations of miltefosine were measured on study days 8, 15, 22 and 30, while a punch skin biopsy was taken on day 22. A physiologically based pharmacokinetic (PBPK) model was developed to evaluate the distribution of miltefosine into the skin. RESULTS: Following the allometric weight-based dosing regimen, median miltefosine concentrations on day 22 were 43.73â µg/g (IQR: 21.94-60.65â µg/g) in skin and 33.29â µg/mL (IQR: 25.9-42.58â µg/mL) in plasma. The median individual concentration ratio of skin to plasma was 1.19 (IQR: 0.79-1.9). In 87% (45/52) of patients, skin exposure was above the suggested EC90 PK target of 10.6â mg/L associated with in vitro susceptibility. Simulations indicated that the residence time of miltefosine in the skin would be more than 2-fold longer than in plasma, estimated by a mean residence time of 604 versus 266 hours, respectively. CONCLUSION: This study provides the first accurate measurements of miltefosine penetration into the skin, demonstrating substantial exposure and prolonged retention of miltefosine within the skin. These findings support the use of miltefosine in cutaneous manifestations of leishmaniasis. In combination with parasitological and clinical data, these results are critical for the future optimization of combination therapies with miltefosine in the treatment of PKDL.
Subject(s)
Amphotericin B , Antiprotozoal Agents , Leishmaniasis, Cutaneous , Leishmaniasis, Visceral , Phosphorylcholine , Skin , Humans , Phosphorylcholine/analogs & derivatives , Phosphorylcholine/pharmacokinetics , Phosphorylcholine/administration & dosage , Phosphorylcholine/therapeutic use , Antiprotozoal Agents/pharmacokinetics , Antiprotozoal Agents/administration & dosage , Antiprotozoal Agents/therapeutic use , Male , Adult , Leishmaniasis, Cutaneous/drug therapy , Leishmaniasis, Cutaneous/parasitology , Female , Skin/parasitology , Leishmaniasis, Visceral/drug therapy , Middle Aged , Young Adult , Amphotericin B/pharmacokinetics , Amphotericin B/therapeutic use , Amphotericin B/administration & dosage , Adolescent , Asia, SouthernABSTRACT
BACKGROUND: Post-kala-azar dermal leishmaniasis (PKDL) is a dermatosis which can occur after successful treatment of visceral leishmaniasis (VL) and is a public health problem in VL endemic areas. We conducted a systematic scoping review to assess the characteristics of published PKDL clinical studies, understand the scope of research and explore the feasibility and value of developing a PKDL individual patient data (IPD) platform. METHODS: A systematic review of published literature was conducted to identify PKDL clinical studies by searching the following databases: PubMed, Scopus, Ovid Embase, Web of Science Core Collection, WHO Global Index Medicus, PASCAL, Clinicaltrials.gov, Ovid Global Health, Cochrane Database and CENTRAL, and the WHO International Clinical Trials Registry Platform. Only prospective studies in humans with PKDL diagnosis, treatment, and follow-up measurements between January 1973 and March 2023 were included. Extracted data includes variables on patient characteristics, treatment regimens, diagnostic methods, geographical locations, efficacy endpoints, adverse events and statistical methodology. RESULTS: A total of 3,418 records were screened, of which 56 unique studies (n = 2,486 patients) were included in this review. Out of the 56 studies, 36 (64.3%) were from India (1983-2022), 12 (21.4%) from Sudan (1992-2021), 6 (10.7%) were from Bangladesh (1991-2019), and 2 (3.6%) from Nepal (2001-2007). Five (8.9%) studies were published between 1981-1990 (n = 193 patients), 10 (17.9%) between 1991-2000 (n = 230 patients), 10 (17.9%) between 2001-2010 (n = 198 patients), and 31 (55.4%) from 2011 onwards (n = 1,865 patients). Eight (14.3%) were randomised clinical trials, and 48 (85.7%) were non-randomised studies. The median post-treatment follow-up duration was 365 days (range: 90-540 days) in 8 RCTs and 360 days (range: 28-2,373 days) in 48 non-randomised studies. Disease diagnosis was based on clinical criterion in 3 (5.4%) studies, a mixture of clinical and parasitological methods in 47 (83.9%) and was unclear in 6 (10.7%) studies. Major drugs used for treatment were miltefosine (n = 636 patients), liposomal amphotericin B (L-AmB) (n = 508 patients), and antinomy regimens (n = 454 patients). Ten other drug regimens were tested in 270 patients with less than 60 patients per regimen. CONCLUSIONS: Our review identified studies with very limited sample size for the three major drugs (miltefosine, L-AmB, and pentavalent antimony), while the number of patients combined across studies suggest that the IPD platform would be valuable. With the support of relevant stakeholders, the global PKDL community and sufficient financing, a PKDL IPD platform can be realised. This will allow for exploration of different aspects of treatment safety and efficacy, which can potentially guide future healthcare decisions and clinical practices.
Subject(s)
Antiprotozoal Agents , Leishmaniasis, Cutaneous , Leishmaniasis, Visceral , Humans , Leishmaniasis, Visceral/drug therapy , Leishmaniasis, Cutaneous/drug therapy , Antiprotozoal Agents/therapeutic use , Observational Studies as Topic , Clinical Trials as Topic , Feasibility Studies , Treatment Outcome , India/epidemiology , Bangladesh/epidemiologyABSTRACT
There are close links between solar UV radiation, climate change, and plastic pollution. UV-driven weathering is a key process leading to the degradation of plastics in the environment but also the formation of potentially harmful plastic fragments such as micro- and nanoplastic particles. Estimates of the environmental persistence of plastic pollution, and the formation of fragments, will need to take in account plastic dispersal around the globe, as well as projected UV radiation levels and climate change factors.
Subject(s)
Solar Energy , Ultraviolet Rays , Ultraviolet Rays/adverse effects , Climate Change , Environmental Pollution , WeatherABSTRACT
AZD1222 (ChAdOx1 nCoV-19) is a replication-deficient adenoviral vectored coronavirus disease-19 (COVID-19) vaccine that is manufactured as SII-ChAdOx1 nCoV-19 by the Serum Institute of India Pvt Ltd following technology transfer from Oxford University/AstraZeneca. The non-inferiority of SII-ChAdOx1 nCoV-19 with AZD1222 was previously demonstrated in an observer-blind, phase 2/3 immuno-bridging study (trial registration: CTRI/2020/08/027170). In this analysis of immunogenicity and safety data 6 months post first vaccination (Day 180), 1,601 participants were randomized 3:1 to SII-ChAdOx1 nCoV-19 or AZD1222 (immunogenicity/reactogenicity cohort n = 401) and 3:1 to SII-ChAdOx1 nCoV-19 or placebo (safety cohort n = 1,200). Immunogenicity was measured by anti-severe acute respiratory syndrome coronavirus 2 spike (anti-S) binding immunoglobulin G and neutralizing antibody (nAb) titers. A decline in anti-S titers was observed in both vaccine groups, albeit with a greater decline in SII-ChAdOx1 nCoV-19 vaccinees (geometric mean titer [GMT] ratio [95% confidence interval (CI) of SII-ChAdOx1 nCoV-19 to AZD1222]: 0.60 [0.41-0.87]). Consistent similar decreases in nAb titers were observed between vaccine groups (GMT ratio [95% CI]: 0.88 [0.44-1.73]). No cases of severe COVID-19 were reported following vaccination, while one case was observed in the placebo group. No causally related serious adverse events were reported through 180 days. No thromboembolic or autoimmune adverse events of special interest were reported. Collectively, these data illustrate that SII-ChAdOx1 nCoV-19 maintained a high level of immunogenicity 6 months post-vaccination. SII-ChAdOx1 nCoV-19 was safe and well tolerated.
Subject(s)
COVID-19 , ChAdOx1 nCoV-19 , Adult , Humans , COVID-19 Vaccines/adverse effects , Follow-Up Studies , COVID-19/prevention & control , Immunoglobulin G , Immunogenicity, Vaccine , Antibodies, ViralABSTRACT
This Assessment Update by the Environmental Effects Assessment Panel (EEAP) of the United Nations Environment Programme (UNEP) considers the interactive effects of solar UV radiation, global warming, and other weathering factors on plastics. The Assessment illustrates the significance of solar UV radiation in decreasing the durability of plastic materials, degradation of plastic debris, formation of micro- and nanoplastic particles and accompanying leaching of potential toxic compounds. Micro- and nanoplastics have been found in all ecosystems, the atmosphere, and in humans. While the potential biological risks are not yet well-established, the widespread and increasing occurrence of plastic pollution is reason for continuing research and monitoring. Plastic debris persists after its intended life in soils, water bodies and the atmosphere as well as in living organisms. To counteract accumulation of plastics in the environment, the lifetime of novel plastics or plastic alternatives should better match the functional life of products, with eventual breakdown releasing harmless substances to the environment.
Subject(s)
Plastics , Water Pollutants, Chemical , Humans , Plastics/toxicity , Ecosystem , Ultraviolet Rays , Climate Change , Water Pollutants, Chemical/analysisABSTRACT
The COVID-19 pandemic has emerged as a critical global health crisis, demanding urgent and effective strategies for containment. While some knowledge exists about epitope sequences recognized by human immune cells and their activation of CD8+ T cells within the HLA context, comprehensive information remains limited. This study employs reverse vaccinology to explore antigenic HLA-restricted T-cell epitopes capable of eliciting durable immunity. Screening reveals 187 consensus epitopes, with 23 offering broad population coverage worldwide, spanning over 5000 HLA alleles. Sequence alignment analysis highlights the genetic distinctiveness of these peptides from Homo sapiens and their intermediate to high TAP binding efficiency. Notably, these epitopes share 100 % sequence identity across strains from nine countries, indicating potential for a uniform protective immune response among diverse ethnic populations. Docking simulations further confirm their binding capacity with the HLA allele, validating them as promising targets for SARS-CoV-2 immune recognition. The anticipated epitopes are connected with suitable linkers and adjuvant, and then assessed for its translational efficacy within a bacterial expression vector through computational cloning. Through docking, it is observed that the chimeric vaccine construct forms lasting hydrogen bonds with Toll-like receptor (TLR4), while immune simulation illustrates an increased cytotoxic response aimed at CD8+ T cells. This comprehensive computational analysis suggests the chimeric vaccine construct's potential to provoke a robust immune response against SARS-CoV-2. By delineating these antigenic fragments, our study offers valuable insights into effective vaccine and immunotherapy development against COVID-19, contributing significantly to global efforts in combating this infectious threat.
Subject(s)
COVID-19 , Viral Vaccines , Humans , SARS-CoV-2 , COVID-19/prevention & control , Vaccinology , Pandemics/prevention & control , Molecular Docking Simulation , Epitopes, T-Lymphocyte/chemistry , Epitopes, B-Lymphocyte , Computational Biology , Vaccines, SubunitABSTRACT
Application of nanomaterials is gaining tremendous interest in the field of wood science and technology for value addition and enhancing performance of wood and wood-based composites. This review focuses on the use of nanomaterials in improving the properties of wood and wood-based materials and protecting them from weathering, biodegradation, and other deteriorating agents. UV-resistant, self-cleaning (superhydrophobic) surfaces with anti-microbial properties have been developed using the extraordinary features of nanomaterials. Scratch-resistant nano-coatings also improve durability and aesthetic appeal of wood. Moreover, nanomaterials have been used as wood preservatives for increasing the resistance against wood deteriorating agents such as fungi, termites and borers. Wood can be made more resistant to ignition and slower to burn by introducing nano-clays or nanoparticles of metal-oxides. The use of nanocellulose and lignin nanoparticles in wood-based products has attracted huge interest in developing novel materials with improved properties. Nanocellulose and lignin nanoparticles derived/synthesized from woody biomass can enhance the mechanical properties such as strength and stiffness and impart additional functionalities to wood-based products. Cellulose nano-fibres/crystals find application in wide areas of materials science like reinforcement for composites. Incorporation of nanomaterials in resin has been used to enhance specific properties of wood-based composites. This review paper highlights some of the advancements in the use of nanotechnology in wood science, and its potential impact on the industry.
Subject(s)
Lignin , Nanostructures , Lignin/analysis , Wood/chemistry , Nanotechnology , Cellulose/chemistry , Nanostructures/chemistryABSTRACT
Because of environmental and health impacts, there is an ongoing necessity to develop sustainable primary explosives to replace existing lead-based analogues. Now we describe a potential primary explosive, dipotassium 4,6-dinitro-5,7-dioxidobenzo[c][1,2,5]oxadiazole 1-oxide (K2DNDP), which exhibits an excellent thermal stability (Tdec = 281 °C), positive oxygen balance (+4.79%), and a calculated crystal density of ρ = 2.274 g cm-3 at 100 K. Its physicochemical properties concomitantly with its straightforward synthesis make it a potential replacement for lead-based initiators.
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A large body of evidence has shown a direct link between arsenic exposure and drug resistance to Leishmania parasites against antimonial preparations in visceral leishmaniasis (VL) hyper-endemic regions, especially in India and its sub-continent. However, the implicated roles of arsenic on the VL host, pathophysiological changes, and immune function have not yet been clarified, particularly at the reported concentration of arsenic in the VL hyper-endemic area of Bihar, India. Herein, we exposed the mouse VL model to arsenic (0.5 mg/L to 2 mg/L) through their drinking water and analyzed its effect on T cells proliferation, Th1/Th2-mediators, MAPK signaling cascade, and parasite load in preclinical models. Coherently, the parasite count in Giemsa stained spleen imprint has been investigated and found significant positive associations with levels of arsenic exposure. The liver and kidney function tests (AST, ALT, ALP, BUN, Creatinine, Urea, etc.) are apparent to hepatonephric toxicity in arsenic exposed VL mice compared to unexposed. This observation appears to be consistent with the up-regulated expression of immune regulatory Th2 mediators (IL-4, IL-10, TGF-ß) and down-regulated expression of Th1 mediators (IL-12, IFN-γ, TNF-α) with a suppressed leishmanicidal function of macrophage (ROS, NO, iNOS). We also established that arsenic exposure modulated the host ERK-1/2 and p38 MAPK signaling cascade, limited T lymphocyte proliferation, and a lower IgG2a/IgG1 ratio to favor the Leishmania parasite survival inside the host. This study suggests that the contorted Th1-subtype and exacerbated Th2-subtype immune responses are involved in the increased susceptibility and pathogenesis of Leishmania parasite among subjects/individuals regularly exposed to arsenic.
Subject(s)
Arsenic , Drinking Water , Leishmania donovani , Leishmaniasis, Visceral , Humans , Animals , Mice , Leishmaniasis, Visceral/parasitology , Arsenic/toxicity , Disease ProgressionABSTRACT
BACKGROUND: People with HIV (PLHIV) face increased cardiovascular disease (CVD) risk due to inflammation and immune activation. Aging further amplifies this risk. Limited data exist on CVD risk in older PLHIV in India despite 2.14 million PLHIV with higher CVD risk factors. METHODS: In a cross-sectional study in Bihar, India, 73 PLHIV and 30 control participants were enrolled. Demographics, social factors, clinical information, and CVD risk factors were collected. HbA1c levels and lipid profiles were analyzed, and 10-year CVD risk scores were calculated using the Framingham risk score (FRS) and Qrisk3. Quality of life (QoL) was assessed using WHOQOL- HIV-BREF. RESULTS: Results showed higher LDL levels in non-HIV older participants and higher HDL levels in younger PLHIV participants. BMI differed significantly, with higher BMI in non-HIV older individuals and lower BMI in younger PLHIV individuals. Older PLHIV participants had significantly higher mean FRS and Q-Risk scores compared to older non-PLHIV and younger PLHIV groups. Among older PLHIV participants, six had higher CVD risk per FRS, while none in the other groups were classified as high CVD risk. Psychological, social relations and spirituality domains were highly deteriorated in older PLHIV, scoring 44.48, 42.72, and 41.2, respectively. The physical domain scored 57.6, and the environment scored 52.72 in the WHOQOL-HIV bref. CONCLUSION: In conclusion, older PLHIV in Bihar, India, face higher CVD risk compared to younger PLHIV and non-HIV individuals. FRS and Q-Risk scores effectively assessed CVD risk, identifying higher risk in older PLHIV. Age and BMI were significant predictors of high CVD risk. These findings emphasize CVD risk assessment and tailored management for older PLHIV. The QoL assessment findings indicate moderate deterioration in psychological, social relations, and spirituality domains among older PLHIV individuals. These results suggest greater challenges in psychological well-being, social interactions, and spirituality compared to the overall sample. Further research with larger samples and longitudinal designs is needed to confirm and extend these findings.
Subject(s)
Cardiovascular Diseases , HIV Infections , Humans , Aged , Quality of Life , HIV Infections/complications , Risk Factors , Cardiovascular Diseases/epidemiology , Cross-Sectional Studies , Heart Disease Risk FactorsABSTRACT
INTRODUCTION: Visceral leishmaniasis (VL) is a parasitic disease with an estimated 30 000 new cases occurring annually. Despite anaemia being a common haematological manifestation of VL, the evolution of different haematological characteristics following treatment remains poorly understood. An individual participant data meta-analysis (IPD-MA) is planned to characterise the haematological dynamics in patients with VL. METHODS AND ANALYSIS: The Infectious Diseases Data Observatory (IDDO) VL data platform is a global repository of IPD from therapeutic studies identified through a systematic search of published literature (PROSPERO registration: CRD42021284622). The platform currently holds datasets from clinical trials standardised to a common data format. Corresponding authors and principal investigators of the studies indexed in the IDDO VL data platform meeting the eligibility criteria for inclusion were invited to be part of the collaborative IPD-MA. Mixed-effects multivariable regression models will be constructed to identify determinants of haematological parameters by taking clustering within study sites into account. ETHICS AND DISSEMINATION: This IPD-MA meets the criteria for waiver of ethical review as defined by the Oxford Tropical Research Ethics Committee (OxTREC) granted to IDDO, as the research consists of secondary analysis of existing anonymised data (exempt granted on 29 March 2023, OxTREC REF: IDDO). Ethics approval was granted by the ICMR-Rajendra Memorial Research Institute of Medical Sciences ethics committee (letter no.: RMRI/EC/30/2022) on 4 July 2022. The results of this analysis will be disseminated at conferences, the IDDO website and peer-reviewed publications in open-access journals. The findings of this research will be critically important for control programmes at regional and global levels, policymakers and groups developing new VL treatments. PROSPERO REGISTRATION NUMBER: CRD42021284622.
Subject(s)
Leishmaniasis, Visceral , Humans , Leishmaniasis, Visceral/drug therapy , Systematic Reviews as Topic , Meta-Analysis as TopicABSTRACT
Background: Over time, COVID-19 testing has significantly declined across the world. However, it is critical to monitor the virus through surveillance. In late 2020, WHO released interim guidance advising the use of the existing Global Influenza Surveillance and Response System (GISRS) for the integrated surveillance of influenza and SARS-CoV-2. Methods: In July 2021, we initiated a pan-India integrated surveillance for influenza and SARS-CoV-2 through the geographically representative network of Virus Research and Diagnostic Laboratories (VRDLs) across 26 hospital and laboratory sites and 70 community sites. A total of 34,260 cases of influenza-like illness (ILI) and Severe acute respiratory infection (SARI) were enrolled from 4 July 2021 to 31 October 2022. Findings: Influenza A(H3) and B/Victoria dominated during 2021 monsoon season while A(H1N1)pdm09 dominated during 2022 monsoon season. The SARS-CoV-2 "variants of concern" (VoC) Delta and Omicron predominated in 2021 and 2022, respectively. Increased proportion of SARI was seen in extremes of age: 90% cases in < 1 year; 68% in 1 to 5 years and 61% in ≥ 8 years age group. Approximately 40.7% of enrolled cases only partially fulfilled WHO ILI and SARI case definitions. Influenza- and SARS-CoV-2-infected comorbid patients had higher risks of hospitalization, ICU admission, and oxygen requirement. Interpretation: The results depicted the varying strains and transmission dynamics of influenza and SARS-CoV-2 viruses over time, thus emphasizing the need to continue and expand surveillance across countries for improved decision making. The study also describes important information related to clinical outcomes of ILI and SARI patients and highlights the need to review existing WHO ILI and SARI case definitions.
Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza, Human , Pneumonia , Virus Diseases , Humans , Influenza, Human/epidemiology , COVID-19 Testing , Influenza A Virus, H1N1 Subtype/genetics , Genomics , India/epidemiologyABSTRACT
More than 70 million individuals have been exposed to environmental arsenic toxicity, worldwide. United Nation Children's Fund (UNICEF) policy brief -2018 report to mitigate arsenic in drinking water, emphasizes assessing, and changing the knowledge, attitudes, and practices (KAP) as one of the long-term effective solutions to be implemented as a part of surveillance strategies. This study aims to develop a valid and reliable tool to assess knowledge, attitude, and practices of arsenic and its risk in general health. A cross-sectional survey of N=449 general population was conducted in the outpatient department of Rajendra Memorial Research Institute of Medical Sciences-Indian Council for Medical Research for data collection. The construct validation of the questionnaire was done using Exploratory Factor Analysis, Confirmatory factor analysis. The Item-Content Validity Index(I-CVI) and Scale-Content Validity Index (S-CVI) Kappa scores were used to analyze the content validity of the items. The I-CVI ranges from 0.70 to 1, the and the moderate to high cumulative content validity is S-CVI/Universal Agreement=0.84; S-CVI/Average =0.96. Following the principal component analysis, the cumulative Kaiser-Meyer-Olkin measure of sampling adequacy (KMO) was 0.91 and the three domains in the tool (Kaiser-Meyer-Olkin measure of sampling adequacy for Knowledge (0.917), Attitude (0.825) & Practices (0.80)) were within the acceptable range. The Barret's test for sphericity was (P <0.001) and was highly acceptable. The Confirmatory Factor Analysis model of Nu-KAP has demonstrated excellent model fit where, majority of fit indices has sown good fit (X2/df=1.88, Root Mean Square Error of Approximation = 0.04, Comparative Fit Index=0.98, Goodness of Fit Index = 0.93, and Tucker Lewis Index=0.977). The Cronbach's alpha of 19 item tool was 0.72. The Nu-KAPQ questionnaire demonstrated exceptional validity and reliability while also capturing and integrating all pertinent psychometric analytic domains. Conclusively, this questionnaire can be used to assess psychometric properties associated with arsenic bridging the gap in current research to understand people's perception towards arsenic, since it is a crucial component of arsenic mitigation.
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With an aim to improve the overall physical stability of high-performing 3,5-dinitro-functionalised bispyrazolymethanes, a hydroxyl functionality was introduced at the fourth position to obtain 1,1'-methylenebis(3,5-dinitro-1H-pyrazol-4-ol) and its energetic salts. Superior oxygen balance and energy in comparison to the amino substituent at the 4th position and enhanced sensitivity with respect to the nitro and azido substituents helped in unlocking the potential of less explored N-alkylated-4-hydroxy-3,5-dinitropyrazoles. Fine-tuning of properties via dicationic salt formation, which is not feasible in any other reported symmetrically connected pyrazole-based energetic materials, resulted in improved physical and thermal stabilities, as well as energetic performance. Hirshfeld surface analysis, electrostatic potential analysis, the study of aromaticity and weakest Mayer-bond order analysis helped further in studying the structure-property relationship of the synthesized compounds with respect to different reported methylene-bridged symmetrical compounds.
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Japanese encephalitis (JE) is a mosquito-borne disease that causes neuronal damage and inflammation of microglia, and in severe cases, it can be fatal. JE infection can resist cellular immune responses and survive in host cells. Japanese encephalitis virus (JEV) infects macrophages and peripheral blood lymphocytes. In addition to regulating biological signaling pathways, microRNAs in cells also influence virus-host interactions. Under certain circumstances, viruses can change microRNA production. These changes affect the replication and spread of the virus. Host miRNAs can contain viral pathogenicity by downregulating the antiviral immune response pathways. Simultaneous profiling of miRNA and messenger RNA (mRNA) could help us detect pathogenic factors, and dual RNA detection is possible. This work highlights important miRNAs involved in human JE infection. In this study, we have shown the important miRNAs that play significant roles in JEV infection. We found that during JEV infection, miRNA-155, miR-29b, miRNA-15b, miR-146a, miRNA-125b-5p, miRNA-30la, miR-19b-3p, and miR-124, cause upregulation of human genes whereas miRNA-432, miRNA-370, microRNA-33a-5p, and miRNA-466d-3p are responsible for downregulation of human genes respectively. Further, these miRNAs are also responsible for the inflammatory effects. Although several other miRNAs critical to the JEV life cycle are yet unknown, there is currently no evidence for the role of miRNAs in persistence.