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1.
PLoS Negl Trop Dis ; 18(4): e0011635, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38626228

RESUMO

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.

2.
Glob Chang Biol ; 30(4): e17279, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38619007

RESUMO

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.


Assuntos
Energia Solar , Raios Ultravioleta , Raios Ultravioleta/efeitos adversos , Mudança Climática , Poluição Ambiental , Tempo (Meteorologia)
3.
Int J Biol Macromol ; 265(Pt 2): 130754, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38508555

RESUMO

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.


Assuntos
COVID-19 , Vacinas Virais , Humanos , SARS-CoV-2 , COVID-19/prevenção & controle , Vacinologia , Pandemias/prevenção & controle , Simulação de Acoplamento Molecular , Epitopos de Linfócito T/química , Epitopos de Linfócito B , Biologia Computacional , Vacinas de Subunidades
4.
Photochem Photobiol Sci ; 23(4): 629-650, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38512633

RESUMO

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.


Assuntos
Plásticos , Poluentes Químicos da Água , Humanos , Plásticos/toxicidade , Ecossistema , Raios Ultravioleta , Mudança Climática , Poluentes Químicos da Água/análise
5.
Hum Vaccin Immunother ; 20(1): 2304974, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38512394

RESUMO

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.


Assuntos
COVID-19 , ChAdOx1 nCoV-19 , Adulto , Humanos , Vacinas contra COVID-19/efeitos adversos , Seguimentos , COVID-19/prevenção & controle , Imunoglobulina G , Imunogenicidade da Vacina , Anticorpos Antivirais
6.
Org Lett ; 26(9): 1952-1958, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38411560

RESUMO

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.

7.
Int J Biol Macromol ; 262(Pt 2): 130025, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38340917

RESUMO

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.


Assuntos
Lignina , Nanoestruturas , Lignina/análise , Madeira/química , Nanotecnologia , Celulose/química , Nanoestruturas/química
8.
Sci Rep ; 13(1): 21461, 2023 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-38052913

RESUMO

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.


Assuntos
Arsênio , Água Potável , Leishmania donovani , Leishmaniose Visceral , Humanos , Animais , Camundongos , Leishmaniose Visceral/parasitologia , Arsênio/toxicidade , Progressão da Doença
9.
Curr HIV Res ; 21(6): 354-360, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38141189

RESUMO

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.


Assuntos
Doenças Cardiovasculares , Infecções por HIV , Humanos , Idoso , Qualidade de Vida , Infecções por HIV/complicações , Fatores de Risco , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Fatores de Risco de Doenças Cardíacas
10.
BMJ Open ; 13(12): e074841, 2023 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-38101841

RESUMO

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.


Assuntos
Leishmaniose Visceral , Humanos , Leishmaniose Visceral/tratamento farmacológico , Revisões Sistemáticas como Assunto , Metanálise como Assunto
11.
Front Public Health ; 11: 1218292, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37927860

RESUMO

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.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Pneumonia , Viroses , Humanos , Influenza Humana/epidemiologia , Teste para COVID-19 , Vírus da Influenza A Subtipo H1N1/genética , Genômica , Índia/epidemiologia
12.
Chem Commun (Camb) ; 59(95): 14110-14113, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-37916387

RESUMO

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.

13.
Biol Trace Elem Res ; 2023 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-37924414

RESUMO

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.

14.
Artigo em Inglês | MEDLINE | ID: mdl-37888811

RESUMO

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.

15.
BMJ Open ; 13(10): e074679, 2023 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-37898487

RESUMO

INTRODUCTION: Visceral leishmaniasis (VL) is a parasitic disease with an estimated 30 000 new cases occurring annually. There is an observed variation in the efficacy of the current first-line therapies across different regions. Such heterogeneity could be a function of host, parasite and drug factors. An individual participant data meta-analysis (IPD-MA) is planned to explore the determinants of treatment outcomes. METHODS AND ANALYSIS: The Infectious Diseases Data Observatory (IDDO) VL living systematic review (IDDO VL LSR) library is an open-access resource of all published therapeutic studies in VL since 1980. For this current review, the search includes all clinical trials published between 1 January 1980 and 2 May 2021. Studies indexed in the IDDO VL LSR library were screened for eligibility for inclusion in this IPD-MA. Corresponding authors and principal investigators of the studies meeting the eligibility criteria for inclusion were invited to be part of the collaborative IPD-MA. Authors agreeing to participate in this collaborative research were requested to share the IPD using the IDDO VL data platform. The IDDO VL data platform currently holds data sets from clinical trials standardised to a common data format and provides a unique opportunity to identify host, parasite and drug determinants of treatment outcomes. Multivariable regression models will be constructed to identify determinants of therapeutic outcomes using generalised linear mixed-effects models accounting for within-study site clustering. 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 04-07-2022. The results of this IPD-MA will be disseminated at conferences, IDDO website and any peer-reviewed publications. All publications will be open source. Findings of this research will be critically important for the control programmes at regional/global levels, policy makers and groups developing new VL treatments. PROSPERO REGISTRATION: CRD42021284622.


Assuntos
Leishmaniose Visceral , Parasitos , Humanos , Animais , Leishmaniose Visceral/tratamento farmacológico , Resultado do Tratamento , Revisões Sistemáticas como Assunto , Metanálise como Assunto
16.
J Org Chem ; 88(21): 15085-15096, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37847075

RESUMO

In the quest to synthesize high-performing insensitive high-energy density materials (HEDMs), the main challenge is establishing an equilibrium between energy and stability. For this purpose, we explored 4-hydroxy-3,5-dinitropyrazole- and tetrazole-based energetic scaffolds connected via a N-methylene-C bridge. The hydroxy functionality between nitro groups on the pyrazole ring promotes physical stability via inter- and intramolecular hydrogen bonding and contributes to oxygen balance, supporting better energetic performance. Due to two acidic sites (OH and NH) with different reactivities, a series of monocationic and dicationic salts were synthesized, and their overall performance was compared. All compounds synthesized in this study have high physical stability with impact sensitivity >40 J and friction sensitivity >360 N. Monocationic salts were generally found to have better thermal stability with respect to their corresponding dicationic energetic salts, which showed better energetic performance. The salt formation strategy effectively improved the thermal stability of 2 (Td = 168 °C), where most energetic salts have decomposition temperatures higher than 220 °C. All of the compounds were characterized through IR, multinuclear NMR spectroscopy, high-resolution mass spectrometry (HRMS), and elemental analysis. The structure-property relationship was studied using Hirshfeld surface analysis, noncovalent interaction (NCI) analysis, and electrostatic potential studies.

17.
Sci Rep ; 13(1): 14915, 2023 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-37689764

RESUMO

Transparent wood (TW) has garnered significant global attention due to its unique properties. In this study, TW composites were fabricated using two timber species of different density classes: Ailanthus triphysa (common name: Ailanthus wood) and Hevea brasiliensis (common name: Rubberwood). Sodium hydroxide (NaOH) and Hydrogen peroxide-based alkali method was used to modify the lignin in these veneer samples, producing a white cellulose template with a fully intact hierarchical cell structure. Subsequently, a cost-effective thermosetting unsaturated polyester resin (UPR) was infiltrated into the redesigned framework and polymerized to create rigid nanostructured transparent composites. High optical haze (of 94% and 89%) and favourable light transmittance of 59 and 55 percent were exhibited by the UPR-TW composites made from rubberwood and ailanthus wood, respectively. TW was characterised using Scanning electron microscopy and Fourier-transform infrared spectroscopy. The mechanical properties of TW were measured and compared with those of natural wood and pure-polymer. Furthermore, the anisotropic light diffusion behaviour displayed by TW in accordance with the fibre orientation indicates the utility of material as a potential light shaping device. Therefore, a cost-effective and commercially viable strategy to fabricate multipurpose TW composites using a combination of lesser-known timber species (LKTS) and UPR resin was successfully demonstrated.

18.
Med J Armed Forces India ; 79(5): 500-505, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37719909

RESUMO

Post kala-azar dermal leishmaniasis (PKDL) is a skin disease that usually occurs among individuals with a past history of visceral leishmaniasis (VL). PKDL cases act as a reservoir of parasites and may play a significant role in disease transmission. Hence, prompt detection and complete treatment of PKDL cases are crucial for the control and elimination of VL. The purpose of this review was to highlight the barriers to effective control and prevention of VL/PKDL as well as potential solutions in India. Main obstacles are lack of knowledge about the disease and its vector, poor treatment-seeking behaviours, ineffective vector control measures, lack of confirmatory diagnostics in endemic areas, limited drug choices, treatment noncompliance among patients, drug resistance, and a lack of an adequate number of trained personnel in the health system. Therefore, in order to control and successfully eliminate VL in the Indian subcontinent, early detection of PKDL cases, improved diagnosis and treatment, raising awareness, and effective vector control mechanisms are necessary.

19.
Int J Biol Macromol ; 253(Pt 5): 127073, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37774824

RESUMO

Leishmania donovani is the causative unicellular parasite for visceral leishmaniasis (VL); and FeS proteins are likely to be very essential for their survival and viability. Cytosolic FeS cluster assembly (CIA) machinery is one of the four systems for the biosynthesis and transfer of FeS clusters among eukaryotes; Cfd1 and Nbp35 are the scaffold components for cytosolic FeS cluster biogenesis. We investigated the role of CIA machinery components and purified Cfd1 and Nbp35 proteins of L. donovani. We also investigated the interactive nature between LdCfd1 and LdNbp35 proteins by in silico analysis, in vitro co-purification, pull down assays along with in vivo immuno-precipitation; which inferred that both LdCfd1 and LdNbp35 proteins are interacting with each other. Thus, our collective data revealed the interaction between these two proteins which forms a stable complex that can be attributed to the cellular process of FeS clusters biogenesis, and transfer to target apo-proteins of L. donovani. The expression of Cfd1 and Nbp35 proteins in Amp B resistant parasites is up-regulated leading to increased amount of FeS proteins. Hence, it favors increased tolerance towards ROS level, which helps parasites survival under drug pressure contributing in Amphotericin B resistance.


Assuntos
Proteínas Ferro-Enxofre , Leishmania donovani , Proteínas de Saccharomyces cerevisiae , Leishmania donovani/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Ligação ao GTP
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