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1.
Sci Rep ; 14(1): 10660, 2024 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724525

RESUMO

Influenza Like Illness (ILI) and Severe Acute Respiratory Infection (SARI) cases are more prone to Influenza and SARS-CoV-2 infection. Accordingly, we genetically characterized Influenza and SARS-CoV-2 in 633 ILI and SARI cases by rRT-PCR and WGS. ILI and SARI cases showed H1N1pdm09 prevalence of 20.9% and 23.2% respectively. 135 (21.3%) H1N1pdm09 and 23 (3.6%) H3N2 and 5 coinfection (0.78%) of H1N1pdm09 and SARS-CoV-2 were detected. Phylogenetic analysis revealed H1N1pdm09 resemblance to clade 6B.1A.5a.2 and their genetic relatedness to InfA/Perth/34/2020, InfA/Victoria/88/2020 and InfA/Victoria/2570/2019. Pan 24 HA and 26 NA nonsynonymous mutations and novel HA (G6D, Y7F, Y78H, P212L, G339R, T508K and S523T) and NA (S229A) mutations were observed. S74R, N129D, N156K, S162N, K163Q and S164T alter HA Cb and Sa antibody recognizing site. Similarly, M19T, V13T substitution and multiple mutations in transmembrane and NA head domain drive antigenic drift. SARS-CoV-2 strains genetically characterized to Omicron BA.2.75 lineage containing thirty nonsynonymous spike mutations exhibited enhanced virulence and transmission rates. Coinfection although detected very minimal, the mutational changes in H1N1pdm09 and SARS-CoV-2 virus infected individuals could alter antibody receptor binding sites, allowing the viruses to escape immune response resulting in better adaptability and transmission. Thus continuous genomic surveillance is required to tackle any future outbreak.


Assuntos
COVID-19 , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Filogenia , SARS-CoV-2 , Humanos , Vírus da Influenza A Subtipo H1N1/genética , SARS-CoV-2/genética , Influenza Humana/virologia , Influenza Humana/epidemiologia , COVID-19/virologia , COVID-19/epidemiologia , Adulto , Pessoa de Meia-Idade , Masculino , Feminino , Adolescente , Adulto Jovem , Genoma Viral/genética , Idoso , Coinfecção/virologia , Coinfecção/epidemiologia , Criança , Pré-Escolar , Síndrome Respiratória Aguda Grave/virologia , Síndrome Respiratória Aguda Grave/epidemiologia , Mutação , Lactente
2.
Artigo em Inglês | MEDLINE | ID: mdl-38630259

RESUMO

PURPOSE: We evaluated the feasibility, acceptability and preliminary efficacy of a standardized nurse delivered mobile phone intervention to improve adherence to antiretroviral treatment and clinical outcomes. METHODS: Feasibility and acceptability of the phone intervention was assessed with rates of eligibility, completed visits, and attritions. Intervention fidelity was assessed by checking recorded calls and feedback. Efficacy was assessed using a randomized controlled trial in which 120 women living with HIV and psychosocial vulnerabilities, were randomized to Treatment as Usual (TAU = 60) or TAU plus the mobile phone intervention (N = 60). Trained basic nurses delivered the theory-guided, standardized mobile phone intervention for mental health issues and psychosocial risk factors to improve antiretroviral treatment (ART) adherence and retention in care and improve clinical outcomes. Blind raters performed the assessments at 6, 12 and 24 weeks post-randomization. RESULTS: Adherence diminished over time in the TAU only group, while it was sustained in the TAU Plus group, only dropping at 24 weeks after the intervention had been discontinued. Among participants with depressive symptoms (CESD ≥ 16), the intervention had significant improvement in adherence rates (p < 0.01), psychological quality of life (p < 0.05) and illness perception (p < 0.05) compared to those in the TAU only group. Greater improvements of quality of life subscales were observed in the TAU Plus group among participants with less psychological vulnerability (PSV < 2). HIV RNA was not significantly different between the groups at week 24. CONCLUSIONS: The mobile-delivered counseling intervention was feasible and acceptable and shows promise among women living with HIV and psychosocial vulnerabilities in rural South India. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02319330 [Registered on: December 18, 2014].

3.
Indian J Med Res ; 159(2): 121-129, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38577854

RESUMO

ABSTRACT: Leprosy, an ancient disease, continues to be a public health concern as it remains endemic in several countries. After reaching the elimination target (1/10,000) as a public health problem in 2005 in India, around 1.2 lakh cases have been detected every year over the last decade indicating active transmission of leprosy bacillus (Mycobacterium leprae). Single-nucleotide polymorphisms (SNPs), genomic insertions/deletions and variable-number tandem repeats (VNTRs) have been identified as genetic markers for tracking M. leprae transmission. As the leprosy bacilli cannot be cultured in vitro, molecular testing of M. leprae genotypes is done by polymerase chain reaction-based sequencing which provides a practical alternative for the identification of strains as well as drug resistance-associated mutations. Whole-genome sequencing (WGS) of M. leprae directly from clinical samples has also proven to be an effective tool for identifying genetic variations which can further help refine the molecular epidemiological schemes based on SNPs and VNTRs. However, the WGS data of M. leprae strains from India are scarce, being responsible for a gross under-representation of the genetic diversity of M. leprae strains present in India and need to be addressed suitably. Molecular studies of leprosy can provide better insight into phylogeographic markers to monitor the transmission dynamics and emergence of antimicrobial resistance. An improved understanding of M. leprae transmission is essential to guide efficient leprosy control strategies. Therefore, this review compiles and discusses the current status of molecular epidemiology, genotyping and the potential of genome-wide analysis of M. leprae strains in the Indian context.


Assuntos
Hanseníase , Mycobacterium leprae , Humanos , Mycobacterium leprae/genética , DNA Bacteriano/genética , Hanseníase/epidemiologia , Hanseníase/genética , Polimorfismo de Nucleotídeo Único/genética , Epidemiologia Molecular
4.
iScience ; 27(5): 109663, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38655200

RESUMO

This study investigates the efficacy of proteomic analysis of human remains to identify active infections in the past through the detection of pathogens and the host response to infection. We advance leprosy as a case study due to the sequestering of sufferers in leprosaria and the suggestive skeletal lesions that can result from the disease. Here we present a sequential enzyme extraction protocol, using trypsin followed by ProAlanase, to reduce the abundance of collagen peptides and in so doing increase the detection of non-collagenous proteins. Through our study of five individuals from an 11th to 18th century leprosarium, as well as four from a contemporaneous non-leprosy associated cemetery in Barcelona, we show that samples from 2 out of 5 leprosarium individuals extracted with the sequential digestion methodology contain numerous host immune proteins associated with modern leprosy. In contrast, individuals from the non-leprosy associated cemetery and all samples extracted with a trypsin-only protocol did not. Through this study, we advance a palaeoproteomic methodology to gain insights into the health of archaeological individuals and take a step toward a proteomics-based method to study immune responses in past populations.

5.
J Cancer Res Ther ; 20(1): 71-78, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38554301

RESUMO

INTRODUCTION: Linear accelerator (LINAC) embedded with kV source-imager system is capable to do image-guided radiotherapy. The only disadvantage of cone-beam computed tomography image acquisition during treatment is the extra radiation dose to the patient. The aim of this study is to optimize the CBCT imaging doses likely to be received by the patient undergoing radiotherapy without affecting image quality. MATERIAL AND METHODS: The imaging dose to the patient was estimated on CTDI phantoms. The effect of additional filters of different materials (copper, brass, aluminum of thickness 0.1 mm each) was evaluated to find the optimized dose imaging technique. For the pelvis, a single imaging protocol available on the machine was used, whereas for the head and neck region, two protocols, high-quality head and standard-dose head were used. The image quality was assessed on CATPHAN-504 phantom using Owl CATPHAN® QA online tool. A new term "Image Assessment score" (IAS) was introduced to evaluate the image quality. RESULT: In the pelvis protocol, CBCT imaging doses with an additional 0.1-mm brass, copper, and aluminum filter were measured to be reduced by 7.1%, 4.7%, and 2.5%, respectively, whereas for high-quality head protocol, the dose reduction was 25.4% (with brass filter), 22% (with copper filter), and 3.1% (with aluminum filter). For the standard-dose head protocol, doses were reduced by 7.5%, 2.8%, and 2.1% with additional 0.1-mm brass copper and aluminum filters, respectively. Acceptable image quality was observed with all the filters. CONCLUSION: Although the reconstructed images were found somewhat noisier, they did not affect the purpose of imaging, that is, treatment position verification. It was observed that these extra filters further reduce the imaging dose without much affecting the image quality.


Assuntos
Cobre , Tomografia Computadorizada de Feixe Cônico Espiral , Zinco , Humanos , Alumínio , Tomografia Computadorizada de Feixe Cônico/métodos , Imagens de Fantasmas
6.
J Cancer Res Ther ; 20(1): 389-395, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38554351

RESUMO

INTRODUCTION: Total skin electron beam therapy, commonly known as TSET, is a good choice of treatment for patients suffering from mycosis fungoides. The aim of this study was to introduce a new approach to the beam profile measurement using diodes and to calculate the monitor units required for the TSET treatment by the use of a simple setup of output measurement. Dosimetric measurements required for the treatment were taken to establish the Stanford technique in the department, and the measured data was compared with the published data. MATERIALS AND METHODS: High-energy Linear Accelerator Clinac-DHX, Varian medical system, Palo Alto, CA, was commissioned for TSET. The output of the machine was measured by the use of a Parallel-Plate Chamber (PPC40) as per the TRS 398 recommendation. Diode dosimeters (EDD2 and EDD5) were used for beam profile measurements due to easy setup and to reduce the measurement time. RESULTS: Homogeneous dose distribution within a field size of 80 cm x160 cm was observed with the variation of -5.0% on the horizontal axis and -5.4% on the vertical axis. The calculated monitor unit to deliver 200 cGy per fraction per field at the source to surface (SSD) of 416 cm was 489 MU. CONCLUSION: The technique described for the output measurements is simple and accurate. Results of the absorbed dose and MU measured were within good agreement compared to the published literature.


Assuntos
Aceleradores de Partículas , Radiometria , Humanos , Dosagem Radioterapêutica , Radiometria/métodos
7.
Med Eng Phys ; 124: 104102, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38418030

RESUMO

ECG beat classification or arrhythmia detection through artificial intelligence (AI) is an active topic of research. It is vital to recognize and detect the type of arrhythmia for monitoring cardiac abnormalities. The AI-based ECG beat classification algorithms proposed in the literature suffer from two main drawbacks. Firstly, some of the works have not considered any unseen test data to validate the performance of their algorithms. Secondly, the accuracy of detecting superventricular ectopic beats (SVEB) needs to be improved. In this work, we address these issues by considering an inter-patient paradigm where the test dataset is collected from a different set of subjects than the training data. Also, the proposed methodology detects SVEB with an F1 score of 89.35%, which is better than existing algorithms. We have used the Fourier decomposition method (FDM) for multi-scale analysis of ECG signals and extracted time-domain and statistical features from the narrow-band signal components obtained using FDM. Feature selection techniques, including the Kruskal-Wallis test and minimum redundancy maximum relevance (mRMR) have been used to select only the relevant features and rank these features to remove any redundancy. Since the dataset used is highly imbalanced, Mathew's correlation coefficient (MCC) has also been used to analyze the performance of the proposed method. Support vector machine classifier with linear kernel achieves an overall 98.03% accuracy and 91.84% MCC for the MIT-BIH arrhythmia dataset.


Assuntos
Inteligência Artificial , Processamento de Sinais Assistido por Computador , Humanos , Eletrocardiografia , Algoritmos , Arritmias Cardíacas/diagnóstico , Máquina de Vetores de Suporte , Frequência Cardíaca
8.
Gene Ther ; 31(5-6): 255-262, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38273095

RESUMO

Retinitis pigmentosa (RP) is a heterogeneous disease and the main cause of vision loss within the group of inherited retinal diseases (IRDs). IRDs are a group of rare disorders caused by mutations in one or more of over 280 genes which ultimately result in blindness. Modifier genes play a key role in modulating disease phenotypes, and mutations in them can affect disease outcomes, rate of progression, and severity. Our previous studies have demonstrated that the nuclear hormone receptor 2 family e, member 3 (Nr2e3) gene reduced disease progression and loss of photoreceptor cell layers in RhoP23H-/- mice. This follow up, pharmacology study evaluates a longitudinal NR2E3 dose response in the clinically relevant heterozygous RhoP23H mouse. Reduced retinal degeneration and improved retinal morphology was observed 6 months following treatment evaluating three different NR2E3 doses. Histological and immunohistochemical analysis revealed regions of photoreceptor rescue in the treated retinas of RhoP23H+/- mice. Functional assessment by electroretinogram (ERG) showed attenuated photoreceptor degeneration with all doses. This study demonstrates the effectiveness of different doses of NR2E3 at reducing retinal degeneration and informs dose selection for clinical trials of RhoP23H-associated RP.


Assuntos
Modelos Animais de Doenças , Receptores Nucleares Órfãos , Degeneração Retiniana , Retinose Pigmentar , Animais , Retinose Pigmentar/genética , Retinose Pigmentar/metabolismo , Camundongos , Receptores Nucleares Órfãos/genética , Degeneração Retiniana/genética , Degeneração Retiniana/metabolismo , Degeneração Retiniana/etiologia , Eletrorretinografia , Retina/metabolismo , Retina/patologia , Terapia Genética/métodos
9.
Arch Microbiol ; 206(2): 68, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238530

RESUMO

SARS-CoV-2 has expressively changed its sequences during the COVID-19 pandemic situation by encompassing persistent evolutionary mutational changes resulting in the emergence of many clades and lineages. Evolution of these SARS-CoV-2 variants have significantly imparted fitness advantage to the virus, enhanced its transmissibility and severity of the disease. These new variants are a potential threat to the vaccine efficacy as well. It is therefore pertinent to monitor the evolution of these variants and their epidemiological and clinical impact, in a geographic setting. This study has thus looked into the geographic distribution and genetic diversity of SARS-CoV-2 variants and the evolutionary circulation of different clades in Chhattisgarh (CG) state from March 2020 to July 2023. A total of 3018 sequences were retrieved from the GISAID database, in which 558 were submitted by us. The demographic data revealed male preponderance of 56.45% versus 43.54% females, with the overall mean age of 36.5 years. SARS-CoV-2 sequences represented many variants viz., Delta (55%), Omicron (22%) and others (15%) with a small proportion of recombinant (5%), Kappa (2%), and Alpha (1%). The viral clades G was found predominant for a year from initial days of pandemic in March, 2020 to January, 2021 which then subsequently evoluted to subclade GK (Delta B.1.617.2) and remained in circulation in CG till November, 2021. From December 2021, the GRA (Omicron B.1.1.529) variant had replaced GK to become the dominant strain and continues to predominate in present time. GRA clade is however continuously encompassing new recombinant strains, having various non-synonymous mutations especially in spike protein. The non-synonymous mutation P314L in ORF1b, S84L in ORF8 and D614G in spike protein were found as the pan mutation carried over from clade G to GRA. The continuous evolution in SARS-CoV2 warrants periodical geographic genomic surveillance monitoring to timely detect any new variants having the potential of causing future outbreak.


Assuntos
COVID-19 , SARS-CoV-2 , Feminino , Masculino , Humanos , Adulto , SARS-CoV-2/genética , COVID-19/epidemiologia , Pandemias , RNA Viral , Glicoproteína da Espícula de Coronavírus/genética , Genômica , Índia/epidemiologia , Mutação
10.
J Infect Chemother ; 30(6): 531-535, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38141720

RESUMO

INTRODUCTION: The importance of DNA repair enzymes in maintaining genomic integrity is highlighted by the hypothesis that DNA damage by reactive oxygen/nitrogen species produced inside the host cell is essential for the mutagenesis process. Endonuclease III (Nth), formamidopyrimide (Fpg) and endonuclease VIII (Nei) DNA glycosylases are essential components of the bacterial base excision repair process. Mycobacterium leprae lost both fpg/nei genes during the reductive evolution event and only has the nth (ML2301) gene. This study aims to characterize the mutations in the nth gene of M. leprae strains and explore its correlation with drug-resistance. METHOD: A total of 91 M. leprae positive DNA samples extracted from skin biopsy samples of newly diagnosed leprosy patients from NSCB Hospital Jabalpur were assessed for the nth gene as well as drug resistance-associated loci of the rpoB, gyrA and folP1 genes through PCR followed by Sanger sequencing. RESULTS: Of these 91 patients, a total of two insertion frameshift mutations, two synonymous and seven nonsynonymous mutations were found in nth in seven samples. Sixteen samples were found to be resistant to ofloxacin and one was found to be dapsone resistant as per the known DRDR mutations. No mutations were found in the rpoB region. Interestingly, none of the nth mutations were identified in the drug-resistant associated samples. CONCLUSION: The in-silico structural analysis of the non-synonymous mutations in the Nth predicted five of them were to be deleterious. Our results suggest that the mutations in the nth gene may be potential markers for phylogenetic and epidemiological studies.


Assuntos
Hanseníase , Mycobacterium leprae , Humanos , Mycobacterium leprae/genética , Hansenostáticos/farmacologia , Hansenostáticos/uso terapêutico , Hanseníase/genética , Hanseníase/tratamento farmacológico , Filogenia , Farmacorresistência Bacteriana/genética , Mutação , DNA Bacteriano/genética , Índia , Reparo do DNA/genética
11.
Sci Total Environ ; 912: 169283, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38110096

RESUMO

This study coupled the green water and blue water accounting with the existing standard Budyko framework and Fu's 1-parameter Budyko framework to diagnose the basin hydrological behavior. Both Budyko frameworks were employed to determine green water consumption (ETGreen) and blue water consumption (ETBlue) which, in turn, were used to map the blue water index (BWI) hotspots and green water index (GWI) bright spots. The relative contributions of green water and blue water were quantified for sustaining water and food security. A new methodology is proposed using BWI and GWI for partitioning the Gross Primary Production (GPP) and Water Use Efficiency (WUE) into GPPBlue, GPPGreen and WUEBlue and WUEGreen. The methodology was applied to five sub-basins of the Central Godavari River Basin (CGRB): Purna, Dhalegaon, GR Bridge, Yeli and Delta. Results showed that all five basins exhibited larger deviations from the theoretical Budyko curve of Fu's 1-parameter Budyko framework than did the standard Budyko framework and the Dhalegaon basin showed the largest deviations. The partitioning of GPP and WUE by the proposed methodology showed that the proportion of GPPGreen to the total GPP was much higher than that of the GPPBlue. Similarly, the proportion of WUEGreen to WUE was more than that of WUEBlue. The mapping of GPPBlue and GPPGreen, and WUEBlue and WUEGreen showed that the Delta and Yeli basins had the highest values of both GPPGreen & GPPBlue and WUEBlue and WUEGreen (bright spot basins) and the Dhalegaon and parts of GR Bridge basin had the lowest values (hot spot basins). The proposed partitioning of GPP and WUE will help identify the relative contributions of green water and blue water (for managing agricultural waters) and formulate agronomical and engineering practices for stakeholders and policy makers for increasing the overall WUE and GPP to sustain water and food security.


Assuntos
Hidrologia , Água , Agricultura , Rios , Segurança Alimentar
12.
Front Glob Womens Health ; 4: 1147762, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38099272

RESUMO

Introduction: Globally, 600,000 mothers (15-49 years) die every year due to pregnancy and childbirth-related complications. Wide variations are seen in cultural practices and beliefs surrounding this period of a woman's life. The present study explores the cultural beliefs and practices of women and families during pregnancy and the postnatal period in order to understand what behavioral management strategies are required to improve maternal and infant outcomes during pregnancy and the postpartum period. Methods: The study was conducted in a rural area of Punjab, from December 2019 to March 2021. A total of 20 women (up to 3 months postpartum, age >18 years, were interviewed. Results: In general, women described eating varied and fairly healthy diets during pregnancy, especially nutritious warm food, following traditional practices. Other cultural practices included restrictions on movement and mobile phone use and the use of unsafe home remedies to promote infant safety and wellbeing, such as using gripe water, applying black pencil to the baby's eyes, and feeding the baby honey. A few were not inclined to engage with these and other cultural expectations, preferring instead to follow contemporary practices influenced by social media. These practices included being accompanied by a family member during delivery, celebrating the baby's birth regardless of sex, and early bathing post-delivery. Discussion: It can be concluded that while many traditional practices are still followed in India, there are new beliefs and behaviors arising from an intersection between culture and technology. Developing strategies that acknowledge older beliefs and modern approaches is essential to promoting better antenatal and postpartum care.

13.
Front Public Health ; 11: 1226980, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37920577

RESUMO

Tuberculosis (TB) is a significant public health problem among the Saharia community, an underprivileged tribal group in the west-central part of India. There are several challenges for India's TB control program to curtail TB in the Saharia tribe. Malnutrition, poor health sector facilities, lower socio-economic status, and substance abuse are interconnected and synergistic factors contributing to a high burden of TB in the Saharia tribe. In this review, efforts are made to collate the findings of previous studies discussing the causes of high burden of TB in the Saharia tribe, social gaps for mitigating these preventable risk factors of TB in the Saharia tribe, and the plausible solutions for closing these gaps. The concept of Health in All Policies and intersectoral co-ordination is needed for the reduction of TB in the Saharia tribe and to make India TB-free by the year 2025.


Assuntos
Tuberculose Pulmonar , Tuberculose , Humanos , Grupos Populacionais , Prevalência , Tuberculose/epidemiologia , Fatores de Risco
14.
Res Sq ; 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37790487

RESUMO

Background: Postnatal care, crucial for preventing and assessing complications after birth, remains low in India. An interactive mHealth community-based postnatal intervention was implemented to promote healthy maternal behaviors through knowledge and social support in rural Northern India. However, there is limited information on how virtual health interventions in resource-constrained settings are perceived by the users and which elements influence their engagement and sustained participation. Objective: We explored the user perceptions of acceptability and impact of a virtual interactive maternal and child health intervention pilot tested in Punjab State, India, including their perspectives on barriers and facilitators to engage with this intervention. Methods: This qualitative study was embedded within extensive mixed-method research, and oriented by the Realist Evaluation approach. Sixteen participants were recruited from the parent study. They were identified by purposive sampling to cover diverse levels of attendance and engagement with the intervention. In-depth interviews were conducted by phone. Following translation, a framework analysis was completed to search for the main themes. Feedback was requested from intervention moderators during the process to prioritize local interpretation. Results: Study participants reported overall satisfaction with the intervention. The mothers appreciated the educational material provided and the communication with other participants and health professionals. Across context, intervention, and actor domains, the barriers most commented on were network and connectivity challenges, lack of time due to household responsibilities, and feeling uncomfortable sharing personal experiences. Family buy-in and support were fundamental for overcoming the high domestic workload and baby care. Another facilitator mentioned was moderators' guidance on using the different intervention modalities. Regarding perceived impact, participants shared that MeSSSSage increased their capability and motivation to breastfeed, seek care as needed, and use contraception according to their preferences. Finally, participants suggested adding more topics to the educational content and adjusting the dynamics within the group calls to improve the intervention. Conclusions: This study identifies the high acceptability and perceived impact of a novel postnatal care program in a rural setting, including the users' perceived barriers to engaging with the intervention and possible solutions to overcome them. These findings enable refinement of the ongoing intervention, providing a more robust framing for its scalability and long-term sustainability. On a larger scale, conclusions from this research provide new insights and encouragement to global stakeholders who aspire to improve maternal and neonatal outcomes in low-income and middle-income countries through mHealth.

15.
Front Immunol ; 14: 1209513, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37849762

RESUMO

The SARS-CoV-2 omicron variants keep accumulating a large number of mutations in the spike (S) protein, which contributes to greater transmissibility and a rapid rise to dominance within populations. The identification of mutations and their affinity to the cellular angiotensin-converting enzyme-2 (ACE-2) receptor and immune evasion in the Delhi NCR region was under-acknowledged. The study identifies some mutations (Y505 reversion, G339H, and R346T/N) in genomes from Delhi, India, and their probable implications for altering the immune response and binding affinity for ACE-2. The spike mutations have influenced the neutralizing activity of antibodies against the omicron variant, which shows partial immune escape. However, researchers are currently exploring various mitigation strategies to tackle the potential decline in efficacy or effectiveness against existing and future variants of SARS-CoV-2. These strategies include modifying vaccines to target specific variants, such as the omicron variant, developing multivalent vaccine formulations, and exploring alternative delivery methods. To address this, it is also necessary to understand the impact of these mutations from a different perspective, especially in terms of alterations in antigenic determinants. In this study, we have done whole genome sequencing (WGS) of SARS-CoV-2 in COVID-19 samples from Delhi, NCR, and analyzed the spike's mutation with an emphasis on antigenic alterations. The impact of mutation in terms of epitope formation, loss/gain of efficiency, and interaction of epitopes with antibodies has been studied. Some of the mutations or variant genomes seem to be the progenitors of the upcoming variants in India. Our analyses suggested that weakening interactions with antibodies may lead to immune resistance in the circulating genomes.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , COVID-19/genética , Anticorpos , Epitopos , Índia/epidemiologia , Glicoproteínas
16.
Diagn Microbiol Infect Dis ; 107(4): 116084, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37832201

RESUMO

Mycobacterium leprae is classified into four SNP genotypes and 16 subtypes (from 1A to 4P) that exhibit phylogeographical association reported from around the world. Among them, genotypes 1D and 3I represent more than 60% of M. leprae strains. Here, we report a new method for M. leprae genotyping which identifies the genotypes 1D and 3I by combining multiplex PCR amplification and restriction fragment length polymorphism (RFLP) of a M. leprae DNA amplicons using AgeI restriction enzyme. Agarose gel electrophoresis showed a deletion of 11 bp only among 3I genotypes by electrophoresis. When this multiplex PCR reaction is subjected to AgeI digestion, successful restriction digestion shows three bands for all the genotypes except 1D where only two bands were observed due to loss of restriction site. This method gives us the advantage of 1-step identification of the two most prevalent strains of M. leprae without using specialized equipments such as the Sanger sequencing system or quantitative PCR.


Assuntos
Reação em Cadeia da Polimerase Multiplex , Mycobacterium leprae , Humanos , Mycobacterium leprae/genética , Polimorfismo de Fragmento de Restrição , Genótipo , Sequência de Bases , DNA Bacteriano/genética
17.
Antibiotics (Basel) ; 12(3)2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36978316

RESUMO

Klebsiella pneumoniae (Kp) has gained prominence in the last two decades due to its global spread as a multidrug-resistant (MDR) pathogen. Further, carbapenem-resistant Kp are emerging at an alarming rate. The objective of this study was (1) to evaluate the prevalence of ß-lactamases, especially carbapenemases, in Kp isolates from India, and (2) determine the most prevalent sequence type (ST) and plasmids, and their association with ß-lactamases. Clinical samples of K. pneumoniae (n = 65) were collected from various pathology labs, and drug susceptibility and minimum inhibitory concentrations (MIC) were detected. Whole genome sequencing (WGS) was performed for n = 22 resistant isolates, including multidrug-resistant (MDR) (n = 4), extensively drug-resistant (XDR) (n = 15), and pandrug-resistant (PDR) (n = 3) categories, and genomic analysis was performed using various bioinformatics tools. Additional Indian MDRKp genomes (n = 187) were retrieved using the Pathosystems Resource Integration Center (PATRIC) database. Detection of ß-lactamase genes, location (on chromosome or plasmid), plasmid replicons, and ST of genomes was carried out using CARD, mlplasmids, PlasmidFinder, and PubMLST, respectively. All data were analyzed and summarized using the iTOL tool. ST231 was highest, followed by ST147, ST2096, and ST14, among Indian isolates. blaampH was detected as the most prevalent gene, followed by blaCTX-M-15 and blaTEM-1. Among carbapenemase genes, blaOXA-232 was prevalent and associated with ST231, ST2096, and ST14, which was followed by blaNDM-5, which was observed to be prevalent in ST147, ST395, and ST437. ST231 genomes were most commonly found to carry Col440I and ColKP3 plasmids. ST16 carried mainly ColKP3, and Col(BS512) was abundantly present in ST147 genomes. One Kp isolate with a novel MLST profile was identified, which carried blaCTX-M-15, blaOXA-1, and blaTEM-1. ST16 and ST14 are mostly dual-producers of carbapenem and ESBL genes and could be emerging high-risk clones in India.

18.
Biomed Phys Eng Express ; 9(3)2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36796085

RESUMO

Purpose. Films and TLDs have been the common choices for passivein-vivodose measurement in radiotherapy. In the brachytherapy applications, it is very difficult to report and verify the dose at multiple localized high dose gradient regions and also the dose to organ at risk. This study was carried out to introduce a new and accurate calibration method for GafChromic EBT3 films irradiated using Ir-192 photon energy from miniature High Dose Rate (HDR) Brachytherapy source.Materials and methods. Film holder made of Styrofoam was used to hold the EBT3 film at its center. It was placed inside the mini water phantom and the films were irradiated by Ir-192 source of microSelectron HDR afterloading brachytherapy system. Two different setups: Single catheter-based film exposure and dual catheter-based film exposure were compared. The films scanned on a flatbed scanner were analysed in three different color channels: red, green, and blue using Image J software. The dose calibration graphs were generated using the third-order polynomial equations fitted on the data points from two different methods of calibration procedure. Maximum and mean dose difference between TPS calculated and measured was analyzed.Results. The measured dose difference from the TPS calculated doses were evaluated for the three groups of dose ranges (low, medium and high). In the high dose range, standard uncertainty of dose difference are ±2.3%, ±2.9%, and ±2.4% respectively for the red, green, and blue color channel when the TPS calculated dose was compared with single catheter based film calibration equation. Whereas it is observed as 1.3%, 1.4% and 3.1% for the red, green, and blue color channels respectively when compared with the dual catheter based film calibration equation. A test film was exposed to a TPS calculated dose of 666 cGy to validate the calibration equations, single catheter based film calibration equation estimated the dose difference as -9.2%, -7.8% and -3.6% respectively in the red, green, and blue color channels whereas the same were observed as 0.1%, 0.2% and 6.1% respectively when dual catheter based film calibration equation was applied.Conclusion.Source miniature size, reproducible positioning of the film and catheter system inside water medium are the major challenges in the film calibration with Ir-192 beam. To overcome these situations dual catheter-based film calibration was found more accurate and reproducible as compare to the single catheter based film calibration.


Assuntos
Dosimetria Fotográfica , Radioisótopos de Irídio , Calibragem , Dosimetria Fotográfica/métodos , Catéteres , Água
19.
J Biomol Struct Dyn ; 41(14): 6866-6882, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35980746

RESUMO

SARS-CoV-2, the causing agent of coronavirus disease (COVID-19), first broke out in Wuhan and rapidly spread worldwide, resulting in a global health emergency. The lack of specific drugs against the coronavirus has made its spread challenging to control. The main protease (Mpro) is a key enzyme of SARS-CoV-2 used as a key target in drug discovery against the coronavirus. Medicines derived from plant phytoconstituents have been widely exploited to treat various diseases. The present study has evaluated the potential of Illicium verum (star anise) phytoconstituents against Mpro by implementing a computational approach. We performed molecular docking and molecular dynamics simulation study with a set of 60 compounds to identify their potential to inhibit the main protease (Mpro) of SARS-CoV-2. DFT study and post dynamics free energy calculations were also performed to strengthen the findings. The identified four compounds by docking study exhibited the highest potential compared to other selected phytoconstituents. Further, density functional theory (DFT) calculation, molecular dynamics simulation and post dynamics MM-GBSA energy calculation predicted Verimol-G as a potential compound, which formed stable interactions through the catalytic dyad residues. The HOMO orbital energy (-0.250038) from DFT and the post dynamics binding free energy calculation (-73.33 Kcal/mol) correlate, suggesting Verimol-G is the best inhibitor compared to the other phytoconstituents. This compound also complies with the ADME properties of drug likeliness. Thus, based on a computational study, we suggest that Verimol G may be developed as a potential inhibitor against the main protease to combat COVID-19.Communicated by Ramaswamy H. Sarma.

20.
Res Sq ; 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38196635

RESUMO

Background: Significant disruptions in the perinatal continuum of care occur postpartum in India, despite it being a critical time to optimize maternal health and wellbeing. Group-oriented mHealth approaches may help mitigate the impact of limited access to care and the lack of social support that characterize this period. Our team developed and pilot tested a provider-moderated group intervention to increase education, communication with providers, to refer participants to in-person care, and to connect them with a virtual social support group of other mothers with similarly aged infants through weekly calls and text chat. Methods: We analyzed the preliminary effectiveness of the pilot intervention on maternal health knowledge through 6 months postpartum among 135 participants in Punjab, India who responded to baseline and endline surveys. We described change in knowledge of maternal danger signs, birth preparedness, postpartum care use, postpartum physical and mental health, and family planning use over time between individuals in group call (synchronous), other intervention (asynchronous), and control groups. Results: Participant knowledge regarding danger signs was low overall regarding pregnancy, childbirth and the postpartum period (mean range of 1.13 to 2.05 at baseline and 0.79 to 2.10 at endline). Group call participants had a significantly higher increase over time in knowledge of danger signs than other intervention and control group participants. Birth preparedness knowledge ranged from mean 0.89-1.20 at baseline to 1.31-2.07 at baseline, with group call participants having significantly greater increases in comparison to the control group. Group call participants had nearly three-fold increased odds of postpartum health check with a clinical provider than other intervention participants (OR 2.88, 95% CI 1.07-7.74). No differences were noted in postpartum depressive and anxiety symptoms. Conclusions: Preliminary effectiveness results are promising, yet further robust testing of the MeSSSSage intervention effectiveness is needed. Further development of strategies to support health knowledge and behaviors and overcoming barriers to postpartum care access can improve maternal health among this population.

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