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The Kirsten rat sarcoma viral (KRAS) oncogene is the most frequently mutated isoform of RAS, associated with 85 % of RAS-driven cancers. KRAS functions as a signaling hub, participating in various cellular signaling pathways and regulating a wide range of important activities, including cell proliferation, differentiation, growth, metabolism, and migration. Despite being the most frequently altered oncogenic protein in solid tumors, over the past four decades, KRAS has historically been considered "undruggable" owing to a lack of pharmacologically targetable pockets within the mutant isoforms. However, improvements in drug design and development have culminated in the development of selective inhibitors for KRAS mutants. Recent developments have led to the successful targeting of the KRASG12C mutant through covalent inhibitors that exploit the unique cysteine residue introduced by the mutation at 12th position. These inhibitors bind covalently to C12, locking KRAS in its inactive GDP-bound state and preventing downstream signaling. Some of these inhibitors have shown encouraging results in KRASG12C mutant cancer patients but suffer from drug resistance, toxicity, and low therapeutic efficacy. Recently, there have been great advancements in the discovery of drugs that directly target the switch I (S-I), switch-II (S-II) and S-I/II interface sites of KRAS mutant proteins. These include KRASG12C inhibitors like AMG510 (Sotorasib) and MRTX849 (Adagrasib), which have got FDA approval for non-small cell lung cancer harboring the KRASG12C mutation. There is no approved drug for cancers harboring other KRAS mutations, although efforts have expanded to target other KRAS mutations and the Switch I/II interface, aiming to disrupt KRAS-driven oncogenic signaling. Structure-activity relationship (SAR) studies have been instrumental in optimizing the binding affinity, selectivity, and pharmacokinetic properties of these inhibitors, leading to the development of promising therapeutic agents like Sotorasib and Adagrasib. This review provides an overview of the KRAS pathway, KRAS binding sites, strategies for direct and indirect inhibition using small molecules, and SAR based on the co-crystal structures of inhibitors with KRAS mutants which is expected to offer new hope for patients with KRAS-driven cancers through the development of new KRAS-targeted drugs.
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Triple-negative breast cancer (TNBC) is an aggressive subtype accounting for ~10-20% of all human BC and is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) amplification. Owing to its unique molecular profile and limited targeted therapies, TNBC treatment poses significant challenges. Unlike other BC subtypes, TNBC lacks specific molecular targets, rendering endocrine therapies and HER2-targeted treatments ineffective. The chemotherapeutic regimen is the predominant systemic treatment modality for TNBC in current clinical practice. However, the efficacy of chemotherapy in TNBC is variable, with response rates varying between a wide range of patients, and the emerging resistance further adds to the difficulties. Furthermore, TNBC exhibits a higher mutational burden and is acknowledged as the most immunogenic of all BC subtypes. Consequently, the application of immune checkpoint inhibition has been investigated in TNBC, yielding promising outcomes. Recent evidence identified extracellular vesicles (EVs) as an important contributor in the context of TNBC immunotherapy. In view of the extraordinary ability of EVs to transfer bioactive molecules, such as proteins, lipids, DNA, mRNAs, and small miRNAs, between the cells, EVs are considered a promising diagnostic biomarker and novel drug delivery system among the prospects for immunotherapy. The present review provides an in-depth understanding of how EVs influence TNBC progression, its immune regulation, and their contribution as a predictive biomarker for TNBC. The final part of the review focuses on the recent key advances in immunotherapeutic strategies for better understanding the complex interplay between EVs and the immune system in TNBC and further developing EV-based targeted immunotherapies.
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BACKGROUND: Overweight and obesity among school-going children is an emerging public health problem in the country. The information available on the true extent of obesity and overweight among school-aged children is limited. Hence, the present study has been conducted to determine the prevalence of overweight and obesity among high school students in Jharkhand, India. METHODOLOGY: This was a cross-sectional study conducted among 1162 students of government and private schools of Ormanjhi block, Ranchi district, from July 2022 to December 2022. A predesigned, semi-structured, pre-tested questionnaire containing different sections namely sociodemographic characteristics, and health parameters were used for the study subjects. Clinical examination and anthropometric measurements of height, weight, and waist and hip circumferences were taken using standard equipment to calculate body mass index (BMI) and central obesity (waist-hip ratio). RESULTS: The prevalence of overweight and obesity was more at 14 years of age (30.2%), among boys (18.1%), and among students practicing the Islam religion (51.1%). Moreover, the prevalence of overweight and obesity was found to be highest in private schools (66.2%), and that was statistically significant (p<0.001). CONCLUSION: The prevalence of overweight and obesity was found to be significant with respect to age, gender, and religion. The findings from this study would be helpful in raising awareness among students, parents, teachers, and health professionals about the influence of overweight and obesity on a child's physical, social, and psychological well-being, and this, in turn, would facilitate parents, students, and teachers in the adoption of a healthy lifestyle.
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Globally, polycyclic aromatic hydrocarbons (PAHs) pollution is primarily driven by their release into the air through various combustion processes, including burning fossil fuels such as coal, oil, and gas in motor vehicles, power plants, and industries, as well as burning organic matter like wood, tobacco, and food in fireplaces, cigarettes, and grills. Apart from anthropogenic pollution sources, PAHs also occur naturally in crude oil, and their potential release during oil extraction, refining processes, and combustion further contributes to contamination and pollution concerns. PAHs are resistant and persistent in the environment because of their inherent features, viz., heterocyclic aromatic ring configurations, hydrophobicity, and thermostability. A wide range of microorganisms have been found to be effective degraders of these recalcitrant contaminants. The presence of hydrocarbons as a result of numerous anthropogenic activities is one of the primary environmental concerns. PAHs are found in soil, water, and the air, making them ubiquitous in nature. The presence of PAHs in the environment creates a problem, as their presence has a detrimental effect on humans and animals. For a variety of life forms, PAH pollutants are reported to be toxic, carcinogenic, mutation-inducing, teratogenic, and immune toxicogenics. Degradation of PAHs via biological activity is an extensively used approach in which diverse microorganisms (fungal, algal, clitellate, and protozoan) and plant species and their derived composites are utilized as biocatalysts and biosurfactants. Some microbes have the ability to transform and degrade these PAHs, allowing them to be removed from the environment. The goal of this review is to provide a critical overview of the existing understanding of PAH biodegradation. It also examines current advances in diverse methodologies for PAH degradation in order to shed light on fundamental challenges and future potential.
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Contaminantes Ambientales , Hidrocarburos Policíclicos Aromáticos , Humanos , Animales , Hidrocarburos Policíclicos Aromáticos/análisis , Contaminación Ambiental , Suelo , Percepción , Monitoreo del Ambiente/métodosRESUMEN
Background The Indian state of Jharkhand has the highest rate of wasting (29%) among young children. Mobile audio call follow-up can be used to assess such children with severe acute malnutrition (SAM). Aim This study evaluated SAM children during the COVID-19 outbreak and learn more about the status of their home/community care, and caregivers' awareness of integrated child development services (ICDS) and COVID-19 prevention. Methods Contact numbers of caregivers for discharged children were obtained from 54 malnutrition treatment centers (MTCs). In April and June 2020, mentors conducted follow-up interviews using mobile phone calls. Results Seven children (1.72%) were reported dead and 400 were alive, mostly girls (59.5%). Only a few caregivers observed post-discharge ailments (15.4%) and weight loss (7.7%) in their children. Children aged six to 24 months were characterized by continued breastfeeding (88.0%) at most five to six times a day (45.8%). Most of the children were not fed as per maternal infant and young child feeding protocols. Age in months with an adjusted odds ratio (OR) of 0.55 (1.00-1.11) as a 95% confidence interval (CI), age category, with an adjusted OR of 4.32 (1.71- 10.94) as 95% CI, and breastfeeding with adjusted OR 1.85 (1.07- 3.21) as 95% CI were three major predictors for a well-fed child. Conclusion Community involvement is crucial in the follow-up of children with SAM for effective rehabilitation. Mobile phone audio call follow-up is a relatively cost-effective approach to tackle geographic barriers and COVID-19 lockdown-induced situations. There are major gaps mainly in informing caregivers on how to manage COVID-19 with breastfeeding.
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Introduction: The harmful use of alcohol is increasing at a huge pace leading to the occurrence of multiple diseases and has become a leading risk factor for global burden of diseases. Aims and Objectives: The aim of this study is to assess the health profile of adult women and to find out the medical and social effects of alcohol consumption. Methodology: A cross-sectional study was conducted in the rural field practice area, Ormanjhi of RIMS, Ranchi, for a duration of 27 months (September 2016 to November 2018) among 336 women by multistage random sampling. A pretested semi-structured questionnaire was used for data collection. Templates were generated in MS Excel sheet and analysis of data was done using SPSS software (20.0). Results: The mean BMI of the study subjects was 21.62 ± 3.33 kg/m2. Anaemia was present in 42.6% of the women, 10.4% women were hypertensive and 9.2% were suffering from diabetes. The association between alcohol consumption and occurrence of co-morbidities was found insignificant. The social effects of alcoholism varied ranging from going into debts seen in 35.42% of the women; 62.5% of the women were criticised about their drinking habit by relatives or children. About 9.5% of the women were found to consume alcohol during their last pregnancy, and among women who were on regular intake of alcohol even during pregnancy, majority (65.62%) of them delivered by normal vaginal delivery. Conclusion: Alcohol consumption among females caused several adverse social consequences without any significant effect on health.
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The past several decades have witnessed the emergence and re-emergence of many infectious viral agents, flaviviruses, influenza, filoviruses, alphaviruses, and coronaviruses since the advent of human deficiency virus (HIV). Some of them even become serious threats to public health and have raised major global health concerns. Several different medicinal compounds such as anti-viral, anti-malarial, and anti-inflammatory agents, are under investigation for the treatment of these viral diseases. These therapies are effective improving recovery rates and overall survival of patients but are unable to heal lung damage caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, there is a critical need to identify effective treatments to combat this unmet clinical need. Due to its antioxidant and immunomodulatory properties, stem cell therapy is considered a novel approach to regenerate damaged lungs and reduce inflammation. Stem cell therapy uses a heterogeneous subset of regenerative cells that can be harvested from various adult tissue types and is gaining popularity due to its prodigious regenerative potential as well as immunomodulatory and anti-inflammatory properties. These cells retain expression of cluster of differentiation markers (CD markers), interferon-stimulated gene (ISG), reduce expression of pro-inflammatory cytokines and, show a rapid proliferation rate, which makes them an attractive tool for cellular therapies and to treat various inflammatory and viral-induced injuries. By examining various clinical studies, this review demonstrates positive considerations for the implications of stem cell therapy and presents a necessary approach for treating virally induced infections in patients.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/terapia , Interferones , Pulmón , Trasplante de Células MadreRESUMEN
There is increasing evidence suggesting the role of microbiome alterations in relation to pancreatic adenocarcinoma and tumor immune functionality. However, molecular mechanisms of the interplay between microbiome signatures and/or their metabolites in pancreatic tumor immunosurveillance are not well understood. We have identified that a probiotic strain (Lactobacillus casei) derived siderophore (ferrichrome) efficiently reprograms tumor-associated macrophages (TAMs) and increases CD8 + T cell infiltration into tumors that paralleled a marked reduction in tumor burden in a syngeneic mouse model of pancreatic cancer. Interestingly, this altered immune response improved anti-PD-L1 therapy that suggests promise of a novel combination (ferrichrome and immune checkpoint inhibitors) therapy for pancreatic cancer treatment. Mechanistically, ferrichrome induced TAMs polarization via activation of the TLR4 pathway that represses the expression of iron export protein ferroportin (FPN1) in macrophages. This study describes a novel probiotic based molecular mechanism that can effectively induce anti-tumor immunosurveillance and improve immune checkpoint inhibitors therapy response in pancreatic cancer.
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Adenocarcinoma , Neoplasias Pancreáticas , Probióticos , Ratones , Animales , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/metabolismo , Adenocarcinoma/metabolismo , Sideróforos , Microambiente Tumoral , Ferricromo/uso terapéutico , Monitorización Inmunológica , Inhibidores de Puntos de Control Inmunológico , Probióticos/farmacología , Neoplasias PancreáticasRESUMEN
Cervical cancer (CC) is a preventable disease using proven interventions, specifically prophylactic vaccination, pervasive disease screening, and treatment, but it is still the most frequently diagnosed cancer in women worldwide. Patients with advanced or metastatic CC have a very dismal prognosis and current therapeutic options are very limited. Therefore, understanding the mechanism of metastasis and discovering new therapeutic targets are crucial. New sequencing tools have given a full visualization of the human transcriptome's composition. Non-coding RNAs (NcRNAs) perform various functions in transcriptional, translational, and post-translational processes through their interactions with proteins, RNA, and even DNA. It has been suggested that ncRNAs act as key regulators of a variety of biological processes, with their expression being tightly controlled under physiological settings. In recent years, and notably in the past decade, significant effort has been made to examine the role of ncRNAs in a variety of human diseases, including cancer. Therefore, shedding light on the functions of ncRNA will aid in our better understanding of CC. In this review, we summarize the emerging roles of ncRNAs in progression, metastasis, therapeutics, chemo-resistance, human papillomavirus (HPV) regulation, metabolic reprogramming, diagnosis, and as a prognostic biomarker of CC. We also discussed the role of ncRNA in the tumor microenvironment and tumor immunology, including cancer stem cells (CSCs) in CC. We also address contemporary technologies such as antisense oligonucleotides, CRISPR-Cas9, and exosomes, as well as their potential applications in targeting ncRNAs to manage CC.
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Exosomas , Neoplasias del Cuello Uterino , Exosomas/genética , Exosomas/metabolismo , Femenino , Humanos , Células Madre Neoplásicas/metabolismo , Pronóstico , ARN no Traducido/genética , ARN no Traducido/metabolismo , Microambiente Tumoral , Neoplasias del Cuello Uterino/genéticaRESUMEN
A multicentric study is being conducted in which children with severe acute malnutrition (SAM) aged 6-59 months are identified with only weight-for-height z-score (WHZ) < - 3 criteria. The present study aimed to assess associations of anthropometric parameters and body composition parameters, to improve treatment of SAM. We conducted a cross-section assessment using the enrolment data of children who participated in a multi-centric longitudinal controlled study from five Indian states. Fat-free mass (FFM) and fat mass (FM) were determined by bio-electrical impedance analysis (BIA). Six hundred fifty-nine children were enrolled in the study using WHZ < -3 criteria. Available data shows that WHZ, WAZ and BMIZ were significantly associated with FFMI while MUACZ was significantly associated with both FMI and FFMI. Children with both severe wasting and severe stunting had significantly lower FFMI compared to those who were only severely wasted. All forms of anthropometric deficits appear to adversely impact FFM and FM.Trial registrationThe study is registered with Clinical Trial Registration of India (Registration No.: CTRI/2020/09/028013 dated 24/09/2020).
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Chemotherapy is one of the prime treatment options for cancer. However, the key issues with traditional chemotherapy are recurrence of cancer, development of resistance to chemotherapeutic agents, affordability, late-stage detection, serious health consequences, and inaccessibility. Hence, there is an urgent need to find innovative and cost-effective therapies that can target multiple gene products with minimal adverse reactions. Natural phytochemicals originating from plants constitute a significant proportion of the possible therapeutic agents. In this article, we reviewed the advances and the potential of Withania somnifera (WS) as an anticancer and immunomodulatory molecule. Several preclinical studies have shown the potential of WS to prevent or slow the progression of cancer originating from various organs such as the liver, cervix, breast, brain, colon, skin, lung, and prostate. WS extracts act via various pathways and provide optimum effectiveness against drug resistance in cancer. However, stability, bioavailability, and target specificity are major obstacles in combination therapy and have limited their application. The novel nanotechnology approaches enable solubility, stability, absorption, protection from premature degradation in the body, and increased circulation time and invariably results in a high differential uptake efficiency in the phytochemical's target cells. The present review primarily emphasizes the insights of WS source, chemistry, and the molecular pathways involved in tumor regression, as well as developments achieved in the delivery of WS for cancer therapy using nanotechnology. This review substantiates WS as a potential immunomodulatory, anticancer, and chemopreventive agent and highlights its potential use in cancer treatment.
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BACKGROUND: The Breast Health Initiative (BHI) was launched to demonstrate a scalable model to improve access to early diagnosis and treatment of breast cancer. METHODS: A package of evidence-based interventions was codesigned and implemented with the stakeholders, as part of the national noncommunicable disease program, through the existing primary health care system. Data from the first 18 months of the BHI are presented. RESULTS: A total of 108,112 women received breast health education; 48% visited the health facilities for clinical breast examination (CBE), 3% had a positive CBE result, and 41% were referred to a diagnostic facility. The concordance of CBE findings between health care providers and adherence to follow-up care improved considerably, with more women visiting the diagnostic facilities and completing diagnostic evaluation within 1 month from initial screening, and with only 9% lost to follow-up. The authors observed a clinically meaningful decrease in time to complete diagnostic evaluation with biopsy, from 37 to 9 days. CONCLUSIONS: The results demonstrate the feasibility and effectiveness of implementing a large-scale, decentralized breast cancer early detection program delivered through the existing primary health care system in India.
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Neoplasias de la Mama , Detección Precoz del Cáncer , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/terapia , Femenino , Educación en Salud , Humanos , India/epidemiología , Tamizaje Masivo/métodos , Derivación y ConsultaRESUMEN
Background: The first 1000 days of life is a unique window of opportunity when the foundation of overall optimum health and neurodevelopmental growth across the lifespan is established. Objective: To explore the level of knowledge and practice of service providers in delivering maternal, infant, and young child nutrition (MIYCN) services at the point of care. Methodology: This was a cross-sectional study done in the department of Obstetrics and Gynecology and Pediatrics of RIMS, Ranchi, Jharkhand from May to September 2019. Result: The practices and counseling skills of nursing staff pertaining to maternal nutrition interventions like IFA and calcium supplements was good. Though counseling on maternal minimum dietary diversity, frequency, and quantity of meals was done during the antenatal care period, its knowledge and expected total weight gain during pregnancy were suboptimal. The practice of early initiation of breastfeeding was significantly higher in those who delivered normally (79%) than those by cesarean section (7%). The nursing staff's knowledge and technical skills on early initiation and exclusive breastfeeding were good, but inadequate for cesarean section. Forty-one percentage of recently delivered women were counseled on colostrum feeding, 17% about positioning and attachment, and 38% on exclusive breastfeeding (EBF) during the first 6 months. In the pediatrics OPD and immunization clinic, 93% of mothers with an infant below 6 months of age, received counseling on EBF, 47% on feeding during illness, and 13% on breastfeeding difficulties and their solutions. Sixty percentage of mothers of children >6 months old received counseling on timely introduction of complementary feeding and 40% on minimum dietary diversity. Forty percentage of mothers were counseled on feeding techniques during and after illness. Conclusion: The nursing staffs were providing the services related to MIYCN during antenatal, intranatal, and postnatal services, sick child visits, and immunization visits but their technical knowledge and skills on the specific components were not in accordance with the standard guidelines.
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Gastrointestinal (GI) cancers are one of the leading causes of death worldwide. Although various approaches are implemented to improve the health condition of GI patients, none of the treatment protocols promise for eradicating cancer. However, a treatment mechanism against any kind of disease condition is already existing executing inside the human body. The 'immune system' is highly efficient to detect and destroy the unfavorable events of the body including tumor cells. The immune system can restrict the growth and proliferation of cancer. Cancer cells behave much smarter and adopt new mechanisms for hiding from the immune cells. Thus, cancer immunotherapy might play a decisive role to train the immune system against cancer. In this review, we have discussed the immunotherapy permitted for the treatment of GI cancers. We have discussed various methods and mechanisms, periodic development of cancer immunotherapies, approved biologicals, completed and ongoing clinical trials, role of various biopharmaceuticals, and epigenetic factors involved in GI cancer immunotherapies.
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Neoplasias Gastrointestinales , Inmunoterapia , Neoplasias Gastrointestinales/terapia , Humanos , Factores Inmunológicos , Inmunoterapia/métodosRESUMEN
The G-quadruplexes (G4s) are a class of DNA secondary structures with guanine rich DNA sequences that can fold into four stranded non-canonical structures. At the genomic level, their pivotal role is well established in DNA replication, telomerase functions, constitution of topologically associating domains, and the regulation of gene expression. Genome instability mediated by altered G4 formation and assembly has been associated with multiple disorders including cancers and neurodegenerative disorders. Multiple tools have also been developed to predict the potential G4 regions in genomes and the whole genome G4 maps are also being derived through sequencing approaches. Enrichment of G4s in the cis-regulatory elements of genes associated with tumorigenesis has accelerated the quest for identification of G4-DNA binding ligands (G4DBLs) that can selectively bind and regulate the expression of such specific genes. In this context, the analysis of G4DBL responsive transcriptome in diverse cancer cell lines is inevitable for assessment of the specificity of novel G4DBLs. Towards this, we assembled the transcripts differentially regulated by different G4DBLs and have also identified a core set of genes regulated in diverse cancer cell lines in response to 3 or more of these ligands. With the mode of action of G4DBLs towards topology shifts, folding, or disruption of G4 structure being currently visualized, we believe that this dataset will serve as a platform for assembly of G4DBL responsive transcriptome for comparative analysis of G4DBLs in multiple cancer cells based on the expression of specific cis-regulatory G4 associated genes in the future.
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Marburg, a RNA virus (MRV), is responsible for causing hemorrhagic fever that affects humans and non-human primates. World Health Organization (WHO), National Institutes of Health (NIH) and Centre of Disease Control and Prevention (CDC) considered this as an extremely dangerous virus, thus categorised as risk group 4, category A priority pathogen and category "A" bioterrorism agent, respectively. Despite of all these alarming concerns, no prophylaxis arrangements are available against this virus till date. In fact, the construction of immunogenic vaccine candidates by traditional molecular immunology methods is time consuming and very expensive. Considering these concerns, herein, we have designed CD4 + T Cell multiepitopes against MRV using in silico approach. The pin-point criteria of the screening and selection of potential epitopes are, non-mutagenic, antigenic, large HLAs coverage, non-toxic and high world population coverage. This kind of methodology and investigations can precisely reduce the expenditure and valuable time for experimental planning in development of vaccines in laboratories. In current scenario, researchers are frequently using in silico approaches to speed up their vaccine-based lab studies. The computational studies are highly valuable for the screening of large epitope dataset into smaller one prior to in vitro and in vivo confirmatory analyses.
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BACKGROUND: Severe acute malnutrition (SAM) is a major underlying cause of mortality among children. Around one third of the world's acutely malnourished children live in India. The WHO recommends community-based management of acute malnutrition (CMAM) for managing children with SAM. In India, different states are implementing community-based SAM treatment programme, hereinafter called CSAM, using varieties of locally produced nutrient dense food items with different nutrient compositions. The study will assess the effectiveness of these state specific CSAM interventions. METHODS: The longitudinal quasi-experimental study will be undertaken in two purposively selected blocks of one district each in the four intervention states and one comparison state. From each state, 200 SAM children identified using weight-for-length/height z-score (WHZ) < - 3 criteria will be enrolled in the study. Their anthropometric data and skinfold thickness will be taken on admission, at sixth week and at discharge by trained field investigators. Other child details, incidence of morbidity and socio-economic details will be collected on admission. To assess food consumption pattern including consumption of locally produced nutrient dense food supplements, dietary assessment, using 24-h dietary recall will be conducted on admission, at sixth week and at discharge. In addition, body composition parameters will be assessed for a sub-set of children using bio-electrical impedance analysis on admission and at discharge to analyse changes in total body water, fat-free mass, and fat mass. Post discharge, all study participants will be followed up monthly until 6 months. Atleast 10% of the sample will be checked for quality assessment. The study's primary outcome is cure rate defined as children attaining WHZ ≥ -2. Secondary outcomes include mean weight gain, mean length of stay, body composition parameters, relapse and mortality rates. Additionally, process evaluation and cost effectiveness analysis will be conducted. DISCUSSION: There is a shortage of robust evidence regarding the effectiveness of locally produced nutrient dense food supplements provided as part of the CSAM intervention in India. This study will contribute to evidence on effective strategies to manage children with uncomplicated SAM in India. The study protocol has all necessary ethical approvals. Written informed consent will be obtained from caregivers of the children. TRIAL REGISTRATION: The study is registered with Clinical Trial Registration of India (Registration No.: CTRI/2020/09/028013 ) Date of registration 24/09/2020.
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In India, the tribal population constitutes almost 8.6% of the nation's total population. Despite their large presence, there are only a few reports available on Mycobacterium tuberculosis (M. tb) strain prevalence in Indian tribal communities considering the mobile nature of this population and also the influence of the mainstream populations they coexist within many areas for their livelihood. This study attempts to provide critical information pertaining to the TB strain diversity, its public health implications, and distribution among the tribal population in eleven Indian states and Andaman & Nicobar (A&N) Island. The study employed a population-based molecular approach. Clinical isolates were received from 66 villages (10 states and Island) and these villages were selected by implying situation analysis. A total of 78 M. tb clinical isolates were received from 10 different states and A&N Island. Among these, 16 different strains were observed by spoligotyping technique. The major M. tb strains spoligotype belong to the Beijing, CAS1_DELHI, and EAI5 family of M. tb strains followed by EAI1_SOM, EAI6_BGD1, LAM3, LAM6, LAM9, T1, T2, U strains. Drug-susceptibility testing (DST) results showed almost 15.4% of clinical isolates found to be resistant to isoniazid (INH) or rifampicin (RMP) + INH. Predominant multidrug-resistant (MDR-TB) isolates seem to be Beijing strain. Beijing, CAS1_DELHI, EAI3_IND, and EAI5 were the principal strains infecting mixed tribal populations across India. Despite the small sample size, this study has demonstrated higher diversity among the TB strains with significant MDR-TB findings. Prevalence of Beijing MDR-TB strains in Central, Southern, Eastern India and A&N Island indicates the transmission of the TB strains.
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Etnicidad , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/genética , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/microbiología , Antituberculosos/farmacología , Proteínas Bacterianas/genética , Técnicas de Tipificación Bacteriana , ARN Polimerasas Dirigidas por ADN/genética , Farmacorresistencia Bacteriana , Farmacorresistencia Bacteriana Múltiple , Femenino , Genes Bacterianos , Humanos , India/epidemiología , Islas , Masculino , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Filogenia , Prevalencia , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/microbiologíaRESUMEN
Background Early initiation of breastfeeding (EIBF) is one of the most important predictors for the survival of a child, spacing between two children, and prevention from childhood infections. Breastfeeding plays an important role in reducing child mortality and morbidity but the practice of EIBF globally is way behind the required time for initiation of breastfeeding after delivery. So, we planned to evaluate the early time of initiation of breastfeeding among the postnatal mothers and to determine the predictors of early initiation of breastfeeding in a tertiary hospital setting. Methodology A hospital-based cross-sectional study was conducted in the postnatal ward of Rajendra Institute of Medical Sciences (RIMS), Ranchi, Jharkhand for a period of three months (March-May 2017). Our study included 200 postnatal mothers who delivered normal and healthy babies. Mother-infant dyads enrolled in our study were interviewed personally during six hours of the postpartum period. Irrespective of the mode of delivery, all babies born during the study period whose mothers consented to be a part of the study were included. Data collected were entered in MS Excel and analyzed using IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp. Results A total of 200 postnatal mothers fulfilling the study criteria were enrolled during the study. Of them, the majority 98 (49%) belonged to the age group 18-25 years. A hundred and twenty-six (63%) of them resided in rural areas, 182 (91%) were housewives, and only 86 (43%) of them had completed secondary education & above. Early initiation of breastfeeding was found to be only 43 (21.5%) among postnatal mothers. Predictors found to be statistically significant with EIBF were mother's residential status [odds ratio (OR): 2.98; 95% confidence interval (CI): 1.25-7.13], educational status of mother (OR: 3.18; 95% CI: 1.12-9.01) mode of delivery of the baby (OR: 8.93; 95% CI: 2.66-30.06) and ante-natal care (ANC) visits (OR: 0.441; 95% CI: 0.311-0.651). Women's age, religion, ethnicity, occupation, type of family, and socioeconomic status displayed no statistically significant relationship with EIBF. Conclusions It is concluded that nearly one-fifth of mothers in the study initiated breastfeeding within one hour of post-delivery. Maternal education, frequent ANC visits, place of residence, and mode of delivery were also associated with EIBF in India. Nursing staff, as well as clinicians, should reinforce the importance of early initiation of breastfeeding by providing proper health education to post-natal beneficiaries.
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Oral cancer is common worldwide but lacks robust diagnostics and therapeutics. Lifestyle factors, such as tobacco chewing and smoking, are significantly associated with oral cancers. Mapping the changes in the global proteome, secretome and post-translational modifications (PTMs) during tobacco exposure of oral keratinocytes hold great potential for understanding the mechanisms of oral carcinogenesis, not to mention for innovation toward clinical interventions in the future. On the other hand, although advances in mass spectrometry (MS)-based techniques have enabled the deep mining of complex proteomes, a large portion of the mass spectrometric data remains unassigned. These unassigned spectral data can be researched for multiple post-translational modifications (multiPTMs). Using data mining of publicly available proteomics data, we report, in this study, a multiPTM analysis of high-resolution MS-derived datasets on cellular proteome and secretome of chronic tobacco-treated oral keratinocytes. We identified 800 PTM sites in 496 proteins. Among them, 43 PTM sites in 37 proteins were found to be differentially expressed, accounting for their protein-level expression. Enrichment analysis of the proteins with altered phosphosite expression and the known kinases of these phosphosites discovered the overrepresentation of certain biological processes such as splicing and hemidesmosome assembly. These findings contribute to a deeper understanding of omics level changes in chronic tobacco-treated oral keratinocytes, and by extension, pathophysiology of oral cancers.