Epigenetic dysregulation in cancers by isocitrate dehydrogenase 2 (IDH2).

Recent advances in genome-wide studies have revealed numerous epigenetic regulations brought about by genes involved in cellular metabolism. Isocitrate dehydrogenase (IDH), an essential enzyme, that converts isocitrate into -ketoglutarate (KG) predominantly in the tricarboxylic acid (TCA) cycle, has gained particular importance due to its cardinal role in the metabolic pathway in cells. IDH1, IDH2, and IDH3 are the three isomeric IDH enzymes that have been shown to regulate cellular metabolism. Of particular importance, IDH2 genes are associated with several cancers, including gliomas, oligodendroglioma, and astrocytomas. These mutations lead to the production of oncometabolite D-2-hydroxyglutarate (D-2-HG), which accumulates in cells promoting tumor growth. The enhanced levels of D-2-HG competitively inhibit α-KG dependent enzymes, inhibiting cell TCA cycle, upregulating the cell growth and survival relevant HIF-1α pathway, promoting DNA hypermethylation related epigenetic activity, all of which synergistically contribute to carcinogenesis. The present review discusses epigenetic mechanisms inIDH2 regulation in cells and further its clinical implications.

Rationalizing irrational prescribing-infection-related attitudes and practices across paediatric surgery specialties in a hospital in South India.

Background and objectives: Antibiotic use in paediatric surgical specialties is understudied. We investigated the antibiotic prescribing practices of paediatric general and cardiovascular surgical teams in a tertiary hospital in South India. Methods: Mixed-methods study including observations from ward rounds, semi-structured interviews, and review of antibiotic prescribing. Field notes from observations and interview transcripts were coded using NVivo and thematically analysed. Data collection and analysis were iterative and continued until thematic saturation. Quantitative data were analysed using descriptive statistics. Results: Data included 62 h of observation, 24 interviews, one case study and 200 patient chart reviews (100/specialty). Senior surgeons make key decisions, referring to their own experience when prescribing antibiotics. Being outcome-driven, the doctors often prescribe antibiotics at the earliest indication of infection with a reluctance to de-escalate, even when an infection is not diagnosed. This practice is more acute among surgeons who consider themselves responsible for their patients' health and attribute the consistently low surgical site infection rates to this practice.In general surgery, 83.3% (80/96; 4 lost to follow-up) of patients were prescribed antibiotics for the duration of their stay with oral antibiotics prescribed at discharge. The surgeons use antibiotics prophylactically for patients who may be vulnerable to infection. The antimicrobial stewardship team was considered to have limited influence in the decision-making process. Conclusions: Outcome-driven decision-making in surgery leads to overprescription of antibiotics and prolonged surgical prophylaxis. The rationale for suboptimal practices is complicated by the surgeons' beliefs about the contextual determinants of health in India.

A comprehensive review on nutritional, nutraceutical, and industrial perspectives of perilla (Perilla frutscens L.) seeds - An orphan oilseed crop.

There is a growing need to mainstream orphan or underutilized crops to enhance nutritional security and sustainable agriculture. Among these, Perilla frutescens L. is an important crop due to its rich nutritional and phytochemical content which makes it significant in nutrition, medicine, and industrial sector. Perilla seeds are mainly rich in ω-3 fatty acids, dietary fiber, amino acids, vitamins, and minerals, high α-linolenic acid, which contributes to their health benefits. This review explores the nutritional profile of perilla seeds and highlights its unique composition compared to other oilseed crops. It also analyzes the phytochemical components of perilla seeds and their various biological activities, including antioxidant, antidiabetic, antiobesity, cardioprotective, anticancer, antimicrobial, neuroprotective, and anti-inflammatory effects. These activities demonstrate the potential of perilla seeds in both pharmaceutical and food sectors. The review also covers recent advancements in genomics and transgenic research discussing potential areas for crop improvement. Additionally, it explores the use of perilla seeds in functional foods, blending perilla oil with other oils, and their applications in enhancing product formulations. This review offers valuable insights for researchers, students, policymakers, environmentalists, and industry professionals by detailing the potential of perilla seeds across various sectors. The findings support sustainable agriculture, crop diversification, and innovative product development, thus contributing to the integration of perilla into mainstream agriculture.

Toxicological study on ibuprofen and selenium in freshwater mussel Lamellidens marginalis and exploring the microbial cytochrome through modelling and quantum mechanics approaches for its toxicity degradation in contaminated environment.

Toxicological stress in aquatic organisms is caused by the discharge of hundreds of toxic pollutants and contaminants among which the current study concentrates on the toxic effect of non-steroidal anti-inflammatory drug ibuprofen (IBF) and the trace element selenium (Se). In this study, IBF and Se toxicity on freshwater mussel Lamellidens marginalis was studied for 14 days, and in silico predictions for their degradation were made using Molecular modelling and Quantum Mechanical approaches. The degrading propensity of cytochrome c oxidase proteins from Trametes verticillatus and Thauera selenatis (Turkey tail fungi and Gram-negative bacteria) is examined into atom level. The results of molecular modelling study indicate that ionic interactions occur in the T. selenatis-HEME bound complex by Se interacting directly with HEME, and in the T. versicolor-HEME bound complex by IBF bound to a nearby region of HEME. Experimental and theoretical findings suggest that, the toxicological effects of Se and IBF pollution can be reduced by bioremediation with special emphasis on T. versicolor, and T. selenatis, which can effectively interact with Se and IBF present in the environment and degrade them. Besides, this is the first time in freshwater mussel L. marginalis that ibuprofen and selenium toxicity have been studied utilizing both experimental and computational methodologies for their bioremediation study.

Potential inhibitors of VEGFR1, VEGFR2, and VEGFR3 developed through Deep Learning for the treatment of Cervical Cancer.

Cervical cancer stands as a prevalent gynaecologic malignancy affecting women globally, often linked to persistent human papillomavirus infection. Biomarkers associated with cervical cancer, including VEGF-A, VEGF-B, VEGF-C, VEGF-D, and VEGF-E, show upregulation and are linked to angiogenesis and lymphangiogenesis. This research aims to employ in-silico methods to target tyrosine kinase receptor proteins-VEGFR-1, VEGFR-2, and VEGFR-3, and identify novel inhibitors for Vascular Endothelial Growth Factors receptors (VEGFRs). A comprehensive literary study was conducted which identified 26 established inhibitors for VEGFR-1, VEGFR-2, and VEGFR-3 receptor proteins. Compounds with high-affinity scores, including PubChem ID-25102847, 369976, and 208908 were chosen from pre-existing compounds for creating Deep Learning-based models. RD-Kit, a Deep learning algorithm, was used to generate 43 million compounds for VEGFR-1, VEGFR-2, and VEGFR-3 targets. Molecular docking studies were conducted on the top 10 molecules for each target to validate the receptor-ligand binding affinity. The results of Molecular Docking indicated that PubChem IDs-71465,645 and 11152946 exhibited strong affinity, designating them as the most efficient molecules. To further investigate their potential, a Molecular Dynamics Simulation was performed to assess conformational stability, and a pharmacophore analysis was also conducted for indoctrinating interactions.

Patient Advocates for Clinical Research (PACER): A Step Toward Ethical, Relevant, and Truly Participatory Clinical Research in India.

Background Clinical research presents a promising path for improving healthcare in contemporary India. Yet, researchers identify gaps in trust, awareness, as well as misconceptions about being a '"guinea pig." We proposed building the capacity of training patient advocacy groups (PAGs) in patient-centered clinical research and through them creating aware patients as research partners. Methodology Patient Advocates for Clinical Research (PACER) is a tiered program to share information and education about clinical research with PAGs. Tier one is a self-paced online learning course, followed by workshops on clinical research, Good Clinical Practice, research consent, case studies, and group discussions. Results A total of 20 PAGs represented by 48 participants, active in areas of pediatric cancer, breast cancer, multiple myeloma, type I diabetes, spinal muscular atrophy, sickle cell disease, and inflammatory bowel diseases, participated. Among 48 participants 30 successfully completed the online course (multiple-choice question evaluation score cut-off >70%), attaining an average score of 23.9 ± 2.1 out of 30. Overall, 48 participants attended workshop 1 and 45 workshop 2, with 140 participants joining the focus group discussion (FGD). An overall improvement of 9.4% (𝜒2 = 46.173; p < 0.001) for workshop 1 and 8.2% (𝜒2 = 25.412; p < 0.001) for workshop 2 was seen in knowledge gain about clinical research. The FGD raised issues such as misleading information from research teams, unethical recruitment, incomprehensible information sheets, and limited trial-related knowledge fostering fear of participation in clinical research. Conclusions Multimodal and tiered learning of clinical research such as that used by PACER has a good participatory and learning response from PAGs and may be further explored.

Evaluating the Quality of Life of Beneficiaries After Providing Financial Aid by a Multi-specialty Tertiary Care Hospital.

Background Financial aid programs offered by multi-specialty tertiary care hospitals play a crucial role in ensuring equitable access to healthcare. This study investigates the effect of financial aid on the quality of life (QoL) of beneficiaries, aiming to provide a comprehensive understanding of the multifaceted relationship between healthcare support and overall well-being. Aim The study's objectives included assessing changes in pre- and post-aid QoL, identifying influencing factors, understanding beneficiary experiences, and evaluating the effectiveness of financial aid programs. Methods The study adopted quantitative assessments through QoL questionnaires developed based on the WHO BREF questionnaire and insights obtained through interviews. A representative sample of beneficiaries was selected, informed consent was obtained, and an institutional ethical certificate was also obtained. Results The findings overwhelmingly support the alternative hypothesis. The alternative hypothesis was that after receiving financial support, recipients' quality of life would increase. Quantitative analysis revealed a statistically significant enhancement in the QoL of beneficiaries across physical, mental, and social well-being domains. The quality of life scores of patients before and after receiving the support was statistically tested using a paired t-test, and the quality of life score has improved significantly with a p-value of 4.156 × 10-28 (p value<0.001). The comparison of quality of life scores of the control group with the patient's group before getting the support was tested using an independent sample t-test and found to be non-significant (p=0.496), while a similar comparison between the control group and the patient's group after receiving the support was found to be statistically highly significant with a p-value of 8.721 × 10-28 (p-value<0.001). Conclusions This research demonstrates the substantial impact of financial aid on the QoL of beneficiaries in a multi-specialty tertiary care hospital setting. It underlines the importance of addressing economic barriers and providing patient-centered, holistic support. These insights have broader implications for healthcare policy and practice, promoting a more comprehensive approach to patient well-being.

The Spectrum of Central Nervous System Tumors at a Tertiary Care Center Primarily Serving a Rural Population.

Background Central nervous system (CNS) tumors cause significant mortality and morbidity in all age groups. There was no data about the histological spectrum of all CNS tumors in the tertiary care center serving primarily the rural population of Uttar Pradesh. Aims and objectives The present study aimed to describe the histopathological spectrum of all CNS tumors reported in a rural tertiary care center at Saifai, Uttar Pradesh. It also aimed to provide an overview of the descriptive epidemiology of CNS tumors. Material and methods This was a retrospective, cross-sectional study. The study duration was three years. A total of 115 cases of CNS tumors were studied during that period. Cases were classified according to their histological types, and results were analyzed. Results The most common histological group was neuroepithelial tumors, with 53 cases (46.08%). This group had 36 cases of astrocytic tumors (31.3%), three cases of oligodendroglial tumors (2.6%), five cases of oligoastrocytic tumors (4.34%), five cases of ependymal tumors (4.34%), and four cases of embryonal tumors (3.47%). The second most common tumor was meningeal tumors, with 32 cases (27.82%). The male/female ratio (M/F) ratio was 0.7. Females were found to be more affected by almost all histologic categories. Most meningiomas (89.6%) were of World Health Organization (WHO) grade I (26 cases out of 29). Astrocytic tumors showed WHO grade I, II, III, and IV tumors in two cases (5.5%), twelve cases (33.3%), four cases (11.1%), and eighteen cases (50%), respectively. In the younger age group (0-20 years), ependymoma and medulloblastoma were most common, followed by pilocytic astrocytoma and schwannoma. Conclusion In this region, neuroepithelial tumors were seen more commonly than meningioma. Females were found to be more affected by CNS tumors. This study has provided relevant data, which can be used for research and better patient management. Further studies with the incorporation of advanced radiological investigation and immunohistochemistry have been recommended.

Regional variations in antimicrobial susceptibility of community-acquired uropathogenic Escherichia coli in India: Findings of a multicentric study highlighting the importance of local antibiograms.

Objectives: Evidence-based prescribing is essential to optimize patient outcomes in cystitis. This requires knowledge of local antibiotic resistance rates. Diagnostic and Antimicrobial Stewardship (DASH) to Protect Antibiotics (https://dashuti.com/) is a multicentric mentorship program guiding centers in preparing, analyzing and disseminating local antibiograms to promote antimicrobial stewardship in community urinary tract infection. Here, we mapped the susceptibility profile of Escherichia coli from 22 Indian centers. Methods: These centers spanned 10 Indian states and three union territories. Antibiograms for urinary E. coli from the outpatient departments were collated. Standardization was achieved by regional online training; anomalies were resolved via consultation with study experts. Data were collated and analyzed. Results: Nationally, fosfomycin, with 94% susceptibility (inter-center range 83-97%), and nitrofurantoin, with 85% susceptibility (61-97%), retained the widest activity. The susceptibility rates were lower for co-trimoxazole (49%), fluoroquinolones (31%), and oral cephalosporins (26%). The rates for third- and fourth-generation cephalosporins were 46% and 52%, respectively, with 54% (33-58%) extended-spectrum ß-lactamase prevalence. Piperacillin-tazobactam (81%), amikacin (88%), and meropenem (88%) retained better activity; however, one center in Delhi recorded only 42% meropenem susceptibility. Susceptibility rates were mostly higher in South, West, and Northeast India; centers in the heavily populated Gangetic plains, across north and northwest India, had greater resistance. These findings highlight the importance of local antibiograms in guiding appropriate antimicrobial choices. Conclusions: Fosfomycin and nitrofurantoin are the preferred oral empirical choices for uncomplicated E. coli cystitis in India, although elevated resistance in some areas is concerning. Empiric use of fluoroquinolones and third-generation cephalosporins is discouraged, whereas piperacillin/tazobactam and aminoglycosides remain carbapenem-sparing parenteral agents.

Pharmacist roles in antimicrobial stewardship: a qualitative study from India, South Africa and the United Kingdom.

Objective: To explore pharmacist roles in antimicrobial stewardship (AMS) in India, South Africa (SA), United Kingdom (UK) and the factors that contribute to their participation in the programme in these countries. Methods: Data were collected between April 2019 and March 2022 through semi-structured interviews with key AMS stakeholders from India (Kerala); SA (Western Cape province) and the UK (England). Interviews were conducted face to face or via Zoom and Skype platforms, audio recordings were transcribed verbatim and thematically analysed using a grounded theory approach aided by NVivo 12 software. Results: We interviewed 38 key AMS stakeholders (pharmacists and doctors). India and the UK have dedicated AMS pharmacists (Doctor of Pharmacy and Master of Pharmacy graduates with opportunities for additional post-graduate qualifications respectively). Pharmacists in the UK lead AMS programmes, while in India, predominantly in the private sector, pharmacists drive AMS in collaboration with clinicians. In SA, pharmacists (Bachelor of Pharmacy graduates) participate in AMS out of their own commitment in addition to their pharmacy responsibilities. Private sector pharmacists drive AMS while public sector pharmacists participate in clinician-led AMS programmes. Current pharmacy curricula do not provide adequate training in AMS, and this limitation shapes pharmacist roles and acceptance in AMS among clinicians in India and SA. Support of mentors (doctors/senior pharmacists) and self-motivated learning are key factors for effective pharmacist involvement in AMS. Conclusions: A contextually developed, standardized and accessible AMS training programme along with pharmacy curricula modification to include AMS, may facilitate prominent pharmacist roles in AMS.

Current state of education, training and practices in antimicrobial stewardship among pharmacy students: A cross-sectional survey from Kerala, India.

PURPOSE: Pharmacists are recognised in guidelines from across the globe as key stakeholders in antimicrobial stewardship (AMS) initiatives. The current study aims to assess the current practices and level of training and education in relation to AMS among pharmacy students from Kerala, India. METHODS: A cross-sectional web-based survey was developed and disseminated among doctor of pharmacy 5th year students and interns from selected pharmacy colleges across Kerala through key informants. Descriptive statistics were used to analyse the responses. RESULTS: The response rate was 34.8% (157/450). Whilst the majority of respondents (89.8%, 141/157) recalled being taught about antimicrobial resistance (AMR) as part of the pharmacy curricula, 84.7% (133/157) believed they didn't have sufficient knowledge about AMR. Most of the respondents (64.9%, 102/157) had not received any AMS training. Clinical posting in AMS was the preferred mode of training suggested by most respondents. Respondents who audited antimicrobials as part of their clinical postings (77.9%, 88/113) reported their main responsibility was review of patient records for assessing the appropriateness of antimicrobials (68.2%, 60/88). Inappropriate selection of antimicrobials was the most common error identified by respondents (38.1%, 43/113) and the key method of communicating their recommendation was informing the prescriber in person (46%, 52/113). CONCLUSION: Whilst pharmacy students are reviewing antimicrobial prescriptions as part of their clinical postings, their education and training in AMR and AMS remain low. The inclusion of practical clinical training for pharmacy students as part of their curricula can be a cost-effective way to promote AMS initiatives.

Comparison of clinical performance of obturating materials in pulpectomies: A randomized clinical trial.

BACKGROUND: Chemomechanical debridement is insufficient to disinfect all bacteria from the root canals of primary teeth, and obturation of canals with an appropriate material thus acquires excellent importance and remains a critical step in the ultimate success of pulpectomy. AIM: The aim of the study was to compare and evaluate Endoflas, Metapex, and a mixture of calcium hydroxide (CH) and zinc oxide (ZnO) as obturating materials (OMs) in primary mandibular second molars. MATERIALS AND METHODS: Seventy-five mandibular second primary molars requiring pulpectomies were identified in children aged 4-8 years. They were randomly allocated to the three treatment groups according to the type of OM received using the block randomization technique. After the completion of chemomechanical debridement, the canals were filled with Endoflas, Metapex, and CH-ZnO mixture, respectively. The intergroup clinical and radiographic comparison was made based on Coll and Sadrian criteria to decipher their clinical performance at 1, 3, and 6 months. RESULTS: No statistically significant differences between the groups were observed at any evaluation time interval (P > 0.05). At 6 months, the clinical success rates were 95.2% in Endoflas, 96% in Metapex, and 95.8% in the CH and ZnO mixture groups, respectively. The materials, however, behaved differently in different clinical situations. CONCLUSION: Based on the observations, all three OMs showed similar clinical success in maintaining tooth functioning, but their use can be restricted to indications. However, prospective studies with longer follow-ups with more stringent eligibility criteria are required to reach more definitive conclusions.

Genome-wide runs of homozygosity signatures in diverse Indian goat breeds.

The present study analyzed ROH and consensus ROH regions in 102 animals of eleven diverse Indian goat (Capra hircus) breeds using whole genome sequencing. A total of 51,705 ROH and 21,271 consensus regions were identified. The mean number of ROH per animal was highest in the meat breed, Jharkhand Black (2693) and lowest in the pashmina breed, Changthangi (60). The average length of ROH (ALROH) was maximum in Kanniadu (974.11 Kb) and minimum in Tellicherry (146.98 Kb). Long ROH is typically associated with more recent inbreeding, whereas short ROH is connected to more ancient inbreeding. The overall ROH-based genomic inbreeding (FROH) was highest for Jharkhand Black (0.602) followed by Kanniadu (0.120) and Sangamneri (0.108) among all breeds. FROH of Jharkhand Black was higher than Kanniadu  up to 5 Mb ROH length category. However, in > 20 Mb ROH length category, Kanniadu (0.98)  exhibited significantly higher FROH than Jharkhand Black (0.46). This  implies that Kanniadu had higher levels of recent inbreeding than Jharkhand Black. Despite this, due to the presence of both recent and ancient inbreeding, Jharkhand Black  demonstrated higher overall FROH compared to Kanniadu. ROH patterns revealed dual purpose (meat and dairy) and pashmina breeds as less consanguineous while recent inbreeding was apparent in meat breeds. Analysis of ROH consensus regions identified selection sweeps in key genes governing intramuscular fat deposition, meat tenderisation, lean meat production and carcass weight (CDK4, ALOX15, CASP9, PRDM16, DVL1) in meat breeds; milk fat percentage and mammary gland development (POLD1, NOTCH2, ARHGAP35) in dual purpose (meat and dairy) breeds; while cold adaptation and hair follicle development (APOBEC1, DNAJC3, F2RL1, FGF9) in pashmina breed. MAPK, RAS, BMP and Wnt signaling pathways associated with hair follicle morphogenesis in Changthangi were also identified. PCA analysis based on ROH consensus regions revealed that meat breeds are more diverse than other goat breeds/populations. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03921-y.

Mentorship as an overlooked dimension of research capacity strengthening: how to embed value-driven practices in global health.

Mentorship in global health remains an overlooked dimension of research partnerships. Commitment to effective mentorship models requires value-driven approaches. This includes having an understanding of (1) what mentorship means across different cultural and hierarchical boundaries in the health research environment, and (2) addressing entrenched power asymmetries across different aspects including funding, leadership, data and outputs, and capacity strengthening. Existing guidance towards equity and sustainability fails to inform how to navigate complex relationships which hinder effective mentorship models. We focus this perspective piece on human capacity strengthening in research partnerships through mentorship. Using a case study of a research partnership, we describe the lessons learnt and the challenges faced in the mentor mentee relationship while maintaining an effective and sustainable partnership. Human capacity strengthening must research projects and collaborations, and recognise local leadership and ownership. To be transformative and effective, practices need to be driven by common values across research teams.

Antimicrobial resistance and the great divide: inequity in priorities and agendas between the Global North and the Global South threatens global mitigation of antimicrobial resistance.

To limit the catastrophic effects of the increasing bacterial resistance to antimicrobials on health, food, environmental, and geopolitical security, and ensure that no country or region is left behind, a coordinated global approach is required. In this Viewpoint, we argue that the diverging resource availabilities, needs, and priorities of the Global North and the Global South in terms of the actions required to mitigate the antimicrobial resistance pandemic are a direct threat to success. We argue that evidence suggests a need to prioritise and support infection prevention interventions (ie, clean water and safe sanitation, increased vaccine coverage, and enhanced infection prevention measures for food production in the Global South contrary to the focus on research and development of new antibiotics in the Global North) and to recalibrate global funding resources to address this need. We call on global leaders to redress the current response, which threatens mitigation of the antimicrobial resistance pandemic.

Markers of Oxidative Stress and Tyrosinase Activity in Melasma Patients: A Biochemical Investigation.

BACKGROUND: Melasma is a skin hyperpigmentary disorder that develops over time. Genetic factors, oxidative stress, female sex hormones, and UV light may all play a role in the disorder's progression. AIMS: To compare the levels of oxidative stress and tyrosinase activity in melasma patients with healthy volunteers. METHODS: After written consent, 130 patients were enrolled in a case-control study. 65 cases were of melasma disorder, and 65 were served as control. Homogenized skin tissues were taken and used to estimate superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx) (antioxidants), malondialdehyde (MDA) and tyrosine hydroxylase (TH). RESULTS: Melasma patients had lower basal levels of systemic antioxidants than healthy subjects. Tyrosinase activity was shown to be greater in lesional skin than in non-lesional skin. In controls, there was a good positive relationship between TH and MDA and an excellent negative relationship between GPx and GSH. In melasma patients, there were significant associations between CAT, GPx, SOD and MDA. CONCLUSIONS: Increased oxidative stress may affect tyrosinase activity and eumelanin synthesis via the anabolic pathway of melanin synthesis, according to our findings. In conclusion, we discovered a negative relationship between antioxidants and tyrosinase activity.

Epidemiology and preventability of hospital-onset bacteremia and fungemia in 2 hospitals in India.

OBJECTIVE: Studies evaluating the incidence, source, and preventability of hospital-onset bacteremia and fungemia (HOB), defined as any positive blood culture obtained after 3 calendar days of hospital admission, are lacking in low- and middle-income countries (LMICs). DESIGN, SETTING, AND PARTICIPANTS: All consecutive blood cultures performed for 6 months during 2020-2021 in 2 hospitals in India were reviewed to assess HOB and National Healthcare Safety Network (NHSN) reportable central-line-associated bloodstream infection (CLABSI) events. Medical records of a convenience sample of 300 consecutive HOB events were retrospectively reviewed to determine source and preventability. Univariate and multivariable logistic regression analyses were performed to identify factors associated with HOB preventability. RESULTS: Among 6,733 blood cultures obtained from 3,558 hospitalized patients, there were 409 and 59 unique HOB and NHSN-reportable CLABSI events, respectively. CLABSIs accounted for 59 (14%) of 409 HOB events. There was a moderate but non-significant correlation (r = 0.51; P = .070) between HOB and CLABSI rates. Among 300 reviewed HOB cases, CLABSIs were identified as source in only 38 (13%). Although 157 (52%) of all 300 HOB cases were potentially preventable, CLABSIs accounted for only 22 (14%) of these 157 preventable HOB events. In multivariable analysis, neutropenia, and sepsis as an indication for blood culture were associated with decreased odds of HOB preventability, whereas hospital stay ≥7 days and presence of a urinary catheter were associated with increased likelihood of preventability. CONCLUSIONS: HOB may have utility as a healthcare-associated infection metric in LMIC settings because it captures preventable bloodstream infections beyond NHSN-reportable CLABSIs.

Unveiling the ESR1 Conformational Stability and Screening Potent Inhibitors for Breast Cancer Treatment

BACKGROUND: The current study recognizes the significance of estrogen receptor alpha (ERα) as a member of the nuclear receptor protein family, which holds a central role in the pathophysiology of breast cancer. ERα serves as a valuable prognostic marker, with its established relevance in predicting disease outcomes and treatment responses. METHOD: In this study, computational methods are utilized to search for suitable drug-like compounds that demonstrate analogous ligand binding kinetics to ERα. RESULTS: Docking-based simulation screened out the top 5 compounds - ZINC13377936, NCI35753, ZINC35465238, ZINC14726791, and NCI663569 against the targeted protein. Further, their dynamics studies reveal that the compounds ZINC13377936 and NCI35753 exhibit the highest binding stability and affinity. CONCLUSION: Anticipating the competitive inhibition of ERα protein expression in breast cancer, we envision that both ZINC13377936 and NCI35753 compounds hold substantial promise as potential therapeutic agents. These candidates warrant thorough consideration for rigorous In vitro and In vivo evaluations within the context of clinical trials. The findings from this current investigation carry significant implications for the advancement of future diagnostic and therapeutic approaches for breast cancer.