Unveiling global public interest and seasonal patterns of antibiotics and antibiotic resistance: An infodemiology study with implications for public health awareness and intervention strategies.

INTRODUCTION: The health-related information-seeking through internet sources has drastically increased throughout the world. This study aimed to analyze the Global public interest on "antibiotics" and "antibiotic resistance". METHODS: The worldwide internet trend for the search terms "antibiotics" and "antibiotic resistance" from February 2017 to February 2022 was obtained using Google trends. The seasonal variation of interest was analyzed using the Seasonal Decomposition of Time Series by Loess. RESULTS: The mean interest for the search term "antibiotics" and "antibiotic resistance" is found to be 78.02 ± 7.5 and 2.3 ± 0.8, which will increase at 2.56 % and 16 % per year. It was observed that there was a significant relationship between antibiotic consumption, the number of physicians, and individuals using the internet in the countries with the search term "antibiotics". The study also indicates that there is a peak in search volume for the term during the COVID-19 Pandemic. CONCLUSION: Our study observed, that antibiotics related search questions on google by the public indicate the chances of antibiotic misuse. The study data suggest the need to raise public awareness about antibiotic use and antibiotic resistance, as well as there is need for intensive monitoring of dispensing and procurement patterns of antibiotics in developing countries.

Eravacycline -Synergistic activity with other antimicrobials in carbapenem resistant isolates of Escherichia coli and Acinetobacter baumannii.

Carbapenem resistant Enterobacteriaceae are unaffected by most used antibiotics. Carbapenem resistance in Gram-negative bacterial isolates poses a concern. Eravacycline is a potent new therapy option to treat organisms that exhibit extended-spectrum -lactamases and carbapenem-resistant Enterobacteriaceae. The chequerboard microdilution panel method was used to evaluate the effectiveness of eravacycline when combined with other antibiotics. Most effective against Escherichia coli isolates was the combination of eravacycline and polymyxin B, with 60% synergism and eravacycline-Ceftazidime combination was the most potent combination against Acinetobacter baumannii with 80% synergism. Eravacycline is having synergistic benefits against carbapenem-resistant isolates when combined with cephalosporins or polymyxin B.

Involvement of inflammatory cytokines and epigenetic modification of the mtTFA complex in T-helper cells of patients' suffering from non-small cell lung cancer and chronic obstructive pulmonary disease.

Dysregulated inflammatory response plays a crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and Non-Small cell lung cancer (NSCLC). Hence, the purpose of this research is to uncover the link between alterations in inflammatory cytokine levels and disease progression in CD4+T cells of patients suffering from COPD and lung cancer. We also investigated the epigenetic regulation of mtTFA to delineate the role of oxidative stress-mediated inflammation in Lung cancer and COPD. The RT2 Profiler PCR array was used to examine the differential expression pattern of inflammatory genes in CD4+ T helper (Th) cells from COPD, NSCLC, and control subjects. Candidate inflammatory gene loci were selected and the enrichment of transcriptional factor and histone modifiers was analysed using ChIP-qPCR. In comparison to control subjects, a set of genes (e.g., BMP2, CCL2, IL5, VEGFA, etc.) are over-expressed whereas another set of genes (e.g., AIMP1, IFNG, LTA, LTB, TNF, etc.) are under-expressed in both COPD and NSCLC patients. The increased percent enrichment of inflammation-associated transcription factors including NF-kB, CREB, HIF1, and MYC at the loci of inflammatory genes was revealed by our chromatin immunoprecipitation (ChIP) data. H3K4me3, H3K9me3, H3K14Ac, HDAC1, 2, 3, 6 all showed dysregulated enrichment at the VEGFA gene locus. One of the epigenetic modifications, histone methylation, was found to be abnormal in the mtTFA complex in COPD and NSCLC patients in comparison to controls. Although there is mounting evidence of several links between these disorders, therapeutic options remain inadequate. Our findings contribute to the body of knowledge about therapeutic techniques that use inflammatory cytokines as a prognostic marker and highlight the need for epigenetic therapy for these debilitating lung diseases.

T helper cell-mediated epitranscriptomic regulation via m6A RNA methylation bridges link between coronary artery disease and invasive ductal carcinoma.

PURPOSE: Invasive ductal carcinoma (IDC) and coronary artery disease (CAD), remains the greatest cause of death annually in women, driven by complex signalling pathways and shared several predisposing risk factors together. Therefore, it is important to find out the common epigenetic modifications which are responsible for possible disease progression from CAD to IDC. METHODS: CD4+T cell isolation by MACS, RT2 profiler PCR array, Gene ontology study, m6A RNA methylation, ChIP-qPCR, Q-PCR, CRISPR/Cas9-mediated knockout/overexpression, Lactate dehydrogenase release assay, RDIP-qPCR. RESULTS: We have identified several epigenetic regulators (e.g., VEGFA, AIMP1, etc.) which are mainly involved in inflammatory pathways in both the diseased conditions. Epitranscriptomic alterations such as m6A RNA methylation found abnormal in CD4+T helper cells in both IDC as well as CAD. CRISPR-Cas9 mediated knockout/overexpression of specific gene (BRCA1) are promising therapeutic approaches in diseased conditions by regulating m6A RNA methylation and also tumor suppressor gene P53. It also affected the R-loop formation which is vulnerable to DNA damage and BRCA1 can also induce CTL mediated cytotoxicity in breast cancer cells. CONCLUSIONS: Therefore, by understanding the modifications of epigenetic mechanisms, their alterations and interactions will aid in the development of newer therapeutic approaches to stop the possible spread from one disease to another.

Clinical characteristics and outcomes of patients with Corona Virus Disease 2019 (COVID-19) at Mercy Health Hospitals, Toledo, Ohio.

IMPORTANCE: The ongoing pandemic of the novel Corona Virus Disease 2019 (COVID-19) is an unprecedented challenge to global health, never experienced before. OBJECTIVE: This study aims to describe the clinical characteristics and outcomes of patients with COVID-19 admitted to Mercy Hospitals. DESIGN AND METHODS: Retrospective, observational cohort study designed to include every COVID-19 subject aged 18 years or older admitted to Mercy Saint (St) Vincent, Mercy St Charles, and Mercy St Anne's hospital in Toledo, Ohio from January 1, 2020 through June 15th, 2020. Primary Outcome Measure was mortality in the emergency department or as an in-patient. RESULTS: 470 subjects including 224 males and 246 females met the inclusion criteria for the study. Subjects with the following characteristics had higher odds (OR) of death: Older age [OR 8.3 (95% CI 1.1-63.1, p = 0.04)] for subjects age 70 or more compared to subjects age 18-29); Hypertension [OR 3.6 (95% CI 1.6-7.8, p = 0.001)]; Diabetes [OR 3.1 (95% CI 1.7-5.6, p<0.001)]; COPD [OR 3.4 (95% CI 1.8-6.3, p<0.001)] and CKD stage 2 or greater [OR 2.5 (95% CI 1.3-4.9, p = 0.006)]. Combining all age groups, subjects with hypertension had significantly greater odds of the following adverse outcomes: requiring hospital admission (OR 2.2, 95% CI 1.4-3.4, p<0.001); needing respiratory support in 24 hours (OR 2.5, 95% CI: 1.7-3.7, p<0.001); ICU admission (OR 2.7, 95% CI 1.7-4.4, p<0.001); and death (OR 3.6, 95% CI 1.6-7.8, p = 0.001). Hypertension was not associated with needing vent in 24 hours (p = 0.07). CONCLUSION: Age and hypertension were associated with significant comorbidity and mortality in Covid-19 Positive patients. Furthermore, people who were older than 70, and had hypertension, diabetes, COPD, or CKD had higher odds of dying from the disease as compared to patients who hadn't. Subjects with hypertension also had significantly greater odds of other adverse outcomes.

Isolation of MRSA, ESBL and AmpC - ß -lactamases from Neonatal Sepsis at a Tertiary Care Hospital.

BACKGROUND AND OBJECTIVES: The emergence of methicillin resistant Staphylococcus aureus (MRSA) and extended spectrum ß-lactamases (ESBLs) in neonatal intensive care unit patients is increasing. This study aims to find out the bacteriological profile in neonatal sepsis and study their antimicrobial susceptibility pattern including detection of MRSA and ESBLs. MATERIALS AND METHODS: This study was conducted for a period of one and a half years from January 2010 to June 2011 in a tertiary care hospital in Chennai. A total of 182 blood samples were collected using sterile precautions. They were processed following standard laboratory protocol. Antibiogram was done using appropriate antibiotics by Kirby-Bauer disc diffusion method. Isolated Staphylococcus aureus were tested for methicillin resistance using Cefoxitin disc (30µg), ESBL was detected using combined disc method, MIC reduction and Polymerase chain reaction, metallobetalactamases using EDTA and Amp-C beta lactamases using AmpC disc test. C-reactive protein (CRP) was estimated for all the cases. RESULTS: Out of the 182 cases, 110 (60.4%) were culture positive. Fifty five (63.9 %) of early onset sepsis cases had Gram negative bacteria (GNB) and 19 (79.1%) of late onset sepsis cases had Gram positive bacteria. Out of the total pathogens, 31 (28.1%) were Klebsiella pneumoniae and 30 (27%) were Staphylococcus aureus. 17 (56.6 %) of Staphylococcus aureus were found to be MRSA and they were 100% sensitive to Vancomycin. 33 (67.3%) of Enterobacteriaceae were ESBL producers. ESBL isolates were 100% sensitive to Imipenem. Three (6.1%) of Enterobacteriaceae were AmpC producers and 3 (27.2%) of Pseudomonas aeruginosa were MBL producers. CRP was positive in 99 (54.3%) cases, out of which 94 (94.9%) were culture positive. CONCLUSION: Klebsiella spp. and Staphylococcus aureus were the commonest bacteria causing neonatal sepsis in this centre. Multidrug resistance among the isolates was common. Early diagnosis and institution of specific antibiotics after studying the sensitivity pattern will help in reducing neonatal morbidity and mortality and prevent emergence of drug resistant strains.