Factors Affecting Survival in Severe and Very Severe COPD after Admission in ICUs of Tertiary Care Centers of India (FAST COPD): Study Protocol for a Multicentric Cohort Study.

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. However, there is a lack of comprehensive data from low- and middle-income countries (LMICs) regarding factors influencing COPD outcomes, particularly in regions where biomass exposure is prevalent. Objective: The Factors Affecting Survival in Severe and Very Severe COPD Patients Admitted to Tertiary Centers of India (FAST) study aims to address this gap by evaluating factors impacting survival and exacerbation rates among COPD patients in LMICs like India, with a specific focus on biomass exposure, clinical phenotypes, and nutritional status in patients admitted to the Intensive Care Unit (ICU). Methods: The FAST study is an observational cohort study conducted in university teaching hospitals across India. The study aims to enroll 1000 COPD patients admitted to the ICU meeting specific inclusion criteria, with follow-up assessments conducted every 6 months over a 2-year period. Data collection includes demographic information, clinical manifestations, laboratory investigations, pulmonary function tests, medications, nutritional status, mental health, and health-related quality of life. Adjudication of exacerbations and mortality will also be undertaken. The FAST study seeks to provide crucial insights into COPD outcomes in LMICs, informing more precise management strategies and mitigating the burden of COPD in these settings. By evaluating factors such as biomass exposure, clinical phenotypes, and nutritional status, the study aims to address key knowledge gaps in COPD research. How to cite this article: Arunachala S, Devapal S, Swamy DSN, Greeshma MV, Ul Hussain I, Siddaiah JB, et al. Factors Affecting Survival in Severe and Very Severe COPD after Admission in ICUs of Tertiary Care Centers of India (FAST COPD): Study Protocol for a Multicentric Cohort Study. Indian J Crit Care Med 2024;28(6):552-560.

Study of Biomarker Discordance between Primary and Recurrent Sites and its Clinical Implications in Metastatic Breast Cancer : A Single Institutional Study from India.

S. Shanthala Immunophenotypic discordance of receptors between primary and metastatic sites significantly impacts treatment outcomes. Current international guidelines recommend rebiopsy of accessible metastatic lesions to reassess tissue biomarkers. While existing literature on biomarker changes is conflicting and heterogeneous, similar studies on the Indian cohort of breast cancer patients are lacking. In this context, we aimed to evaluate the frequencies of biomarker changes between biopsies from primary and recurrent sites, and their association with various clinicopathological characteristics, including the type of metastasis and treatment in metastatic breast cancer (MBC) patients. This is an ambispective study performed at a single center. Immunohistochemical (IHC) expression of paired primary and recurrence samples of MBC patients was reviewed for the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki-67. Concordance, loss, and gain of receptors were assessed based on the Allred scores for ER, PR, and HER2. Ki-67 was assessed based on a 14% cutoff. Further, receptor changes were studied in relation to age, menopausal status, morphology, grade, stage, metastatic sites, interval between biopsies, and treatment. At progression, biopsies were obtained from 41.18% of locoregional recurrence and 58.82% of metastatic sites. Despite high discordance of 47% for ER and 68.6% for PR, true receptor conversion was observed in 9.8%, 21.56%, and 5.88% for ER, PR, and HER2, respectively. There was a significant correlation between age and ER discordance ( p = 0.029). Loss in PR significantly correlated with a gain in Ki-67. Of all the metastatic sites, the lung was significantly associated with PR and Ki-67 concordance ( p = 0.008 and p = 0.0425, respectively). Discordance of receptors was neither related to the sites of biopsy (local recurrence or metastatic site) nor to the time interval between biopsies, prior chemotherapy, or hormone therapy. In conclusion, metastatic progression of the disease is accompanied by age-dependent discordance of ER. Unparalleled changes in PR in relation to ER suggest that ER-independent pathways may influence PR expression in MBC. Furthermore, the concurrence of PR loss with Ki-67 gain indicates an aggressive phenotype with disease progression. Hence, follow-up testing of samples for receptor expression is beneficial in determining prognosis and guiding therapeutic decisions.

Synthesis, Spectral Characterization and Photoluminescence of 3-chloro-6-methoxy-2-(methylsulfanyl)quinoxaline in Different Solvents: An Experimental and Theoretical Investigation Using DFT.

In the present work, we synthesized 3-chloro-6-methoxy-2-(methyl sulfanyl) quinoxaline (3MSQ) using a microwave-assisted synthesis method. The physicochemical structural analysis of the synthesized compound utilizing 1H-NMR, 13C-NMR, and FT-IR spectroscopy techniques. The photophysical properties of 3MSQ was examined through absorption and fluorescence spectroscopy. Spectroscopic analyses revealed a bathochromic shift in both absorption and fluorescence spectra, attributed to the π → π* transition. Ground and excited state dipole moments was experimentally determined using the solvatochromic shift method, employing various correlations such as Lippert's, Bakhshiev's, Kawski-Chamma-Viallet's equations, and solvent polarity parameters. Our findings indicate that the excited state dipole moments exceed those of the ground state, suggesting increased polarity in the excited state. Further, the while detailed bond length, bond angles, dihedral angles, Mulliken charge distribution, ground state dipole moments and HOMO-LUMO energy gap estimated through ab initio computations using Gaussian-09W. The value of energy band gap obtained from both the methods are in good agreement. Furthermore, employing DFT computational analysis, we identified reactive centers such as electrophilic and nucleophilic sites using molecular electrostatic potential (MESP) 3D plots. Additionally, CIE chromaticity analysis was performed to understand the photoluminescent properties of 3MSQ. The insights derived from these analyses contribute to a better understanding of the molecule's electronic structure, photophysical properties, and solute-solvent interactions, thus providing valuable information regarding its behaviour and characteristics under diverse conditions. These results contribute to a comprehensive understanding of the molecular structure and properties of 3-chloro-6-methoxy-2-(methyl sulfanyl) quinoxaline (3MSQ).

Single-row versus transosseous technique in the arthroscopic treatment of rotator cuff tears: a meta-analysis.

PURPOSE: This study aims to compare single-row suture-anchors (SA) versus transosseous arthroscopic (TO) technique in the treatment of patients with rotator cuff tears in terms of clinical structural outcomes at atleast 24 months of follow-up. METHODS: The systematic review was performed according to "PRISMA guidelines" (Preferred Reporting Items for Systematic Reviews and Meta-analyses), in order to identify all the studies comparing clinical, both subjective and objective, outcomes with 24 months follow-up minimum in patients undergoing arthroscopic RC repair with the SR and TO technique. OVID-MEDLINE®, Cochrane, SCOPUS and PubMed were searched from January 2010 to October 2022 to identify relevant studies, using the following key words, that were combined together to achieve maximum search strategy sensitivity: "Rotator cuff tear" OR "repair" OR "shoulder" OR "reconstruction" OR "suture" OR "arthroscopic" OR "single-row" OR "transosseous". RESULTS: Six papers were finally analyzed in this meta-analysis. The weighted mean difference on Constant scores and for ASES for studies considering suture-anchors (SA) group showed good outcomes. The weighted mean difference of Constant scores and of ASES for TO (transosseous) group showed good outcomes. The weighted mean difference of CONSTANT for TO versus SA groups showed no differences in the outcomes of SA and TO techniques for the repair of Rotator Cuff Tears at minimum 24 months follow-up. CONCLUSIONS: The Arthroscopic transosseous rotator cuff repair technique and SA (suture-anchor) technique both lead to significant short-term improvement and satisfactory subjective outcome scores with low complication/failure rates. No differences were found in the final outcome between the two techniques.

Pigmented Microbial Extract (PMB) from Exiguobacterium Species MB2 Strain (PMB1) and Bacillus subtilis Strain MB1 (PMB2) Inhibited Breast Cancer Cells Growth In Vivo and In Vitro.

Breast cancer (BC) continues to be one of the major causes of cancer deaths in women. Progress has been made in targeting hormone and growth factor receptor-positive BCs with clinical efficacy and success. However, little progress has been made to develop a clinically viable treatment for the triple-negative BC cases (TNBCs). The current study aims to identify potent agents that can target TNBCs. Extracts from microbial sources have been reported to contain pharmacological agents that can selectively inhibit cancer cell growth. We have screened and identified pigmented microbial extracts (PMBs) that can inhibit BC cell proliferation by targeting legumain (LGMN). LGMN is an oncogenic protein expressed not only in malignant cells but also in tumor microenvironment cells, including tumor-associated macrophages. An LGMN inhibition assay was performed, and microbial extracts were evaluated for in vitro anticancer activity in BC cell lines, angiogenesis assay with chick chorioallantoic membrane (CAM), and tumor xenograft models in Swiss albino mice. We have identified that PMB from the Exiguobacterium (PMB1), inhibits BC growth more potently than PMB2, from the Bacillus subtilis strain. The analysis of PMB1 by GC-MS showed the presence of a variety of fatty acids and fatty-acid derivatives, small molecule phenolics, and aldehydes. PMB1 inhibited the activity of oncogenic legumain in BC cells and induced cell cycle arrest and apoptosis. PMB1 reduced the angiogenesis and inhibited BC cell migration. In mice, intraperitoneal administration of PMB1 retarded the growth of xenografted Ehrlich ascites mammary tumors and mitigated the proliferation of tumor cells in the peritoneal cavity in vivo. In summary, our findings demonstrate the high antitumor potential of PMB1.

Sigma metric analysis of quality indicators across the testing process as an effective tool for the evaluation of laboratory performance.

Background: Laboratories across the world are successfully using quality indicators (QIs) to monitor their performance. We aimed to analyze the effectiveness of using the peer group comparison and statistical tools such as sigma metrics for periodic evaluation of QIs and identify potential errors in the preanalytical, analytical, and postanalytical phases. Methods: We evaluated the monthly QIs for 1 year. A total of 11 QIs were evaluated across the three phases of the total testing process, using percentage variance, and sigma metric analysis. Results: Our study observed that based on sigma metric analysis, the performance was good for all the QIs except for the number of samples with the inappropriate specimen hemolyzed samples, clotted samples, and turnaround time (Sigma value < 3). The percentage variance of QIs in all the phases was plotted in a Pareto chart, which helped us in identifying turnaround time and internal quality control performance are the key areas that contribute to almost 80% of the errors among all the QIs. Conclusion: Laboratory performance evaluation using QIs and sigma metric analysis helped us in identifying and prioritizing the corrective actions in the key areas of the total testing process.

Vitamin D3 Inhibits the Viability of Breast Cancer Cells In Vitro and Ehrlich Ascites Carcinomas in Mice by Promoting Apoptosis and Cell Cycle Arrest and by Impeding Tumor Angiogenesis.

The incidence of aggressive and resistant breast cancers is growing at alarming rates, indicating a necessity to develop better treatment strategies. Recent epidemiological and preclinical studies detected low serum levels of vitamin D in cancer patients, suggesting that vitamin D may be effective in mitigating the cancer burden. However, the molecular mechanisms of vitamin D3 (cholecalciferol, vit-D3)-induced cancer cell death are not fully elucidated. The vit-D3 efficacy of cell death activation was assessed using breast carcinoma cell lines in vitro and a widely used Ehrlich ascites carcinoma (EAC) breast cancer model in vivo in Swiss albino mice. Both estrogen receptor-positive (ER+, MCF-7) and -negative (ER-, MDA-MB-231, and MDA-MB-468) cell lines absorbed about 50% of vit-D3 in vitro over 48 h of incubation. The absorbed vit-D3 retarded the breast cancer cell proliferation in a dose-dependent manner with IC50 values ranging from 0.10 to 0.35 mM. Prolonged treatment (up to 72 h) did not enhance vit-D3 anti-proliferative efficacy. Vit-D3-induced cell growth arrest was mediated by the upregulation of p53 and the downregulation of cyclin-D1 and Bcl2 expression levels. Vit-D3 retarded cell migration and inhibited blood vessel growth in vitro as well as in a chorioallantoic membrane (CAM) assay. The intraperitoneal administration of vit-D3 inhibited solid tumor growth and reduced body weight gain, as assessed in mice using a liquid tumor model. In summary, vit-D3 cytotoxic effects in breast cancer cell lines in vitro and an EAC model in vivo were associated with growth inhibition, the induction of apoptosis, cell cycle arrest, and the impediment of angiogenic processes. The generated data warrant further studies on vit-D3 anti-cancer therapeutic applications.

BRCA1 expression, its correlation with clinicopathological features, and response to neoadjuvant chemotherapy in high-grade serous ovarian cancer.

AIM: In high-grade serous ovarian cancers (HG-SOC), BRCA1 mutation is one of the predominant mutations reported by various studies. However, the non-mutational mechanisms of BRCA pathway inactivation in HG-SOC are unclear. We evaluated BRCA1 inactivation by estimating its expression with its repressor, ID4, in primary and neoadjuvant chemotherapy (NACT)-treated HG-SOC tumors with known therapeutic responses. METHODS: We evaluated the expression pattern of BRCA1 protein by immunohistochemistry in 119 cases of HG-SOC from a hospital cohort consisting of primary (N = 69) and NACT-treated (N = 50) tumors. Histological patterns (SET), stromal infiltration by lymphocytes (sTILs), and chemotherapy response score (CRS) were estimated by microscopic examination. Gene expression levels of BRCA1, and its repressor ID4, were estimated by qPCR. The association of BRCA1 protein and mRNA with clinicopathological features was studied. The relevance of the BRCA1/ID4 ratio was evaluated in tumors with different CRS. RESULTS: BRCA1 protein expression was observed in 12% of primary and 19% of NACT-treated HG-SOC tumors. We observed moderate concordance between BRCA1 protein and mRNA expression (AUC = 0.677). High BRCA1 mRNA expression was significantly associated with a more frequent SET pattern (p = 0.024), higher sTILs density (p = 0.042), and increased mitosis (p = 0.028). BRCA1-negative tumors showed higher expression of ID4 though not statistically significant. A higher BRCA1/ID4 ratio was associated with high sTILs density in primary (p = 0.042) and NACT-treated tumors (p = 0.040). CONCLUSION: Our findings show the utility of the BRCA1/ID4 ratio in predicting neoadjuvant therapy response, which needs further evaluation in larger cohorts with long-term outcomes.

AATF inhibition exerts antiangiogenic effects against human hepatocellular carcinoma.

Background and aims: Angiogenesis is a key factor in the growth and metastasis of hepatic tumors and thus a potential therapeutic target in hepatocellular carcinoma (HCC). In this study, we aim to identify the key role of apoptosis antagonizing transcription factor (AATF) in tumor angiogenesis and its underlying mechanisms in HCC. Methods: HCC tissues were analyzed for AATF expression by qRT-PCR and immunohistochemistry. Stable clones of control and AATF knockdown (KD) were established in human HCC cells. The effect of AATF inhibition on the angiogenic processes was determined by proliferation, invasion, migration, chick chorioallantoic membrane (CAM) assay, zymography, and immunoblotting techniques. Results: We identified high levels of AATF in human HCC tissues compared to adjacent normal liver tissues, and the expression was found to be correlated with the stages and tumor grades of HCC. Inhibiting AATF in QGY-7703 cells resulted in higher levels of pigment epithelium-derived factor (PEDF) than controls due to decreased matric metalloproteinase activity. Conditioned media from AATF KD cells inhibited the proliferation, migration, and invasion of human umbilical vein endothelial cells as well as the vascularization of the chick chorioallantoic membrane. Furthermore, the VEGF-mediated downstream signaling pathway responsible for endothelial cell survival and vascular permeability, cell proliferation, and migration favoring angiogenesis was suppressed by AATF inhibition. Notably, PEDF inhibition effectively reversed the anti-angiogenic effect of AATF KD. Conclusion: Our study reports the first evidence that the therapeutic strategy based on the inhibition of AATF to disrupt tumor angiogenesis may serve as a promising approach for HCC treatment.

Diagnostic Performance of Ultrasonography Versus Magnetic Resonance Cholangiopancreatography in Biliary Obstruction.

Background In a suspected case of biliary obstruction with clinical and laboratory data suggesting obstructive jaundice, the major goal is to confirm the presence of obstruction, its nature and cause, location, and extent. Ultrasonography (USG) and magnetic resonance cholangiopancreatography (MRCP) are primarily used to diagnose suspected biliary tract illnesses. The aim of the study is to evaluate and compare the accuracy of MRCP and USG with endoscopic retrograde cholangiopancreatography (ERCP)/surgical/histopathological outcomes for finding the cause and level of obstruction in the case of clinically suspected biliary obstruction. Methods This was a prospective observational study conducted at Kalinga Institute of Medical Sciences and Pradyumna Bal Memorial Hospital, Bhubaneswar, India, from September 2020 to September 2022 on 120 patients. It included patients with clinical suspicion of biliary obstruction who underwent both USG and MRCP. Characteristics of the obstruction were evaluated for both benign and malignant lesions through USG and MRCP. The findings were then correlated with ERCP, histopathology, or surgery to calculate the diagnostic performance of the former two modalities. Results Out of 120 patients, USG was correctly able to predict the cause of obstruction in 40 patients. The sensitivity, specificity, and accuracy of detecting the nature of obstruction by USG were 33.3%, 84%, and 48.9%, respectively. The overall diagnostic accuracy of USG in predicting the site of obstruction was 64.3%. MRCP was correctly able to predict the cause of obstruction in 113 patients. The sensitivity, specificity, and accuracy of detecting the nature of obstruction by MRCP were 94.1%, 91.9%, and 94.8% respectively. The overall diagnostic accuracy of MRCP in predicting the site of obstruction was 98.33%. Out of 120 patients, no cause of biliary obstruction could be found in 71 patients by USG, out of which the correct diagnosis was made in 67 patients through MRCP. Conclusion USG should be used as the initial screening modality of choice for predicting the level and nature of obstruction in patients with a clinical suspicion of obstructive jaundice. MRCP should be the radiological investigation of choice in patients with clinical suspicion of obstructive jaundice. MRCP has the potential to become the new "Gold standard" investigation for diagnosis in patients with biliary obstruction owing to its excellent diagnostic performance, and non-invasiveness.

Diagnostic Imageology of Goldenhar Syndrome: Report of a Rare Case.

Goldenhar syndrome is a rare disorder that normally affects just one side and is distinguished by a variety of anomalies in internal organs, vertebrae, and craniofacial tissues. Although this sickness varies genetically and has been linked to a variety of factors, its etiology is unknown. We describe a case of hemifacial microsomia linked with Goldenhar syndrome that was clinically and radiographically investigated using cone-beam computed tomography. Several classical indications of the condition were present in the patient along with few uncommon ones. The many facets of this uncommon disease have been covered, with a focus on early detection and a multidisciplinary approach to treatment.

Revisiting Metaplastic Carcinoma of Breast: An Emphasis on the Clinico-pathological and Immunohistochemical Variables Analyzed at a Tertiary Cancer Centre in South India.

Background & Objective: Metaplastic carcinoma is a diverse variant of invasive breast carcinomas (IBC) characterized by dedifferentiation of malignant cells towards squamous and/or mesenchymal elements. It accounts for 0.3-1.2% of all IBC. These tumors are typically triple-negative by hormonal profiling with a high proliferation index and a dismal prognosis. Lymph node metastasis is an unusual feature in metaplastic carcinoma. Methods: The present study analyses 30 cases (26 cases of modified radical mastectomy and 4 cases of lumpectomy) of metaplastic carcinoma over 2018-2020 (3 years). Four oncopathologists reviewed routine histopathologic and immunohistochemical-stained slides. The clinical details were collected from the Medical Records Department of the Cancer Institute. Results: A total of 20 (66.67%) cases were patients >50 years of age, 21(70%) out of which were diagnosed as invasive carcinoma, grade 3 according to the Nottingham histological score. Five (16.7%) cases presented with lymph node metastasis. While immunohistochemically 28 (93.3%) cases were triple-negativeCK5/6, P63, EGFR, and Ki-67 (more than 40%) positivity was noted in 25 (83.3%) , 26 (86,7%) , 20 (66.7%), and 25 (83.3%) cases, respectively. Conclusion: Metaplastic carcinoma is characteristically triple-negative breast malignancies (TNBC) exhibiting a high Ki-67 index and a lower rate of lymph node metastasis. CK5/6, p63, and EGFR are pertinent immunohistochemical markers that may aid in diagnosis. However, those markers are non-specific for the disease and morphologic features are always the key to diagnosis of the process.

Bioinformatic Tools for the Identification of MicroRNAs Regulating the Transcription Factors in Patients with ß-Thalassemia.

ß-thalassemia is a significant health issue worldwide, with approximately 7% of the world's population having defective hemoglobin genes. MicroRNAs (miRNAs) are short noncoding RNAs regulating gene expression at the post-transcriptional level by targeting multiple gene transcripts. The levels of fetal hemoglobin (HbF) can be increased by regulating the expression of the γ-globin gene using the suppressive effects of miRNAs on several transcription factors such as MYB, BCL11A, GATA1, and KLF. An early step in discovering miRNA:mRNA target interactions is the computational prediction of miRNA targets that can be later validated with wet-lab investigations. This review highlights some commonly employed computational tools such as miRBase, Target scan, DIANA-microT-CDS, miRwalk, miRDB, and micro-TarBase that can be used to predict miRNA targets. Upon comparing the miRNA target prediction tools, 4 main aspects of the miRNA:mRNA target interaction are shown to include a few common features on which most target prediction is based: conservation sites, seed match, free energy, and site accessibility. Understanding these prediction tools' usage will help users select the appropriate tool and interpret the results accurately. This review will, therefore, be helpful to peers to quickly choose a list of the best miRNAs associated with HbF induction. Researchers will obtain significant results using these bioinformatics tools to establish a new important concept in managing ß-thalassemia and delivering therapeutic strategies for improving their quality of life.

A common Matrix metalloproteinase 8 promoter haplotype enhances the risk for hypertension via diminished interactions with nuclear factor kappa B.

OBJECTIVES: Matrix metalloproteinase 8 (MMP8) has a prominent role in collagen turnover in blood vessels and vascular remodeling. The contribution of regulatory single nucleotide polymorphisms in MMP8 to cardiovascular diseases is unclear. We aimed to delineate the influence of MMP8 promoter variations on hypertension. METHODS: A case-control study in unrelated individuals ( n  = 2565) was carried out. Resequencing of the MMP8 proximal promoter, linkage disequilibrium analysis, genotyping of variants and regression analyses were performed. MMP8 promoter-reporter constructs were generated and expressed in human vascular endothelial cells under various conditions. RESULTS: We identified four single nucleotide polymorphisms (SNPs) in the promoter region of MMP8 : -1089A/G (rs17099452), -815G/T (rs17099451), -795C/T (rs11225395), -763A/T (rs35308160); these SNPs form three major haplotypes. Hap3 (viz., GTTT haplotype) carriers showed significant associations with hypertension in two geographically distinct human populations (e.g., Chennai: odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.16-1.86, P  = 2 × 10 -3 ; Chandigarh: OR = 1.85, 95% CI = 1.21-2.81, P  = 4 × 10 -3 ). Hap3 carriers also displayed elevated systolic blood pressure, diastolic blood pressure and mean arterial pressure levels. Hap3 promoter-reporter construct showed lower promoter activity than the wild-type (Hap1) construct. In silico analysis and molecular dynamics studies predicted diminished binding of the transcription factor nuclear factor kappa B (NF-κB) to the functional -815T allele of Hap3 compared to the -815G wild-type allele; this prediction was validated by in-vitro experiments. Hap3 displayed impaired response to tumor necrosis factor-alpha treatment, possibly due to weaker binding of NF-κB. Notably, MMP8 promoter haplotypes were identified as independent predictors of plasma MMP8 and endothelial dysfunction markers (von Willebrand factor and endothelin-1) levels. CONCLUSION: MMP8 promoter GTTT haplotype has a functional role in reducing MMP8 expression during inflammation via diminished interaction with NF-κB and in enhancing the risk of hypertension.

COVID-19 Effects on Geriatric Population and Failures of Aminoquinoline Therapy: Compilation of Studies from EU, USA, and China; Safety and Efficacy of Vaccines in the Prevention and Treatment of COVID-19.

BACKGROUND: Mortality of the older adult population suffering from COVID-19 has been increasing at an alarming rate, and people older than 76 years of age reported 18% mortality. Mainly, the EU and USA exhibited a greater fatality rate due to lack of selective immunization and anti-SARS Co-V-2 therapeutics. Very limited reports are available to delineate the impact of COVID-19 on the geriatric population and the failures of aminoquinoline therapy. METHODS: We performed a substantial literature review in the PubMed/Medline databases to extract the information pertaining to the COVID-19 impact on the geriatric population and recent failures of aminoquinoline therapy in COVID-19 patients of EU, China, USA and the requirement of vaccination. RESULTS AND DISCUSSIONS: Both parental strains and mutant variants of SARS Co-V-2 can induce severe respiratory complications, multiorgan failure, and clotting abnormalities in older adults due to low immunocompetence. Aminoquinoline derivatives, such as chloroquine (CQ) and hydroxychloroquine (HCQ), are preferred primarily for COVID-19 treatment, but several controversies are being reported for its usage worldwide. In this review, we have provided the effects of COVID-19 on the geriatric population of EU and an overview of the mechanism of action of aminoquinolines. Furthermore, CQ and HCQ are not the preferred choice of drugs if the COVID-19 patients already have existing co-morbid conditions viz., diabetes mellitus and hypertension. CONCLUSION: A new advent of COVID-19 vaccines, such as nucleic acid-based (DNA/mRNA) vaccines, protein subunit vaccines, viral vector vaccines, and inactivated vaccines, have been developed for treating SARS-CoV-2 infection after the failure of aminoquinoline therapy in EU, China, and USA patients. However, some of the vaccines are yet to be examined against mutant strains of SARS CoV-2 that originated in the UK, Nigeria, South Africa, Brazil, and India.

STEMI India: reimagining STEMI networks in low- and middle-income countries: Reimagining STEMI.

Effective treatment for ST-elevation myocardial infarction (STEMI) includes the 24/7 availability of reperfusion therapy, which is crucial for good clinical outcomes. In low- and middle-income countries, this is hindered by disparities in resource utilisation, irregularities in access to health care and organisational gaps. Due to the inaccessibility of primary percutaneous coronary intervention (PCI) for most patients, the more feasible and practical approach of pharmacoinvasive management must be incorporated into the systems of care for STEMI. This review focuses on the development of STEMI India, a not-for-profit organisation that aims to advance the field of STEMI management by imparting and disseminating the latest information from around the world on STEMI management to all those involved in STEMI care. The STEMI India model system of care includes a 3-model framework, based on infrastructure and workforce availability, and tailored to meet the needs of the society it caters to. After the successful implementation of the "Tamil Nadu STEMI" project, a nationwide system of care for STEMI has been developed, which has been endorsed by the Cardiological Society of India (CSI) and the Association of Physicians of India (API).

In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial.

Recessive dystrophic epidermolysis bullosa (RDEB) is a lifelong genodermatosis associated with blistering, wounding, and scarring caused by mutations in COL7A1, the gene encoding the anchoring fibril component, collagen VII (C7). Here, we evaluated beremagene geperpavec (B-VEC), an engineered, non-replicating COL7A1 containing herpes simplex virus type 1 (HSV-1) vector, to treat RDEB skin. B-VEC restored C7 expression in RDEB keratinocytes, fibroblasts, RDEB mice and human RDEB xenografts. Subsequently, a randomized, placebo-controlled, phase 1 and 2 clinical trial (NCT03536143) evaluated matched wounds from nine RDEB patients receiving topical B-VEC or placebo repeatedly over 12 weeks. No grade 2 or above B-VEC-related adverse events or vector shedding or tissue-bound skin immunoreactants were noted. HSV-1 and C7 antibodies sometimes presented at baseline or increased after B-VEC treatment without an apparent impact on safety or efficacy. Primary and secondary objectives of C7 expression, anchoring fibril assembly, wound surface area reduction, duration of wound closure, and time to wound closure following B-VEC treatment were met. A patient-reported pain-severity secondary outcome was not assessed given the small proportion of wounds treated. A global assessment secondary endpoint was not pursued due to redundancy with regard to other endpoints. These studies show that B-VEC is an easily administered, safely tolerated, topical molecular corrective therapy promoting wound healing in patients with RDEB.

Design and implementation of thermal collection networks in 3-D IC structures.

The empirical affirmation in the electronics industry is that the power of chips per unit area is growing exponentially. The amount of heat generated is equal to the power; hence as power per unit area increases, so does the amount of heat generated within the chip. Thus, it necessary to mitigate the thermal problems of electronic systems. If not addressed or suppressed, thermal problems can lead to various issues including dielectric breakdown, electromigration, material creeping, unwanted chemical reactions, board warpage, drift in performance, and indirect heating. In this study, a dedicated thermal collection network (TCN) in the back end of the line area of an electronic chip was investigated. This network can help in creating a connection using a thermal through Silicon via (TTSV) to pump up the thermal energy to the heat-sink-fan assembly. Pre-empting heat from the sources could manage the thermal issues arising in chips as well as three-dimensional integrated circuit (3-D IC) structures. The finite-element method was the tool used for analysis. 31.62% of heat suction in TCNs of monolithic ICs, 11.36% in TCNs of 3-D IC structures, and 35.34% of heat suction in junctions of TTSVs compared with different approaches without the postulate used here. This procedure is expected to lead to a new path for redesigning electronic chips and 3-D IC structures.

Safety and feasibility of intravascular ultrasound guided zero-contrast percutaneous coronary intervention-A prospective study.

BACKGROUND: There are published reports of safety and feasibility of percutaneous coronary intervention (PCI) without contrast, using intravascular ultrasound (IVUS) and coronary physiology guidance in chronic kidney disease population. We prospectively evaluated the safety and feasibility of zero-contrast PCI technique. METHODS: In this prospective study, we hypothesized that PCI is feasible without contrast, using IVUS guidance alone without mandatory coronary physiology to rule out slow-flow or no-flow at the end of PCI in a population at risk of contrast-induced acute kidney injury (CI-AKI). In this study, we included 31 vessels in 27 patients at risk of CI-AKI and assessed the primary outcome of technical success at the end of PCI. Major adverse cardio-cerebro vascular events (MACCE) and percent change in estimated glomerular filtration rate(eGFR) one month after PCI were the secondary outcomes of the study. RESULTS: The primary outcome was met in 87.1%(n = 27) of the procedures. Technical failure was seen in 12.9%(n = 4) of the procedures. None of the patients developed MACCE at one-month follow-up. The median percent change in eGFR at one-month follow-up was -8.19%(-24.40%, +0.92%). There was no newer initiation of renal replacement therapy at one-month follow-up. CONCLUSIONS: Zero-contrast PCI is safe and feasible in selective coronary anatomies with IVUS guidance. Coronary physiology is not mandatory to rule out slow-flow or no-flow at the end of procedure. Contrast may be needed to tide over the crisis during the possible complications, namely slow-flow, geographical miss and intraprocedural thrombus.

Role of NRF2 cascade in determining the differential response of cervical cancer cells to anticancer drugs: an in vitro study.

BACKGROUND: Cervical cancers are usually treatable if detected in early stages by a combination of therapies. However, the prognosis of cervical cancer patients with metastasis remains unfavorable due to the fact that most of the cervical carcinomas are either resistant to anticancer drugs or show signs of relapse after initial treatment. Therefore, it is important to control the chemoresistance as it is the key to develop effective treatment options for cervical cancer. OBJECTIVE: The current study aimed at evaluating the differential responses of cervical cancer cells to anti-cancer drugs and assessed whether the differences in the expression profiles of antioxidant genes regulated by nuclear factor erythroid-2-related factor 2 (NRF2), led to the variations in the sensitivities of the cancer cells to treatment. METHODOLOGY: Three cervical cancer cell lines were investigated for their differences in NRF2 pathway by measuring the gene expression and enzyme activity. The differences in the sensitivity to anti-cancer drugs and variation in ROS profile was also evaluated. The addition of exogenous drugs to manipulate the intracellular ROS and its effect on NRF2 pathway genes was also investigated. RESULTS: HeLa and SiHa cells were more sensitive to cisplatin and oxaliplatin treatment than C33A cells. HeLa and SiHa cells had significantly lower NRF2 gene levels, NQO1 enzyme activity and basal GSH levels than C33A cells. Levels of ROS induced were higher in HeLa than C33A cells. CONCLUSION: Overall, the differences in the cellular levels of antioxidant regulatory genes led to the differential response of cervical cancer cells to anti-cancer drugs.