Tanvir Hospital

In individuals with diabetes, the occurrence of heart failure varies from 9% to 22%, marking a fourfold rise compared to the general population. This heightened prevalence is particularly pronounced in diabetic patients aged 60 years or older. Recent studies highlight a rapid increase in mortalities related to cardiomyopathies, attributed to the alarming surge in cases of type 2 diabetes mellitus. Global epidemics like diabetes and heart failure (HF) often referred to as the “deadly duo,” pose a significant burden on society due to heightened hospitalization costs and a grim prognosis. Therefore, it is necessary to implement new strategies for improving the diagnosis and treatment of diabetes and heart failure. Early diagnosis of diabetes and heart failure may have results in keeping patients healthy and it helps in reducing the risk factors of such serious complications. Currently, the application of artificial intelligence (AI) and Machine Learning (ML) in the field of diabetes has increased which may help improve the classification system and may have the possibility to solve this problem at an early stage. In this article, our aim is to examine the multifaceted relationship between diabetes and heart failure using (AI/ML). The application of AI and ML in diabetes and heart failure research has been widely explored in basic biomedical research. Therefore, in this review, we highlighted the impactful use of AI/ML in underlying mechanisms of diabetic cardiomyopathy by using various therapeutic drugs to explore the risk factors and consider their implications on patient response. By unraveling this intricate relationship, we can strive to enhance our knowledge to pave the way for improved preventive measures, early detection, and more effective management of these intertwined titans.

This study aimed to identify promising allosteric inhibitors with the potential to inhibit EGFR1, PI3K, and BRAF kinases as a single agent or in a combination of existing drugs, thus acting as a therapeutic option when traditional drugs fail to give a beneficial response in disease pathology. Upregulation of EGFR1 activates several downstream signaling pathways, resulting in pathophysiological alterations that contribute to cancer. The RAS/RAF/MEK/ERK (MAPK) and PI3K/Akt/mTOR (PI3K/Akt/mTOR) pathways are major downstream signalling partners induced by EGFR1 activation. Despite their vast importance, allosteric FDA-approved drugs targeting EGFR1 and these pathways are not available. The objective of the study is to identify novel multi-kinase small molecules with the potential to inhibit major sites of amplification of cancer signalling pathways, i.e., EGFR1, PI3K/Akt/mTOR, and RAS/RAF/MEK/ERK (MAPK) signalling pathways targeting allosteric sites. In silico methods were used to identify the potential inhibitors using EGFR1, PI3, and BRAF crystal structures complexed with allosteric inhibitors. The potential novel molecules were confirmed for their drug-likeness. Their stability of binding was also confirmed using molecular dynamics simulation studies. To eliminate false negatives, this study used a pharmacophore and structure-based targeting method. The current study was effective in identifying drug-like small molecules, such as ZINC38783966, ZINC01456629, ZINC01456628, and 124173751, 137352549, 137353176, 137352399, 132020316 from ZINC and PubChem database, respectively, with a potential to bind EGFR1 (6DUK), PI3 (4A55) and BRAF (6P3D) at allosteric sites. A 50 ns molecular dynamics investigation also revealed that these potential novel multitarget kinase allosteric inhibitors exhibited stable binding. Alterations in EGFR1, PI3K/Akt/mTOR, and RAS/RAF/MEK/ERK (MAPK) signalling pathways are observed in cancers in high frequency and are also used by viral and environmental toxicants for pathologic purposes. These multi-kinase allosteric inhibitors will provide insight into allosteric drug discovery and deepen our understanding of targeting these pathways, either individually or in combination with orthosteric inhibitors.

More than two billion people suffer from micronutrient deficiencies (MiNDs) globally, with nearly half living in India. The current risk of ‘hidden hunger’ is severe in India due to serious deficiency risks across an array of essential micronutrients. A nationwide advisory board meeting attended by more than 20 Indian health care professionals (HCPs) was conducted to determine their clinical viewpoint on MiND. An in-depth search of PubMed studies emphasizing various aspects of MiND relevant to the Indian scenario was performed and presented to eminent HCPs from across India who then shared their opinions and perspectives based on their clinical experiences associated with MiND.

Abstract Tuberculosis is a highly infectious disease caused by Mycobacterium tuberculosis (M. tb) which is infecting around one‐third of the world population. The majority of individuals develop latent tuberculosis infection (LTBI), but only 10% of LTBI individuals develop active TB. Household contacts (HHC) of TB patients are 10‐60 times more likely to develop the disease than non exposed individuals. Dendritic cells strengthen the immune response against M. tb through the stimulation of CD4+T cells, which differentiate into different types of T helper cells (Th) such as Th1, Th2 and Th17 lineages. Th17 cells play an important role in coordinating pulmonary immune defence and enhance the expression of cytokines (IL‐17A, IL‐17F, IL‐21 and IL‐22), chemokines and antimicrobial peptides that lead to phagocytosis of M. tb. Previous studies have reported that Th17 polymorphisms are associated with TB susceptibility. In this review, we focused on the immuno‐genetic importance of Th17 in TB and screening the HHCfor Th17 genetic variants may help for the early detection of TB infection in individuals who are at risk.

The risk of premalignant and malignant endometrial pathologies increases in the postmenopausal period. Dilatation and curettage fail to diagnose one in ten endometrial pathologies. Hysteroscopy is the gold standard to evaluate the endometrial cavity. Hysteroscopy can identify malignant or benign pathology with approximately 20% false-positive results. Hysteroscopy combined with biopsy increases the accuracy of diagnosis up to 100%. This pictorial review takes you through the hysteroscopic view of normal-looking postmenopausal atrophic uterus, cystic atrophy, benign endometrial pathologies, endometrial hyperplasia, endometrial cancer, tamoxifen-induced endometrial hyperplasia and histiocytic endometritis. The purpose of this pictorial review is to guide the operator in systematic evaluation of the endometrial cavity with special attention to the thickness of the endometrium, vascular architecture, location of the lesion and surface aberrations, which adds value to the diagnosis and management of endometrial pathologies.

Influenza is a highly contagious disease with global annual outbreaks of 3-5 million severe cases and 0.25-0.5 million deaths. The risk is greater in pregnant women that results in high morbidity and mortality. The objective of this study was to see the efficacy of influenza vaccine on pregnant women and their newborn upto 6months. This was a retrospective study (January 2016-March 2018). Records of 346 pregnant women were included in this study (vaccinated: 288; unvaccinated: 58). Women and infants were categorised into Category A, B or C according to the guidelines issued by the Ministry of Health and Family Welfare, India on influenza. The groups were comparable with respect to baseline characteristics. Greater number of women received influenza vaccine during the first trimester (n=117). During the gestation period, majority of the women in the vaccinated group were symptom-free compared with the unvaccinated (92% vs 70.7%). Also, none of the vaccinated women were categorised into category C compared with one who was laboratory tested positive for influenza in the unvaccinated group. Similar results were seen postpartum and more number of infants remained symptom-free in the vaccinated group compared with unvaccinated (69.3% vs 25.9%). More number of infants were born pre-term in the unvaccinated group compared with vaccinated (15.5% vs 8.6%). Immunisation with influenza vaccine in any trimester during pregnancy was found to protect the mother and infants upto 6months of age against seasonal influenza without significant maternal adverse effects. In order to improve vaccination rates, there must be a national vaccination policy and incorporation of maternal immunisation in standard antenatal care.

Tuberculosis (TB) is a multifactorial disease governed by bacterial, host and environmental factors. On the host side, growing evidence shows the crucial role that genetic variants play in the susceptibility to Mycobacterium tuberculosis (Mtb) infection. Such polymorphisms have been described in genes encoding for different cytokines and pattern recognition receptors (PRR), including numerous Toll-like receptors (TLRs). In recent years, several members of the C-type lectin receptors (CTLRs) have been identified as key PRRs in TB pathogenesis. Nevertheless, studies to date have only addressed particular genetic polymorphisms in these receptors or their related pathways in relation with TB. In the present study, we screened the main CTLR gene clusters as well as CTLR pathway-related genes for genetic variation associated with pulmonary tuberculosis (PTB). This case-control study comprised 144 newly diagnosed pulmonary TB patients and 181 healthy controls recruited at the Bhagwan Mahavir Medical Research Center (BMMRC), Hyderabad, India. A two-stage study was employed in which an explorative AmpliSeq-based screening was followed by a validation phase using iPLEX MassARRAY. Our results revealed one SNP (rs3774275) in MASP1 significantly associated with PTB in our population (joint analysis p = 0.0028). Furthermore, serum levels of MASP1 were significantly elevated in TB patients when compared to healthy controls. Moreover, in the present study we could observe an impact of increased MASP1 levels on the lectin pathway complement activity in vitro. In conclusion, our results demonstrate a significant association of MASP1 polymorphism rs3774275 and MASP1 serum levels with the development of pulmonary TB. The present work contributes to our understanding of host-Mtb interaction and reinforces the critical significance of mannose-binding lectin and the lectin-complement pathway in Mtb pathogenesis. Moreover, it proposes a MASP1 polymorphism as a potential genetic marker for TB resistance.