Annulation of quinone methides with 2-benzylidene dithiolanes: synthesis of spirochroman dithiolanes.

An expeditious and regioselective approach towards the construction of a spiro-chroman motif is described. Quinone methides underwent a PTSA catalyzed annulation with 2-benzylidene dithiolanes to afford spiro-chroman dithiolanes in high yields. The synthetic versatility of the dithiolane motif was demonstrated by converting the adduct to coumarin, 3,4-dihydrocoumarin and chroman derivatives.

Identification of Novel Protein Targets of Prodigiosin for Breast Cancer Using Inverse Virtual Screening Methods.

Prodigiosin (PG) is chemically formulated as 4-methoxy-5-[(5-methyl-4-pentyl-2H-pyrrol-2ylidene)methyl]-2,2'-bi-1H-pyrrole and it is an apoptotic agent. Only a few protein targets for PG have been identified so far for regulating various diseases; nevertheless, finding more PG targets is crucial for novel drug discovery research. A bioinformatics method was applied in this work to find additional potential PG targets. Initially, a text mining analysis was conducted to determine the relationship between PG and a variety of metabolic processes. One hundred sixteen proteins from the KEGG pathway were selected for the docking study. Inverse virtual screening was performed by Discovery Studio software 4.1 using CHARMm-based docking tool. Twelve proteins are screened out of 116 because their CDOCKER interaction energy is larger than - 40.22 kcal/mol. The best docking score with PG was reported to be - 44.25 kcal/mol, - 44.99 kcal/mol, and - 40.91 kcal/mol for three novel proteins, such as human epidermal growth factor-2 (HER-2), mitogen-activated protein kinase (MEK), and S6 kinase protein (S6K) respectively. The interactions in the S6K/PG complex are predominantly hydrophobic; however, hydrogen bond interactions can be identified in the MEK/PG and HER-2/PG complexes. The root-mean-square deviation (RMSD) and key interaction score system (KISS) were further used to validate the docking approach. The docking approach employed in this work has a low RMSD value (2.44 Å) and a high KISS score (0.5), indicating that it is significant.

Prevalence and Associated Risk Factors of Primary Open Angle Glaucoma Among Patients With Type 2 Diabetes Mellitus: A Cross-Sectional Study From North India.

Background Glaucoma is a category of disorders that cause visual loss due to damage to the optic nerve. It is the primary cause of irreversible blindness around the globe. In diabetic individuals, intraocular pressure (IOP) was found to be higher than in non-diabetics, and this impact was linked to a rise in fasting blood glucose levels. In light of the foregoing findings, the current investigation was carried out with the goal of determining the prevalence and associated factors for primary open-angle glaucoma in people with diabetes in a tertiary care teaching hospital. Methods This cross-sectional study was carried out in a tertiary care teaching hospital. For a twelve-month period (2021-2022), adult patients (with type 2 diabetes and an age of 18 years or more) attending the ophthalmology out patient department (OPD) were included. Demographic information, socioeconomic data, and medical, familial, and ocular history were all gathered. All individuals with diabetes had an initial ophthalmological evaluation [including best corrected visual acuity (BCVA), slit-lamp biomicroscopy, assessment of peripheral anterior chamber depth (ACD), fundus examination, stereoscopic optic disc evaluation, and IOP measurement] by a senior ophthalmologist. Pearson's Chi-square test was used to compare variables on a nominal scale, whereas the t-test for independent samples was used to examine variables on a continuous scale. Results Our study enrolled a total of 1262 diabetic patients out of which 62.0% of subjects were male. Most of the enrolled subjects belonged to the 61-70 years of age group (35.8%). The eye examination of enrolled subjects showed that out of 1262 diabetic patients, 197 subjects (15.6%) were having primary open-angle glaucoma (POAG). The vision (in the better eye) was analyzed among three groups [no glaucoma or sight-threatening diabetic retinopathy (STDR); only glaucoma; and glaucoma plus STDR] and it was observed that no perception of light (PL) was noticed in 0.2% and 1.2% of subjects in the "no glaucoma or STDR" and "only glaucoma" groups respectively. In our study, the variables significantly associated with the increased prevalence of glaucoma among diabetic subjects included illiteracy, family history of type 2 diabetes mellitus (DM), being hypertensive, non-intake of anti-hypertensive medication, and >10 years duration of DM (p<0.05). Conclusion From our study, we came to the conclusion that there is clear-cut evidence of an increased incidence of POAG in diabetic patients, which was 15.6%. The study also showed a significant association between age, education, diet, hypertension, family history of diabetes and duration of diabetes, and; POAG. However, no significant association was found between gender and POAG.

Validation of antioxidant, antiproliferative, and in vitro anti-rheumatoid arthritis activities of epigallo-catechin-rich bioactive fraction from Camellia sinensis var. assamica, Assam variety white tea, and its comparative evaluation with green tea fraction.

The epigallocatechin-rich polyphenolic fraction of Assam variety white tea, traditionally used for the management of diverse inflammatory ailments and health drink, was investigated through eco-friendly green aqueous extraction, TLC, and HPLC characterization, phytochemical screening, in vitro DPPH assay, anti-proteinase, MTT assay on synovial fibroblast and colon cancer cells, apoptotic FACS analysis, cytokine ELISA, p-STAT3 western blotting, and in silico docking analysis. HPLC-TLC standardized white tea fraction (WT-F) rendered higher extractive-yield (21%, w/w), than green tea fraction(GT-F) (12%, w/w). WT-F containing flavonoids and non-hydrolysable polyphenols showed better antioxidant activity, rather than equivalent GT-F. WT-F demonstrated remarkable anti-rheumatoid-arthritis activity via killing of synovial fibroblast cells (66.1%), downregulation of TNF-α (93.33%), IL-6 (87.97%), and p-STAT3 inhibition (77.75%). Furthermore, WT-F demonstrated better anti-proliferative activity against colon cancer cells (HCT-116). Collectively, our study revealed that the white tea fraction has boundless potential as anti-rheumatoid arthritis and anti-proliferative agent coupled with apoptotic, antioxidant anti-proteinase, and anti-inflammatory properties. PRACTICAL APPLICATIONS: Our eco-friendly extracted bioactive aqueous fraction of white tea, characterized by TLC-HPLC study and phytochemical screening have demonstrated remarkable anti-rheumatoid arthritis property and anti-proliferative action on colon cancer cells including potential anti-oxidant, anti-inflammatory, and anti-proteinase efficacy. The test WT-F sample has shown impressive safety on normal mammalian cells. WT-F has demonstrated better efficacy against rheumatoid arthritis and cancer model compared to equivalent green tea fraction. Traditionally, it is extensively used for boosting immunity, and energy, with cosmetic, and agricultural applications by the native inhabitants. So, the aqueous fraction of WT is suggested to be used as a prophylactic nutraceutical supplement and or therapeutic agent in commercial polyherbal formulation to attenuate and management of auto-inflammatory rheumatoid arthritis and carcinogenesis of colon. It is additionally suggested to establish in vivo rheumatoid arthritis animal and clinical study to validate their pharmacokinetic stability and dose optimization coupled with anti-inflammatory, cytotoxicity, and anti-oxidant property.

Exploration of binding mechanism of triclosan towards cancer markers using molecular docking and molecular dynamics.

The molecule 5-chloro-2-(2,4-dichlorophenoxy) phenol is well-known as Triclosan (TCS), which is also a potential endocrine disrupting synthetic chemical. TCS exposure has been connected to the control of the human enoyl-acyl carrier protein-reductase (hER), which has been linked to a range of life threatening diseases. However, other than hER, the new protein targets for TCS that are responsible for a variety of cancers are yet unclear. The goal of this work is to investigate into the protein binding patterns of TCS and proteins from various cancer signaling pathways. Discovery Studio 4.1 was used to perform molecular docking and molecular dynamics (MD) on the protein-triclosan complex. The proteins were first screened using CHARMM-based docking with a CDOCKER energy greater than -21.40 kcal/mol. The CDOCKER energies of Fas-associated death domain (FADD), Receptor-interacting protein 1 (RIP1), F-κB-inducing kinase (NIK), c-Jun N-terminal kinase (JNK), Apoptosis signal-regulating kinase 1 (ASK1), B-cell lymphoma 2 (Bcl-2), Apoptosis-inducing factor (AIF), α-tubulin, and Actin were -20.68 kcal/mol, -26.88 kcal/mol, -23.43 kcal/mol, -22.21 kcal/mol, -20.40 kcal/mol, -21.10 kcal/mol, -20.98 kcal/mol, -24.67 kcal/mol, and -23.09 kcal/mol respectively. MD was performed on the screened proteins by standard dynamics cascade tool using CHARMM Force field. The MD results were accessed using the energy-time graph, root-mean-square deviation (RMSD), and root mean square fluctuations (RMSF). The 100 conformers of α-tubulin, NIK, FADD, and RIP1 were found to have a trend of increasing RMSD, whereas Bcl-2, ASK1, AIF, Actin, and JNK proteins had lower RMSD values. In compared to FADD, AIF, and JNK, the RMSF variations of the Bcl-2, ASK1, α-tubulin, Actin, NIK, and RIP1 residues were shown to be high. Similar patterns were seen in the energy variations, which range from 1000 kcal/mol to 2000 kcal/mol. RIP1 and Bcl-2 showed more variation in the sidechain RMSF in comparison to FADD, ASK1, AIF, Actin, α-tubulin, NIK and JNK. Thus, it can be postulated that AIF and JNK proteins of apoptosis signaling pathway are pivotal in the TCS mediated reactions.

Association of ischemic electrocardiographic changes in high-altitude areas with coronary angiography.

BACKGROUND: Soldiers native to lowlands, while sojourning at high altitude (HA), are referred to tertiary care centers with electrocardiographic (ECG) abnormalities. Exposure to HA may precipitate myocardial ischemia in subjects with underlying coronary artery disease (CAD). Conversely, it may produce physiological ECG changes mimicking those of CAD, causing a diagnostic dilemma. This study sought to correlate the presence of CAD on coronary angiography (CAG) with a putative diagnosis of CAD based on clinical findings and ECG. METHODS: A prospective study was conducted on patient's from HA areas, referred for evaluation for CAD to a single center at near-sea-level. Thirty-five minimally symptomatic/asymptomatic soldiers with ECG changes suggestive of CAD, underwent CAG. Correlation was sought between ECG and CAG evidence of CAD. RESULTS: The association of CAD on CAG with clinical and ECG diagnosis of CAD was not significant, 4 of the 35 soldiers (11.4%) showing CAG evidence of CAD (chi square 3.849, p = 0.697). The association between symptoms and coronary artery lesions was, also, not significant, only four of twenty-three (17.4%) minimally symptomatic subjects having CAD on CAG. CONCLUSION: Insignificant numbers of previously healthy persons, who present with minimal symptoms and ECG changes suggestive of CAD while sojourning at HA, have coronary artery involvement on CAG. Those with incidental ECG changes, without symptomatology, do not have CAD on CAG.

Analysis of ST-elevation myocardial infarction occurring in soldiers during strenous military training.

BACKGROUND: At our tertiary care cardiology center, we are receiving soldiers who sustained acute ST-Elevation Myocardial Infarction (STEMI) during the strenuous Battle Field Efficiency Test (BPET) and other such activities. METHODS: This was a single-center observational study to assimilate and analyze the precipitating causes, risk factors, symptoms, and the efficacy of the management protocols in soldiers sustaining STEMI during the BPET or other forms of strenuous military training. RESULTS: All 25 soldiers with documented STEMI following strenuous military training presented with chest pain as the primary symptom. 88% had symptoms either during or within 1st hour of the strenuous activity. 76% underwent thrombolysis with an angiographic success rate of 95%. Primary PCI was possible in only 3/25 (12%) of the cases, of which 2 (66%) did not require stenting after thrombus aspiration; 88% of soldiers reported "training for the event" for less than four times/week. CONCLUSION: STEMI precipitated by strenuous unaccustomed military training have exclusively single vessel affection with an excellent response to thrombolysis and thrombus aspiration. Thus, the timely institution of pharmacological or mechanical revascularization therapy has dramatic results in the preservation of ventricular function. The lack of training for the strenuous event provides strong evidence for comprehensive, graded, physical training prior to strenuous military activities to prevent acute coronary syndromes.

A novel and efficient deep learning approach for COVID-19 detection using X-ray imaging modality.

With the exponential growth of COVID-19 cases, medical practitioners are searching for accurate and quick automated detection methods to prevent Covid from spreading while trying to reduce the computational requirement of devices. In this research article, a deep learning Convolutional Neural Network (CNN) based accurate and efficient ensemble model using deep learning is being proposed with 2161 COVID-19, 2022 pneumonia, and 5863 normal chest X-ray images that has been collected from previous publications and other online resources. To improve the detection accuracy contrast enhancement and image normalization have been done to produce better quality images at the pre-processing level. Further data augmentation methods are used by creating modified versions of images in the dataset to train the four efficient CNN models (Inceptionv3, DenseNet121, Xception, InceptionResNetv2) Experimental results provide 98.33% accuracy for binary class and 92.36% for multiclass. The performance evaluation metrics reveal that this tool can be very helpful for early disease diagnosis.

Catheter ablation of complex cardiac arrhythmias: Single-centre experience in Armed Forces.

BACKGROUND: Complex arrhythmia ablation remains a technical challenge despite advances in hardware and mapping techniques. The aim of the study was to analyse the efficacy of radiofrequency ablation of arrhythmias requiring complex electrophysiological procedures at a tertiary-care centre. METHODS: A retrospective study was done for catheter ablation of arrhythmias performed at a single centre from Aug 2012 to Nov 2016 (4 years 4 months). The standard ablation involved conventional catheters with antegrade right heart and retrograde left heart access. The procedure was considered complex, if it involved 3 D electro-anatomical (EA) guidance for mapping or required special hardware and/or trans-septal puncture. RESULTS: Of 333 electrophysiology (EP) cases 265 qualified for ablation. The cohort of arrhythmias requiring complex procedure (n = 94) comprised of supraventricular 15 (15.9%), atrioventricular 43 (44.7%) and ventricular 36 (38.3%). The procedure used three-dimensional EA mapping in 31; trans-septal puncture for left atrial access in 40; and use of special catheters and sheaths in all 94 procedures. The overall success in the complex group after the first procedure was 87.2% versus 88.3% (P < 0.05), and after redo procedure it was 90.4% vs 94.7% (P < 0.05). There were three complications (pericardial perforation: 2; cardioembolism: 1) only in the complex group. The fluoroscopy time for complex was longer than that of the standard procedure (25.10 ± 6.32 versus 15.23 ± 5.33 min, P = 2.54). CONCLUSION: Arrhythmias requiring complex electrophysiological procedure for ablation have a comparable success rate to standard ablation procedure but at the cost of extra hardware, complications and fluoroscopy time.

Assessment of quality of life before and after successful percutaneous transvenous mitral commissurotomy in patients with severe mitral stenosis.

BACKGROUND: Rheumatic mitral stenosis (MS) is a significant cause of morbidity and mortality in India. Percutaneous transvenous mitral commissurotomy (PTMC) has become the procedure of choice for severe MS with pliable leaflets. Despite a wealth of literature on the technical aspects of PTMC, there is a dearth of literature addressing the impact of PTMC on the quality of life (QOL). AIM: The aim of the study is to assess the impact of PTMC on clinical status and QOL of patients with severe MS. MATERIALS AND METHODS: Twenty-five consecutive patients with severe MS undergoing PTMC were included in the study with their informed consent. All patients were subjected to routine blood tests, electrocardiogram, chest X-ray, two-dimensional and color echocardiography, treadmill test (TMT), and World Health Organization (WHO) QOL scale. The echocardiography, TMT, and WHOQOL scale were repeated after the procedure. RESULTS: The procedural success was 98%. The mean (range) mitral valve area preprocedure was 0.82 (0.59-0.92) cm2 and postprocedure was 1.61 (1.51-1.76) cm2. The difference was statistically significant (t = 5.02; P < 0.01). The mean (range) of TMT preprocedure was 4.05 (3.0-7.0) METS and postprocedure was 8.52 (6-12) METS. The difference was statistically significant (T = 3.08; P < 0.01). The mean (range) of QOL assessment pre- and post-procedure on physical domain was 8.83 (8.3-10.1) which increased to 11.11 (10-12.7); on social relationship domain from 9.17 (7.5-12.4) to 11.37 (9.4-12.0); on personal relationship from 11.6 (11-13) to 12.52 (12-13); on environment domain from 10.78 (10.2-11.7) to 11.56 (10.8-12); and on level of independence from 9.02 (8-10) to 12.29 (11.0-13.6). All the differences were statistically significant (Wilcoxon signed-rank test z = -4.376; -4.379; -4.234; -4.200; -4.375; respectively, all P < 0.001 highly significant). CONCLUSIONS: PTMC resulted in a significant improvement in the QOL of patients with severe MS. The significant improvement in QOL post-PTMC may be an indication for offering PTMC at an earlier stage to those patients whose QOL is severely compromised.

Docking-based inverse virtual screening strategy for identification of novel protein targets for triclosan.

Triclosan (TCS) is chemically designated as 5-chloro-2-(2,4-dichlorophenoxy) phenol and is considered as endocrine-disrupting chemical (EDC). The various diseases found due to exposure of TCS, have been linked with modulation of the human enoyl-acyl carrier protein-reductase (hER). However, the new protein targets for TCS other than hER, which are responsible for various diseases, are still unknown. In the present study, a bioinformatics approach was used to identify new possible targets for TCS. A text mining study was initially performed to understand the association of TCS in various biochemical processes. Discovery studio software 4.1 was used to carry out inverse virtual screening for 226 numbers of pathway proteins by docking study using CHARMm based docking tool, and twenty proteins were screened. CDOCKER energy values lower than -12.65 kcal/mol was considered for the screening of selected proteins. Three new proteins; Receptor-interacting protein 1 (RIP1), Apoptosis signal-regulating kinase 1 (ASK1) and B-cell lymphoma 2 (Bcl-2) from Apoptosis Signaling Pathway revealed best CDOCKER energy with triclosan which was -26.88, -23.34 and -22.96 kcal/mol respectively. The interaction of TCS with RIP1 and ASK1 were mostly hydrophobic; however, hydrogen bond type interaction was found in TCS/Bcl2 complex. Therefore, docking-based inverse virtual screening study suggests that TCS has other targets rather than hER, which can modulate various biochemical processes. The docking protocol was validated through evaluation of root-mean-square deviation (RMSD), key interaction score system (KISS) and the relationship between the docking energy and toxicity data available in ToxCast database. Low RMSD value (0.55 ˚A) and high KISS score (0.66) along with higher correlation (R2 = 0.9798) between docking affinity and toxicity indicated that docking protocol can be used to optimize the binding energetics.