Geriatric Oral Health and Quality of Life Among the Indigenous Irula Tribes of Tamil Nadu.

OBJECTIVES: This study aims to assess the oral health-related quality of life (OHRQoL) among the Irula tribes and to know the factors influencing quality of life among the elderly irula tribes of Tamil Nadu. METHODS: This cross-sectional study was conducted in the Northern district of Tamil Nadu, including 486 Irula individuals aged 65 and above. Participants were selected using a multistage sampling method. Data were collected through a structured questionnaire, including the Geriatric Oral Health Assessment Index (GOHAI) to evaluate OHRQoL. The study tool covered demographics, medical history, and oral health issues. Data analysis was performed using SPSS version 23, with logistic regression applied to account for confounders. RESULTS: The sample primarily consisted of individuals aged 65-69 years (55.6%), with a predominance of females (76.3%). The majority were Hindu (94.9%) and lived in nuclear families (88.3%). Educational levels were low, with 66.5% being illiterate. Most participants were agricultural laborers (64.6%) and had low monthly incomes. GOHAI results revealed that many respondents faced significant oral health challenges, including difficulties with eating, speaking, and discomfort. Multivariate analysis showed that educational level significantly affected OHRQoL, with higher education correlating with better quality of life. Arthritis was associated with poorer OHRQoL, while other health conditions did not show significant impacts. CONCLUSION: The study highlights severe oral health issues among the Irula community, with significant physical and psychological impacts. Educational attainment plays a crucial role in OHRQoL, while arthritis notably affects quality of life. The findings emphasize the need for targeted oral health interventions and increased awareness in tribal communities to improve overall health outcomes. Further research in larger populations is necessary to comprehensively understand and address geriatric oral health needs.

Correction: computational design, synthesis, and assessment of 3-(4-(4-(1,3,4-oxadiazol-2-yl)-1H-imidazol-2-yl)phenyl)-1,2,4-oxadiazole derivatives as effective epidermal growth factor receptor inhibitors: a prospective strategy for anticancer therapy.

[This corrects the article DOI: 10.1039/D4MD00055B.].

Computational design, synthesis, and assessment of 3-(4-(4-(1,3,4-oxadiazol-2-yl)-1H-imidazol-2-yl)phenyl)-1,2,4-oxadiazole derivatives as effective epidermal growth factor receptor inhibitors: a prospective strategy for anticancer therapy.

The epidermal growth factor receptor (EGFR) enzyme plays a critical role in governing the cell cycle, positioning it as a promising target for the development of anticancer drugs. In this study, we endeavored to design and synthesize innovative EGFR inhibitors with potential applications in anticancer therapy. A novel series of compounds, namely 3-(4-(4-(1,3,4-oxadiazol-2-yl)-1H-imidazol-2-yl)phenyl)-1,2,4-oxadiazoles (30a-j), were meticulously designed using FBDD efforts and synthesized. The synthesized compounds underwent thorough characterization using 1HNMR, 13CNMR, HRMS, and mass spectrum analyses. The in vitro anticancer activities of the newly developed compounds (30a-j) were evaluated against four human cancer cell lines such as prostate cancer (PC3 & DU-145), lung cancer (A549), and liver cancer (HEPG2) using the MTT method. The results, expressed as IC50 values, demonstrated significant anticancer activity for several compounds, with five compounds (30a, 30b, 30c, 30i, and 30j) exhibiting superior potency compared to the established anticancer drug etoposide. Notably, compound 30a emerged as the most promising compound, displaying potent cytotoxicity. We also conducted a screening of the compounds on the normal Vero cell line, revealing a pronounced selectivity of the compounds against cancer cell lines, with no observable impact on the normal cell lines. Moreover, the synthesized compounds were investigated for their impact on enzyme EGFR activity. The findings revealed a robust inhibitory effect against the EGFR wild-type enzyme and a 10-fold inferior potency against the mutant form of EGFR. This observation underscores the potential of the new derivatives as effective EGFRWT inhibitors with substantial anticancer efficacy. Further studies, including cell cycle analysis and apoptosis assays in HEPG2 cell lines, revealed cell cycle arrest at G1/G0 and G2 phases. We also evaluated the potential influence of compound 30a on the EGFR pathway using western blot analysis, revealing a significant inhibition of EGFR autophosphorylation in HEPG2 cells. In conclusion, our findings highlight the promise of these novel compounds as potent EGFR inhibitors, encouraging further investigation and development for the creation of novel and effective anticancer therapeutics.

The Impact of Red Beetroot Products on Glycemic Profiles: A Systematic Review of Human Evidence.

PURPOSE OF REVIEW: Low-glycemic diets are crucial, particularly for individuals with diet-related diseases such as obesity and diabetes. Therefore, observing the impact of multiple forms of red beetroot-based products on the glycemic profiles of humans under various health conditions has arguably become significant due to beetroot's high fiber content, antioxidants, inorganic nitrates, etc., which this review aims to summarize. RECENT FINDINGS: The relevant articles published between 2000 and 2022 were obtained from PubMed, Scopus, and ScienceDirect by following the PRISMA-P 2020 statement. This systematic review included 18 randomized controlled trials (RCTs), one non-randomized clinical trial (non-RCT), and one quasi-experimental (QE) study, and they covered different health conditions, e.g., type-2 diabetes mellitus (T2DM), obesity, hypertension, etc. The studies produced conflicting results, likely due to differences in the study design, dosage, duration, and population. The risk of bias in most of the RCTs and QE studies included in the review was assessed as low or moderate, and only one non-RCT was assessed as having a high risk of bias. Red beetroot may help maintain the blood sugar levels of humans under different health conditions. However, the existing results on beetroot's potential for glycemic management are unclear due to varied outcomes across studies. Further intervention studies with standardized protocols and diverse participant groups are necessary to assess the role of beetroot products in regulating blood sugar levels before making a definitive judgment.

Recent Progress in the Oral Delivery of Therapeutic Peptides and Proteins: Overview of Pharmaceutical Strategies to Overcome Absorption Hurdles.

Purpose: Proteins and peptides have secured a place as excellent therapeutic moieties on account of their high selectivity and efficacy. However due to oral absorption limitations, current formulations are mostly delivered parenterally. Oral delivery of peptides and proteins (PPs) can be considered the need of the hour due to the immense benefits of this route. This review aims to critically examine and summarize the innovations and mechanisms involved in oral delivery of peptide and protein drugs. Methods: Comprehensive literature search was undertaken, spanning the early development to the current state of the art, using online search tools (PubMed, Google Scholar, ScienceDirect and Scopus). Results: Research in oral delivery of proteins and peptides has a rich history and the development of biologics has encouraged additional research effort in recent decades. Enzyme hydrolysis and inadequate permeation into intestinal mucosa are the major causes that result in limited oral absorption of biologics. Pharmaceutical and technological strategies including use of absorption enhancers, enzyme inhibition, chemical modification (PEGylation, pro-drug approach, peptidomimetics, glycosylation), particulate delivery (polymeric nanoparticles, liposomes, micelles, microspheres), site-specific delivery in the gastrointestinal tract (GIT), membrane transporters, novel approaches (self-nanoemulsifying drug delivery systems, Eligen technology, Peptelligence, self-assembling bubble carrier approach, luminal unfolding microneedle injector, microneedles) and lymphatic targeting, are discussed. Limitations of these strategies and possible innovations for improving oral bioavailability of protein and peptide drugs are discussed. Conclusion: This review underlines the application of oral route for peptide and protein delivery, which can direct the formulation scientist for better exploitation of this route.

Depressive symptoms and their correlates among predoctoral dental students in the United States.

OBJECTIVE: To investigate the prevalence of self-reported depressive symptoms among predoctoral dental students in the United States and examine potential correlates. METHODS: A survey was emailed to all 66 dental schools in the United States, inviting them to distribute it to their predoctoral students. Depressive symptoms were assessed using the Patient Health Questionnaire-9. Data collection occurred from February to April 2020. Multivariable ordinal logistic regression was used to assess associations between demographic variables and depressive symptom severity category, adjusting for potential confounding. RESULTS: Of an estimated 25,000 predoctoral dental students at the 66 schools, 631 students from 21 schools completed the survey. A total of 24.1% were categorized as having minimal or no depressive symptoms, 33.6% as having mild depressive symptoms, and 42.3% as having moderate, moderately severe, or severe depressive symptoms. Gender (p = 0.015) and race/ethnicity (p = 0.002) were significant predictors of severity, adjusting for other variables. Students identifying as female had higher odds of self-reporting greater depressive severity symptoms compared with students identifying as male. Students identifying as African American/Black (non-Hispanic) and Asian/Pacific Islander had higher odds of self-reporting greater depressive severity symptoms compared with students identifying as White. CONCLUSION: There is evidence of a high prevalence of depressive symptoms among predoctoral dental students in the United States. Demographic variables may be risk indicators within this population. Approaches to reduce depressive symptoms among US predoctoral dental students are needed.

Computational Design, Synthesis, and Bioevaluation of 2-(Pyrimidin-4-yl)oxazole-4-carboxamide Derivatives: Dual Inhibition of EGFRWT and EGFRT790M with ADMET Profiling.

The ongoing research in cancer treatment underscores the significance of dual epidermal growth factor receptor (EGFR) kinase inhibitors targeting both mutant and wild-type variants. In this study, employing in silico fragment-based drug design (FBDD) and computational analysis, we have successfully developed a novel chemical series of 2-(pyrimidin-4-yl)oxazole-4-carboxamide (16a-j) derivatives designed as dual EGFR kinase inhibitors. A comparative in vitro anticancer profile of the newly synthesized compounds (16a-j) was tested against a panel of five human cancer cell lines like prostate cancer (PC3 & DU-145), lung cancer (A549), human liver cancer (HEPG2), and breast cancer (MDA-MB-468) by employing MTT method. In this experiment a well-known anticancer agent, Etoposide was used as positive control. Most of the derivatives demonstrated significant cytotoxicity, ranging from excellent to moderate levels. The IC50 values for the synthesized compounds observed between 0.10 ± 0.052 to 9.83 ± 5.96 µM, while the positive control exhibited a range of 1.97 ± 0.45 µM to 3.08 ± 0.135 µM. These results indicate that the synthesized compounds demonstrate higher cytotoxic potency in comparison to the reference compound. Furthermore, all these compounds underwent screening against normal Vero cell lines to assess their cytotoxicity. In each case, the observed cytotoxicity values (IC50) were higher than 22 µM, affirming the compounds selectivity for cancer cell lines. Among the compounds investigated, three compounds (16a, 16e, and 16i) exhibited notable cytotoxicity, while two compounds (16g and 16h) demonstrated exceptional cytotoxicity. The selectivity index of the tested compounds indicates a pronounced preference for targeting cancer cell lines over normal cells. Furthermore, all the compounds 16a-j underwent assessment for their EGFR kinase inhibitory activity against both EGFRWT and mutated EGFRT790M. The results unveiled the potential eligibility of this new series of compounds as effective EGFR inhibitors. Moreover, compound 16h underwent additional testing for cell cycle analysis, revealing its capability to arrest the cell cycle in the G2/M phase and induce apoptosis at the IC50 concentration.

Repurposing of approved antivirals against dengue virus serotypes: an in silico and in vitro mechanistic study.

Dengue is an emerging, mosquito-borne viral disease of international public health concern. Dengue is endemic in more than 100 countries across the world. However, there are no clinically approved antivirals for its cure. Drug repurposing proves to be an efficient alternative to conventional drug discovery approaches in this regard, as approved drugs with an established safety profile are tested for new indications, which circumvents several time-consuming experiments. In the present study, eight approved RNA-dependent RNA polymerase inhibitors of Hepatitis C virus were virtually screened against the Dengue virus polymerase protein, and their antiviral activity was assessed in vitro. Schrödinger software was used for in silico screening, where the compounds were passed through several hierarchical filters. Among the eight compounds, dasabuvir was finally selected for in vitro cytotoxicity and antiviral screening. Cytotoxicity profiling of dasabuvir in Vero cells revealed changes in cellular morphology, cell aggregation, and detachment at 50 µM. Based on these results, four noncytotoxic concentrations of dasabuvir (0.1, 0.25, 0.5, and 1 µM) were selected for antiviral screening against DENV-2 under three experimental conditions: pre-infection, co-infection, and post-infection treatment, by plaque reduction assay. Viral plaques were reduced significantly (p < 0.05) in the co-infection and post-infection treatment regimens; however, no reduction was observed in the pretreatment group. This indicated a possible interference of dasabuvir with NS5 RdRp, as seen from in silico interaction studies, translating into a reduction in virus plaques. Such studies reiterate the usefulness of drug repurposing as a viable strategy in antiviral drug discovery. In this drug repurposing study, dasabuvir, a known anti-hepatitis C drug, was selected through virtual screening and assessed for its anti-dengue activity.

Prevalence of activity limitation and its associated predictor among the elderly in Tamil Nadu, India: A community-based cross-sectional study.

BACKGROUND: Functional disability develops in a dynamic and progressive manner. As people age, their health problems worsen and they lose the ability to perform activities of daily living (ADLs) such as dressing, using the toilet, bathing, and eating. With a better understanding of the underlying risk factors and the related mechanisms of the disablement process, it is possible to make more effective and more efficient programs to prevent or delay the onset of disability in older people. MATERIALS AND METHODS: A community-based, descriptive, cross-sectional study was carried out among 453 elderly from Tamil Nadu, India. A door-to-door interview was used to administer the Katz Index of Independence on ADL. Simple random selection was employed to select the study individuals. To determine the association for particular risk factors, Chi-squared test and binary logistic regression were used. RESULTS: First, our study findings show the prevalence of activity limitation among the elderly using the The Katz Index of Independence. This study shows that the prevalence of activity limitation was 23% among the elderly. Seventy-seven percent had no significant limitations: they are independent. There is a statistically significant association between activity limitation as opposed to gender, visual impairment, depression, urinary incontinence, unintentional injury in the past year, and alcohol consumption. CONCLUSION: The study found that the self-reported prevalence of activity limitation was 23% among the elderly and 77% had no significant limitations. The Katz Index of Independence in activities of daily living may be used as a handy tool to identify the activity limitation in community-based checkups.

Structure-activity relationship mediated molecular insights of DprE1 inhibitors: A Comprehensive Review.

Emerging threats of multi-drug resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) tuberculosis led to the discovery of a novel target which was entitled Decaprenylphosphoryl-ß-D-ribose 2'-epimerase (DprE1) enzyme. DprE1 is composed of two isoforms, decaprenylphosphoryl-ß-D-ribose oxidase (DprE1) and decaprenylphosphoryl-D-2-keto erythro pentose reductase (DprE2). The enzymes, DprE1 and DprE2, regulate the two-step epimerization process to form DPA (Decaprenylphosphoryl arabinose) from DPX (Decaprenylphosphoryl-D-ribose), which is the sole precursor in the cell wall synthesis of arabinogalactan (AG) and lipoarabinomannan (LAM). Target-based and whole-cell-based screening played an imperative role in the identification of the druggable target, DprE1, whereas the druggability of the DprE2 enzyme is not proved yet. To date, diverse scaffolds of heterocyclic and aromatic ring systems have been reported as DprE1 inhibitors based on their interaction mode, i.e. covalent, and non-covalent inhibitors. This review describes the structure-activity relationship (SAR) of reported covalent and non-covalent inhibitors to enlighten about the crucial pharmacophoric features required for DprE1 inhibition, along with in-silico studies which characterize the amino acid residues responsible for covalent and non-covalent interactions.Communicated by Ramaswamy H. Sarma.

Prevalence of viral hepatitis infection in India: A systematic review and meta-analysis.

BACKGROUND: Nowadays, Viral Hepatitis can be comparable to the big three communicable diseases: tuberculosis, HIV/AIDS, and malarial infections. The main purpose of this study was to summarize the prevalence of viral Hepatitis in India from peer-reviewed articles published from February 2000 to February 2021. MATERIALS AND METHODS: We conducted a systematic search on Science Direct, Scopus, Medline, PubMed, Web of Science, Google Scholar, and other open access journals. We evaluated all relevant papers that looked into the prevalence of viral Hepatitis systematically. Finally, 28 studies on viral Hepatitis published from February 2000 to February 2021 have been selected. These studies have been conducted across the northern, southern, central, eastern, and western regions of India. RESULTS: Twenty-eight full-text publications were obtained and evaluated consisting of 45,608 research participants. Hepatitis A was found to range from 2.1% to 52.5%. Hepatitis B was found in a wide range of individuals, ranging from 0.87% to 21.4% of the population. Hepatitis C was found to range from 0.57% to 53.7%. The majority of the children were affected by hepatitis A, and 47.4% of third-trimester pregnant mothers were affected by hepatitis E. Diabetes, hospital admission, history of jaundice, history of surgeries, and heterosexual contact were the leading modes of acquiring HBV and HCV infections. As a result of its great magnitude, this disease poses a severe threat to the national healthcare system. CONCLUSION: Effective public health measures are urgently needed to minimize the burden of viral Hepatitis and eliminate the disease.

An insight into structure-activity relationship of naturally derived biological macromolecules for the treatment of Alzheimer's disease: a review.

Alzheimer's disease (AD) is a neurological disorder that affects millions of people worldwide. There are currently no cures for AD, although various drugs are used to manage the symptoms and reduce the disease's progression. AChE inhibitors such as rivastigmine, donepezil, galantamine, and the NMDA glutamate receptor antagonist memantine are currently FDA-approved drugs used in the treatment of AD. Recently, naturally derived biological macromolecules have shown promising results in the treatment of AD. Several biological macromolecules derived from natural sources are in various stages of preclinical and clinical trials. During the literature search, it was observed that there is a lack of a comprehensive review that particularly focuses on the role of naturally derived biological macromolecules (protein, carbohydrates, lipids, and nucleic acids) in the treatment of AD and the structure-activity relationship (SAR) approach for understanding the medicinal chemistry perspective. This review focuses on the SAR and probable mechanisms of action of biological macromolecules derived from natural sources for the treatment of AD, including peptides, proteins, enzymes, and polysaccharides. The paper further addresses the therapeutic possibilities of monoclonal antibodies, enzymes, and vaccines for the treatment of AD. Overall, the review provides insight into the SAR of naturally derived biological macromolecules in the treatment of AD. The ongoing research in this field holds great promise for the future development of AD treatment and provides hope for individuals affected by this devastating disease.Communicated by Ramaswamy H. Sarma.

Design, Development, and Evaluation of Constant Voltage Iontophoresis for the Transungual Delivery of Efinaconazole.

The efficacy of topical antifungal therapy in onychomycosis has been hindered by the failure of the antimycotic to permeate the nail plate. This research aims to design and develop a transungual system for the effective delivery of efinaconazole utilizing constant voltage iontophoresis. Seven prototype drug-loaded hydrogel formulations (E1-E7) were prepared to assess the influence of solvent (ethanol) and cosolvent (Labrasol®) on transungual delivery. Optimization was performed to evaluate the effect of three independent variables; voltage, solvent-to-cosolvent ratio, and penetration enhancer (PEG 400) concentration on critical quality attributes (CQAs), such as drug permeation and loading into the nail. The selected hydrogel product was characterized for pharmaceutical properties, efinaconazole release from the nail, and antifungal activity. Preliminary data indicates ethanol, Labrasol®, and voltage influence the transungual delivery of efinaconazole. Optimization design indicates a significant impact by applied voltage (p-0.0001) and enhancer concentration (p-0.0004) on the CQAs. Excellent correlation between selected independent variables and CQAs was confirmed by the high desirability value (0.9427). A significant (p < 0.0001) enhancement in the permeation (~78.59 µg/cm2) and drug loading (3.24 µg/mg) was noticed in the optimized transungual delivery with 10.5 V. FTIR spectral data indicates no interaction between the drug and excipients, while the DSC thermograms confirmed the amorphous state of the drug in the formulation. Iontophoresis produces a drug depot in the nail that releases above the minimum inhibitory concentration level for an extended period, potentially reducing the need for frequent topical treatment. Antifungal studies further substantiate the release data and have shown remarkable inhibition of Trichophyton mentagrophyte. Overall, the promising results obtained here demonstrate the prospective of this non-invasive method for the effective transungual delivery of efinaconazole, which could improve the treatment of onychomycosis.

Correlates of burnout in predoctoral dental students in the United States.

OBJECTIVE: The purpose of this research was to investigate correlates of burnout among predoctoral dental students in the United States. METHODS: All 66 dental schools in the US were invited to distribute a survey on topics such as demographics, year of dental school, and burnout to their predoctoral students. Burnout was assessed via the Maslach Burnout Inventory-Human Services Survey, which has three subscales: emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA). Multivariable modeling was conducted via generalized linear models using the lognormal distribution to adjust for confounding. RESULTS: The survey was completed by 631 students from 21 dental schools. When adjusting for confounding, students identifying as African American/Black (Non-Hispanic) (regression coefficient [95% CI]: -0.13 (-0.23, -0.02]) or Asian/Pacific Islander (-0.08 [-0.13, -0.02]) reported feeling significantly lower PA than students identifying as white. Students identifying as female reported feeling significantly greater EE (0.18 [0.10, 0.26]), but significantly less DP (-0.26 [-0.44, -0.09]), than students identifying as male. Third- (0.28 [0.07, 0.50]) and fourth-year (0.40 [0.17, 0.63]) students reported significantly higher EE than first-year students, while second- (0.40 [0.18, 0.62]), third- (1.06 [0.59, 1.53]), and fourth-year (1.31 [0.82, 1.81]) students reported significantly higher DP than first-year students. CONCLUSIONS: Risk indicators for burnout among US predoctoral dental students may depend on the dimension of burnout. Identifying those at higher risk of burnout can facilitate the implementation of counseling and other effective intervention strategies. Such identification can also provide insight into how the dental school environment might be contributing to the marginalization of those at higher risk.

A qualitative study to explore the ethnomedicine practices towards hepatitis among the Irula traditional healers in Tamil Nadu, India.

Introduction: Irulas are known for their traditional medicine and healing practices. Ethnomedicine primarily describes the traditional medical approaches that take consideration of the cultural perspectives on health, illness, disease while addressing the delivery of healthcare and therapeutic modalities. The current study explores the ethnomedical practices towards hepatitis among the Irula traditional healers in Tamil Nadu. Methodology: A Community-based in-depth interview (IDI) study was conducted among eight traditional healers (5 males and 3 females) from Irula settlements in Dharmapuri, Kancheepuram, and Chengalpattu districts. Apart from traditional healers, 11 Irula adults were interviewed to understand their cultural perspectives on health and illness. Results: The major themes that emerged from the codes were the perception towards traditional healing and the process of treatment on hepatitis, the list of important conditions treated by the traditional healers, and the list of medicinal plants used for treating people. Conclusion: This qualitative study highlights the voices of the Irula tribal community and offers a rich source of information about ethnomedicine practices towards hepatitis among the Irula traditional healers in Tamil Nadu, India.

Characteristics and immediate outcomes of patients who underwent percutaneous balloon mitral valvuloplasty at the Jakaya Kikwete Cardiac Institute, Tanzania.

BACKGROUND: For rheumatic mitral stenosis (MS), a multidisciplinary evaluation is mandatory to determine the optimal treatment: medical, percutaneous balloon mitral valvuloplasty (PBMV) or valve surgery. Clinical and imaging evaluations are essential for procedural risk assessment and outcomes. PBMV interventions are increasingly available in Africa and are feasible options for selected candidates. Enhancing PBMV training/skills transfer across most of African countries is possible. OBJECTIVES: The aim of this study was to provide insight into the clinical practice of patients with rheumatic MS evaluated for PBMV in a Tanzanian teaching hospital and to define the role of imaging, and evaluate the heart team and training/skills transfer in PBMV interventions. METHODS: From August 2019 to May 2022, 290 patients with rheumatic MS were recruited consecutively in the Tanzania Mitral Stenosis study. In total, 43 (14.8%) patients were initially evaluated for eligibility for PBMV by a heart team. We carried out the clinical assessment, laboratory investigations, transthoracic/oesophageal echocardiography (TTE/TEE) and electrocardiography. RESULTS: The median age was 31 years (range 11-68), and two-thirds of the patients were female (four diagnosed during pregnancy). Two patients had symptomatic MS at six and eight years. Nine patients had atrial fibrillation with left atrial thrombus in three, and two were detected by TEE. Nine patients in normal sinus rhythm had spontaneous echo contrast. The mean Wilkins score was 8.6 (range 8-12). With re-evaluation by the local and visiting team, 17 patients were found to have unfavourable characteristics: Bi-commissural calcification (four), ≥ grade 2/4 mitral regurgitation (six), high scores and left atrial thrombus (three), left atrial thrombus (two), and severe pulmonary hypertension (two). Three patients died before the planned PBMV. Eleven patients were on a waiting list. We performed PBMV in 12 patients, with success in 10 of these, and good short-term outcomes [mean pre-PBMV (16.03 ± 5.52 mmHg) and post-PBMV gradients (3.08 ± 0.44 mmHg, p < 0.001)]. There were no complications. CONCLUSIONS: PBMV had good outcomes for selected candidates. TEE is mandatory in pre-PBMV screening and for procedural guidance. In our cohort, patients with Wilkins score of up to 11 underwent successful PBMV. We encourage PBMV skills expansion in low- and middle-income countries, concentrating on expertise centres.

Molecular docking and dynamics supported investigation of antiviral activity of Lichen metabolites of Roccella montagnei: an in silico and in vitro study.

Lichens are symbiotic organisms that have been traditionally used for treating different kinds of ailments. As there are only a few reports on the antiviral activity of lichens, we thought of evaluating the anti-Herpes simplex virus-1 (HSV-1) activity of methanolic extract of Roccella montagnei and their isolated compounds. Fractionation of crude methanolic extract of Roccella montagnei by column chromatography isolated two pure compounds. Antiviral activity was assessed using a CPE inhibition assay at non-cytotoxic concentrations on Vero cells. Molecular docking and dynamics studies were carried out against Herpes simplex type-1 thymidine kinase to understand the binding interactions of the isolated compounds with reference to acyclovir. Isolated compounds were characterized as methyl orsellinate and montagnetol by spectral methods. Methanolic extract of Roccella montagnei exhibited an EC50 value of 56.51 µg/ml, while the compounds methyl orsellinate and montagnetol offered EC50 values of 13.50 µg/ml and 37.52 µg/ml, respectively, against HSV-1 viral infection on Vero cell lines. The selectively index (SI) of montagnetol (10.93) was found to be higher when compared to that of methyl orsellinate (5.55), indicating its better anti-HSV-1 activity. The docking and dynamics studies showed montagnetol was stable throughout the 100 ns, having better interactions and docking scores with HSV-1 thymidine kinase than methyl orsellinate, as well as the standard. To understand the mechanism of montagnetol's anti-HSV-1 activity, more research is required, and this could lead to the discovery of new and effective antiviral agents.Communicated by Ramaswamy H. Sarma.

Role of multi-targeted bioactive natural molecules and their derivatives in the treatment of Alzheimer's disease: an insight into structure-activity relationship.

Alzheimer's disease (AD) is a complex neurodegenerative disorder involving cognitive dysfunction like short-term memory and behavioral changes as the disease progresses due to other unaltered physiological factors. The solution for this problem is Multi-targeted Drugs (MTDs), which can affect multiple determinants to realize the multifunctional effects. Acetylcholinesterase (AChE) inhibitors donepezil, rivastigmine, galantamine, and N-methyl-D-aspartate (NMDA) receptor antagonist memantine are FDA-approved drugs used to treat AD symptomatically. The key objective of this review is to understand multitargeted bioactive natural molecules that could be considered as leads for further development as effective drugs for treating AD, along with understanding its pharmacology and structure-activity relationship (SAR). Understanding the molecular mechanism of the AD pathophysiology, the role of existing drugs, treatment of AD via amyloid beta (Aß) plaque, and neurofibrillary tangle (NFT) inhibition by natural bioactive molecules were also discussed in the review. The current quest and recent advancements with natural bioactive compounds like physostigmine, resveratrol, curcumin, and catechins, along with the study of in silico SAR, were reported in the present study. This review summarises the structural properties required for bioactive natural molecules to show anti-Alzheimer's activity by emphasizing on SAR of several bioactive natural molecules targeting various AD pathologies, their key molecular interactions that are critical for target specificity, their role as multitargeted ligands, used with adjunctive therapy for AD followed by related US patents granted recently. This article highlights the significance of the structural features of natural bioactive molecules in the treatment of AD and establishes a connection between them.Communicated by Ramaswamy H. Sarma.