Recommendations of apex health bodies remain localized: not in conformity with international implementation policy for urological disorders.

In developing/underdeveloped countries there is still a great burden of adverse drug reaction (ADR), morbidity and mortality because of poor regulations and implementation of preventive measures. These countries try to copy/follow guidelines from international bodies like American Urology Association (AUA), European Association of Urology (EAU), AGS, UMC and WHO irrespective of their country of origin and success in implementation. Although recommendations of these organizations are obligatory, yet these are taken as the gold standard for good clinical practices. This manuscript highlights difference in view point of various apex health organizations in formulating health policies for prevention, diagnosis, treatment and ADR monitoring for urological disorders. Lacking role of regulatory bodies in implementation of existing policies may lead to potentially inappropriate medication and produce a great economic burden. This analysis has prompted us to recommend that these apex bodies should have better coordination in producing a single value document, make it mandatory part of curricula in medical schools for better awareness, awareness campaigns and separate reporting column in ADR form.

Development of a High Penetration Safe Irrigant from Withania somnifera.

Background: Herbal medicine is regaining a strong position in health care by virtue of better safety and minimal toxicity as compared to conventional chemotherapies. It is making a place in dental care in the form of various toothpastes, lotions, and mouthwashes. It has been analyzed that very few discrete herbal irrigants have an action comparable to that of sodium hypochlorite. No data about any study on penetration depth and penetration area for herbal-based irrigants used in root canal treatment are available. Aim: The aim of this study was to assess the efficacy of Withania somnifera extracts by assessing its penetration depth and area inside dentinal tubules using a confocal laser scanning microscope. Materials and Methods: Freshly extracted 25 maxillary central incisors were divided into three groups: Group 1: W. somnifera; Group 2: sodium hypochlorite; and Group 3: distilled water. Results: W. somnifera showed better results with respect to penetration depth and area inside the dentinal tubules thansodium hypochlorite. Conclusion: From the study, it can be concluded that W. somnifera extract-based irrigant may be used as an alternative to sodium hypochlorite-based irrigant. It also shows that more herbal drugs need such types of screening and incorporation in dental practice to reduce the potential side effects of the conventional drugs used in daily practice.

Emerging role of MicroRNA-Based theranostics in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC), with its high mortality and short survival rate, continues to be one of the deadliest malignancies despite relentless efforts and several technological advances. The poor prognosis of HCC and the few available treatments are to blame for the low survival rate, which emphasizes the importance of creating new, effective diagnostic markers and innovative therapy strategies. In-depth research is being done on the potent biomarker miRNAs, a special class of non-coding RNA and has shown encouraging results in the early identification and treatment of HCC in order to find more viable and successful therapeutics for the disease. It is beyond dispute that miRNAs control cell differentiation, proliferation, and survival and, depending on the genes they target, can either promote tumorigenesis or suppress it. Given the vital role miRNAs play in the biological system and their potential to serve as ground-breaking treatments for HCC, more study is required to fully examine their theranostic potential.

Knowledge, attitude, and practice of medical interns and postgraduate residents on American Geriatric Society updated Beers criteria.

BACKGROUND: Potentially inappropriate medication (PIM) prevalence in older adults is increasing day by day due to lack of knowledge among medical students and professionals. OBJECTIVE: To determine the knowledge of medical students toward American Geriatric Society (AGS) Beers criteria for PIM prescribing. MATERIALS AND METHODS: This cross-sectional study employed a self-administered questionnaire which was validated and designed to assess the knowledge, attitude, and practice of medical interns and postgraduate residents on Beers criteria for PIMs in older adults. The study was conducted in Faridkot region of Punjab in 2019. This study will utilize a purposive sampling strategy and a convenience sampling of up to 183 participants. Mann-Whitney U or Kruskal-Wallis tests were used to compare different issues as appropriate. P values of <0.05 were considered significant. RESULTS: Out of 183 questionnaires distributed, only 155 participants (response rate 84.6%) had filled the survey and were included in the study. 61.3% (n = 95) of the respondents were males. The mean knowledge score of 155 participants was (5.16 ± 1.56), where the highest score was 9 and the lowest score was 2 out of 10. 15.5% (n = 24) of the participant strongly agreed that Beers criteria use is necessary in clinical setting and would be very helpful. While 22.5% (n = 35) of the participants strongly agreed that PIMs cause adverse drug event (ADE) and drug-related problems (DRPs) in older adults. Age of the participant had a significant effect on the knowledge score (p = 0.009), and participant aged between 31 and 40 years had significantly higher knowledge scores compared with participants falls under 20-30 years. CONCLUSION: Medical students and postgraduate residents had average knowledge of PIMs and are unaware of the standard guidelines in older adults such as the Beers criteria. Lack of formal education or training about Beers guidelines was the main reason responsible for average knowledge among participants.

Micronome Revealed miR-205-5p as Key Regulator of VEGFA During Cancer Related Angiogenesis in Hepatocellular Carcinoma.

The high ratio of global mortality rate to incidence rate and steep increase in incidence of liver cancer warrants need for advancement of innovative cancer treatment and therapy for hepatocellular carcinoma (HCC). miRNAs are fascinating prospects as treatments in the form of miRNA mimics or therapeutic targets because of their capacity to target various mRNAs that are changed in diseased states. Micronome is a tool to find signature miRNA for any disease and there is hardly any study on micronome in HCC. The aim of the present study was to identify the genes involved in tumor growth and angiogenesis in HCC patients and determine the signature miRNA by constructing a micronome. Herein, we performed a comprehensive analysis on dysregulated genes obtained from liver cancer gene databases. Only experimentally validated miRNA of angiogenesis genes were included in the study. Micronome was constructed using Cytoscape software and search tools for the retrieval of interacting genes (STRING) database. Dysregulated genes of HCC were integrated with miRNAs for identification of signature miRNA involved and identify genes (acting as positive or negative regulator) to elucidate the potential regulatory pathway or signaling. The study clearly reflects that hsa-mir-205-5p is the signature miRNA for positively regulating angiogenesis in HCC through VEGFA. These regulatory genes and signature miRNAs may be useful to understand the unique angiogenesis process of HCC and quick development of novel/better and cost effective molecular-targeted treatment strategies in HCC as the responsible regulatory molecules can be pinpointed with limited resources with use of bioinformatics.

Bioinformatics Paradigms in Drug Discovery and Drug Development.

Despite breakthroughs in medical sciences, drug development remains a timeconsuming, expensive, challenging, and inefficient process with a high failure rate for novel therapeutic discoveries. Bioinformatics analysis can speed up drug target identification, drug candidate screening, and refining, but it can also help characterise adverse effects and anticipate drug resistance. Integrated genomics, proteomics, and bioinformatics have resulted in potent new tactics for resolving numerous biochemical problems and establishing new methodologies that result in new biomedical products. As a result, a new research trend emerged to demonstrate the mechanism of therapeutic action, forecast drug resistance, and uncover biomarkers for various disorders. The development of new medications is a complicated procedure. There are two basic approaches to drug design: ligand-based drug design and structure-based drug design. The study of protein structure and function was essential for drug development. Current techniques based on combinatorial approaches such as proteomics, genomics, bioinformatics, molecular docking, and mass spectrometry were applied. This article provides an overview of the combinatorial techniques of proteomics, genomics, and bioinformatics that aid in understanding the drug-creation process.

Chronic Kidney Disease (CKD) - A Brand Ambassador/Alarming Bell for Potentially Inappropriate Medication in Elderly Inpatients.

BACKGROUND: Since the past decade, prevalence of Potentially Inappropriate Medication (PIM) among elderly inpatients has increased drastically. However, limited data is available on PIM indicators and PIMs use among the elderly in patients suffering from Chronic Kidney Disease (CKD). OBJECTIVE: The objective of this study is to determine the prevalence of PIMs in elderly hospitalized patients with CKD. METHODS: A cross-sectional study was carried out on 102 patients in a tertiary care hospital. PIMs were identified using Beers criteria 2019. Chi-square test was used to identify the association between variables and PIMs use. RESULTS: PIMs, as assessed according to AGS updated Beers criteria 2019 was found to be in more than 68.6% of patients of median age 65 years and 3 diagnoses and 7 days median length of stay. Most of the patients (47.1%) had ≥4 diagnosis. The most common comorbidities in patient were diabetes mellitus (n=54) and hypertension (n=55). Most of the subjects (66.7%) were on polypharmacy (5-9 medications/day) and 25.5% were on a higher level of polypharmacy (>10 medicines/day). Approximately 90% of the patients were having very low CrCl < 21ml/min (calculated with the help of Cockcroft- Gault formula). A significant association between PIM use and an increased number of diagnoses, polypharmacy or high-level polypharmacy, was observed. CONCLUSION: The prevalence of PIMs in elderly inpatients suffering from CKD is quite high. The study clearly indicates negligence/ lack of awareness amongst physicians leading to increase in PIM use. Authors propose that the CKD patients should attract special attention of physician and should be treated as brand ambassadors/alarming bell for PIM use.

Integration of System Biology Tools to Investigate Huperzine A as an Anti-Alzheimer Agent.

Aim: The present study aimed to investigate huperzine A as an anti-Alzheimer agent based on the principle that a single compound can regulate multiple proteins and associated pathways, using system biology tools. Methodology: The simplified molecular-input line-entry system of huperzine A was retrieved from the PubChem database, and its targets were predicted using SwissTargetPrediction. These targets were matched with the proteins deposited in DisGeNET for Alzheimer disease and enriched in STRING to identify the probably regulated pathways, cellular components, biological processes, and molecular function. Furthermore, huperzine A was docked against acetylcholinesterase using AutoDock Vina, and simulations were performed with the Gromacs package to take into account the dynamics of the system and its effect on the stability and function of the ligands. Results: A total of 100 targets were predicted to be targeted by huperzine A, of which 42 were regulated at a minimum probability of 0.05. Similarly, 101 Kyoto Encyclopedia of Genes and Genomes pathways were triggered, in which neuroactive ligand-receptor interactions scored the least false discovery rate. Also, huperzine A was predicted to modulate 54 cellular components, 120 molecular functions, and 873 biological processes. Furthermore, huperzine A possessed a binding affinity of -8.7 kcal/mol with AChE and interacted within the active site of AChE via H-bonds and hydrophobic interactions.

Prevalence and predictors of Potentially Inappropriate Psychotropic Medication in older adults with psychiatric illness.

BACKGROUND: There is limited information available on the use of Potentially Inappropriate Psychotropic (PIP) medication in older adults having a psychiatric illness. OBJECTIVE: To determine the prevalence of and predictors of prescribing PIP medications in older adults with psychiatric illness. METHODS: A cross-sectional study was carried out at a tertiary care hospital on 456 patients of either sex, with a median age of 65 years attending the psychiatry outpatient department. Evaluation of PIP medication was done using Beers criteria 2019 and Screening tool of Older Persons Potentially Inappropriate Medication (STOPP) criteria 2015. Bivariate logistic regression was used to find out the predictors of PIP prescribing. RESULTS: Results of the study reflect that a staggering number of older adults, (more than 91% and 73%) out of a total of 456 patients were prescribed with at least one PIP medication identified by Beers criteria and STOPP criteria, respectively. Long-acting benzodiazepine (LABZD) like clonazepam was identified as one of the most commonly prescribed PIP medications by both sets of criteria. Further analysis revealed that older adults from rural background (Odds Ratio (OR) 2.60, 95% Confidence Interval (CI) 1.20-5.65; P = 0.015), Tricyclic Antidepressant (TCA) (OR 0.30, 95% CI 0.12-0.75; P = 0.010), LABZD (OR 33.72, 95% CI 11.27-100.85; P = < 0.001), atypical antipsychotics (OR 22.35, 95% CI 5.31-93.99; P = < 0.001) use were most common predictors for PIP medication prescribing. CONCLUSION: The study suggests that the Beer criteria detects more PIP medication than the STOPP criteria.

Clonazepam tops the list of potentially inappropriate psychotropic (PIP) medications in older adults with psychiatric illness: A cross-sectional study based on Beers criteria 2019 vs STOPP criteria 2015.

BACKGROUND: In older adults, polypharmacy and potentially inappropriate psychotropic (PIP) medication use are prominent prescription challenges. However, there is limited information available on the use of PIP medication in older adults having psychiatry illness. OBJECTIVE: To find out the most commonly prescribed PIP in tertiary care hospitals of developing countries with respect to Beers criteria 2019 and Screening Tool of Older Persons' Potentially Inappropriate Prescriptions (STOPP) and predictors of PIP. METHODS: A cross-sectional analysis of 456 patients of either sex with a median age of 65 years visiting the outpatient department of psychiatry was performed at the tertiary care hospital of North India with respect to Beers criteria 2019 and STOPP criteria 2015. Bivariate logistic regression was used to figure out the predictors of PIP medication. RESULTS: Results of the study reflects a staggering number of older adults, (more than 91 % and 73 %) out of total 456 patients were prescribed with at least one PIP medication as per Beers criteria and STOPP criteria, respectively. Long-acting benzodiazepine like clonazepam, chlordiazepoxide were identified as one of the most commonly prescribed PIP medications with respect to the both set of criteria. Further analysis revealed that polypharmacy (≥5 medications with odds Ratio (OR) 17.33, 95% Confidence Interval (CI) 1.42-210.66, P-0.025) as the sole important predictor for PIP medication. CONCLUSION: According to the Beers criterion and the STOPP criteria, the use of PIP medicine is very prevalent among older adults with psychiatric illness. The Beers criteria dramatically diagnose more PIP medication than STOPP criteria.

Erdafitinib as a Novel and Advanced Treatment Strategy of Metastatic Urothelial Carcinoma.

Urothelial carcinoma has become the ninth most common malignancy in the world. Since the 1980s, diverse studies and treatment methods came out with their possible effects along with certain limitations. Initially, platinum chemotherapy was considered as first-line treatment of the disease. Although it was proved to be effective initially, the most number of cases reported the reoccurrence of the disease. Furthermore, aberrant ligand- dependent and constitutive ligand-independent fibroblast growth factor receptor (FGFR) signaling has been reported in a large number of solid tumors, including urothelial carcinoma that became the basis for FGFR inhibition for the treatment of the disease. Erdafitinib is a pan-FGFR inhibitor that was recently approved in the USA for the treatment of locally advanced or metastatic FGFR3 or FGFR2 urothelial carcinoma. The drug is also being investigated as a treatment for other cancers, including cholangiocarcinoma, liver cancer, non-small cell lung cancer, prostate cancer, lymphoma cancer and oesophageal cancer. This article summarizes the various treatments that evolved for bladder cancer till now, a brief description of the biology of FGFR inhibition, clinical pharmacology, and various clinical trials of erdafitinib.

Prevalence of potentially inappropriate medication and its correlates in elderly hospitalized patients: A cross-sectional study based on Beers criteria.

BACKGROUND: The increase in the prescription of potentially inappropriate medication (PIM) in older adults with significant health consequences is a global concern. This study aimed to determine the prevalence of PIM prescription in older adults as identified by Beers criteria 2015 and 2019. MATERIALS AND METHODS: A cross-sectional study was carried out in older adults aged >65 years at a tertiary care postgraduate teaching hospital. All patients aged ≥65 years irrespective of their gender, admitted in the medical ward of the hospital with single/multiple comorbidities, and prescribed at least one daily medication, were included in the study. Data of patient history, patient case sheet, medication charts, laboratory reports, as well as radiological examinations test reports were retrieved from their files and were captured in a prevalidated data collection form. SPSS used for data analysis; multivariate logistic regression was used to determine the predictors of PIM prescribing and odds ratios (ORs) and 95% confidence intervals for ORs were computed. RESULTS: Study included 323 patients; 61.3% were male, 74% patients were 65-70 years of age, and 78% patients were illiterate. The overall prevalence of PIM uses according to the Beers criteria 2015 and 2019 was 60.1% and 61.9%, respectively. No association found between PIMs prescribes and diagnosis category. Male gender, age 76-80 years, and education 10-12th class were found to be significantly related to PIM prescription. CONCLUSION: This study reflects a critical view of noncompliance of Beers criteria for geriatric healthcare even in tertiary care hospitals in India. Creatinine clearance rate should be kept in view when prescribing medicines for elderly inpatients.

Ayurvedic formulations containing benzoic and ascorbic acids as additives: benzene formation during storage and impact of additives on quality parameters.

OBJECTIVES: Ayurvedic formulations are becoming the prior choice of people as health care supplements. The increasing demand for these formulations has led to extensive development of Ayurvedic pharmaceutical industries worldwide. The reaction between the preservatives (sodium benzoates and ascorbic acid) used in these formulations could generate benzene. Benzene is classified as class-1 human carcinogen and responsible for various short and long term health effects. METHODS: In this study, 25 formulations (containing ascorbic acid and sodium benzoate) of various manufacturers available as over the counter products were obtained and their benzene content were determined using gas chromatograph with flame ionization detector. RESULTS: The result showed that 64% of the formulations were free from benzene contamination whereas 36% of formulations were found to be contaminated with benzene. A simple, less time-consuming, economic, and validated gas chromatographic method for estimation of benzene in Ayurvedic formulations was also developed successfully in present study. CONCLUSIONS: The data revealed that the level of benzene was within permissible limits, yet the presence of a carcinogen in the marketed formulations intended for internal use is an alarming situation.

RNA Binding Proteins and Non-coding RNA's in Cardiovascular Diseases.

Cardiovascular disease (CVD) is the leading cause of mortality as well as morbidity worldwide. The disease has been reported to be chronic in nature and the symptoms of the disease worsen progressively over a long period of time. Inspite of noteworthy achievements have been made in the therapy of CVD yet the available drugs are associated with various undesirable factors including drug toxicity, complexity, resistance and many more. The versatility of RNAs makes them crucial therapeutics candidate for many human diseases. Deeper understanding of RNA biology, exploring new classes of RNA that possess therapeutic potential will help in its successful translation to the clinic. Understanding the mode of action of various RNAs such as miRNA, RNA binding proteins and siRNA in CVD will help in improved therapeutics among patients. Multiple strategies are being planned to determine the future potential of miRNAs to treat a disease. This review embodies the recent work done in the field of miRNA and its role in cardiovascular disease as diagnostic biomarker as well as therapeutic agents. In addition the review highlights the future of miRNAs as a potential therapeutic target and need of designing micronome that may reveal potential predictive targets of miRNA-mRNA interaction.

Small Interfering RNAs and RNA Therapeutics in Cardiovascular Diseases.

Ribonucleic acid (RNA) is being exploited and understood in its many aspects of function and structure for development of valuable tools in the therapeutics of various diseases such as cardiovascular etc. The expanded knowledge regarding function of RNA in the genomics and inside the cell has dramatically changed the therapeutic strategies in the past few years. RNA has become a spotlight of attention for developing novel therapeutic schemes and hence variety of therapeutic strategies is being coming into the picture that includes RNA interference, use of aptamers, role of microRNA (miRNA) that can alter the complex gene expression patterns. It is due to the fact that RNA offers various advantages in disease management as it can be edited and modified in its various forms such as secondary and tertiary structures. Although scientists are in process of manufacturing RNA-targeting therapies using variety of endogenous gene silencing regulators, Small interfering RNAs (Si RNAs), aptamers and microRNA for cardiovascular diseases yet the development of a novel, risk free therapeutic strategy is a major challenge and need of the hour in cardiovascular medicine. In this regard these agents are required to overcome pleothra of barriers such as stability of drug targets, immunogenicity, adequate binding, targeted delivery etc. to become effective drugs. Recent years have witnessed the progress of RNA therapeutic strategies in cardiovascular diseases that are likely to significantly expand the cardiovascular therapeutic repertoire within the next decade. The present manuscript has been compiled to summarize various approaches of siRNA based therapies in cardiovascular diseases along with the advantages, outcomes and limitations if any in this regard. In addition, the future prospects of RNA therapeutic modalities in cardiovascular diseases are summarized.

Association of CD4/CD8 Ratio with Viral Load, Genotype and Cirrhosis in Chronic Hepatitis C.

ABSTRACT: The interplay between Hepatitis C virus (HCV) and immune system, especially T lymphocytes play a major role in the clearance of virus and in development of liver cell injury resulting in replacement of healthy tissue with fibrous scar tissue. OBJECTIVES: To evaluate the association of CD4/CD8 ratio with viral load and genotype of HCV and to evaluate the correlation of CD4/CD8 ratio and CD4 and CD8 cell counts with liver function tests in HCV infected patients. METHODS: Forty patients of Chronic Hepatitis C infection were enrolled for study. Immunophenotyping by flowcytometry for measurement of CD4 and CD8 T cell counts was used and the percentages of cells expressing CD4 and CD8 were estimated per lymphocyte population. HCV viral load quantitative was done by Roche Taqman Method. RESULTS: The CD4/CD8 ratio was not found to have any significant correlation with HCV viral load. However, it showed a significant difference in the two HCV genotypes, the ratio being higher in genotype 3 than in genotype 1. It showed no significant correlation with liver function tests except serum albumin which had significant positive correlation with CD4/CD8 ratio. The ratio was also found to be significantly decreased in patients with cirrhosis of liver. CONCLUSION: Hepatitis C virus genotype but not viral load influences the immune response to HCV infection. The CD4/CD8 ratio significantly decreases in patients with liver cirrhosis than in normal and fatty liver.

Development and Validation of a Novel Stability-Indicating RP-HPLC Method for Simultaneous Determination of Tezacaftor and Ivacaftor in Fixed Dose Combination.

A simple and precise novel stability-indicating method for the simultaneous estimation of tezacaftor and ivacaftor in combined tablet dosage form was developed and validated using reversed-phase high-performance liquid chromatography (RP-HPLC). The method is being reported for the first time and includes an estimation of degradation products produced post-stress conditions without any extraction or derivatization. The chromatographic separation of the drugs was achieved with a Symmetry Shield RP18 Column (100 Å, 5 µm, 4.6 mm × 250 mm) using a mixture of buffer, methanol and acetonitrile (42:27:31 v/v/v) as mobile phase. The buffer used in mobile phase contained 35 mM potassium dihydrogen phosphate, and its pH was adjusted to 7.0 ± 0.02 with 20% orthophosphoric acid. The instrument was set at flow rate of 1.2 mL min-1 at ambient temperature and the wavelength of UV-visible detector at 275 nm. The developed method could be suitable for the quantitative determination of these drugs in pharmaceutical preparations and also for quality control in bulk manufacturing. Stress testing was performed to prove the specificity. No interference was observed from its stress degradation products. The statistical analysis was done by using F-test and t-test at 95% confidence level.

Bioinformatics-Based Tools and Software in Clinical Research: A New Emerging Area.

Nowadays, drug discovery is a long process which includes target identification, validation, lead optimization, and many other major/minor steps. The huge flow of data has necessitated the need for computational support for collection, storage, retrieval, analysis, and correlation of data sets of complex information. At the beginning of the twentieth century, it was cumbersome to elaborate the experimental findings in the form of clinical outcomes, but current research in the field of bioinformatics clearly shows ongoing unification of experimental findings and clinical outcomes. Bioinformatics has made it easier for researchers to overcome various challenges of time-consuming and expensive procedures of evaluation of safety and efficacy of drugs at a much faster and economic way. In the near future, it may be a major game player and trendsetter for personalized medicine, drug discovery, drug standardization, as well as food products. Due to rapidly increasing commercial interest, currently probiotic-based industries are flooding the market with a range of probiotic products under the banner of dietary supplements, natural health products, food supplements, or functional foods. Most of the consumers are attracted toward probiotic formulations due to the rosy picture provided by the media and advertisements about high beneficial claims. These products are not regulated by pharmaceutical regulatory authorities in different countries of origin and are rather regulated as per their intended use. Lack of stipulated quality standard is a major challenge for probiotic industry; hence there would always be a possibility of marketing of ineffective and unsafe products with false claims. Hence it is very important and pertinent to ensure the safety of probiotic formulations available as over-the-counter (OTC) products for ignorant society. At the same time, probiotic industry, being in its initial stages in developing and underdeveloped countries, requires to ensure safe, swift, and successful usage of probiotics. In the absence of harmonized regulatory guidelines, safety, quality, as well as the efficacy of the probiotic strain does not remain a mandate but becomes a choice for the manufacturer. Hence there is an urgent need to screen already marketed probiotic formulations for their safety with respect to specific strains of probiotic. Various conventional methods used by the manufacturers for the identification of probiotic microbes create a blurred image about their status as probiotics. The present manuscript focuses on a bioinformatics-based technique for validation of marketed probiotic formulation using 16s rRNA sequencing and strain-level identification of bacterial species using Ez Texan and laser gene software. This technique gives a clear picture about the safety of the product for human use.