Wiskott Aldrich syndrome protein (WASp)-deficient Th1 cells promote R-loop-driven transcriptional insufficiency and transcription-coupled nucleotide excision repair factor (TC-NER)-driven genome-instability in the pathogenesis of T cell acute lymphoblastic leukemia.

BACKGROUND: T-ALL is an aggressive hematological tumor that develops as the result of a multi-step oncogenic process which causes expansion of hematopoietic progenitors that are primed for T cell development to undergo malignant transformation and growth. Even though first-line therapy has a significant response rate, 40% of adult patients and 20% of pediatric patients will relapse. Therefore, there is an unmet need for treatment for relapsed/refractory T-ALL to develop potential targeted therapies. METHODS: Pediatric T-ALL patient derived T cells were grown under either nonskewingTh0 or Th1-skewing conditions to further process for ChIP-qPCR, RDIP-qPCR and other RT-PCR assays. Endogenous WASp was knocked out using CRISPR-Cas9 and was confirmed using flow cytometry and western blotting. LC-MS/MS was performed to find out proteomic dataset of WASp-interactors generated from Th1-skewed, human primary Th-cells. DNA-damage was assessed by immunofluorescence confocal-imaging and single-cell gel electrophoresis (comet assay). Overexpression of RNaseH1 was also done to restore normal Th1-transcription in WASp-deficient Th1-skewed cells. RESULTS: We discovered that nuclear-WASp is required for suppressing R-loop production (RNA/DNA-hybrids) at Th1-network genes by ribonucleaseH2 (RNH2) and topoisomerase1. Nuclear-WASp is associated with the factors involved in preventing and dissolving R-loops in Th1 cells. In nuclear- WASp-reduced malignant Th1-cells, R-loops accumulate in vivo and are processed into DNA-breaks by transcription-coupled-nucleotide-excision repair (TC-NER). Several epigenetic modifications were also found to be involved at Th1 gene locus which are responsible for active/repressive marks of particular genes. By demonstrating WASp as a physiologic regulator of programmed versus unprogrammed R-loops, we suggest that the transcriptional role of WASp in vivo extends also to prevent transcription-linked DNA damage during malignancy and through modification of epigenetic dysregulations. CONCLUSION: Our findings present a provocative possibility of resetting R-loops as a therapeutic intervention to correct both immune deficiency and malignancy in T-cell acute lymphoblastic leukemia patients and a novel role of WASp in the epigenetic regulation of T helper cell differentiation in T-ALL patients, anticipating WASp's requirement for the suppression of T-ALL progression.

Genome-wide identification and expression analysis of the polygalacturonase gene family in sweetpotato.

BACKGROUND: Polygalacturonase (PG), a crucial enzyme involved in pectin degradation, is associated with various plants' developmental and physiological processes such as seed germination, fruit ripening, fruit softening and plant organ abscission. However, the members of PG gene family in sweetpotato (Ipomoea batatas) have not been extensively identified. RESULTS: In this study, there were 103 PG genes identified in sweetpotato genome, which were phylogenetically clustered into divergent six clades. The gene structure characteristics of each clade were basically conserved. Subsequently, we renamed these PGs according to their locations of the chromosomes. The investigation of collinearity between the PGs in sweetpotato and other four species, contained Arabidopsis thaliana, Solanum lycopersicum, Malus domestica and Ziziphus jujuba, revealed important clues about the potential evolution of the PG family in sweetpotato. Gene duplication analysis showed that IbPGs with collinearity relationships were all derived from segmental duplications, and these genes were under purifying selection. In addition, each promoter region of IbPG proteins contained cis-acting elements related to plant growth and development processes, environmental stress responses and hormone responses. Furthermore, the 103 IbPGs were differentially expressed in various tissues (leaf, stem, proximal end, distal end, root body, root stalk, initiative storage root and fibrous root) and under different abiotic stresses (salt, drought, cold, SA, MeJa and ABA treatment). IbPG038 and IbPG039 were down-regulated with salt, SA and MeJa treatment. According to the further investigation, we found that IbPG006, IbPG034 and IbPG099 had different patterns under the drought and salt stress in fibrous root of sweetpotato, which provided insights into functional differences among these genes. CONCLUSION: A total of 103 IbPGs were identified and classified into six clades from sweetpotato genome. The results of RNA-Seq and qRT-PCR suggested that IbPG006, IbPG034 and IbPG099 might play a significant role in tissue specificity as well as drought and salt stress responses, which showed valuable information for further functional characterization and application of the IbPGs.

Genome-Wide Identification and Expression Analysis of the Xyloglucan Endotransglucosylase/Hydrolase Gene Family in Sweet Potato [Ipomoea batatas (L.) Lam].

The xyloglucan endotransglucosylase/hydrolase (XET/XEH, also named XTH) family is a multigene family, the function of which plays a significant role in cell-wall rebuilding and stress tolerance in plants. However, the specific traits of the XTH gene family members and their expression pattern in different tissues and under stress have not been carried out in sweet potato. Thirty-six XTH genes were identified in I. batatas, all of which had conserved structures (Glyco_hydro_16). Based on Neighbor-Joining phylogenetic analysis the IbXTHs can be divided into three subfamilies-the I/II, IIIA, and IIIB subfamilies, which were unevenly distributed on 13 chromosomes, with the exception of Chr9 and Chr15. Multiple cis-acting regions related to growth and development, as well as stress responses, may be found in the IbXTH gene promoters. The segmental duplication occurrences greatly aided the evolution of IbXTHs. The results of a collinearity analysis showed that the XTH genes of sweet potato shared evolutionary history with three additional species, including A. thaliana, G. max, and O. sativa. Additionally, based on the transcriptome sequencing data, the results revealed that the IbXTHs have different expression patterns in leaves, stems, the root body (RB), the distal end (DE), the root stock (RS), the proximal end (PE), the initiative storage root (ISR), and the fibrous root (FR), and many of them are well expressed in the roots. Differentially expressed gene (DEG) analysis of FRs after hormone treatment of the roots indicated that IbXTH28 and IbXTH30 are up-regulated under salicylic acid (SA) treatment but down-regulated under methyl jasmonate (MeJA) treatment. Attentionally, there were only two genes showing down-regulation under the cold and drought treatment. Collectively, all of the findings suggested that genes from the XTH family are crucial for root specificity. This study could provide a theoretical basis for further research on the molecular function of sweet potato XTH genes.

Efficacy of pharmacological interventions in COVID-19: A network meta-analysis.

AIMS: To perform network meta-analysis for a head-to-head comparison of various interventions used in coronavirus disease 2019 (COVID-19) on mortality, clinical recovery, time to clinical improvement and the occurrence of serious adverse events. METHODS: Systematic search was performed using online databases with suitable MeSH terms including coronavirus, COVID-19, randomized controlled trial, hydroxychloroquine, lopinavir/ritonavir, tocilizumab, remdesivir, favipiravir, dexamethasone and interferon-ß. Data were independently extracted by 2 study investigators and analysed. RESULTS: Out of 1225 studies screened, 23 were included for qualitative and quantitative analysis. Among the drugs studied, dexamethasone reduces mortality by 10%, with a relative risk of 0.90 (95% confidence interval [0.82-0.97]) and increases clinical recovery by 6% (relative risk 1.06, 95% confidence interval [1.02-1.10]) compared to standard of care. Similarly, remdesivir administered for 10 days increased clinical recovery by 10%, reduced time to clinical improvement by 4 days and lowered the occurrence of serious adverse events by 27% as compared to standard of care. CONCLUSION: In comparison to standard of care, dexamethasone was found to increase clinical recovery and lower mortality; remdesivir was significantly associated with a lower risk of mortality as compared to tocilizumab and higher clinical recovery and shorter time to clinical improvement as compared to hydroxychloroquine and tocilizumab; remdesivir followed by tocilizumab were found to have lesser occurrence of serious adverse events in patients with moderate to severe COVID-19.

Evaluation of pharmacological interventions in the management of adenomyosis: a systematic review.

PURPOSE: Medical management of adenomyosis largely revolves around symptom management, with very few drugs having received regulatory approval for the disease. However, the level of evidence supporting the use of pharmacological interventions is low, making it difficult to establish their efficacy in the treatment of adenomyosis. Hence, the aim of our systematic review is to identify the strength of evidence currently available and evaluate the effectiveness of different medical interventions in the management of adenomyosis. METHODS: The search was performed in MEDLINE, Embase, Cochrane Library, CENTRAL and ClinicalTrials.gov. Articles published between 1 January 2010 and 30 November 2020 were considered. Randomized controlled trials and observational studies that assessed the efficacy of medical interventions in patients with adenomyosis were included. The quality of the data was analyzed using RevMan 5.3 software. RESULTS: LNG-IUS (levonorgestrel intrauterine system), dienogest and gonadotropin-releasing hormone (GnRH) analogues were effective in reducing pain, uterine volume and menstrual bleeding. However, these data were largely obtained in the non-trial setting and were fraught with issues that included patient selection, short duration of therapy, small sample size, and limited long-term safety and effectiveness data. CONCLUSIONS: Although LNG-IUS, dienogest and GnRH analogues have better evidence for effectiveness in adenomyosis, the need of the hour is to thoroughly evaluate other novel molecules for adenomyosis using well-designed randomized controlled trials.

Extent of knowledge and attitudes on plagiarism among undergraduate medical students in South India - a multicentre, cross-sectional study to determine the need for incorporating research ethics in medical undergraduate curriculum.

BACKGROUND: Undergraduate medical students in India participate in various research activities However, plagiarism is rampant, and we hypothesize that it is the lack of knowledge on how to avoid plagiarism. This study's objective was to measure the extent of knowledge and attitudes towards plagiarism among undergraduate medical students in India. METHODS: It was a multicentre, cross-sectional study conducted over a two-year period (January 2018 - December 2019). Undergraduate medical students were given a pre-tested semi-structured questionnaire which contained: (a) Demographic details; (b) A quiz developed by Indiana University, USA to assess knowledge; and (c) Attitudes towards Plagiarism (ATP) questionnaire. RESULTS: Eleven medical colleges (n = 4 government medical colleges [GMCs] and n = 7 private medical colleges [PMCs]) participated. A total of N = 4183 students consented. The mean (SD) knowledge score was 4.54 (1.78) out of 10. The factors (adjusted odds ratio [aOR]; 95% Confidence interval [CI]; p value) that emerged as significant predictors of poor knowledge score were early years of medical education (0.110; 0.063, 0.156; < 0.001) and being enrolled in a GMC (0.348; 0.233, 0.463; < 0.001).The overall mean (SD) scores of the three attitude components namely permissive, critical and submissive norms were 37.56 (5.25), 20.35 (4.20) and 31.20 (4.28) respectively, corresponding to the moderate category. CONCLUSION: The overall knowledge score was poor. A vast majority of study participants fell in the moderate category of attitude score. These findings warrant the need for incorporating formal training in the medical education curriculum.

TEVAR for complicated and uncomplicated type B aortic dissection-Systematic review and meta-analysis.

BACKGROUND: Type B aortic dissection (TBAD), is defined as a dissection involving the aorta distal to left subclavian artery with the ascending aorta and the aortic arch not affected. TBAD is classified due to the time frame and presence of complications. Complicated TBAD (co-TBAD) patients have a greater mortality rate than uncomplicated TBAD (un-TBAD) and thoracic endovascular aortic repair (TEVAR) is considered the gold-standard intervention for these clinical challenges. METHODS: We undertook a systematic review of the literature regarding TEVAR intervention in co-TBAD and un-TBAD. A comprehensive search was undertaken across four major databases and was evaluated and assessed until June 2020. RESULTS: A total of 16,104 patients were included in the study (7772 patients co-TBAD and 8352 un-TBAD). A significantly higher proportion of comorbidities were seen in co-TBAD patients compared with un-TBAD. Acute dissection was more frequent in the co-TBAD group (73.55% vs. 66.91%), while chronic dissection was more common in un-TBAD patients (33.8% vs. 70.73%). Postprocedure stroke was higher in co-TBAD (5.85% vs. 3.92%; p < .01), while postprocedural renal failure was higher in un-TBAD patients (7.23 vs. 11.38%; p < .01). No difference was observed in in-hospital mortality however the 30 days mortality was higher in the co-TBAD group. One-year survival was higher in the uncomplicated group but this difference was not observed in the 5-year survival. CONCLUSION: In our analysis we can appreciate that despite significantly higher comorbidities in the co-TBAD cohort, there was no difference in in-hospital mortality between the two groups and the 5-year survival did not have any difference.

Clinical Pharmacokinetic Drug Interaction Potential of MenoAct851 in Adult, Female Healthy Volunteers.

BACKGROUND: MenoAct851 (Varanasi BioResearch Pvt. Ltd., Varanasi, India) is a patented polyherbal formulation developed to manage menopause symptoms that can be taken along with other allopathic medicines. OBJECTIVE: The present study aims to evaluate the drug interaction potential of MenoAct851 to inhibit cytochrome (CY) P450 in vitro in rats, and to measure its effects on simvastatin pharmacokinetic parameters in healthy human volunteers. METHODS: CYP450-carbon monoxide assay of MenoAct851 was performed in rat liver microsomes to calculate the percentage inhibition. Fluorometric assays of CYP3A4 and CYP2D6 determined half maximal inhibitory concentration value. A double-blind, randomized, placebo-controlled drug interaction study of MenoAct851 was conducted in 24 healthy adult female volunteers aged 25 to 50 years. The selected volunteers were randomized to receive placebo or MenoAct851 500 mg BID PO for 14 days. On the 15th day, each group received 40 mg single-dose simvastatin. Blood samples were drawn at different intervals to measure simvastatin pharmacokinetic parameters. RESULTS: The mean (SD) CYP450 concentration of the diluted microsome sample was calculated and found to be 0.405 (0.12) nmol/mg. The inhibitory potential of MenoAct851 (41.16% [1.24%]) was found to be less than ketoconazole. Half maximal inhibitory concentration values of MenoAct851 on CYP3A4 and CYP2D6 were 11.96 (1.04) µg/mL and 15.24 (0.58) µg/mL, respectively, but they were higher than respective positive controls. There was no statistically significant difference between MenoAct851 and placebo groups concerning the pharmacokinetic parameters such as Cmax, Tmax, t½, and mean residence time of simvastatin; however, AUC showed a significant difference (P < 0.05) between the groups. CONCLUSIONS: MenoAct851 produced weaker interaction potential with CYP3A4 and CYP2D6 substrates based on in vitro assays, but the findings of clinical pharmacokinetic analysis indicate that MenoAct851 increased the AUC of simvastatin and simvastatin hydroxy acid. Therefore, coadministration of MenoAct851 might lead to drug-herb interaction, thereby affecting the therapeutic effect of CYP3A4 substrates. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

Prognostic role of soluble ST2 in acute coronary syndrome with diabetes.

BACKGROUND: Acute coronary syndrome (ACS) patients are at an increased risk of major adverse cardiovascular events (MACE). The objective of our study was to assess whether cardiac biomarker like soluble ST2 (sST2) can predict MACE among ACS patients with diabetes. MATERIALS AND METHODS: A total of 122 patients with ACS were included in the study. sST2 level in blood plasma samples was quantified using enzyme-linked immunosorbent assay (ELISA). Prognostic utility of sST2 for the primary outcome of MACE which included mortality, rehospitalization due to chest pain, unstable angina, recurrent myocardial infarction (MI) and stroke, was assessed during follow-up. RESULTS: The median follow-up period was of 180 days. ROC (receiver operating characteristic) curve demonstrated that elevated levels of sST2 were able to predict mortality, and MACE in ACS patients, along with increased risk of occurrence of MACE and mortality in ACS patients having diabetes. Kaplan-Meier plots revealed a significant increase in the occurrence of MACE in diabetic ACS patients (P = 0.006; by log-rank test). Cox regression analysis revealed that sST2 is not an independent predictor of mortality and MACE in ACS patients having diabetes; however, high sST2 level was found to be a predictor of MACE in all ACS subjects in the fully adjusted model with a hazard ratio (HR) of 5.8 (P = 0.032). CONCLUSION: The current study indicates that elevated levels of sST2 might be a suitable biomarker to evaluate the risk of future adverse cardiovascular events in ACS patients with diabetes.

Increased secretion of exopolysaccharide and virulence potential of a mucoid variant of Salmonella enterica serovar Montevideo under environmental stress.

During an investigation to increase the recovery of Salmonella enterica from Oregano, an increased expression of exopolysaccharide was induced in Salmonella serovar Montevideo. The atypical mucoid (SAL242S) and the non-mucoid (SAL242) strains of Montevideo were compared and characterized using various methods. Serotyping analysis demonstrated that both strains are the same serovar Montevideo. Electron microscopy (EM) of cultured SAL242S cells revealed the production of a prominent EPS-like structure enveloping aggregates of cells that are composed of cellulose. Mucoid cells possessed a higher binding affinity for Calcofluor than that of the non-mucoid strain. Genotypic analysis revealed no major genomic differences between these morphotypes, while expression analyses using a DNA microarray shows that the mucoid variant exhibited heightened expression of genes encoding proteins produced by the SPI-1 type III secretion system. This increased expression of SPI1 genes may play a role in protecting Salmonella from environmental stressors. Based on these observations, Salmonella serovar Montevideo mucoid variant under stressful or low-nutrient environments presented atypical growth patterns and phenotypic changes, as well as an upregulated expression of virulence factors. These findings are significant in the understanding of survival abilities of Salmonella in a various food matrices.

End points in heart failure-are we doing it right?

PURPOSE: Heart Failure (HF) continues to be associated with high mortality and morbidity. We attempted to identify the most common end points used in phase 3 clinical trials of heart failure and discuss their merits and demerits. METHODS: Literature evaluation was done using the databases PubMed and Clinicaltrials.gov from January 2010 to December 2016 to identify randomised clinical trials (RCTs) evaluating the effect of therapeutic drugs on heart failure. Following the literature search, the data on the primary end points were extracted from each of the selected trials. The most recurrent and important end points of Phase III clinical trials for HF over the last six years were identified for further discussion. RESULTS: From our search, it was observed that the most common end points used in trials with acute heart failure (AHF) were composite end point, dyspnea, CV death and most common end points used in trials with chronic heart failure (CHF) were composite end point, 6 minute walk test (6MWT), CV death or HFH, Vo2 max, all cause mortality, left ventricular ejection fraction (LVEF), and dyspnea. CONCLUSION: Choosing the appropriate end points is a critical step in the study design that could turn the tide in the beleaguered drug development pipeline of HF, resulting in the right molecule reaching the HF community.

Tubercular infection after arthroscopic rotator cuff repair.

Tubercular septic arthritis after shoulder arthroscopy has not been reported in the English literature to our knowledge. A case of Tubercular septic arthritis of the shoulder following arthroscopic rotator cuff repair is presented. The sinus and the wound healed well, and laboratory parameters returned to normal, which suggests that the infection was well controlled with the treatment follow-up of 1 year. But the functional score was poor due to repeated surgeries; long-standing infection and the arthritic changes developed. Tubercular infection can occur after arthroscopic shoulder surgery especially in healthcare workers in zones endemic for Tuberculosis. Level of evidence V.

Novel drug targets in clinical development for heart failure.

BACKGROUND: Heart Failure continues to be a leading cause of mortality and morbidity worldwide. The dismal prognosis of patients in acute heart failure (AHF) can be altered only by exploring novel drug molecules. Although the treatment for chronic heart failure (CHF) has seen remarkable progress, there is still a need to develop molecules that could improve the long-term survival outcomes. PURPOSE: To review the drug targets for acute and chronic heart failure and the molecules acting on these targets. METHODS: The article discusses on the mechanism of how the potential drug targets can be modulated to alter the pathophysiological processes in heart failure. Current evidence on molecules acting on these targets has also been described from published literature using the PubMed and Clinical Trials.gov databases. RESULTS: Some of the molecules that are currently being explored for AHF includeomecamtiv mecarbil which activates cardiac myosin ATPase, istaroxime an ionotropicagent that activates SERCA2a pump activity, ularitide and carperitide which are ANP(atrial natriuretic peptide) analogues and recombinant relaxin. Some of the targets forCHF include stabilization of ryanodine receptors, renin inhibition, neprilysin inhibition, neuregulins and SERCA2a gene therapy. CONCLUSION: Clinical trials in heart failure must be designed to minimize the risk of "drug failures." Nevertheless, it is hoped that in the days to come, drugs with superior efficacy and safety will eventually be produced from the surge of molecules that are in the pipeline.

Efficacy of Preemptive Analgesia on Pain Perception After Simple Tooth Extraction: A Prospective Study.

Background and objective This study aims to explore the concept of preemptive analgesia, which is the technique of administration of analgesic agents before the painful stimulus. This bridges the time gap between the onset of action of the analgesic agents and the wear-off of local anesthesia. Existing literature also brings up the concept of central sensitization, which is the hyper-activity of the nervous system in response to a noxious stimulus. Administration of preemptive analgesia prevents central sensitization and hence provides prolonged analgesia to the patient. For the benefit of this study, tab. Etoricoxib 90 mg was used as the analgesic agent. In addition, this study aims to investigate the effects of the administration of tab. Etoricoxib 90 mg 30 minutes before extraction of a single mandibular third molar on the effects of pain experienced by the patient after tooth extraction as compared to a placebo. Methodology This was a double-blinded, prospective, observational study. The pain experienced by 50 participants in each group was measured at 1 hour, 6 hours, 12 hours, and 24 hours postoperatively using a visual analog scale (VAS). The independent samples t-test was then conducted to evaluate the results and draw out conclusions. Results The average difference in pain experienced was maximum in the first hour after the procedure. The mean VAS score reported by patients was 3.14 in the study group but was 6.40 in the control group within the first hour. This difference was reduced in the first six hours after the procedure, with the average score being 3.82 in the study and 7.16 in the control group. The difference was the least after 12 hours, with the study group experiencing a VAS score of 4.64 and controls experiencing a VAS score of 6.14. After the first 24 hours, the mean VAS score was 3.80 in the study group and 5.60 in the control group. Conclusions Preemptive administration of tab. Etoricoxib 90 mg can reduce postextraction pain in healthy adult patients as compared to placebo tablets, with a maximum difference in pain reduction seen at the end of the first six hours (P = 0.012) and the minimum at the end of 12 hours (P = 0.0197).

"Emerging clinical approaches in diabetic cardiomyopathy: insights from clinical trials and future directions".

AIM: We aim to explore the potential of diverse treatments, including perhexiline, calcium channel blockers, anti-hypertensives, PDE5 inhibitors, anti-anginal drugs, aldose reductase inhibitors, and SGLT-2 inhibitors, supported by clinical evidence. Additionally, this review seeks to identify novel therapeutic targets and future avenues for improving cardiovascular outcomes in diabetic populations. METHOD: We performed a comprehensive literature review of English-language studies across multiple electronic databases, such as PubMed, ScienceDirect, Scopus, and Google Scholar, focusing on clinical trials. The search utilized keywords including 'Anti-hyperglycaemic drug,' 'Diabetic cardiomyopathy,' 'DPP-4 inhibitors,' 'GLP-1 receptor agonists,' 'Heart failure,' and 'SGLT-2 inhibitors.' RESULT: We assessed clinical investigations in the treatment of cardiomyopathy and diabetes mellitus (DM) that are enhancing our understanding through trials evaluating the Polypill, Perhexiline, Eplerenone, IMB-1018972, AT-001, tadalafil, and dapagliflozin inhibitors. The development of new targeted interventions is of paramount importance due to the overlooked early symptoms, the complexity of the cellular and molecular pathways involved, and the absence of effective drug therapies. CONCLUSION: Pharmacological treatments like GLP-1 agonists, SGLT-2 inhibitors, NHE-1, NHE-3, and PPAR-γ agonists show promise for treating DCM. These treatments improve myocardial glucose absorption, address dysregulated glucose and lipid metabolism, and lower heart failure and cardiovascular events. Further research is needed to confirm effectiveness and safety.

Efficacy of Ketorolac Tromethamine Diluted Saline Irrigant on Postoperative Sequelae in Patients Undergoing Lower Third Molar Impaction Surgery: A Prospective Clinical Study.

Background Lower third molar surgery is very commonly performed for minor oral surgery by an oral and maxillofacial surgeon. One of the main chief complaints that patients report back to the clinic after getting their lower third molar impaction surgery is immediate postoperative pain. In our study, we have compared the efficacy of ketorolac tromethamine diluted saline solution over plain saline solution used as an irrigant in reducing postoperative swelling and pain. Aim The aim of the current study is to analyse the efficiency of ketorolac tromethamine diluted saline solution over normal saline without any drug dilution in reducing postoperative sequelae like pain and swelling after surgical removal of the lower third molar. Materials and methods This study was carried out at the Department of Oral and Maxillofacial Surgery, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, from April 2023 to July 2023. The study included 50 individuals who wanted to prophylactically get the lower third molar removed surgically. These participants were divided into two groups. One group received ketorolac diluted saline irrigant while the other group received plain saline (0.9% NaCl) as irrigant. Postoperatively, pain and swelling were evaluated in both groups. Both pain and swelling were measured preoperatively, postoperatively after 48 hours, and postoperatively after seven days. The swelling was measured using a 4-point measuring scale, and pain measurement was done using a 10-point visual analogue scale. Statistical analysis was done using Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 23.0, Armonk, NY). For the comparison of continuous variables between the two groups, an unpaired t-test was used. The normality of the results obtained was checked using the Shapiro-Wilk test. The results were considered statistically significant if the P-value was less than 0.05. Results Based on the results obtained it was found that participants who were included in the ketorolac saline group had comparatively lower postoperative pain scores than participants in the plain saline group and this was statistically significant (P=0.001). Postoperative swelling was also comparatively lower in the ketorolac tromethamine saline group but the results were not statistically significant at the end of day 7 (P=0.09). Conclusion Upon observing the cumulative results obtained, we conclude that ketorolac saline (10mg/100mL) was more efficacious in terms of pain reduction than the regular saline solution in impacted lower third molar surgery.

Clinical trial trends over the last 5 years among the BRICS (Brazil, Russia, India, China, and South Africa) nations.

Purpose: Although the Americas and Europe have historically dominated the global research landscape, emerging economies - Brazil, Russia, India, China, and South Africa (BRICS) have significantly increased their contributions in recent years. This article studies clinical trial trends in the BRICS nations between 2018 and 2022 and compares it with trends in the G7 nations (comprising Canada, France, Germany, Italy, Japan, the UK, the USA, and the European Union). This will help stakeholders in planning drug development strategies. Materials and Methods: Data were collected from the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and the World Bank database. An electronic search was done for the total number of trials registered between January 1, 2018, and March 15, 2023. Information was analyzed based on the year of registration, therapeutic area, type of intervention, sponsorship, and type of special population. The trial density indices (TDIs) were calculated based on population (Xi) and gross domestic product (GDP) (Yi) using author-derived formulae. Results: Altogether 2, 77, 536 trials from the BRICS and G7 were registered. China and the US had the most trials among the BRICS and G7, respectively. Between 2018 and 2022, the gap between the BRICS and G7 steadily reduced. The most common indication for clinical trials among the BRICS was cancer. Based on population, the TDI was the highest in China and the lowest in Russia. In proportion to the GDP, the TDI was maximum in Russia and minimum in India. Conclusion: There is a remarkable reduction in the gap in clinical trial trends between the BRICS and G7 nations. Among the BRICS, India and China are at the forefront in drug development. There is scope for improvement in trial density based on India's population and GDP. Stakeholders are likely to utilize the strengths of the BRICS as an attractive destination for investment in this area.

Advancing Longevity: Exploring Antiaging Pharmaceuticals in Contemporary Clinical Trials Amid Aging Dynamics.

Aging is an inevitable biological process that significantly impacts human health, leading to a decline in cellular function and an increase in cellular damage. This study elucidates the burgeoning potential of antiaging pharmaceuticals in mitigating the thriving burden of chronic conditions linked to advancing age. It underscores the pivotal role of these pharmacotherapeutic agents in fostering longevity free from debilitating age-related afflictions, notably cardiovascular disorders, neoplastic processes, and neurodegenerative pathologies. While commendable strides have been made evident in preclinical models, it is crucial to thoroughly investigate their effectiveness and safety in human groups. In addition, ethical concerns about fair access, societal impacts, and careful resource distribution are significant in discussions about developing and using antiaging medications. By approaching the development and utilization of antiaging medications with diligence and foresight, we can strive toward a future where individuals can enjoy extended lifespans free from the debilitating effects of age-related ailments.

Comparison of Efficacy of Platelet-Rich Plasma With and Without Topical Minoxidil for Hair Growth in Patients With Androgenetic Alopecia: A Prospective Study.

Introduction Androgenetic pattern of alopecia is a common problem occurring in men, which mostly arises from their younger age. There are many therapies advocated in the literature for hair loss reduction, and one of them is platelet-rich plasma (PRP) therapy. This study aimed to assess the efficacy of combined PRP therapy with topical minoxidil over PRP as monotherapy in hair loss reduction and regeneration of new hair. Materials and methods The study was conducted at our institute in the Department of Oral and Maxillofacial Surgery at Saveetha Dental College and Hospital. The study consisted of 40 participants, 20 of whom had only PRP therapy as part of their treatment, while the other 20 participants received PRP combined with topical minoxidil as treatment. Both group participants were evaluated for postoperative hair shaft diameter and hair follicle density. Parameters were measured preoperatively and postoperatively after one month, two months, and three months. Data analysis was done with the help of SPSS, with P-values less than 0.05 considered statistically significant. The Mann-Whitney U test was used to compare the two groups for measurement of hair shaft diameter, and for comparison between hair follicle density, an unpaired t-test was used. Results It was found that the mean hair shaft diameter in the PRP with minoxidil group was higher than that of the PRP group for one month (P = 0.023), two months (P = 0.001), and three months (P = 0.001) postoperative periods, and the results were statistically significant. Hair follicle density (mean hair quantity) was higher in the PRP group than in the PRP with the minoxidil group in the first postoperative month. However, this difference was not statistically significant (P = 0.08). While the mean hair quantity in the PRP with minoxidil group was higher than that in the PRP group for two months (P = 0.45) and three months (P = 0.001) postoperative periods, the results were statistically significant only at the three-month postoperative period. Conclusion It can be concluded that injectable autologous PRP with minoxidil as a topical agent is a better treatment option for the improvement of both hair quality (hair shaft diameter) and hair quantity (hair follicle density) compared to plain autologous injectable PRP monotherapy.

Exploring the immunomodulatory potential of Brahmi (Bacopa monnieri) in the treatment of invasive ductal carcinoma.

Bacopa monnieri (L) Wettst, commonly known as Brahmi, stands as a medicinal plant integral to India's traditional medical system, Ayurveda, where it is recognized as a "medhya rasayana"-a botanical entity believed to enhance intellect and mental clarity. Its significant role in numerous Ayurvedic formulations designed to address conditions such as anxiety, memory loss, impaired cognition, and diminished concentration underscores its prominence. Beyond its application in cognitive health, Brahmi has historically been employed in Ayurvedic practices for the treatment of inflammatory diseases, including arthritis. In contemporary biomedical research, Bacopa monnieri can attenuate the release of pro-inflammatory cytokines TNF-α and IL-6 in animal models. However, there remains a paucity of information regarding Bacopa's potential as an anticancer agent, warranting further investigation in this domain. Based on previous findings with Brahmi (Bacopa monnieri), the current study aims to find out the role of Brahmi plant preparation (BPP) in immunomodulatory actions on IDC. Employing a specific BPP concentration, we conducted a comprehensive study using MTT assay, ELISA, DNA methylation analysis, Western blotting, ChIP, and mRNA profiling to assess BPP's immunomodulatory properties. Our research finding showed the role of BPP in augmenting the action of T helper 1 (TH1) cells which secreted interferon-γ (IFN-γ) which in turn activated cytotoxic T-lymphocytes (CTL) to kill the cells of IDC (*p < 0.05). Moreover, we found out that treatment with BPP not only increased the activities of tumor-suppressor genes (p53 and BRCA1) but also decreased the activities of oncogenes (Notch1 and DNAPKcs) in IDC (*p < 0.05). BPP had an immense significance in controlling the epigenetic dysregulation in IDC through the downregulation of Histone demethylation & Histone deacetylation and upregulation of Histone methylation and Histone acetylation (*p < 0.05). Our Chromatin immunoprecipitation (ChIP)-qPCR data showed BPP treatment increased percentage enrichment of STAT1 & BRCA1 (*p < 0.05) and decreased percentage enrichment of STAT3, STAT5 & NF ΚB (*p < 0.05) on both TBX21 and BRCA1 gene loci in IDC. In addition, BPP treatment reduced the hypermethylation of the BRCA1-associated-DNA, which is believed to be a major factor in IDC (*p < 0.05). BPP not only escalates the secretion of type 1 specific cytokines but also escalates tumor suppression and harmonizes various epigenetic regulators and transcription factors associated with Signal Transducer and Activator of Transcription (STAT) to evoke tumor protective immunity in IDC.