Maternal and Child Health Training of Traditional Birth Attendants and Pregnancy Outcomes: A Systematic Review and Meta-analysis.

INTRODUCTION: In remote communities, maternal and child health is often compromised due to limited access to healthcare. Simultaneously, these communities historically rely greatly on traditional birth attendants (TBAs). However, optimal integration of these traditional methods with modern healthcare practices remains a topic of debate. We assessed the effect of maternal and child health training of traditional birth attendants on adverse pregnancy outcomes. METHODS: We conducted a systematic review and meta-analysis to answer the above research question. We independently screened studies using databases like PubMed, Scopus, and CENTRAL, extracted data, and assessed the study quality. Due to fewer original studies in this field, we considered both pre-post and between-group differences to assess the effect of differences. These were synthesised separately, assessed against a p-value function, and subjected to sensitivity analyses. RESULTS: We included six interventional studies. Training TBAs reduced the risk of perinatal mortality [0.69, 0.61-0.78] and 7-day neonatal mortality [0.65, 0.53-0.80] but not stillbirth [0.70, 0.39-1.26]. In randomized controlled trials, there is a lower risk of perinatal mortality [0.73, 0.67-0.79] and neonatal mortality [0.70, 0.62-0.80] but not stillbirth [0.81, 0.56-1.18] with trained traditional birth attendants. There are methodological concerns with most existing studies, including domains like allocation concealment. DISCUSSION: There is some evidence of the benefit of training TBAs, though of a low to very low certainty. Due to fewer studies, inconsistent estimates for different critical outcomes, and concerns with the existing studies, further well-designed studies can give more insights. They can also help optimize the contents of TBA training interventions. PROTOCOL: CRD42023412935 (PROSPERO).

PeRinatal, neOnatal, and Maternal OuTcomEs with azithromycin prophylaxis in pregnancy and labour (PROMOTE-PROPHYLAXIS): systematic review and meta-analysis.

Background: Initial randomised controlled trials (RCTs) showed that prophylactic azithromycin in pregnant women improved maternal and neonatal outcomes; however, the recent evidence did not show any benefit to neonatal survival. There is conflicting evidence over the role of azithromycin prophylaxis in antenatal and intrapartum periods. We explored whether azithromycin prophylaxis in pregnant women improves maternal and neonatal outcomes. Methods: For this systematic review and meta-analysis registered on PROSPERO [CRD42023411093], we searched seven databases (PubMed, Scopus, Embase, Cochrane Library, EBSCOHost, ProQuest, and Web of Science) and clinical trial registries until 04/23/2024, for RCTs evaluating antenatal/intrapartum azithromycin prophylaxis against placebo/routine care in pregnant women. The primary outcome was neonatal mortality. Intrapartum and antenatal administration were assessed separately. We used random-effects meta-analysis. The risk of bias was assessed using the Cochrane RoB 2 tool. The GRADE approach was used to evaluate the certainty of the evidence. Findings: Screening 2161 records retrieved 20 RCTs (56,381 participants). Intrapartum azithromycin may make little or no difference to neonatal mortality [5 RCTs, 44,436 participants; Risk Ratio (RR): 1.02, 95% CI 0.86-1.20, I 2  = 0%, very low certainty], and maternal mortality [3 RCTs, 44,131 participants, RR: 1.26, 0.65-2.42, I 2  = 0%, low certainty]. Similarly, antenatal azithromycin may have little or no effect on neonatal mortality [3 RCTs; 5304 participants; RR: 0.74, 0.35-1.56, I 2  = 43%, very-low certainty] and maternal mortality [3 RCTs; 8167 participants RR: 1.62, 0.67-3.91, I 2  = 0%, low certainty]. There is no data on long-term adverse outcomes and antimicrobial resistance. Interpretation: Low to very low certainty evidence suggests that intrapartum or antenatal azithromycin prophylaxis in pregnant women might not reduce maternal or neonatal mortality. Funding: None.

Provider's satisfaction with telemedicine services for tribals of Western Rajasthan: A qualitative analysis.

Background: There are significant barriers to healthcare access in tribal areas, even though for every 834 people, there is one public physician (registered allopathic and AYUSH doctors). More than 86% of hospital visits occur in rural areas. Furthermore, the bulk of them travel long distances to reach hospitals. A telemedicine center was established in the aspirational tribal district of Sirohi, Rajasthan, to provide accessible quality health care. Objective: To understand providers' attitudes and satisfaction with telemedicine services for tribal populations. Materials and Methods: This cross-sectional, mixed-method study enrolled consultants from various clinical departments of AIIMS Jodhpur (n = 23) who provide teleconsultations to the tribal population. Result: The mean score of the satisfactory index was 54.7 ± 22.04. The higher score is 87.4 regarding the ability to use the technology platform during teleconsultation. The lower score was 34.7 for video quality during teleconsultation at STHR. 91.3% found this a beneficial model for the tribal population. Consultants providing teleconsultations expressed that this model is a boon for tribal patients as a screening tool and will save time and money for improved accessibility. Conclusion: Positive indications of teleconsultation with a provider's utility, acceptability, and satisfaction. Most marginalized people can efficiently access all levels of (primary, secondary, or tertiary) health care from experts through telemedicine, which will broaden outreach in hard-to-reach or inaccessible tribal or rural areas.

Glucagon-like peptide-1 receptor agonists in adolescents with overweight or obesity with or without type 2 diabetes multimorbidity-a systematic review and network meta-analysis.

AIM: To synthesize the evidence on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in adolescents with overweight or obesity. MATERIALS AND METHODS: For this systematic review and network meta-analysis, we searched five databases and registries until 2 March 2024 for eligible randomized controlled trials (RCTs). The primary outcome was weight change. We did a pairwise meta-analysis to compare GLP-1RAs and placebo, followed by a drug-wise network meta-analysis (NMA) to compare GLP-1RAs against each other. RESULTS: We screened 770 records to include 12 RCTs with 883 participants. The evidence suggests that GLP-1RAs reduced weight (mean difference -4.21 kg, 95% confidence interval [CI] -7.08 to -1.35) and body mass index (BMI; mean difference -2.11 kg/m2, 95% CI -3.60 to -0.62). The evidence on waist circumference, body fat percentage and adverse events (AEs) was very uncertain. The results remained consistent with subgroup analyses for coexisting type 2 diabetes. Longer therapy duration led to a greater reduction in weight and BMI. In the NMA, semaglutide led to the greatest weight reduction, followed by exenatide, liraglutide and lixisenatide. CONCLUSIONS: The evidence suggests that GLP-1RAs reduce most weight-related outcomes in adolescents, with semaglutide being the most efficacious. There is uncertain evidence on body fat and serious AEs, probably due to fewer studies and low incidence, respectively. Larger RCTs with head-to-head comparisons, pragmatic design, adiposity-related outcomes, and economic evaluation can further guide the use and choice of GLP-1RAs.

Targeting self-care adherence for glycaemic control in multimorbid type 2 diabetes mellitus with depression using bupropion: a protocol for cross-over randomised controlled trial.

INTRODUCTION: Diabetes and depression are among the 10 biggest health burdens globally. They often coexist and exhibit a strong bidirectional relationship. Depression leads to decreased adherence to self-care activities. This impacts glycaemic control and worsens type 2 diabetes mellitus (T2D). Both conditions have a synergistic effect and lead to greater complications, hospitalisations, healthcare expenditure and a worse quality of life. There is no consensus on managing people with comorbid T2D and depression. Bupropion is an efficacious antidepressant with many properties suitable for T2D with depression, including a favourable metabolic profile, persistent weight loss and improvement in sexual dysfunction. We will assess the efficacy and safety of add-on bupropion compared with standard care in people with T2D and mild depression. This study can give valuable insights into managing the multimorbidity of T2D and depression. This can help mitigate the health, social and economic burden of both these diseases. RESEARCH DESIGN AND METHODS: This cross-over randomised controlled trial will recruit people with T2D (for 5 years or more) with mild depression. They will be randomised to add-on bupropion and standard care. After 3 months of treatment, there will be a washout period of 1 month (without add-on bupropion while standard treatment will continue). Following this, the two arms will be swapped. Participants will be assessed for glycosylated haemoglobin, adherence to diabetes self-care activities, lipid profile, urine albumin-to-creatinine ratio, autonomic function, sexual function, quality of life and adverse events. ETHICS AND DISSEMINATION: The Institutional Ethics Committee at All India Institute of Medical Sciences, Jodhpur has approved this study (AIIMS/IEC/2022/4172, 19 September 2022). We plan to disseminate the research findings via closed group discussions at the site of study, scientific conferences, peer-reviewed published manuscripts and social media. TRIAL REGISTRATION NUMBER: CTRI/2022/10/046411.

Nutritional and microbiota-based therapeutic interventions for alcohol-associated liver disease: From pathogenesis to therapeutic insights.

Alcohol-associated liver disease (ALD) manifests as a consequence of prolonged and excessive alcohol consumption. This disease is closely associated with the interplay between gut health and liver function, which can lead to complex pathophysiological changes in the body. This review offers a comprehensive exploration of ALD's multifaceted nature, with a keen focus on its pathogenesis and the potential of nutritional and microbiota-based therapies. Insights derived from diverse case studies are utilized to shed light on how interventions can rebalance the gut microbiome and enhance liver function in ALD patients. Furthermore, the feasibility of liver transplantation and stem cell therapy as ultimate measures for ALD has been discussed, with acknowledgment of the inherent risks and challenges accompanying them. ALD's complexity underscores the necessity for a thorough understanding of its etiology and progression to devise effective treatments that mitigate its profound impact on an individual's health.

Electronic-PRO Measures for adverse events Of Treatment In ONcology (E-PROMOTION).

PURPOSE: Cancer patients struggle with the trauma of the disease and its treatment. PRO-CTCAE was developed to improve the recording of underreported symptomatic toxicities. We evaluated the improvement and ease in reporting symptomatic adverse events through add-on PRO-CTCAE (via a mobile application) compared to standard clinician-reported outcomes in routine clinical practice. We also evaluated changes in the health-related quality of life (HRQoL). METHODS: 110 cancer patients were studied for three weeks between their first and second chemotherapy session. HRQoL was assessed using EORTC QLQ-c30. RESULTS: Fifty-three patients self-reported their symptomatic adverse events on the day 7th & day 14th after the first cycle of chemotherapy. For the other fifty-seven patients, recording of adverse events was done by standard clinician-reported outcomes. All the patients in the study group reported adverse events compared to only 21 % in the standard reporting group. All 15 domains of adverse events were reported in the self-reporting group compared to only 5 in the standard reporting group. The self-reporting group had a significantly better overall quality of life. CONCLUSIONS: Self-reporting of adverse events using mobile app-based PRO-CTCAE helps patients and clinicians with better documentation of symptomatic toxicities of chemotherapy, reducing the burden on physicians and improving patient satisfaction. Mobile app-based self-reporting empowers cancer patients undergoing treatment, improves their quality of life, and should be implemented in routine clinical practice. Wider implementation can lead to further optimised solutions.

Minocycline in depression not responding to first-line therapy: A systematic review and meta-analysis.

BACKGROUND: Major depressive disorder is often resistant to first-line treatment, with around 30% failing to respond to traditional therapy. Treatment-resistant depression results in prolonged hospitalization and healthcare costs. Anti-inflammatory drugs have shown promising results in depression not responding to initial therapy. Minocycline has anti-inflammatory properties and crosses the blood-brain barrier. It has demonstrated varied results in several randomized controlled trials (RCTs). METHODS: We assessed the efficacy of minocycline compared to placebo in depression not responding to one first-line antidepressant via a systematic review and meta-analysis. We performed a comprehensive literature search across PubMed, Cochrane, and Scopus for RCTs. We visualized the results using forest plots and drapery plots. We assessed and explored heterogeneity using I2, prediction interval, and meta-regression. Then, we rated the certainty of the evidence. RESULTS: Four RCTs revealed a non-significant difference in depression severity [-3.93; 95% CI: -16.14 to 8.28], rate of response [1.15; 0.33-4.01], and rate of remission [0.94; 0.44-2.01]. However, the reduction in depression severity is significant at a trend of P < .1. The high between-study heterogeneity (I2 = 78%) for depression severity could be answered by meta-regression (P = .02) for the duration of therapy. CONCLUSION: There is no significant difference with minocycline compared to placebo for depression not responding to first-line antidepressant therapy. However, the treatment response varies with treatment duration and patients' neuroinflammatory state. Thus, larger and longer RCTs, especially in diverse disease subgroups, are needed for further insight. This is needed to allow greater precision medicine in depression and avoid elevated healthcare expenditure associated with hit-and-trial regimens. REGISTRATION: CRD42023398476 (PROSPERO).

Are paid tools worth the cost? A prospective cross-over study to find the right tool for plagiarism detection.

Background: The increasing pressure to publish research has led to a rise in plagiarism incidents, creating a need for effective plagiarism detection software. The importance of this study lies in the high cost variation amongst the available options for plagiarism detection. By uncovering the advantages of these low-cost or free alternatives, researchers could access the appropriate tools for plagiarism detection. This is the first study to compare four plagiarism detection tools and assess factors impacting their effectiveness in identifying plagiarism in AI-generated articles. Methodology: A prospective cross-over study was conducted with the primary objective to compare Overall Similarity Index(OSI) of four plagiarism detection software(iThenticate, Grammarly, Small SEO Tools, and DupliChecker) on AI-generated articles. ChatGPT was used to generate 100 articles, ten from each of ten general domains affecting various aspects of life. These were run through four software, recording the OSI. Flesch Reading Ease Score(FRES), Gunning Fog Index(GFI), and Flesch-Kincaid Grade Level(FKGL) were used to assess how factors, such as article length and language complexity, impact plagiarism detection. Results: The study found significant variation in OSI(p < 0.001) among the four software, with Grammarly having the highest mean rank(3.56) and Small SEO Tools having the lowest(1.67). Pairwise analyses revealed significant differences(p < 0.001) between all pairs except for Small SEO Tools-DupliChecker. Number of words showed a significant correlation with OSI for iThenticate(p < 0.05) but not for the other three. FRES had a positive correlation, and GFI had a negative correlation with OSI by DupliChecker. FKGL negatively correlated with OSI by Small SEO Tools and DupliChecker. Conclusion: Grammarly is unexpectedly most effective in detecting plagiarism in AI-generated articles compared to the other tools. This could be due to different softwares using diverse data sources. This highlights the potential for lower-cost plagiarism detection tools to be utilized by researchers.

Mapping of traditional healthcare providers and their healing approaches in a tribal community of district Sirohi, Rajasthan.

Introduction: Traditional applications of medicinal plants in healthcare practices provide indication to new therapeutic concepts; hence, their relevance is highly recognized. The objective of the study was to map the traditional healers from the aspirational district and scientific documentation of their healing practices to treat various diseases. Method: This was community-based study in tribal subpopulation zone of district Sirohi. The data was collected through field survey and interviews of tribal healers by using semi-structured questionnaire. Result: We identified 1015 tribal healers (68% male and 32% female), and all belong to Bhil, Meena, and Garasia communities of district Sirohi. The mean age was 60.45 ± 16.56 years, 82.6% healers were uneducated, and 12.6% had primary education, while 1.2% were graduates. Tribal healers act as primary point of care for tribal community and practiced various treatment modalities including herbal healing (32.7%), diviners (28.9%), child birth attendant (24.7%), and bone setters (13.7%). We recorded 88 herbal healing practices from tribal communities of district Sirohi and scientifically documented. The common diseases treated by tribal healers included wound healing, skin infection, fever, arthritis, pain, diarrhea, cough, and cold. The Fabaceae family was credited with highest number (17%) of plants used by herbal healers. It was also noted that some of the plants used for medicinal purpose are endangered and overexhausted. Conclusion: Ethnopharmacological data is the foundation for further validation and value addition of herbal healthcare practices. The mapping of indigenous knowledge holders and scientific documentation of their knowledge might be a crucial step for providing clue regarding new therapeutic molecules.

Pharmacological treatment and vaccines in monkeypox virus: a narrative review and bibliometric analysis.

Mpox (earlier known as monkeypox) virus infection is a recognized public health emergency. There has been little research on the treatment options. This article reviews the specific drugs used to treat mpox virus infection and the vaccines used here. Instead of focusing on the mechanistic basis, this review narrates the practical, real-life experiences of individual patients of mpox virus disease being administered these medicines. We conducted a bibliometric analysis on the treatment of the mpox virus using data from several databases like PubMed, Scopus, and Embase. The research on this topic has grown tremendously recently but it is highly concentrated in a few countries. Cidofovir is the most studied drug. This is because it is indicated and also used off-label for several conditions. The drugs used for mpox virus infection include tecovirimat, cidofovir, brincidofovir, vaccinia immune globulin, and trifluridine. Tecovirimat is used most frequently. It is a promising option in progressive mpox disease in terms of both efficacy and safety. Brincidofovir has been associated with treatment discontinuation due to elevated hepatic enzymes. Cidofovir is also not the preferred drug, often used because of the unavailability of tecovirimat. Trifluridine is used topically as an add-on agent along with tecovirimat for ocular manifestations of mpox virus disease. No study reports individual patient data for vaccinia immune globulin. Though no vaccine is currently approved for mpox virus infection, ACAM 2000 and JYNNEOS are the vaccines being mainly considered. ACAM 2000 is capable of replicating and may cause severe adverse reactions. It is used when JYNNEOS is contraindicated. Several drugs and vaccines are under development and have been discussed alongside pragmatic aspects of mpox virus treatment and prevention. Further studies can provide more insight into the safety and efficacy of Tecovirimat in actively progressing mpox virus disease.

Apremilast Add-On Benefits Over Conventional Drugs (ABCD) in Unstable Non-segmental Vitiligo: A 12-Week Single-Center Randomized Controlled Trial.

Background Apremilast is an oral phosphodiesterase-4 enzyme inhibitor that modulates the immune system by increasing intracellular cyclic adenosine monophosphate levels and inhibiting inflammatory cytokines synthesis. We aimed to compare the efficacy and safety of add-on apremilast in combination therapy with standard treatment in patients with unstable, non-segmental vitiligo. Methods The study was a 12-week randomized, controlled, parallel-group, open-labeled trial. The control group received standard treatment (n=15), and the intervention group received 30 mg apremilast twice daily in addition to standard treatment (n= 16). Time to the first sign of re-pigmentation, halt in progression, and change in vitiligo area scoring index (VASI) score is the primary outcomes. Normality was assessed, and appropriate parametric and nonparametric tests were undertaken. Results Thirty-seven participants were randomized into two groups, and analysis was done on thirty-one participants. Over the treatment duration of 12 weeks, the median time to observe the first sign of re-pigmentation was four weeks in the add-on apremilast group compared to seven weeks in the control group (p=0.018). The halt in progression was observed more in the add-on Apremilast group (93.75%) compared to the control group (66.66%) (p=0.08). The VASI score decreased by 1.24 in the add-on apremilast group and 0.05 in the control group (p= 0.754). Parameters including body surface area, dermatology life quality index, and body mass index reduced significantly, while the visual analog scale increased significantly in the add-on apremilast group. However, results were comparable between groups. Conclusions Treatment with add-on apremilast accelerated clinical improvement. It also reduced disease progression and improved the disease index among participants. However, add-on apremilast had a lower tolerability profile than the control group.

Therapeutic spectrum of piperine for clinical practice: a scoping review.

Translation of traditional knowledge of herbs into a viable product for clinical use is still an uphill task. Piperine, a pungent alkaloid molecule derived from Piper nigrum and Piper longum possesses diverse pharmacological effects. Traditionally, pepper is used for arthritis, bronchitis, gastritis, diarrhea, snake bite, menstrual pain, fever, and bacterial infections, etc. The anti-inflammatory, antioxidant and immunomodulatory actions of piperine are the possible mechanisms behind its therapeutic potential. Various in-silico and experimental studies have shown piperine as a possible promising molecule in coronavirus disease (COVID-19), ebola, and dengue due to its immunomodulatory and antiviral activities. The other important clinical applications of piperine are due to its bio enhancing effect on drugs, by modulating, absorption in the gastrointestinal tract, altering activities of transporters like p-glycoprotein substrates, and modulating drug metabolism by altering the expression of cytochrome P450 or UDP-glucuronosyltransferase enzymes. Piperine attracted clinicians in treating patients with arthritis, metabolic syndrome, diabetes, skin infections, gastric and liver disorders. This review focused on systematic, evidence-based insight into the use of piperine in clinical settings and mechanistic details behind its therapeutic actions. Also, highlights a number of clinical trials of piperine at various stages exploring its clinical application in cancer, neurological, respiratory, and viral disease, etc.

The use of antivirals in the treatment of human monkeypox outbreaks: a systematic review.

OBJECTIVES: Human monkeypox virus (MPXV) infection is a recently declared public health emergency of international concern by the World Health Organization. Besides, there is scant literature available on the use of antivirals in MPXV infection. This systematic review compiles all evidence of various antivirals used on their efficacy and safety and summarizes their mechanisms of action. METHODS: A review was done of all original studies mentioning individual patient data on the use of antivirals in patients with MPXV infection. RESULTS: Of the total 487 non-duplicate studies, 18 studies with 71 individuals were included. Tecovirimat was used in 61 individuals, followed by cidofovir in seven and brincidofovir (BCV) in three individuals. Topical trifluridine was used in four ophthalmic cases in addition to tecovirimat. Of the total, 59 (83.1%) were reported to have complete resolution of symptoms; one was experiencing waxing and waning of symptoms, only one (1.8%) had died, and the others were having a resolution of symptoms. The death was thought unrelated to tecovirimat. Elevated hepatic panels were reported among all individuals treated with BCV (leading to treatment discontinuation) and five treated with tecovirimat. CONCLUSION: Tecovirimat is the most used and has proven beneficial in several aggravating cases. No major safety concerns were detected upon its use. Topical trifluridine was used as an adjuvant treatment option along with tecovirimat. BCV and cidofovir were seldom used, with the latter often being used due to the unavailability of tecovirimat. BCV was associated with treatment discontinuation due to adverse events.

Assesement of serum Sfrp5/Wnt-5a level and its utility in the risk stratification of treatment naïve patients with metabolic syndrome.

Our study focused on investigating the clinical significance of serum Sfrp5/Wnt-5a levels as a risk marker in metabolic syndrome (MetS). The study involved a total of 107 treatment-naive MetS cases and 100 controls with similar age and sex belonging to northern India. The profiling of clinical, biochemical, and anthropometric variables was done. ELISA methods were employed for serum cytokine estimation. Serum Sfrp5 was inversely correlated with BMI, WC, SBP, DBP, FPG, TG, fasting insulin level, and HOMA-IR in both males and females. The best cutoff value for Sfrp5 to predict MetS in males was ≤40.48 ng/ml (sensitivity 53.70% and specificity 90.48%), while in female, it was ≤66.67 ng/ml (sensitivity 98.11% and specificity 34.48%). MetS occurrence decreased with increasing concentration of Sfrp5 with an odds ratio (OR) of 0.95 (95% CI = 0.92-0.98, P < .001) in male and 0.93 (95% CI = 0.91-0.97, P < .001) in female. Quartile analysis revealed that odds of MetS significantly decreased in quartile 4 vs. 1, 0.06 (95% CI = 0.01-0.25), P = .001 and 0.13 (95% CI = 0.04-0.44), P = .001, respectively, in male and female. The inverse association of serum concentration of Sfrp5 with MetS might have a useful addition to the available risk marker as well as a therapeutic target for MetS.

Bugs as Drugs: Understanding the Linkage between Gut Microbiota and Cancer Treatment.

The commensal microbiota is known to regulate host physiology. Dysbiosis or compromised resilience in the microbial ecology is related to the impending risk of cancer. A potential link between cancer and microbiota is indicated by a lot of evidence. The current review explores in detail the various links leading to and /or facilitating oncogenesis, providing sound reasoning or a basis for its utilization as potential therapeutic targets. The present review emphasizes the existing knowledge of the microbiome in cancer and further elaborates on the factors, like genetic modifications, effects of dietary components, and environmental agents, that are considered to assess the direct and indirect effect of microbes in the process of oncogenesis and on the host's health. Strategies modulating the microbiome and novel biotherapeutics are also discussed. Pharmacomicrobiomics is one such niche accounting for the interplay between the microbiome, xenobiotic, and host responses, which is also looked upon. The literature search strategy for this review was conducted by following the methodology of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The method includes the collection of data from different search engines, like PubMed, ScienceDirect, SciFinder, etc., to get coverage of relevant literature for accumulating appropriate information regarding microbiome, cancer, and their linkages. These considerations are made to expand the existing literature on the role of gut microbiota in the host's health, the interaction between host and microbiota, and the reciprocal relationship between the microbiome and modified neoplastic cells. Potential therapeutic implications of cancer microbiomes that are yet unexplored and have rich therapeutic dividends improving human health are discussed in detail in this review.

SNPs of FOXO1 and Their Interactions Contributes to the Enhanced Risk of Diabetes Among Elderly Individuals.

We have assessed the impact of three single nucleotide polymorphisms (SNPs) of Forkhead Box O1 (FOXO1) and their interaction on susceptibility of type 2 diabetes mellitus in geriatric population from northern India. We genotyped three SNPs (rs2721068, rs17446614, and rs4581585) of FOXO1 gene in 190 elderly individuals with diabetes and 182 unrelated healthy controls of similar ethnicity by using TaqMan SNP assays. SNP-SNP and SNP-environment interactions among polymorphic loci were studied by the multifactor dimensionality reduction (MDR) method. The AA genotype carriers of rs17446614 was associated with the increased susceptibility of diabetes in both adjusted and unadjusted model, whereas rs4581585 was associated with the risk in unadjusted model only. Genotype and minor allele interaction with quantitative parameters revealed that AA genotype of rs17446614 had significantly higher fasting plasma glucose (FPG) in diabetic subjects, also minor allele (A) in patients was positively associated with FPG and glycated hemoglobin. Haplotype Trs2721068Grs17446614Trs4581585 increases the risk of diabetes, whereas carrier of haplotypes Crs2721068Grs17446614Crs4581585 and Crs2721068 Grs17446614Trs4581585 were protective. The MDR analysis revealed that interaction of rs17446614 with body mass index (BMI) increased the susceptibility of diabetes. Therefore presence of rs17446614 variant and its interaction with BMI and haplotype Trs2721068Grs17446614Trs4581585 modulates the risk of diabetes and can be used as a promising tool for identifying high-risk individuals.

A Narrative Review of Potential Future Antidiabetic Drugs: Should We Expect More?

Prevalence of diabetes mellitus, a chronic metabolic disease characterized by hyperglycemia, is growing worldwide. The majority of the cases belong to type 2 diabetes mellitus (T2DM). Globally, India ranks second in terms of diabetes prevalence among adults. Currently available classes of therapeutic agents are used alone or in combinations but seldom achieve treatment targets. Diverse pathophysiology and the need of therapeutic agents with more favourable pharmacokinetic-pharmacodynamics profile make newer drug discoveries in the field of T2DM essential. A large number of molecules, some with novel mechanisms, are in pipeline. The essence of this review is to track and discuss these potential agents, based on their developmental stages, especially those in phase 3 or phase 2. Unique molecules are being developed for existing drug classes like insulins, DPP-4 inhibitors, GLP-1 analogues; and under newer classes like dual/pan PPAR agonists, dual SGLT1/SGLT2 inhibitors, glimins, anti-inflammatory agents, glucokinase activators, G-protein coupled receptor agonists, hybrid peptide agonists, apical sodium-dependent bile acid transporter (ASBT) inhibitors, glucagon receptor antagonists etc. The heterogeneous clinical presentation and therapeutic outcomes in phenotypically similar patients is a clue to think beyond the standard treatment strategy.