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Poongothai Venkatachalapathy,1 Sruthi Padhilahouse,1 Mohan Sellappan,1 Tharunika Subramanian,2 Shilia Jacob Kurian,3 Sonal Sekhar Miraj,3 Mahadev Rao,3 Ashwin Ashok Raut,4 Rupinder Kaur Kanwar,4 Jitendra Singh,4 Sagar Khadanga,5 Sukumar Mondithoka,5 Murali Munisamy4 1Department of Pharmacy Practice, Karpagam College of Pharmacy, Coimbatore, Tamilnadu, India; 2Karpagam Faculty of Medical Sciences and Research, Coimbatore, India; 3Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India; 4Translational Medicine Centre, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India; 5Department of General Medicine, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, IndiaCorrespondence: Murali MunisamyTranslational Medicine Centre, All India Institute of Medical Sciences, Bhopal, 462020, Madhya Pradesh, India, Tel +91-9600-883-284Email murali.tmc@aiimsbhopal.edu.inAbstract: Type 2 diabetes mellitus (T2DM) is the most common form of diabetes, and is rising in incidence with widespread prevalence. Multiple gene variants are associated with glucose homeostasis, complex T2DM pathogenesis, and its complications. Exploring more effective therapeutic strategies for patients with diabetes is crucial. Pharmacogenomics has made precision medicine possible by allowing for individualized drug therapy based on a patient’s genetic and genomic information. T2DM is treated with various classes of oral hypoglycemic agents, such as biguanides, sulfonylureas, thiazolidinediones, meglitinides, DPP4 inhibitors, SGLT2 inhibitors, α-glucosidase inhibitors, and GLP1 analogues, which exhibit various pharmacogenetic variants. Although genomic interventions in monogenic diabetes have been implemented in clinical practice, they are still in the early stages for complex polygenic disorders, such as T2DM. Precision DM medicine has the potential to be effective in personalized therapy for those suffering from various forms of DM, such as T2DM. With recent developments in genetic techniques, the application of candidate-gene studies, large-scale genotyping investigations, genome-wide association studies, and “multiomics” studies has begun to produce results that may lead to changes in clinical practice. Enhanced knowledge of the genetic architecture of T2DM presents a bigger translational potential. This review summarizes the genetics and pathophysiology of T2DM, candidate-gene approaches, genome-wide association studies, personalized medicine, clinical relevance of pharmacogenetic variants associated with oral hypoglycemic agents, and paths toward personalized diabetology.Keywords: pharmacogenomics, personalized medicine, type 2 diabetes, antidiabetic drugs

Objective of the study was to find the association of vitamin D receptor (VDR) polymorphisms (Fokl, Taql and Apal) with vitamin D levels in diabetic foot ulcer (DFU) patients in South India. In this case-control study, plasma vitamin D levels and VDR genotype frequencies of 70 cases (DFU patients) were compared with 70 diabetic (diabetes mellitus [DM] [non-DFU]) patients and 70 apparently healthy controls (HC) from South India. Plasma vitamin D levels were measured using the ELISA technique, and genotyping of VDR polymorphisms was carried out using real-time polymerase chain reaction. Logistic regression was used to find the association between DFU versus HC and DFU versus DM traits. Association analysis was performed based on additive, dominant and recessive models with age and gender as covariates. A 45.7% of DFU patients have sufficient vitamin D levels than 48.6% and 40% of DM patients and HC, respectively. Linkage disequilibrium analysis for DFU versus HC and DFU versus DM traits shows that single nucleotide polymorphisms (SNPs) Taq1 (rs731236) and Apal (rs7975232) are in strong linkage disequilibrium in DFU patients. The alleles and genotype frequencies were similar in all three groups. Although the additive model does not show statistical significance, age and sex correlate with the three SNPs (Fokl, Taql and Apal). No association was found between VDR gene polymorphisms and vitamin D levels in DFU patients in Southern India. On the other hand, age and sex correlate with the three SNPs., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: The coronavirus disease (COVID-19) led to a global health crisis. Inappropriate use of antibiotics in COVID-19 patients has been a concern, leading to antimicrobial resistance. This study evaluated the patterns and predictors of empirical antibiotic therapy in COVID-19 patients and associated outcomes., Methods: A hospital-based retrospective study was conducted with 525 patients admitted to Kasturba Hospital, Manipal, India, with moderate and severe COVID-19 from 1 March to 1 August 2021. They were divided based on empirical therapy, and predictors of antibiotic usage were assessed by logistic regression., Results: Four hundred and eighty (91.4%) COVID-19 patients received at least one course of antibiotics, with 440 (83.8%) initiating empirical therapy. Patients with severe COVID-19 manifestations were more likely to be prescribed empirical antibiotics. Multivariable analysis showed that patients initiated on empirical antibiotics had significantly elevated levels of procalcitonin [OR: 3.91 (95% CI: 1.66-9.16) ( p  = 0.001)], invasive ventilation [OR: 3.93 (95% CI: 1.70-9.09) ( p  = 0.001)], shortness of breath [OR: 2.25 (95% CI: 1.30-3.89) ( p  = 0.003)] and higher CRP levels [OR: 1.01 (95% CI: 1.00-1.01) ( p  = 0.005)]. Most antibiotics (65.9%) were prescribed from the 'Watch' group, the highest being ceftriaxone. Only 23.8% of the patients had microbiologically confirmed infections., Conclusion: The study identified predictors for initiating empirical antibacterial therapy in our setting.

Background: The pleiotropic effect of cholecalciferol (vitamin D 3 ) has gained significant momentum and has been explored widely., Objectives: The study aimed to investigate the antimicrobial effect of cholecalciferol against S. aureus and E. coli ., Methods: An in vitro study was performed for the antimicrobial effect of cholecalciferol against S. aureus and E. coli . The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined following the broth microdilution method., Results: The MIC value of cholecalciferol against both S. aureus and E. coli was 0.312 mg/ml, and the MBC for both organisms was 1.25 mg/ml. However, we also observed a significant antimicrobial effect in the dimethyl sulfoxide (DMSO) control at 12.5% (v/v). Therefore, the observed antimicrobial effect may be attributed to DMSO, indicating cholecalciferol does not directly inhibit S. aureus and E. coli ., Conclusion: This study indicates that cholecalciferol does not directly inhibit S. aureus and E. coli. Hence, we suggest exploring the antibacterial properties of other vitamin D analogs, such as calcitriol or its synergetic effect with other antimicrobial agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Ferritin, an intracellular protein, has a pivotal role in immune dysregulation. Hyperferritinemia has been associated with higher disease severity and adverse clinical outcomes in COVID-19, including mortality. We aimed to study the association of serum ferritin levels with disease severity and clinical outcomes and its severity prediction potential in COVID-19 patients., Methods: This retrospective study included 870 adult patients with symptomatic COVID-19 infection hospitalized between July 1, 2020 to December 21, 2020. All the patients had a positive polymerase chain reaction test result of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Results: The median age was 55 (IQR:40, 65) years with a male predominance [66.32% (n = 577)], among 870 COVID-19. Of these, 413 (47.47%) had mild COVID-19, and 457 (52.53%) had moderate plus severe COVID-19 disease. Median ferritin levels were significantly high in moderate to severe COVID-19 infection compared to mild [545.8 (326.0, 1046.0) vs 97.3 (52.65-155.5) (p = 0.001)], and in patients who developed a complication compared to without complications [380 (177.05, 863.15) vs 290 (110.9, 635) (p = 0.002). A slight elevation in median ferritin levels was observed in patients who had an ICU stay than non-ICU [326 (129.8, 655) vs 309 (119.1, 684) (p = 0.872)]. The cut-off for ferritin was identified at >287.4 ng/ml for mild versus moderate plus severe COVID-19 infections., Conclusion: Moderate to severe COVID-19 patients have elevated ferritin levels. Patients with more than 287.4 ng/ml ferritin value would have greater chances of developing moderate to severe COVID-19 infections., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the review work in this paper., (© 2023 The Authors.)

Despite the advancement in wound care, the effective therapy of chronic diabetic ulcers continues to be a challenge. Wound healing is a highly controlled process, which involves a sequence of complex overlapping steps. This healing pathway comprises of hemostasis, inflammation, proliferative, and remodeling phases. Recent evidence suggests that phytomedicines can prevent or repair different kinds of destructive cellular damage, including chronic wounds. Several phytochemicals such as polyphenols, alkaloids, flavonoids, terpenoids, and glycosides have pleiotropic effects, including stimulation of fibroblast proliferation, the main step in wound healing. Besides, the mechanism involves induction of collagen synthesis, migration, and reepithelization and their antimicrobial, antioxidant, anti-inflammatory, and immunomodulatory actions. Similarly, the use of phytochemicals alone or as an adjuvant with standard therapy has demonstrated promising results in managing complications in the diabetic foot. For instance, the extract of Carica papaya has been shown antioxidant, antimicrobial, and anti-inflammatory, and immunomodulatory effects, which, together with proteolytic enzymatic activity, contributes to its wound healing property. It is generally believed that phytotherapy has no or minimal toxicity than synthetic therapeutic agents, favoring its use in diabetic foot ulcer management. The current review highlights the selected phytochemicals and their sources; and potential application in diabetic foot ulcer management.Key teaching points and nutritional relevanceCurrently, phytochemicals have been shown wide potential in disease. management including alleviating clinical manifestations, preventing degenerative disease, and curing illness.Increased evidence of phytochemical as anti-infective and anti-inflammatory suggests its role in the management of diabetic foot ulcer(DFU).Potential benefit along with minimal adverse effect favors its application as adjuvant therapy.Further research is needed to standardize its dose and formulation to enhance its clinical application in DFU management.

Background: Cefepime is a fourth-generation cephalosporin with a broad spectrum coverage and anti-pseudomonal activity. The safety profile of cefepime was relatively favourable until neurotoxicity was first reported in 1999. Despite cefepime-induced neurotoxicity (CIN), it continues to be a principal part of parenteral treatment for various infections., Objective: The study aimed to determine the incidence and risk factors for CIN compared to other antibiotics., Methods: A retrospective cohort study was conducted involving 738 patients over eight months in Kasturba Medical College and Hospital, Manipal, India. Patients with cefepime were selected as study cohort (SC; n= 496), and other antibiotics were included in the reference cohort (RC; n=242)., Results: The results showed that 53 (10.7%) patients developed neurotoxicity in the SC, whereas 12 (5%) patients in the RC. A significant association was found between neurotoxicity and cefepime use (X 2 =6.641; p=0.01). SC has a 2.29 times increased risk of neurotoxicity than RC (OR: 2.29; 95% CI: 1.2-4.38). Risk estimation showed that renal failure patients had a 5.5 times higher risk for CIN than non-renal failure patients (OR: 5.5; 95% CI: 2.98 - 10.17). CIN symptoms were disorientation (38.5%), loss of consciousness (23.1%), drowsiness (18.5%), etc. The calculated number needed to harm (NNH) for cefepime was 17.2., Conclusion: The study found a higher incidence of CIN compared to other antibiotics-induced neurotoxicity and a harmful association between cefepime use and CIN development. Besides, renal failure is a risk factor for CIN. Therefore, the study warrants the use of cefepime, where no other alternatives are available., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Diabetes mellitus (DM) and tuberculosis (TB) have been recognized as reemerging epidemics, especially in developing countries. Among all the risk factors, diabetes causes immunosuppression, increasing the risk of active TB three times. Vitamin D has been found as a link between DM-TB co-morbidity., Objective: Vitamin D affects the immune response, suppresses Mycobacterium tuberculosis (Mtb) growth, and affects insulin secretion. The present systematic review determines the effect of vitamin D supplementation on clinical and therapeutic outcomes of DM-TB patients., Method: A comprehensive literature search was carried out in PubMed, Cochrane, Web of Science, and Scopus database to determine eligible studies from inception to January 2021. Out of the 639 articles retrieved, three randomized controlled trials (RCTs) were included in the systematic review., Result: The effect of vitamin D3 or oral cholecalciferol supplementation was assessed on outcomes, such as duration to sputum smear conversion, TB scores improvement, change in glycemic parameters, including HbA1c, FBS, and PLBS, and laboratory parameters, such as Hb, ESR, and CRP. Duration of sputum smear conversion was decreased by two weeks in the vitamin D3 supplemented group in two studies. TB score improvement and changes in glycemic parameters were inclined towards supplemented group; however, they were not significant., Conclusion: The overall effect of vitamin D3 supplementation on TB patients with DM was not significant. Further studies are required in the future examining the effect of supplementation on outcomes in this population., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The net use of plastic has increased and this augmentation in plastic usage results in ever- growing accumulation of plastic waste in our ecosystems. Regrettably, a portion of this waste is the microplastics including microbeads, which are tiny plastic particles <5 mm in diameter. Microbeads are used in our personal care products. Although, legislative ban of microbeads in some developed countries has proven effective, but many countries do not take any legal action. Hence, microbead-containing products are openly sold in international market and entered into the food chain and disturb it. In human beings and animals, plastic when ingested causes internal bleeding, abrasion, ulcers and blockage of the digestive tract. The present review highlighted the bioaccumulation of microbeads via the food chain and its adverse effect on environment health. Moreover, different scientific views and suggestions for eradication of the problem and present scenario of the use of microbeads in some Asian countries have also been discussed.

Vitamin D deficiency (VDD) partly explains geographical differences in COVID-19 susceptibility, severity, and mortality. VDD among African-Americans, diabetics, hypertensive, and aged populations possibly explain the higher death rate, aggravated by cocooning. Vitamin D is pleiotropic, mediating bone metabolism, calcium homeostasis, and immune functions, whereas VDD is associated with inflammatory reactions and immune dysfunction, predisposing individuals to severe infections. Vitamin D modulates innate and adaptive immunity via the expression of genes that code antimicrobial peptides (AMPs). And the expression of cluster of differentiation (CD)14, the co-receptor for epidermal toll-like receptor (TLR)4. AMPs stimulate TLR2 in macrophages, increasing the conversion of vitamin D into its active form by cytochrome P450 27B1. Antiviral properties of vitamin D-induced AMPs can shift the polarization of the adaptive immune response from helper T cells (Th)1 to the more regulatory Th2 responses that suppress immune over-reactivity by preventing cytokine storm, which is already demonstrated during the Spanish flu episode. Vitamin D induces antiviral effects by both direct and indirect mechanisms via AMPs, immunomodulation, the interplay between major cellular and viral elements, induction of autophagy and apoptosis, variation of genetic and epigenetic factors. The crosstalk between vitamin D and intracellular signaling pathways may operate as a primary regulatory action on viral gene transcription. VDD may increase the likelihood of infection with enveloped viruses, including retrovirus, hepatitis, and dengue. Global data correlates severe VDD with COVID-19 associated coagulopathy, disrupted immune response and mortality, reduced platelet count, and prolonged prothrombin time, suggesting benefits from supplementation.Key teaching pointsVitamin D induces antiviral effects by direct and indirect mechanisms via AMPs, immunomodulation, induction of autophagy, etc.Epidemiology of VDD partly explains geographical differences in COVID-19 susceptibility, severity, and mortality.Global data correlates severe VDD with COVID-19 associated coagulopathy, disrupted immune response and mortality, reduced platelet count, and prolonged prothrombin time, together suggesting benefits from supplementation.Many clinical trials are underway globally to delineate the role of vitamin D in both prevention and treatment of COVID-19.

Saving lives and flattening the curve are the foremost priorities during the ongoing pandemic spread of SARS-CoV-2. Developing cutting-edge technology and collating available evidence would support frontline health teams. Nutritional adequacy improves general health and immunity to prevent and assuage infections. This review aims to outline the potential role of probiotics in fighting the COVID-19 by covering recent evidence on the association between microbiota, probiotics, and COVID-19, the role of probiotics as an immune-modulator and antiviral agent. The high basic reproduction number (R0) of SARS-CoV-2, absence of conclusive remedies, and the pleiotropic effect of probiotics in fighting influenza and other coronaviruses together favour probiotics supplements. However, further support from preclinical and clinical studies and reviews outlining the role of probiotics in COVID-19 are critical. Results are awaited from many ongoing clinical trials investigating the benefits of probiotics in COVID-19., (Copyright © 2021 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.)

Introduction: Diabetic foot ulcer (DFU) is a major complication of diabetes mellitus, as it can physically and emotionally impact the person. Its management can be challenging and expensive, depending on the severity of the wound and the presence of infection., Background: The fat-soluble molecule, vitamin D, has gained great importance ever since its pleiotropism has been recognized. Its efficacy could be attributed to the presence of vitamin D receptors in most of the body tissues. Vitamin D plays a significant role in cell proliferation, differentiation, and immune modulation. It modulates the T and B cells resulting in the suppression of the immunoglobulins, autoimmunity, and inflammation., Methods: We performed a literature search with the objective to highlight the role of vitamin D in peripheral vascular disease and peripheral neuropathy, which are the major risk factors for DFU, as well as evidences of its role in wound healing and management of DFU., Results: Preclinical and clinical studies have shown that vitamin D influences multiple phases of wound healing and thereby accelerates the process. It modulates various cells involved in proliferation and remodelling phases. Vitamin D also enhances the expression of antimicrobial peptides that help to eliminate the microbes, as well as suppress the proinflammatory responses while enhancing the anti-inflammatory responses., Conclusion: This review concludes vitamin D to have a protective role in the immune and vascular system, improve glycaemic outcomes, and wound healing. Therefore, vitamin D could be a preferred adjuvant in the management of DFU., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Antimicrobial resistance is a global health emergency, and one of the contributing factors is overuse and misuse of antibiotics. India is one of the world's largest consumers of antibiotics, and inappropriate use is potentially widespread. This study aimed to use standardised patients (SPs) to measure over-the-counter antibiotic dispensing in one region., Methods: Three adults from the local community in Udupi, India, were recruited and trained as SPs. Three conditions, in both adults and children, were considered: diarrhoea, upper respiratory tract infection and acute fever. Adult SPs were used as proxies for the paediatric cases., Results: A total of 1522 SP interactions were successfully completed from 279 pharmacies. The proportion of SP interactions resulting in the provision of an antibiotic was 4.34% (95% CI 3.04% to 6.08%) for adult SPs and 2.89% (95% CI 1.8% to 4.4%) for child SPs. In the model, referral to another provider was associated with an OR 0.38 (95% CI 0.18 to 0.79), the number of questions asked was associated with an OR 1.54 (95% CI 1.30 to 1.84) and an SP-pharmacist interaction lasting longer than 3 min was associated with an OR 3.03 (95% CI 1.11 to 8.27) as compared with an interaction lasting less than 1 min., Conclusion: Over-the-counter antibiotic dispensing rate was low in Udupi district and substantially lower than previously published SP studies in other regions of India. Dispensing was lowest when pharmacies referred to a doctor, and higher when pharmacies asked more questions or spent more time with clients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The Food and Drug Administration (FDA) safety review revealed that the use of fluoroquinolones (FQs) is linked with disabling and potentially permanent serious adverse effects. These adverse effects compromise the tendons, muscles, joints, nerves, and central nervous system of the human body. The purpose of the study was to investigate the incidence and risk factors for adverse drug reactions (ADRs) caused by FQs in comparison with other antibiotics used. A retrospective cohort study was conducted over seven months in Kasturba Medical College Hospital, Manipal, India. Patients who were prescribed with FQs were selected as the study cohort (SC; n = 482), and those without FQs were the reference cohort (RC; n = 318). The results showed that 8.5% (41) of patients developed ADRs in the SC, whereas 4.1% (13) of patients developed ADRs in the RC. With oral and parenteral routes of administration, almost a similar number of ADRs were observed. Levofloxacin caused the highest number of ADRs reported, especially with the 750-mg dose. Based on a multiple logistic regression model, FQ use (odds ratio (OR): 2.27; 95% confidence interval (CI): 1.18-4.39; p = 0.015) and concomitant steroid use (OR: 3.19; 95% CI: 1.31-7.79; p = 0.011) were identified as independent risk factors for the development of ADRs among antibiotics users, whereas age was found to be protective (OR: 0.98; 95% CI: 0.97-1.00; p = 0.047). The study found a higher incidence of ADRs related to FQs compared to other antibiotics. The study concludes a harmful association between FQ use and the development of ADRs. Moreover, FQs are not safe compared to other antibiotics. Hence, the use of FQs should be limited to the conditions where no other alternatives are available.

Background: World Health Organization estimated that people with diabetes (DM) are at 2-3 times higher risk for tuberculosis (TB). Studies have shown that DM not only increases the risk of active TB, but also puts co-affected persons at increased risk of poor outcomes., Objectives: To determine the protective effect of metformin against TB in DM patients and also, to investigate the relationship between poor glycemic control and TB., Methods: A case-control study was conducted over 8 months, where cases and controls were selected based on the inclusion and exclusion criteria of the study. The diabetics diagnosed with TB were selected as study group (SG=152) and without TB were as control group (CG=299). Exposure status of metformin in both groups were analyzed., Results: The mean (SD) age of both CG and SG were 55.54±11.82 and 52.80±11.75, respectively. Majority of the subjects in the study were males. The mean hospital stay of SG and CG were 7 days and 6 days, respectively. Poor glycemic control (HbA1c>8) observed in SG (51.7%) vs CG (31.4%). HbA1c value <7 is associated protective factor for TB occurrence [OR=0.52 (95% CI 0.29-0.93)]. The protective effect of metformin against TB was 3.9-fold in diabetics (OR=0.256, 0.16-0.40)., Conclusion: Poor glycemic control among diabetics is a risk factor for TB occurrence. The result shows metformin use is a protective agent against TB infection in diabetics. Hence, incorporation of metformin into standard clinical care would offer a therapeutic option for the prevention of TB., (Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.)

Introduction: Diabetes type II is a complex disease with unclear pathophysiology. Lack of adherence and high cost of medicines invariably make the management of diabetes type II highly challenging. Newer fixed drug combinations (FDC) are cost effective and can improve the medication adherence thereby prevent the complications of diabetes. Safety and efficacy of newer FDCs are not well established in all populations. Moreover, extrapolating the efficacy and safety data globally may not be pragmatic. Our review will discuss newer chemical combinations available for the treatment of diabetes type II. Areas covered: In the present review, the authors discussed the newer FDCs available as add on therapy to the existing pharmacological interventions of diabetes type II that have shown promising results in various randomised trials with regard to efficacy and safety. Expert opinion: Safety and efficacy data of newer FDCs available as an adjuvant therapy to conventional pharmacological interventions in diabetes type II revealed that fewer new FDCs are promising with their high efficacy and low adverse effect. However, there is a need to explore the place in therapy to establish the utility of FDC in diabetes type II management.