Evaluating Yoga-Based Intervention Versus the American Diabetes Association Exercise Regimen in Conjunction With Standard Care for Autonomic Neuropathy in Diabetes Mellitus: An Exploratory Clinical Trial.

INTRODUCTION: Diabetic autonomic neuropathy (DAN) is a prevalent yet often overlooked complication of diabetes mellitus (DM), impacting multiple organs and substantially elevating the risk of morbidity and mortality. This study aimed to assess the effectiveness of yoga-based intervention (YBI) compared to the American Diabetes Association exercise regimen (ADA Ex. Regime) and standard care for treating autonomic neuropathy in type 2 DM. METHODS: This open-label exploratory clinical trial featured two parallel study arms: Group A (Intervention), which received YBI alongside standard care, and Group B, which adhered to the ADA Ex. Regime in conjunction with standard care. A total of 80 participants aged 35-60, diagnosed with type 2 DM and autonomic neuropathy, were equally allocated to both groups. Data collection included nerve conduction velocity (NCV) tests, autonomic function tests (AFTs), as well as evaluations of depression and quality of life. RESULTS: YBI demonstrated a drop in parasympathetic tone compared to the ADA Ex. Regime. Following a six-month intervention, the sympathetic activity indicator (SD2) exhibited a significantly lower value in the YBI group than in the ADA Ex. Regime group, indicating a positive effect (p < 0.05), while the ADA Ex. Regime showed more improvement in certain areas of NCV (e.g., left and right peroneal NCV, right and left peroneal F-latency), notable differences were observed in alkaline phosphatase levels, depression scores, and WHO-5 wellness, all reaching statistical significance at p < 0.05. CONCLUSIONS: The study findings observed that a 24-week YBI significantly reduced in symptoms of diabetic neuropathy and stress. Although the ADA Ex. Regime demonstrated greater improvement in specific aspects of NCV compared to YBI, YBI outperformed the ADA Ex. Regime in enhancing WHO-5 wellness and reducing depression symptoms.

A Validated Chiral Chromatography Method for Enantiomeric Separation of Pomalidomide in Human Plasma.

In the present work, new chiral stationary phase high-performance liquid chromatography (CSP-HPLC) method was established and validated for the quantification of pomalidomide (PMD) enantiomers in human plasma. The chromatographic enantiomeric separation was achieved on a Daicel-CSP, Chiralpack IA 4.6 × 250 mm, 5 µm; because of its advantages of high degree of retention, high resolution capacity, better reproducibility, ability to produce lower back pressure and low degree of tailing. The mobile phase was maintained as methanol: glacial acetic acid (499.50 ml:50 µL). Ultraviolet wavelength for detection was 220 nm. PMD enantiomer-I and enantiomer-II were separated at 8.83 and 15.34 min, respectively. Limit of detection and limit of quantification for each enantiomer and the calibration curve of standard PMD was linear in range between 10-5,000 ng mL-1. The method was validated according to The International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use (ICH(Q2R1)) specific guidelines. We found no interference peak with PMD chromatogram obtained. This is a simple, reliable and specific method for detection and quantification of enantiomer of PMD in human plasma sample.

Navigating the Antiretroviral Therapy Switch Conundrum: Unveiling the Dilemma of Drug Resistance and Disease Progression in HIV/AIDS.

There is a need to establish consensus for harmonization in antiretroviral (ARV) therapy (ART) switch treatment strategy and address the dilemma that exists in terms of subpar immune response to therapy or an immunologic deterioration while on therapy. The purpose of this review is to identify the factors that contribute to ARV treatment failure, such as insufficient dosage, drug interactions, poor adherence, drug resistance, and poor medication absorption. It is crucial to adopt a more efficient strategy to address this challenging dilemma. After ARV treatment failure, the aim of therapy is virologic suppression, which targets plasma viral load below the limits of detection as assessed by very sensitive tests with lower limits of quantification of 20 to 75 RNA copies/ml. The therapeutic objectives when complete virologic suppression is not possible, should be to maintain or restore immunologic function, stop the progression of the clinical illness, and minimize the emergence of new drug resistance that could further restrict the options for ARV drugs. Treatment history and drug-resistance testing, including the findings of previous and ongoing resistance tests, should be considered while selecting ARV regimens. Hence, the treatment approach post-ARV failure can be personalized based on clinical, immunologic, virologic, or as a mix of the three domains on a case-to-case basis. The evaluation of projected ARV activity should be based on treatment history and previous resistance test findings.

Computational Analysis of Lenalidomide and Pomalidomide Enantiomers' Binding Interactions With Prostaglandin (PG)-Protein: Implications for Inflammatory Activity in Cancer.

BACKGROUND: Lenalidomide and Pomalidomide are chiral immunomodulatory drugs (IMiDs) and have antiangiogenic and anti-immunomodulatory activity. Each enantiomer may have distinct binding and biological activity. This study aimed to explore the in-silico binding of both enantiomers of Lenalidomide and Pomalidomide with Prostaglandin and its potential impact on persisting inflammatory activity in cancer. This can further provide insight into the transport of pro-inflammatory mediators and their potential implications for the inflammatory microenvironment within tumors. MATERIALS AND METHODS: Molecular docking studies were performed to explore the binding potential of both enantiomers of Lenalidomide and Pomalidomide with Pg protein. The crystal structure of Pg-protein (PDB ID: 1IW7) was obtained from the Protein Data Bank. RESULTS: The binding energies for (-)-Lenalidomide and (+)-Lenalidomide were -6.7 and -7.2 kcal/mol, respectively, while the binding energies for (-)-Pomalidomide and (+)-Pomalidomide were -7.8 and -8.1 kcal/mol, respectively. The binding mode analysis revealed that all four compounds formed hydrogen bonds with key amino acid residues of Pg-protein. The hydrogen bond distances for (-)-Lenalidomide, (+)-Lenalidomide, (-)-Pomalidomide, and (+)-Pomalidomide were 2.1 Å, 2.0 Å, 2.2 Å, and 2.1 Å, respectively. CONCLUSIONS: The present study suggests that both enantiomers of Lenalidomide and Pomalidomide have a high affinity for Pg-protein and can effectively target the Pg-protein pathway to persist inflammatory activity in cancer. By targeting inflammation-mediated processes, these drugs may offer a novel strategy to combat tumor progression.

Development and validation of a novel chiral chromatographic method for separation of lenalidomide enantiomers in human plasma.

Lenalidomide (LND) is an analogue of thalidomide that is second generation immunomodulatory drugs (IMiDs). LND contains asymmetric carbon atom and exist R and S enantiomer. S (-) form of enantiomer are considered to be more potent and biologically active in tumor cell. It is available in racemic form for clinical use. The study aims to develop and validate enantiomer separation of LND in human plasma. The chromatographic enantiomeric separation was achieved on a Daicel-CSP, Chiralpack IA 4.6 × 250 mm_5 µm. The mobile phase was constituted in combination of methanol:glacial acetic acid at a concentration of 499.50 ml: 50 µl. UV wavelength detection was 220 nm. The RSD% for all validation parameters was found to be within the acceptable limit. The chiral chromatographic (chiral stationary phase-high-performance liquid chromatography [CSP-HPLC]) method developed and validated for the quantitative estimation of LND enantiomers S (-) and R (+) in human plasma sample is accurate, precise, robust, stable and selective.

Growing concerns on male reproductive health amidst COVID-19 pandemic.

Blood-testis barrier is body's innate mechanism to defend germ cells by creating a physical and immunological barrier. But some viral infections are known to evade it. As ACE2 and TMPRSS2 are present all over the body including male reproductive tract, it is worth exploring how coronavirus disease (COVID-19) could possibly affect male fertility. A review of literature was done using search engines like PubMed, Medline, Google Scholar, etc., and all the latest articles up to May 2021 were considered. Some studies have substantiated the presence of orchitis in COVID patients using semen and tissue samples. Though most studies report the absence of virus in testis, involvement of seminiferous tubules has been seen in pathological analysis suggesting defective spermatogenesis. This can be primarily attributed to inflammation and increased vascular permeability. Other factors that could affect male fertility are fever, autoimmune response, drugs, and erectile dysfunction. Male fertility is an important aspect of health care and must be looked into. Further studies can be done to understand host immunity towards SARS-CoV-2 in the testis. It will be worthwhile to know whether viral orchitis and its sequelae are acute or chronic in nature, and if they are reversible. Effect of the virus on female reproductive tract can also be assessed further. Counselling can be given to affected/recovering patients along with correct selection of drugs to prevent these long-term complications.

In vitro study of elution kinetics and biological activity of piperacillin/tazobactam and gentamicin in acrylic bone cement.

BACKGROUND: Antibiotics differ in their elution characteristics from bone cement. But no such data is available on piperacillin and tazobactam. Therefore, we performed an in vitro observational study to examine (1) in vitro elution characteristics of piperacillin and tazobactam from bone cement, (2) their biological activity using minimum inhibitory concentration and (3) elution characteristics and biological activity when combined with gentamicin in bone cement. HYPOTHESIS: The null hypothesis was that piperacillin and tazobactam after elution from bone cement can achieve concentrations higher than minimum inhibitory concentration. MATERIAL AND METHODS: Forty milligrams bone cement was mixed with the following combination of antibiotics: without any antibiotic (sample A, control), 4g/0.50g piperacillin/tazobactam (sample B), 6g/0.75g piperacillin/tazobactam (sample C), 8g/1.0g piperacillin/tazobactam (sample D) and 4g/0.50g piperacillin/tazobactam and 400mg gentamicin (sample E). Samples were analysed on reverse-phase ultra-high-performance liquid chromatography. Antibacterial activity in the elute were tested against standard American Type Culture Collection (ATCC) strains. RESULTS: Detectable drug elution for piperacillin and tazobactam was seen till 21days. Peak drug levels for all formulations were seen at 48hours (140.8 & 297.5µg/mL for samples B of piperacillin and tazobactam respectively). About 0.83-1.24% of piperacillin and 23.17-29.17% of tazobactam were released from the samples. Gentamicin improved elution of piperacillin and tazobactam: 140.8 vs. 919.9µg/mL (p=0.000) for samples B & E of piperacillin respectively and 297.5 & 1138.4µg/mL (p=0.001) for samples B & E of tazobactam respectively at 2days. Sample E showed complete inhibition of tested microorganisms, while B sample was microbiologically less active compared to E on day 5. CONCLUSIONS: Piperacillin and tazobactam eluted successfully from bone cement and also retained antimicrobial activity after elution. Maximum elution was seen up to day 2 after which it reduced drastically. Antimicrobial action was seen up to 7days. LEVEL OF EVIDENCE: III; comparative study.

Transforming growth factor-ß1 (C509T, G800A, and T869C) gene polymorphisms and risk of ischemic stroke in North Indian population: A hospital-based case-control study.

BACKGROUND: Transforming growth factor-beta 1 (TGF-ß1) is a multifunctional pleiotropic cytokine involved in inflammation and pathogenesis of cerebrovascular diseases. There is limited information on the association between variations within the TGF-ß1 gene polymorphisms and risk of ischemic stroke (IS). The aim of this study was to investigate the association of the TGF-ß1 gene (C509T, G800A, and T869C) polymorphisms, and their haplotypes with the risk of IS in North Indian population. METHODS: A total of 250 IS patients and 250 age- and sex-matched controls were studied. IS was classified using the Trial of Org 10172 in Acute Stroke Treatment classification. Conditional logistic regression analysis was used to calculate the strength of association between TGF-ß1 gene polymorphisms and risk of IS. Genotyping was performed using SNaPshot method. RESULTS: Hypertension, diabetes, dyslipidemia, alcohol, smoking, family history of stroke, sedentary lifestyle, and low socioeconomic status were found to be associated with the risk of IS. The distribution of C509T, G800A and T869C genotypes was consistent with Hardy-Weinberg Equilibrium in the IS and control groups. Adjusted conditional logistic regression analysis showed a significant association of TGF-ß1 C509T (odds ratio [OR], 2.1; 95% CI; 1.2-3.8; P = 0.006), G800A (OR, 4.4; 95% CI; 2.1-9.3; P < 0.001) and T869C (OR, 2.6; 95% CI; 1.5-4.5; P = 0.001) with the risk of IS under dominant model. Haplotype analysis showed that C509-A800-T869 and T509-G800-C869 haplotypes were significantly associated with the increased risk of IS. C509T and T869C were in strong linkage disequilibrium (D' =0.51, r2 = 0.23). CONCLUSION: Our results suggest that TGF-ß1 polymorphisms and their haplotypes are significantly associated with the risk of IS in North Indian population.