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1.
Developmental Impacts of Epigenetics and Metabolism in COVID-19.
Naik, N, Patel, M, Sen, R
Journal of developmental biology. 2024;(1)
Abstract
Developmental biology is intricately regulated by epigenetics and metabolism but the mechanisms are not completely understood. The situation becomes even more complicated during diseases where all three phenomena are dysregulated. A salient example is COVID-19, where the death toll exceeded 6.96 million in 4 years, while the virus continues to mutate into different variants and infect people. Early evidence during the pandemic showed that the host's immune and inflammatory responses to COVID-19 (like the cytokine storm) impacted the host's metabolism, causing damage to the host's organs and overall physiology. The involvement of angiotensin-converting enzyme 2 (ACE2), the pivotal host receptor for the SARS-CoV-2 virus, was identified and linked to epigenetic abnormalities along with other contributing factors. Recently, studies have revealed stronger connections between epigenetics and metabolism in COVID-19 that impact development and accelerate aging. Patients manifest systemic toxicity, immune dysfunction and multi-organ failure. Single-cell multiomics and other state-of-the-art high-throughput studies are only just beginning to demonstrate the extent of dysregulation and damage. As epigenetics and metabolism directly impact development, there is a crucial need for research implementing cutting-edge technology, next-generation sequencing, bioinformatics analysis, the identification of biomarkers and clinical trials to help with prevention and therapeutic interventions against similar threats in the future.
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2.
Recent advances in Bacillus-mediated plant growth enhancement: a paradigm shift in redefining crop resilience.
Patani, A, Patel, M, Islam, S, Yadav, VK, Prajapati, D, Yadav, AN, Sahoo, DK, Patel, A
World journal of microbiology & biotechnology. 2024;(2):77
Abstract
The Bacillus genus has emerged as an important player in modern agriculture, revolutionizing plant growth promotion through recent advances. This review provides a comprehensive overview of the critical role Bacillus species play in boosting plant growth and agricultural sustainability. Bacillus genus bacteria benefit plants in a variety of ways, according to new research. Nitrogen fixation, phosphate solubilization, siderophore production, and the production of growth hormones are examples of these. Bacillus species are also well-known for their ability to act as biocontrol agents, reducing phytopathogens and protecting plants from disease. Molecular biology advances have increased our understanding of the complex interplay between Bacillus species and plants, shedding light on the genetic and metabolic underpinnings of these interactions. Furthermore, novel biotechnology techniques have enabled the development of Bacillus-based biofertilizers and biopesticides, providing sustainable alternatives to conventional chemical inputs. Apart from this, the combination of biochar and Bacillus species in current biotechnology is critical for improving soil fertility and encouraging sustainable agriculture through enhanced nutrient retention and plant growth. This review also emphasizes the Bacillus genus bacteria's ability to alleviate environmental abiotic stresses such as drought and salinity, hence contributing to climate-resilient agriculture. Moreover, the authors discuss the challenges and prospects associated with the practical application of Bacillus-based solutions in the field. Finally, recent advances in Bacillus-mediated plant growth promotion highlight their critical significance in sustainable agriculture. Understanding these improvements is critical for realizing the full potential of Bacillus genus microorganisms to address current global food production concerns.
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3.
Optimizing warfarin dosing for patients with atrial fibrillation using machine learning.
Petch, J, Nelson, W, Wu, M, Ghassemi, M, Benz, A, Fatemi, M, Di, S, Carnicelli, A, Granger, C, Giugliano, R, et al
Scientific reports. 2024;(1):4516
Abstract
While novel oral anticoagulants are increasingly used to reduce risk of stroke in patients with atrial fibrillation, vitamin K antagonists such as warfarin continue to be used extensively for stroke prevention across the world. While effective in reducing the risk of strokes, the complex pharmacodynamics of warfarin make it difficult to use clinically, with many patients experiencing under- and/or over- anticoagulation. In this study we employed a novel implementation of deep reinforcement learning to provide clinical decision support to optimize time in therapeutic International Normalized Ratio (INR) range. We used a novel semi-Markov decision process formulation of the Batch-Constrained deep Q-learning algorithm to develop a reinforcement learning model to dynamically recommend optimal warfarin dosing to achieve INR of 2.0-3.0 for patients with atrial fibrillation. The model was developed using data from 22,502 patients in the warfarin treated groups of the pivotal randomized clinical trials of edoxaban (ENGAGE AF-TIMI 48), apixaban (ARISTOTLE) and rivaroxaban (ROCKET AF). The model was externally validated on data from 5730 warfarin-treated patients in a fourth trial of dabigatran (RE-LY) using multilevel regression models to estimate the relationship between center-level algorithm consistent dosing, time in therapeutic INR range (TTR), and a composite clinical outcome of stroke, systemic embolism or major hemorrhage. External validation showed a positive association between center-level algorithm-consistent dosing and TTR (R2 = 0.56). Each 10% increase in algorithm-consistent dosing at the center level independently predicted a 6.78% improvement in TTR (95% CI 6.29, 7.28; p < 0.001) and a 11% decrease in the composite clinical outcome (HR 0.89; 95% CI 0.81, 1.00; p = 0.015). These results were comparable to those of a rules-based clinical algorithm used for benchmarking, for which each 10% increase in algorithm-consistent dosing independently predicted a 6.10% increase in TTR (95% CI 5.67, 6.54, p < 0.001) and a 10% decrease in the composite outcome (HR 0.90; 95% CI 0.83, 0.98, p = 0.018). Our findings suggest that a deep reinforcement learning algorithm can optimize time in therapeutic range for patients taking warfarin. A digital clinical decision support system to promote algorithm-consistent warfarin dosing could optimize time in therapeutic range and improve clinical outcomes in atrial fibrillation globally.
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4.
The impact of obstructive sleep apnea treatment on microvascular complications in patients with type 2 diabetes: a feasibility randomized controlled trial.
Makhdom, EA, Maher, A, Ottridge, R, Nicholls, M, Ali, A, Cooper, BG, Ajjan, RA, Bellary, S, Hanif, W, Hanna, F, et al
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2024
Abstract
STUDY OBJECTIVES Obstructive sleep apnea (OSA) is associated with an increased risk of diabetes-related complications. Hence, it is plausible that Continuous Positive Airway Pressure (CPAP) could have a favorable impact on these complications. To assess the feasibility of conducting a randomized control trial (RCT) in patients with type 2 diabetes (T2D) and OSA over 2 years. METHODS An open-label multicenter feasibility RCT of CPAP vs no CPAP in patients with T2D and OSA. Patients with resting oxygen saturation <90%, central apnea index >15/hour or Epworth Sleepiness Scale (ESS) ≥11 were excluded. OSA was diagnosed using a multichannel portable device (ApneaLink Air, ResMed). The primary outcome measures were related to feasibility, and the secondary outcomes were changes in various clinical and biochemical parameters related to diabetes outcomes. RESULTS Eighty-three (40 CPAP vs 43 no CPAP) patients were randomized, with a median (IQR) follow-up of 645 [545, 861] days. CPAP compliance was inadequate, with a median usage of approximately 3.5 hours/night. Early CPAP use predicted longer-term compliance. The adjusted analysis showed a possible favorable association between being randomized to CPAP and several diabetes-related endpoints (chronic kidney disease (CKD), neuropathy, and quality of life (QoL)). CONCLUSIONS It was feasible to recruit, randomize, and achieve a high follow-up rate over 2 years in patients with OSA and T2D. CPAP compliance might improve by a run-in period before randomization. A full RCT is necessary to assess the observed favorable association between CPAP and CKD, neuropathy, and QoL in patients with T2D. CLINICAL TRIAL REGISTRATION Registry: ISRCTN; URL: https://www.isrctn.com/ISRCTN12361838; Title: The impact of sleep disorders in patients with type 2 diabetes; Identifier: ISRCTN12361838.
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5.
National and regional prevalence of gestational diabetes mellitus in India: a systematic review and Meta-analysis.
Mantri, N, Goel, AD, Patel, M, Baskaran, P, Dutta, G, Gupta, MK, Yadav, V, Mittal, M, Shekhar, S, Bhardwaj, P
BMC public health. 2024;(1):527
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) is frequently misdiagnosed during pregnancy. There is an abundance of evidence, but little is known regarding the regional prevalence estimates of GDM in India. This systematic review and meta-analysis aims to provide valuable insights into the national and regional prevalence of GDM among pregnant women in India. METHODS We conducted an initial article search on PubMed, Scopus, Google Scholar, and ShodhGanga searches to identify quantitative research papers (database inception till 15th June,2022). This review included prevalence studies that estimated the occurrence of GDM across different states in India. RESULTS Two independent reviewers completed the screening of 2393 articles, resulting in the identification of 110 articles that met the inclusion criteria, which collectively provided 117 prevalence estimates. Using a pooled estimate calculation (with an Inverse square heterogeneity model), the pooled prevalence of GDM in pregnant women was estimated to be 13%, with a 95% confidence interval (CI) ranging from 9 to 16%.. In India, Diabetes in Pregnancy Study of India (DIPSI) was the most common diagnostic criteria used, followed by International Association of Diabetes and Pregnancy Study Groups (IADPSG) and World Health Organization (WHO) 1999. It was observed that the rural population has slightly less prevalence of GDM at 10.0% [6.0-13.0%, I2=96%] when compared to the urban population where the prevalence of GDM was 12.0% [9.0-16.0%, I2 = 99%]. CONCLUSIONS This review emphasizes the lack of consensus in screening and diagnosing gestational diabetes mellitus (GDM), leading to varied prevalence rates across Indian states. It thoroughly examines the controversies regarding GDM screening by analyzing population characteristics, geographic variations, diagnostic criteria agreement, screening timing, fasting vs. non-fasting approaches, cost-effectiveness, and feasibility, offering valuable recommendations for policy makers. By fostering the implementation of state-wise screening programs, it can contribute to improving maternal and neonatal outcomes and promoting healthier pregnancies across the country.
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6.
Micro-vascular complications of post-transplant diabetes mellitus in renal transplant recipients- an observational study.
Abdullah, , Momin, I, Kaul, A, Bhadauria, D, Prasad, N, Behera, M, Patel, M, Kushwaha, R, Yachha, M, Srivastava, A
Transplant immunology. 2024;:102012
Abstract
INTRODUCTION The incidence of post-transplant diabetes mellitus (PTDM) ranges from 2.5% to 20% in kidney transplant recipients. Diabetic retinopathy (DR), diabetic kidney disease (DKD), and distal symmetric polyneuropathy (DSPN) are the microvascular complications frequently seen in both type 1 and 2 diabetes mellitus (DM). However, the data regarding these complications in patients with PTDM is lacking. METHOD A retrospective and prospective observational study of PTDM conducted at a tertiary care hospital from November 2018 to December 2020. 115 kidney transplant recipients who had PTDM of ≥5 years duration were included and analysed. RESULTS The mean duration of PTDM was 8.8 ± 3.0 years, and the mean of all available HbA1c values was 7.0 ± 0.9%. while none of the patients had evidence of diabetic retinopathy on direct ophthalmoscopy, 37.4% of patients (n = 43) had DSPN and this was associated with the duration of PTDM and age. The mean estimated glomerular filtration rate (eGFR) was 59.24 ± 21.82 ml/min/1.73m2, and patients had a median proteinuria of 620 mg/day (IQR 1290). Out of 115 patients, 20% of them (n = 23) underwent graft kidney biopsy, and 10 biopsies were diagnosed as de-novo DKD. Patients with biopsy proven DKD had a mean PTDM duration of 143.3 ± 52.4 months; a mean HbA1c level of 7.9 ± 1.3%; a mean eGFR of 44.8 ± 21.8 ml/min; and a median proteinuria of 2653 mg (IQR 2758). An additional analysis of all 23 biopsied patients showed that HbA1c level and degree of proteinuria were significantly associated with de-novo DKD. CONCLUSION PTDM in transplant patients had milder microvascular complications than usually expected in Type 1/2 diabetes in non-transplant patients. DR was not strongly associated with DKD in PTDM patients. Furthermore, de-novo DKD development was associated with poor glycaemic control and increased proteinuria.
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7.
Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation to Elucidate the Molecular Targets and Potential Mechanism of Phoenix dactylifera (Ajwa Dates) against Candidiasis.
Adnan, M, Siddiqui, AJ, Ashraf, SA, Bardakci, F, Alreshidi, M, Badraoui, R, Noumi, E, Tepe, B, Sachidanandan, M, Patel, M
Pathogens (Basel, Switzerland). 2023;(11)
Abstract
Candidiasis, caused by opportunistic fungal pathogens of the Candida genus, poses a significant threat to immunocompromised individuals. Natural compounds derived from medicinal plants have gained attention as potential sources of anti-fungal agents. Ajwa dates (Phoenix dactylifera L.) have been recognized for their diverse phytochemical composition and therapeutic potential. In this study, we employed a multi-faceted approach to explore the anti-candidiasis potential of Ajwa dates' phytochemicals. Utilizing network pharmacology, we constructed an interaction network to elucidate the intricate relationships between Ajwa dates phytoconstituents and the Candida-associated molecular targets of humans. Our analysis revealed key nodes in the network (STAT3, IL-2, PTPRC, STAT1, CASP1, ALB, TP53, TLR4, TNF and PPARG), suggesting the potential modulation of several crucial processes (the regulation of the response to a cytokine stimulus, regulation of the inflammatory response, positive regulation of cytokine production, cellular response to external stimulus, etc.) and fungal pathways (Th17 cell differentiation, the Toll-like receptor signaling pathway, the C-type lectin receptor signaling pathway and necroptosis). To validate these findings, molecular docking studies were conducted, revealing the binding affinities of the phytochemicals towards selected Candida protein targets of humans (ALB-rutin (-9.7 kJ/mol), STAT1-rutin (-9.2 kJ/mol), STAT3-isoquercetin (-8.7 kJ/mol), IL2-β-carotene (-8.5 kJ/mol), CASP1-β-carotene (-8.2 kJ/mol), TP53-isoquercetin (-8.8 kJ/mol), PPARG-luteolin (-8.3 kJ/mol), TNF-βcarotene (-7.7 kJ/mol), TLR4-rutin (-7.4 kJ/mol) and PTPRC-rutin (-7.0 kJ/mol)). Furthermore, molecular dynamics simulations of rutin-ALB and rutin-STAT1 complex were performed to gain insights into the stability and dynamics of the identified ligand-target complexes over time. Overall, the results not only contribute to the understanding of the molecular interactions underlying the anti-fungal potential of specific phytochemicals of Ajwa dates in humans but also provide a rational basis for the development of novel therapeutic strategies against candidiasis in humans. This study underscores the significance of network pharmacology, molecular docking and dynamics simulations in accelerating the discovery of natural products as effective anti-fungal agents. However, further experimental validation of the identified compounds is warranted to translate these findings into practical therapeutic applications.
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8.
Clinical utility of serum 17-hydroxyprogesterone as a marker for medical therapy for male infertility: recommendations based on clinical scenarios.
Reddy, R, Mason, M, Patel, M, Ramasamy, R
International journal of impotence research. 2023;(2):79-81
Abstract
Traditional serum hormone testing in the evaluation of male infertility consists of testosterone, follicle-stimulating hormone, luteinizing hormone, and estradiol. Based on these values, medical therapy is often initiated in an attempt to increase intratesticular testosterone levels and, in turn, promote spermatogenesis. While this hormone panel provides serum testosterone levels, it does not evaluate intratesticular testosterone, obviously an important factor that is critical for spermatogenesis. 17-hydroxyprogesterone (17-OHP) is an intermediate in the steroidal pathway of cholesterol to testosterone conversion that has recently demonstrated promise as an accurate serum biomarker for intratesticular testosterone. At present, 17-OHP has not been widely adopted as a clinical tool in the evaluation of male infertility, which likely stems, in part, from a lack of concrete indications for its use. In this review, we present five commonly encountered scenarios of male infertility where the utilization of 17-OHP has aided in the management and provided a more personalized approach to treatment.
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9.
Molecular pathology and therapeutics of the diabetic foot ulcer; comprehensive reviews.
Patel, M, Patel, V, Shah, U, Patel, A
Archives of physiology and biochemistry. 2023;:1-8
Abstract
Diabetes mellitus (DM) is a chronic metabolic condition linked to high blood sugar levels. Diabetes causes complications like neuropathy, nephropathy, and retinopathy. Diabetes foot ulcer (DFU) is a significant and serious wound healing issue resulting from uncontrolled DM. The main causes of the development of the DFU are oxidative stress brought on by the NO moiety, release of pro-inflammatory cytokines like tumour necrosis factor (TNF)-α and interleukin (IL-1), cellular dysfunction, and pathogenic microorganisms including staphylococcus and streptococcus species. The two main types of wounds that are prevalent in DFU patients are neuropathic and neuroischemic. If this wound is not properly treated or cared for, a lower limb may have to be amputated. There are several therapy options for DFU, including antibiotics, debridement, dressings, nano formulations, and growth factor preparations like PDGF-BB, to help the wound heal and prevent amputation. Other novel approaches involved the use of nerve taps, microneedle patches, nanotechnology-based formulations and stem cell applications to promote healing. There are possibilities of drug repurposing for the DFU treatment based on targeting specific enzymes. This article summarises the current pathophysiological aspects of DFU and its probable future targets.
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10.
Is Coffee and Tea a Threat or Ally to Cardiovascular Health?
Mendpara, V, Garg, S, Shah, P, Bhavsar, J, Anamika, F, Patel, M, Munjal, RS, Gupta, V, Garg, N, Jain, R
Cureus. 2023;(12):e49991
Abstract
Tea and coffee have become ingrained in our daily lives and have become the most widely consumed drinks after water. Their effects vary on an individual basis depending upon the amount of daily consumption, genetic polymorphisms, and the presence of comorbidities. Non-habitual individuals experience an initial, brief increase in blood pressure due to caffeine's vasoactive effects. Caffeine also appears to be protective against arrhythmias and heart failure. Along with having a generally cardioprotective profile, they have also demonstrated to have a favorable impact on insulin resistance and reduced risk of diabetes mellitus. Physicians often practice caution and advise patients with known cardiovascular diseases to refrain from drinking caffeine; however, studies have shown that drinking two to three cups a day has either no or some beneficial effects on both patients with or without cardiac disorders like arrhythmias. This article focuses on the effects of tea and coffee on the cardiovascular system as well as the potential mechanisms involved.