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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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A Systematic Review Exploring the Cardiovascular and Renal Effects of Empagliflozin in Patients With Heart Failure With Reduced Ejection Fraction.
Athiyaman, S, Randhi, B, Gutlapalli, SD, Pu, J, Zaidi, MF, Patel, M, Atluri, LM, Gonzalez, NA, Sakhamuri, N, Venugopal, S
Cureus. 2022;(10):e29896
Abstract
The major cause of death in the United States is heart disease. The global burden of illness and mortality from heart failure is substantial. Despite recent innovations in the treatment of heart failure, the prognosis is still poor. To identify, evaluate, and summarize the findings of all relevant studies of a drug that is equally efficacious but rather cost-effective, empagliflozin compared to the other sodium-glucose cotransporter-2 (SGLT2) inhibitors was studied. It is licensed by the Food and Drug Administration (FDA), acts by preventing the reabsorption of glucose from the kidney, and exhibits promising advantages in heart failure. We systematically explored PubMed, PubMed Central (PMC), and Medical Literature Analysis and Retrieval System Online (MEDLINE) for randomized controlled trials (RCTs) and observational studies related to cardiovascular and renal outcomes of empagliflozin in patients with heart failure with reduced ejection fraction (HFrEF). After performing scoping search and search strategy, studies were screened for quality assessment using the Cochrane risk of bias assessment tool. We screened 60 articles by titles, abstract, and exclusion and inclusion criteria, after which eight final randomized controlled trials (RCTs) with 18,659 participants treated with empagliflozin and placebo were used for the systematic review. This systematic review's objective is to investigate and explore the full range of empagliflozin's effects and advantages on cardiac structure, function, and hemodynamics and renal function in patients with heart failure with reduced ejection fraction (EF) in order to better understand the drug's effects and related mechanisms.
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Duodenal-Jejunal Bypass Liner for the management of Type 2 Diabetes Mellitus and Obesity: A Multicenter Randomized Controlled Trial.
Ruban, A, Miras, AD, Glaysher, MA, Goldstone, AP, Prechtl, CG, Johnson, N, Chhina, N, Al-Najim, W, Aldhwayan, M, Klimowska-Nassar, N, et al
Annals of surgery. 2022;(3):440-447
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Abstract
OBJECTIVE The aim of this study was to examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) while in situ for 12 months and for 12 months after explantation. SUMMARY BACKGROUND DATA This is the largest randomized controlled trial (RCT) of the DJBL, a medical device used for the treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopic interventions have been developed as potential alternatives to those not eligible or fearful of the risks of metabolic surgery. METHODS In this multicenter open-label RCT, 170 adults with inadequately controlled T2DM and obesity were randomized to intensive medical care with or without the DJBL. Primary outcome was the percentage of participants achieving a glycated hemoglobin reduction of ≥20% at 12 months. Secondary outcomes included weight loss and cardiometabolic risk factors at 12 and 24 months. RESULTS There were no significant differences in the percentage of patients achieving the primary outcome between both groups at 12 months [DJBL 54.6% (n = 30) vs control 55.2% (n = 32); odds ratio (OR) 0.93, 95% confidence interval (CI): 0.44-2.0; P = 0.85]. Twenty-four percent (n = 16) patients achieved ≥15% weight loss in the DJBL group compared to 4% (n = 2) in the controls at 12 months (OR 8.3, 95% CI: 1.8-39; P = .007). The DJBL group experienced superior reductions in systolic blood pressure, serum cholesterol, and alanine transaminase at 12 months. There were more adverse events in the DJBL group. CONCLUSIONS The addition of the DJBL to intensive medical care was associated with superior weight loss, improvements in cardiometabolic risk factors, and fatty liver disease markers, but not glycemia, only while the device was in situ. The benefits of the devices need to be balanced against the higher rate of adverse events when making clinical decisions. TRIAL REGISTRATION ISRCTN30845205. isrctn.org; Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership reference 12/10/04.
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Small RNA sequencing and identification of papaya (Carica papaya L.) miRNAs with potential cross-kingdom human gene targets.
Jha, N, Mangukia, N, Gadhavi, H, Patel, M, Bhavsar, M, Rawal, R, Patel, S
Molecular genetics and genomics : MGG. 2022;(4):981-997
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Abstract
Several studies have demonstrated potential role of plant-derived miRNAs in cross-kingdom species relationships by transferring into non-plant host cells to regulate certain host cellular functions. How nutrient-rich plants regulate host cellular functions, which in turn alleviate physiological and disease conditions in the host remains to be explored in detail. This computational study explores the potential targets, putative role, and functional implications of miRNAs derived from Carica papaya L., one of the most cultivated tropical crops in the world and a rich source of phytochemicals and enzymes, in human diet. Using the next-generation sequencing, -Illumina HiSeq2500, ~ 30 million small RNA sequence reads were generated from C. papaya young leaves, resulting in the identification of a total of 1798 known and 49 novel miRNAs. Selected novel C. papaya miRNAs were predicted to regulate certain human targets, and subsequent annotation of gene functions indicated a probable role in various biological processes and pathways, such as MAPK, WNT, and GPCR signaling pathways, and platelet activation. These presumptive target gene in humans were predominantly linked to various diseases, including cancer, diabetes, mental illness, and platelet disorder. The computational finding of this study provides insights into how C. papaya-derived miRNAs may regulate certain conditions of human disease and provide a new perspective on human health. However, the therapeutic potential of C. papaya miRNA can be further explored through experimental studies.
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2D Materials-Based Aptamer Biosensors: Present Status and Way Forward.
Sen, RK, Prabhakar, P, Bisht, N, Patel, M, Mishra, S, Yadav, AK, Venu, DV, Gupta, GK, Solanki, PR, Ramakrishnan, S, et al
Current medicinal chemistry. 2022;(37):5815-5849
Abstract
Current advances in constructing functional nanomaterials and elegantly designed nanostructures have opened up new possibilities for the fabrication of viable field biosensors. Two-dimensional materials (2DMs) have fascinated much attention due to their chemical, optical, physicochemical, and electronic properties. They are ultrathin nanomaterials with unique properties such as high surface-to-volume ratio, surface charge, shape, high anisotropy, and adjustable chemical functionality. 2DMs such as graphene-based 2D materials, Silicate clays, layered double hydroxides (LDHs), MXenes, transition metal dichalcogenides (TMDs), and transition metal oxides (TMOs) offer intensified physicochemical and biological functionality and have proven to be very promising candidates for biological applications and technologies. 2DMs have a multivalent structure that can easily bind to single-stranded DNA/RNA (aptamers) through covalent, non-covalent, hydrogen bond, and π-stacking interactions, whereas aptamers have a small size, excellent chemical stability, and low immunogenicity with high affinity and specificity. This review discussed the potential of various 2D material-based aptasensor for diagnostic applications, e.g., protein detection, environmental monitoring, pathogens detection, etc.
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Phytochemical-loaded liposomes for anticancer therapy: an updated review.
Chavda, VP, Vihol, D, Mehta, B, Shah, D, Patel, M, Vora, LK, Pereira-Silva, M, Paiva-Santos, AC
Nanomedicine (London, England). 2022;(8):547-568
Abstract
The major obstacles observed in current chemotherapy are severe adverse effects, narrow therapeutic indexes and multidrug resistance. Anticancer phytochemicals are extracted and purified from natural plants, providing alternative therapeutic approaches with recognized biomedical benefits. However, poor bioavailability, high dose requirements and non-specific targeting have made those molecules less effective. To tackle those issues, liposomal nanovesicles for phytochemical delivery are taken into consideration for improving the therapeutic effectiveness by increasing transportation across cell barriers and conferring attractive cancer-specific targeting capabilities. In the present review, the liposomal approaches of anticancer phytochemicals are discussed, and recent advances in these formulations applied to cancer phytotherapy are further reviewed by an informed approach.
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Perioperative management of antithrombotic therapy: a case-based narrative review.
Chen, AT, Patel, M, Douketis, JD
Internal and emergency medicine. 2022;(1):25-35
Abstract
The periprocedural management of patients who are receiving vitamin K antagonists, direct oral anticoagulants and antiplatelet therapy is a common and challenging clinical scenario as the decision to interrupt or continue these medications is anchored on patient and procedure-related risks for bleeding and thrombosis. Adding to the complexity of clinical management is the fact that anticoagulants have varied pharmacokinetic and pharmacodynamic properties and indications for clinical use. In many minimal-bleed-risk procedures, anticoagulants can be safely continued, without interruption, whereas in cases where anticoagulants cannot be safely continued, the timing of interruption and resumption, as well as the need for heparin bridging requires consideration. Perioperative antithrombotic management scenarios occur most often in patients with atrial fibrillation, mechanical heart valves, coronary stents, and cerebrovascular disease as such patients are likely to be prescribed anticoagulant and/or antiplatelet therapy. The objective of this case-based narrative review is to provide a practical evidence-based approach to the perioperative management of patients on anticoagulation and antiplatelet therapy. Four clinical scenarios will be provided: (1) managing patients in whom anticoagulants can be continued; (2) perioperative management of direct oral anticoagulants; (3) management of patients on dual antiplatelet therapy; and (4) anticoagulant management for emergency or urgent surgery.
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Thymus musilii Velen. Methanolic Extract: In Vitro and In Silico Screening of Its Antimicrobial, Antioxidant, Anti-Quorum Sensing, Antibiofilm, and Anticancer Activities.
Noumi, E, Ahmad, I, Bouali, N, Patel, H, Ghannay, S, ALrashidi, AA, Abdulhakeem, MA, Patel, M, Ceylan, O, Badraoui, R, et al
Life (Basel, Switzerland). 2022;(1)
Abstract
Thymus musilii Velen. is a rare plant species cultivated in the Ha'il region (Saudi Arabia) under greenhouse conditions. In this work, we described, for the first time, the phytochemical composition, antimicrobial, antioxidant, anti-quorum sensing, and anticancer activities of T. musilii methanolic extract using both experimental and computational approaches. The obtained results showed the identification of eight small-like peptides and eighteen phyto-compounds by using high-resolution liquid chromatography-mass spectrometry (HR-LCMS) dominated mainly by compounds belonging to isoprenoid, fatty acyl, flavonoid, and alkaloid classes. The tested extracts exhibited high antifungal and antibacterial activity with the mean diameter of growth inhibition zones ranging from 12.33 ± 0.57 mm (Pseudomonas aeruginosa ATCC 27853) to 29.33 ± 1.15 mm (Candida albicans ATCC 10231). Low minimal inhibitory concentrations were recorded for the tested micro-organisms ranging from 0.781 mg/mL to 12.5 mg/mL. While higher doses were necessary to completely kill all tested bacterial and fungal strains. Thyme extract was able to scavenge DPPH•, ABTS•+, β-carotene, and FRAP free radicals, and the IC50 values were 0.077 ± 0.0015 mg/mL, 0.040 ± 0.011 mg/mL, 0.287 ± 0.012 mg/mL, and 0.106 ± 0.007 mg/mL, respectively. The highest percentage of swarming and swimming inhibition was recorded at 100 µg/mL with 39.73 ± 1.5% and 25.18 ± 1%, respectively. The highest percentage of biofilm inhibition was recorded at 10 mg/mL for S. typhimurium ATCC 14028 (53.96 ± 4.21%) and L. monocytogenes ATCC 7644 (49.54 ± 4.5 mg/mL). The in silico docking study revealed that the observed antimicrobial, antioxidant, and anticancer activities of the constituent compounds of T. musilii are thermodynamically feasible, notably, such as those of the tripeptides (Asn-Met-His, His-Cys-Asn, and Phe-His-Gln), isoprenoids (10-Hydroxyloganin), and diterpene glycosides (4-Ketoretinoic acid glucuronide).
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Preprocedural coronary computed tomography angiography in chronic total occlusion percutaneous coronary intervention: Insights from the PROGRESS-CTO registry.
Simsek, B, Jaffer, FA, Kostantinis, S, Karacsonyi, J, Koike, H, Doshi, D, Alaswad, K, Gorgulu, S, Goktekin, O, Khatri, J, et al
International journal of cardiology. 2022;:20-25
Abstract
BACKGROUND Preprocedural coronary computed tomography angiography (CCTA) can be useful in procedural planning for chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS We examined the clinical, angiographic and procedural characteristics and outcomes of cases with vs. without preprocedural CCTA in PROGRESS-CTO (NCT02061436). Multivariable logistic regression was used to adjust for confounding factors. RESULTS Of 7034 CTO PCI cases, preprocedural CCTA was used in 375 (5.3%) with increasing frequency over time. Patients with preprocedural CCTA had a higher prevalence of prior coronary artery bypass graft surgery (39% vs. 27%, p < 0.001) and angiographically unfavorable characteristics including higher prevalence of proximal cap ambiguity (52% vs. 33%, p < 0.001) and moderate/severe calcification (59% vs. 41%, p < 0.001) compared with those without CCTA. CCTA helped resolve proximal cap ambiguity in 27%, identified significant calcium not seen on diagnostic angiography in 18%, changed estimated CTO length by >5 mm in 10%, and was performed as part of initial coronary artery disease work up in 19%. CCTA cases had higher J-CTO (2.6 ± 1.2 vs. 2.3 ± 1.3, p < 0.001) and PROGRESS-CTO (1.3 ± 1.0 vs. 1.2 ± 1.0 p = 0.027) scores. After adjusting for potential confounders, cases with preprocedural CCTA had similar technical success (odds ratio [OR]: 1.18, 95% confidence interval [CI], 0.83-1.67) and incidence of major adverse cardiovascular events (OR: 1.47, 95% CI, 0.72-3.00). CONCLUSION Preprocedural CCTA was used in ~5% of CTO PCI cases. While CCTA may help with procedural planning, especially in complex cases, technical success and MACE were similar with or without CCTA.
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Impact of diabetes on COVID-19 mortality and hospital outcomes from a global perspective: An umbrella systematic review and meta-analysis.
Kastora, S, Patel, M, Carter, B, Delibegovic, M, Myint, PK
Endocrinology, diabetes & metabolism. 2022;(3):e00338
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Abstract
INTRODUCTION To date, COVID-19 has claimed 4.9 million lives. Diabetes has been identified as an independent risk factor of serious outcomes in people with COVID-19 infection. Whether that holds true across world regions uniformly has not been previously assessed. METHODS This study offers the first umbrella systematic review and meta-analysis to analyse the collective and geographically stratified mortality, ICU admission, ventilation requirement, illness severity and discharge rate amongst patients with diabetes. Five databases (EMBASE, MEDLINE, CAB Abstracts, PsychInfo and Web of Science) and 3 additional sources (SSRN's eLibrary, Research Square and MedRxiv) were searched from inception to 30 August 2021. Prospective and retrospective cohort studies, reporting the association between diabetes and one or more COVID-19 hospitalization outcomes, were included. This meta-analysis was registered on PROSPERO, CRD42021278579. Abbreviated MeSH terms used for search were as follows: (Diabetes) AND (2019 Novel Coronavirus Disease), adapted per database requirements. Exclusion criteria exclusion criteria were as follows: (1) none of the primary or secondary outcomes of meta-analysis reported, (2) no confirmed COVID-19 infection (laboratory or clinical) and (3) no unexposed population (solely patients with diabetes included). Quality of the included studies were assessed using the Newcastle-Ottawa Scale (NOS) whilst quality of evidence by the GRADE framework. Studies that were clinically homogeneous were pooled. Summative data and heterogeneity were generated by the Cochrane platform RevMan (V. 5.4). RESULTS Overall, 158 observational studies were included, with a total of 270,212 of participants, median age 59 [53-65 IQR] of who 56.5% were male. A total of 22 studies originated from EU, 90 from Far East, 16 from Middle East and 30 from America. Data were synthesized with mixed heterogeneity across outcomes. Pooled results highlighted those patients with diabetes were at a higher risk of COVID-19-related mortality, OR 1.87 [95%CI 1.61, 2.17]. ICU admissions increased across all studies for patients with diabetes, OR 1.59 [95%CI 1.15, 2.18], a result that was mainly skewed by Far East-originating studies, OR 1.94 [95%CI 1.51, 2.49]. Ventilation requirements were also increased amongst patients with diabetes worldwide, OR 1.44 [95%CI 1.20, 1.73] as well as their presentation with severe or critical condition, OR 2.88 [95%CI 2.29, 3.63]. HbA1C levels under <70 mmol and metformin use constituted protective factors in view of COVID-19 mortality, whilst the inverse was true for concurrent insulin use. CONCLUSIONS Whilst diabetes constitutes a poor prognosticator for various COVID-19 infection outcomes, variability across world regions is significant and may skew overall trends.
