The Roles of Proton-Sensing G-Protein-Coupled Receptors in Inflammation and Cancer.

The precise regulation of pH homeostasis is crucial for normal physiology. However, in tissue microenvironments, it can be impacted by pathological conditions such as inflammation and cancer. Due to the overproduction and accumulation of acids (protons), the extracellular pH is characteristically more acidic in inflamed tissues and tumors in comparison to normal tissues. A family of proton-sensing G-protein-coupled receptors (GPCRs) has been identified as molecular sensors for cells responding to acidic tissue microenvironments. Herein, we review the current research progress pertaining to these proton-sensing GPCRs, including GPR4, GPR65 (TDAG8), and GPR68 (OGR1), in inflammation and cancer. Growing evidence suggests that GPR4 and GPR68 are mainly pro-inflammatory, whereas GPR65 is primarily anti-inflammatory, in various inflammatory disorders. Both anti- and pro-tumorigenic effects have been reported for this family of receptors. Moreover, antagonists and agonists targeting proton-sensing GPCRs have been developed and evaluated in preclinical models. Further research is warranted to better understand the roles of these proton-sensing GPCRs in pathophysiology and is required in order to exploit them as potential therapeutic targets for disease treatment.

Efficacy of Nicorandil in Preventing Myocardial Injury and Cardiovascular Outcomes in Patients Undergoing Percutaneous Coronary Intervention (PCI): A Systematic Review and Meta-Analysis.

Percutaneous coronary intervention (PCI) is a common procedure for treating coronary artery disease, but it carries a risk of periprocedural myocardial injury (PMI). This meta-analysis evaluated the efficacy of nicorandil, a hybrid compound with nitrate-like and potassium channel-opening properties, in preventing PMI during PCI. A comprehensive literature search identified 14 studies involving 1,762 patients, with 882 receiving nicorandil and 880 in the control group. The analysis revealed that nicorandil significantly reduced the incidence of PMI (RR: 0.73, 95% CI: 0.61-0.86) and major adverse cardiovascular events (MACE) (RR: 0.76, 95% CI: 0.58-0.99) compared to the control group. Nicorandil's cardioprotective effects are attributed to its ability to improve coronary blood flow, precondition the myocardium, and reduce oxidative stress and inflammation. These findings suggest that nicorandil could be a valuable adjunctive therapy during PCI, potentially improving patient outcomes. However, the study had limitations, including variations in drug administration methods and a lack of individual-level data for subgroup analysis. Future research should focus on optimizing dosing regimens and administration timing and comparing nicorandil's effectiveness with other cardioprotective agents.

Early Penile and Donor Site Sensory Outcomes After Innervated Radial Forearm Free Flap Phalloplasty: A Pilot Prospective Study.

BACKGROUND: Radial forearm free flap phalloplasty (RFFF) is a set of complex reconstructive procedures aimed at creating an aesthetic and functional penis in transgender patients. Sensory recovery in the neophallus and donor site is crucial for optimizing outcomes, but the few prior studies that exist assess neophallus sensation at limited locations and time points. The purpose of this study was to prospectively quantify sensory outcomes in the neophallus and donor site following RFFF phalloplasty. METHODS: Sensation testing occurred prospectively over February 2019-January 2021 on Stage 1 RFFF phalloplasty patients using the Pressure Specified Sensory Device (PSSD). On the neophallus, one-point discrimination (1PS) pressure threshold and lengthwise sensory recovery were measured at six circumferential locations proximally to distally. On the donor site, 1PS was measured at three locations on the donor hand. RESULTS: Nineteen patients were included (average age 34.0 years old, range 18-53 years). Among patients that received neophallus testing (n = 13), eight had at least two follow-up appointments. Six of these patients had sensation as of their most recent measurement (75.0%), with an average of 73 days to regain sensation. There was a significantly greater proportion of patients with sensation at the right ventral (80.0% after 3 months vs. 11.1%-60.0% before 3 months, p = 0.024) and right lateral (100.0% after 3 months vs. 11.1%-60.0% before 3 months, p = 0.004) aspects of the neophallus over time. Pressure required to elicit sensation decreased by 18.0% from 1 week-1 month postoperatively to 3-7.7 months postoperatively in the right ventral neophallus (96.2 g/mm2 ± 11.3 g/mm2 to 56.6 ± 39.9 g/mm2, p = 0.037). Among patients that received donor site testing (n = 11), mixed effects regression analysis with random intercepts demonstrated significant changes in the thumb (3.4 g/mm2 ± 1.4 g/mm2, p < 0.05) and webspace (13.5 g/mm2 ± 4.9 g/mm2, p < 0.01) that returned to baseline at 3 months postoperatively (1.7 g/mm2 ± 1.0 g/mm2, p > 0.05, and 2.3 g/mm2 ± 4.0 g/mm2, p > 0.05, respectively). CONCLUSION: This pilot study demonstrates that quantitative sensory testing can be used to monitor post-phalloplasty sensory changes. Recovery was significantly associated with contralateral (i.e, right side in a left forearm RFF) aspects of the neophallus, suggesting a possible pattern of circumferential sensory innervation via RFFF sensory nerves. Future studies with a larger sample size and longer follow-ups are necessary to fully characterize sensory recovery in phalloplasty patients.

Comparison of Clinical Outcomes Between Antegrade and Retrograde Techniques for Chronic Total Occlusion Revascularizations: A Systematic Review and Meta-Analysis.

Chronic total occlusions (CTOs) present significant challenges in interventional cardiology. This meta-analysis aims to compare the efficacy and safety of retrograde versus antegrade techniques in CTO percutaneous coronary intervention (PCI). A systematic review and meta-analysis were conducted following PRISMA guidelines. Electronic databases were searched through June 20, 2024. Studies comparing outcomes between antegrade and retrograde methods for CTO-PCI were included. Primary outcomes were procedural and technical success. Secondary outcomes included major adverse cardiac events (MACE), all-cause mortality, and myocardial infarction. The final analysis included seventeen studies. The antegrade approach showed a 5% higher likelihood of technical success (OR: 1.05, 95% CI: 1.02-1.09) and 14% higher odds of procedural success (OR: 1.14, 95% CI: 1.10-1.19) compared to the retrograde approach. The antegrade group also demonstrated lower risks of MACE, all-cause mortality, and myocardial infarction (RR: 0.40, 95% CI: 0.26-0.63). This meta-analysis suggests that the antegrade approach in CTO-PCI is associated with higher success rates and lower risks of adverse outcomes compared to the retrograde approach. However, the retrograde technique remains crucial for complex lesions and patients with multiple comorbidities.

Systematic Review and Meta-Analysis on the Impact of Atrial Fibrillation on Outcomes in Patients With Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition affecting the gastrointestinal tract, often leading to symptoms like abdominal pain and diarrhea. Given the increasing evidence linking systemic inflammation to atrial fibrillation development, investigating IBD as a potential risk factor for atrial fibrillation becomes imperative. This meta-analysis aims to evaluate the impact of atrial fibrillation on inpatient outcomes, resource utilization, and length of hospital stays among IBD patients. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines, a systematic literature search was conducted across multiple databases, including Embase, PubMed, Scopus, and Web of Science, from the inception of databases to June 5, 2024. Eligible studies included prospective or retrospective studies with definitive diagnoses of ulcerative colitis, Crohn's disease, or IBD, demonstrating the influence of atrial fibrillation. Data were extracted, and quality assessment was performed using the Newcastle-Ottawa Scale. The meta-analysis comprised 842,149 IBD patients, with 71,221 having atrial fibrillation. Pooled analysis revealed a significant association between atrial fibrillation and heightened all-cause mortality risk (risk ratio (RR): 1.42, 95% confidence interval (CI): 1.16 to 1.74, p<0.01). However, no significant differences were observed in the incidence of acute myocardial infarction, acute kidney injury, or acute respiratory failure between patients with and without atrial fibrillation. IBD patients with comorbid atrial fibrillation face higher mortality rates, potentially due to systemic inflammation, thromboembolism risks, polypharmacy, and the complexities of managing both conditions concurrently. Early identification and integrated management of atrial fibrillation in IBD patients are crucial to improving outcomes. Larger, multi-center studies are needed to explore the underlying mechanisms and develop tailored treatment strategies.

Evaluating the Efficacy of Coronary Sinus Reducer Implantation in the Management of Refractory Angina: A Systematic Review and Meta-Analysis.

The coronary sinus reducer (CSR), a minimally invasive device, has emerged as a promising alternative for improving myocardial perfusion in these patients. This meta-analysis evaluated the effectiveness of CSR implantation in patients with refractory angina. A comprehensive search of PubMed, EMBASE, and Web of Science databases identified 10 relevant studies with a pooled sample size of 799 patients. The analysis focused on changes in the Canadian Cardiovascular Society (CCS) classification score, Seattle Angina Questionnaire (SAQ) score, and six-minute walk distance (6MWD) from baseline to follow-up. Results showed significant improvements across all measured outcomes. CCS scores decreased significantly post-CSR implantation, indicating reduced angina severity. SAQ scores improved across all domains, including physical limitation, anginal stability, anginal frequency, treatment satisfaction, and quality of life, suggesting enhanced overall well-being. The 6MWD also increased significantly, reflecting improved functional capacity. These findings highlight CSR's potential as an effective treatment option for patients with refractory angina who have exhausted traditional therapies. CSR implantation appears to alleviate angina symptoms, improve quality of life, and enhance exercise tolerance. Future research should prioritize larger, multi-center randomized controlled trials to validate these findings. Long-term follow-up studies are needed to assess sustained benefits and potential risks.

Comparison of Potassium-Competitive Acid Blockers and Proton Pump Inhibitors in Patients With Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This meta-analysis evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) compared to proton pump inhibitors (PPIs) in treating gastroesophageal reflux disease (GERD). A comprehensive literature search was conducted across multiple databases, and 11 randomized controlled trials comparing PCABs with PPIs were included. The primary outcome was the healing of erosive esophagitis (EE), with secondary outcomes, including relief of heartburn symptoms and adverse events. The analysis included 11 studies and a pooled sample of 4,108 GERD patients. Results showed that PCABs were significantly more effective in healing EE compared to PPIs (OR: 1.67, 95% CI: 1.24-2.24, p<0.01). PCABs also demonstrated a higher rate of complete resolution of heartburn symptoms, although this difference did not reach statistical significance (OR: 1.43, 95% CI: 0.98-2.09, p=0.06). In terms of safety, there was no significant difference in adverse events between PCABs and PPIs (OR: 0.91, 95% CI: 0.79-1.04, p=0.18), including serious adverse events. The superior efficacy of PCABs can be attributed to their unique pharmacological properties, which allow for more rapid and potent acid suppression compared to PPIs. However, the long-term safety profile of PCABs, particularly newer agents, requires further investigation. The study was limited by the predominance of vonoprazan among the PCABs studied and the focus on patients with EE rather than non-erosive reflux disease. In conclusion, this meta-analysis suggests that PCABs are more effective than PPIs in treating GERD, particularly in healing EE, while maintaining a comparable safety profile. Future research should focus on evaluating a wider range of PCABs, assessing their efficacy in non-erosive reflux disease, and investigating their long-term safety in GERD management.

Assessing the Effect of Sodium-Glucose Cotransporter 2 Inhibitor (SGLT2i) on Outcomes in Patients With Acute Myocardial Infarction: A Systematic Review and Meta-Analysis.

After acute myocardial infarction, patients are at increased risk for adverse outcomes, including heart failure and death. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown promising cardiovascular benefits, but their efficacy in patients after myocardial infarction is not well established. This study aimed to evaluate the efficacy of SGLT2i in preventing cardiovascular outcomes in patients after myocardial infarction through a systematic review and meta-analysis. We conducted a comprehensive literature search of PubMed, Cochrane, EMBASE, and Web of Science for randomized controlled trials (RCTs) and retrospective and prospective studies evaluating SGLT2i in patients after myocardial infarction. The primary outcomes were major adverse cardiovascular events (MACEs) and all-cause mortality. Secondary outcomes included cardiovascular mortality, recurrent myocardial infarction, revascularization, and rehospitalization. Data were pooled using a random-effects model, and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. The meta-analysis included eight studies (three RCTs and five observational studies) with a follow-up duration ranging from 4 to 24 months. SGLT2i were associated with a significantly lower risk of MACE (RR: 0.71, 95% CI: 0.52-0.97, p = 0.03) and rehospitalization (RR: 0.64, 95% CI: 0.51-0.82, p<0.01) compared to controls. Although not statistically significant, the risk of all-cause mortality (RR: 0.79, 95% CI: 0.53-1.18, p = 0.25) and cardiovascular mortality was lower in the SGLT2i group. This meta-analysis suggests that SGLT2i may improve cardiovascular outcomes in patients after myocardial infarction, particularly by reducing the risk of MACEs and rehospitalization. However, larger trials with high-risk populations are needed to confirm these findings and elucidate the underlying mechanisms.

Effect of Elevated Neutrophil-to-Lymphocyte Ratio on Adverse Outcomes in Patients With Myocardial Infarction: A Systematic Review and Meta-Analysis.

Myocardial infarction (MI), a leading cause of morbidity and mortality globally, is characterized by an underlying inflammatory process driven by atherosclerosis. The neutrophil-to-lymphocyte ratio (NLR), a readily available and cost-effective marker of systemic inflammation, has emerged as a potential predictor of adverse outcomes in patients with MI. This meta-analysis aimed to evaluate the association between elevated NLR and the risk of major adverse cardiovascular events (MACE) and all-cause mortality in patients with MI. A comprehensive literature search was conducted across multiple databases, including Embase, Web of Science, PubMed, and OVID Medicine, to identify relevant studies published from January 1, 2011, onward. Studies reporting the effect of NLR values on MACE and mortality in adult patients with MI, including both ST-elevation (STEMI) and non-ST-elevation (NSTEMI) subtypes, were included. Data extraction and quality assessment were performed independently by multiple authors. The meta-analysis included 37 studies, comprising a total of 18 studies evaluating the risk of MACE and 30 studies assessing all-cause mortality. The pooled analysis revealed a significantly increased risk of MACE (odds ratio [OR] 1.86, 95% confidence interval [CI] 1.53-2.28, P < 0.01) and all-cause mortality (OR 2.29, 95% CI 1.94-2.70, P < 0.01) in patients with elevated NLR compared to those without elevated NLR. Subgroup analyses stratified by follow-up duration and study design further supported the consistent association between elevated NLR and adverse outcomes. In conclusion, this meta-analysis demonstrates a significant association between elevated NLR and an increased risk of MACE and all-cause mortality in patients with MI. These findings highlight the potential clinical utility of NLR as a prognostic marker and underscore the importance of further research to validate its predictive value and establish optimal cutoff values for risk stratification in this patient population.

Computational approach for drug discovery against Gardnerella vaginalis in quest for safer and effective treatments for bacterial vaginosis.

Bacterial vaginosis (BV), primarily attributed to Gardnerella vaginalis, poses significant challenges due to antibiotic resistance and suboptimal treatment outcomes. This study presents an integrated approach to identify potential drug targets and screen compounds against this bacterium by leveraging a computational methodology. Subtractive proteomics of the reference strain ASM286196v1/UMB0386 (assembly accession: GCA_002861965.1) facilitated the prioritization of proteins with essential bacterial functions and pathways as potential drug targets. We selected 3-deoxy-7-phosphoheptulonate synthase (aroG gene product; also known as DAHP synthase) for downstream analysis. Molecular docking was employed in PyRx (AutoDock Vina) to predict binding affinities between aroG inhibitors from the ZINC database and 3-deoxy-7-phosphoheptulonate synthase. Molecular dynamics simulations of 100 ns, using GROMACS, validated the stability of drug-target interactions. Additionally, ADMET profiling aided in the selection of compounds with favorable pharmacokinetic properties and safety profile for human hosts. PBPK profiling showed that ZINC98088375 had the highest bioavailability and efficient systemic circulation. Conversely, ZINC5113880 demonstrated the lowest absorption rate (39.661%). Moreover, cirrhosis, steatosis, and renal impairment appeared to influence blood concentration of the drug, impacting bioavailability. The integrative -omics approach utilized in this study underscores the potential of computer-aided drug design and offers a rational strategy for targeted inhibitor discovery against G. vaginalis. The strategy is an attempt to address the limitations of current BV treatments, including antibiotic resistance, and pave way for the development of safer and more effective therapeutics.

Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors in Preventing Heart Failure in Patients Receiving Anthracycline-Based Cancer Therapy: A Systematic Review and Meta-Analysis.

Anthracyclines are effective chemotherapeutic agents widely used to treat various cancers, but their use is limited by the risk of cardiotoxicity and heart failure. While strategies like dose reduction have been explored, there are no well-established therapies to mitigate this risk. Emerging evidence suggests sodium-glucose cotransporter 2 inhibitors (SGLT2i) may have cardioprotective effects, providing a rationale for investigating their potential utility in anthracycline-treated patients. We conducted a systematic review and meta-analysis to synthesize available evidence on the efficacy of SGLT2i in reducing heart failure incidence and mortality in patients undergoing anthracycline-based cancer therapy. Relevant studies were identified through comprehensive database searches and screened based on predefined criteria. Data extraction and quality assessment were performed independently by two reviewers. Four observational studies, encompassing 5,590 patients, were included. The pooled analysis showed a higher but non-significant risk of developing heart failure in the non-SGLT2i group compared to the SGLT2i group (RR = 0.67, 95% CI: 0.40-1.41). The risk of all-cause mortality was significantly lower in patients receiving SGLT2i (RR = 0.55, 95% CI: 0.39-0.77). This meta-analysis suggests SGLT2i are associated with a lower risk of mortality and heart failure incidence in anthracycline-treated patients, although larger studies are needed to confirm these findings. The mechanisms underlying these potential benefits require further elucidation. Despite limitations, this analysis highlights the promising role of SGLT2i as a cardioprotective strategy in this high-risk population.

Effects of Targeted Hypercapnia on Mortality and Length of Stay of Post-cardiac Arrest Patients: A Systematic Review and Meta-Analysis.

Therapeutic hypercapnia has been proposed as a potential strategy to enhance cerebral perfusion and improve outcomes in patients after cardiac arrest. However, the effects of targeted hypercapnia remain unclear. We conducted a systematic review and meta-analysis to evaluate the impact of hypercapnia compared to normocapnia on mortality and length of stay in post-cardiac arrest patients. We searched major databases for randomized controlled trials and observational studies comparing outcomes between hypercapnia and normocapnia in adult post-cardiac arrest patients. Data on in-hospital mortality and the ICU and hospital length of stay were extracted and pooled using random-effects meta-analysis. Five studies (two randomized controlled trials (RCTs) and three observational studies) with a total of 1,837 patients were included. Pooled analysis showed hypercapnia was associated with significantly higher in-hospital mortality compared to normocapnia (56.2% vs. 50.5%, OR 1.24, 95% CI 1.12-1.37, p<0.001). There was no significant heterogeneity (I2 = 25%, p = 0.26). No statistically significant differences were found for ICU length of stay (mean difference 0.72 days, 95% CI -0.51 to 1.95) or hospital length of stay (mean difference 1.13 days, 95% CI -0.67 to 2.93) between the groups. Sensitivity analysis restricted to mild hypercapnia studies did not alter the mortality findings. This meta-analysis did not find a mortality benefit with targeted hypercapnia compared to normocapnia in post-cardiac arrest patients. The results align with current guidelines recommending a normal partial pressure of arterial carbon dioxide (PaCO2) target range and do not support routinely targeting higher carbon dioxide levels in this setting.

Core proteome mediated subtractive approach for the identification of potential therapeutic drug target against the honeybee pathogen Paenibacillus larvae.

Background & Objectives: American foulbrood (AFB), caused by the highly virulent, spore-forming bacterium Paenibacillus larvae, poses a significant threat to honey bee brood. The widespread use of antibiotics not only fails to effectively combat the disease but also raises concerns regarding honey safety. The current computational study was attempted to identify a novel therapeutic drug target against P. larvae, a causative agent of American foulbrood disease in honey bee. Methods: We investigated effective novel drug targets through a comprehensive in silico pan-proteome and hierarchal subtractive sequence analysis. In total, 14 strains of P. larvae genomes were used to identify core genes. Subsequently, the core proteome was systematically narrowed down to a single protein predicted as the potential drug target. Alphafold software was then employed to predict the 3D structure of the potential drug target. Structural docking was carried out between a library of phytochemicals derived from traditional Chinese flora (n > 36,000) and the potential receptor using Autodock tool 1.5.6. Finally, molecular dynamics (MD) simulation study was conducted using GROMACS to assess the stability of the best-docked ligand. Results: Proteome mining led to the identification of Ketoacyl-ACP synthase III as a highly promising therapeutic target, making it a prime candidate for inhibitor screening. The subsequent virtual screening and MD simulation analyses further affirmed the selection of ZINC95910054 as a potent inhibitor, with the lowest binding energy. This finding presents significant promise in the battle against P. larvae. Conclusions: Computer aided drug design provides a novel approach for managing American foulbrood in honey bee populations, potentially mitigating its detrimental effects on both bee colonies and the honey industry.

Vitamin B12 Supplementation in Psychiatric Practice.

PURPOSE OF REVIEW: Vitamin B12 (B12, cobalamin) deficiency has been associated with neuropsychiatric symptoms, suggesting a role for B12 supplementation both as a treatment for psychiatric symptoms due to B12 deficiency and as an augmentation strategy for pharmacological treatments of psychiatric disorders. This critical review discusses the major causes of B12 deficiency, the range of psychiatric and non-psychiatric manifestations of B12 deficiency, the indications for testing B12 levels, and the evidence for B12 supplementation for major psychiatric disorders. RECENT FINDINGS: We find that high-quality evidence shows no benefit to routine B12 supplementation for mild depressive symptoms or to prevent depression. There is very limited evidence on the role of B12 supplementation to augment antidepressants. No high-quality evidence to date suggests a role for routine B12 supplementation in any other major psychiatric disorder. No formal guidelines indicate when clinicians should test B12 levels for common psychiatric symptoms, in the absence of major risk factors for deficiency or cardinal symptoms of deficiency. No robust evidence currently supports routine B12 supplementation for major psychiatric disorders. However, psychiatrists should be aware of the important risk factors for B12 deficiency and should be able to identify symptoms of B12 deficiency, which requires prompt testing, medical workup, and treatment. Testing for B12 deficiency should be considered for atypical or severe psychiatric presentations.

Testosterone Promotes Nerve Tethering and Acellular Biomaterial Perineural Fibrosis in a Rat Wound Repair Model.

Objective: Nerve scarring after traumatic or iatrogenic exposure can lead to impaired function and pain. Nerve-adjacent biomaterials promoting a regenerative tissue response may help reduce perineural fibrosis. Our prior work suggests that testosterone may promote fibrotic skin scarring, but it is unknown how testosterone alters nerve fibrosis or shifts the response to biomaterials. Approach: Sterilized Lewis rats received either testosterone cypionate (+T) or placebo (-T) biweekly. Fifteen days later, wounds were created over the sciatic nerve and covered with an acellular matrix (AM) or closed via primary closure (PC). At day 42, force gauge testing measured the force required to mobilize the nerve, and wound tissue was analyzed. Results: Nerve mobilization force was greater in +T versus -T wounds (p < 0.01). Nerves tore before gliding in 60% of +T versus 6% of -T rats. Epidermal gap (p < 0.01), scar width (p < 0.01), and cross-sectional scar tissue area (p = 0.02) were greater in +T versus -T rats. +T versus -T rats expressed less Col-3 (p = 0.02) and CD68 (p = 0.02). Nerve mobilization force trended nonsignificantly higher for PC versus AM wounds and for +T versus -T wounds within the AM cohort. Innovation: Testosterone increases nerve tethering in the wound healing milieu, altering repair and immune cell balances. Conclusion: Testosterone significantly increases the force required to mobilize nerves in wound beds and elevates histological markers of scarring, suggesting that testosterone-induced inflammation may increase perineural adhesion. Testosterone may reduce the potential anti-tethering protective effect of AM. Androgen receptor antagonism may represent a therapeutic target to reduce scar-related nerve morbidity.

Evaluating User Experience and DNA Yield from Self-Collection Devices.

BACKGROUND: The COVID-19 pandemic emphasized an urgent need for devices used in the self-collection of biospecimens in an evolving patient care system. The mailing of biospecimen self-collection kits to patients, with samples returned via mail, provides a more convenient testing regimen, but could also impart patient sampling variabilities. User compliance with device directions is central to downstream testing of collected biospecimens and clear instructions are central to this goal. METHODS: Here, we performed an evaluation of 10 oral DNA collection devices involving either swab or saliva self-collection and analyzed ease of use and comfort level with a device, as well as DNA recovery quantity/quality and sample stability. RESULTS: We show that while these DNA quality/quantity metrics are comparable between devices, users prefer direct saliva collection over swab-based devices. CONCLUSIONS: This information is useful in guiding future experiments including their use in human RNA, microbial, or viral sample collection/recovery and their use in clinical testing.

Comparison of Effectiveness and Safety of Apixaban, Dabigatran, and Rivaroxaban in Patients With Valvular Atrial Fibrillation: A Network Meta-Analysis of Randomized-Control Trials and Observational Studies.

The objective of this network meta-analysis was to assess the efficacy and safety of apixaban, dabigatran, rivaroxaban, and edoxaban in patients diagnosed with atrial fibrillation and valvular heart disease. A comprehensive search was conducted across various electronic databases, including PubMed, Embase, and Web of Science, from inception to February 15, 2024. The search strategy utilized a combination of medical subject headings (MeSH) terms and relevant keywords related to valvular heart disease, atrial fibrillation, anticoagulant therapy, and study design, such as randomized controlled trials and observational studies. The outcomes evaluated in this analysis comprised the incidence of stroke or systemic embolism (SE), as well as the occurrences of major bleeding events. A total of 10 studies were incorporated into this meta-analysis, encompassing 40,662 participants. Of these, 12,385 received apixaban, 2,829 received dabigatran, 13,662 received rivaroxaban, 2,582 received edoxaban, and 9,202 received warfarin. The duration of follow-up in the included studies ranged from 3 to 54 months. Among the four direct oral anticoagulants (DOACs) studied, apixaban demonstrated a significant reduction in the risk of stroke or SE when compared to other DOACs and warfarin, highlighting its efficacy in patients with atrial fibrillation and valvular heart disease. Additionally, apixaban exhibited a lower risk of major bleeding events, further emphasizing its favorable safety profile compared to the other agents assessed. In conclusion, our findings suggest that apixaban may be more effective and safer than other DOACs and warfarin in this patient population. However, additional studies are warranted to compare the various DOACs in this cohort to identify the optimal treatment strategy for preventing adverse outcomes.

Comparison of Effectiveness and Safety of Dual Antiplatelet Therapy (DAPT) With Clopidogrel and Aspirin Versus Aspirin Monotherapy in Patients With Mild-to-Moderate Stroke and Transient Ischemic Attack: A Systematic Review and Meta-Analysis.

The aim of this meta-analysis was to assess the effectiveness and safety of the combination of clopidogrel and aspirin in patients with mild ischemic stroke or transient ischemic attack (TIA). The methodologies employed in this meta-analysis strictly followed the commonly used reporting formats for systematic reviews and meta-analyses. The methodologies employed in this meta-analysis strictly followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Until March 25, 2024, we conducted thorough searches on PubMed, EMBASE (Excerpta Medica Database), and the Cochrane Library to locate studies investigating the efficacy and safety of dual antiplatelet therapy (DAPT) in patients with mild or moderate stroke or TIA. Outcomes assessed in this meta-analysis included stroke (including ischemic stroke and hemorrhagic stroke), myocardial infarction, all bleeding events, and moderate to severe bleeding events. A total of 12 studies were included in this meta-analysis. The total number of enrolled patients across these studies was 35,369, with 16,957 receiving DAPT and 18,412 receiving aspirin monotherapy. The risk of developing stroke was significantly lower in patients receiving the combination of clopidogrel and aspirin compared to the aspirin monotherapy group (relative risk (RR): 0.77, 95% confidence interval (CI): 0.72 to 0.83, p-value<0.0001). No significant differences were there in terms of all bleeding events (RR: 1.37, 95% CI: 0.92 to 2.04, p-value: 0.12) and moderate to severe bleeding events (RR: 1.18, 95% CI: 0.86 to 1.63, p-value: 0.30). These findings highlight the importance of carefully weighing the potential benefits against the risks, especially in clinical decision-making for patients with TIA or ischemic stroke. Further research is warranted to elucidate optimal strategies for balancing stroke prevention with bleeding risk mitigation in this patient population.

A Systematic Review and Meta-Analysis on the Identification of Predictors Associated With Insomnia or Sleep Disturbance in Post-stroke Patients.

The aim of this study was to identify the factors associated with sleep disturbances in individuals after a stroke. To systematically identify relevant studies, an extensive search strategy was devised. We conducted comprehensive searches in major electronic databases including PubMed, Embase, PsycINFO, and Cochrane Library. The search was limited to articles published in English between January 1, 2011, and February 10, 2024. Pooled effect estimates, such as odds ratio (OR) or mean difference (MD) along with their confidence interval (CIs), were calculated using random-effects models for categorical variables and continuous variables, respectively. A total of nine studies were included in this meta-analysis. The pooled prevalence of insomnia across the included studies was determined to be 40% (95% CI = 30%-49%), with individual study prevalence ranging from 22% to 72%. A pooled analysis showed that gender demonstrated a statistically significant association with sleep disturbance, with females exhibiting a higher likelihood (OR = 1.49, 95% CI = 1.16-1.91, p = 0.002) compared to males. The National Institutes of Health Stroke Scale (NIHSS) score, a measure of stroke severity, was associated with sleep disturbance (MD = 0.86, 95% CI = 0.56-1.17, p = 0.001), indicating that patients with severe strokes may be more prone to sleep disturbances. These findings underscore the importance of comprehensive evaluation and targeted interventions to address sleep-related issues in stroke patients, particularly those with severe neurological impairment.

Exploring the Prevalence and Characteristics of Obstructive Sleep Apnea Among Idiopathic Pulmonary Fibrosis Patients: A Systematic Review and Meta-Analysis.

The aim of this meta-analysis was to scrutinize the prevalence, characteristics, and outcomes of obstructive sleep apnea (OSA) in individuals with ideopathic pulmonary fibrosis (IPF). We carried out this systematic review and meta-analysis in accordance with the guidelines outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Statement (PRISMA). Two independent researchers systematically searched major databases, including MEDLINE/PubMed, EMBASE, and the Cochrane Library, from January 1, 2000, until December 31, 2023. We included all studies involving adult patients (age >18 years) with IPF that assessed the prevalence and characteristics of OSA in IPF patients. A total of seven studies involving a pooled sample of 411 patients were included in this meta-analysis. The pooled prevalence of OSA among individuals with IPF was found to be 70% (95% CI: 59 to 82%). Individuals with OSA exhibited a significantly higher mean body mass index (BMI) compared to their counterparts. While individuals with both IPF and OSA exhibited higher scores on the Epworth Sleepiness Scale (ESS) compared to those with IPF alone, the OSA group also showed lower oxygen saturation during sleep in comparison to non-OSA patients. In summary, OSA is a prevalent coexisting condition among individuals with IPF. This presence could worsen the nighttime oxygen saturation. Consequently, there is a need for more extensive studies involving more uniform participant groups.