Carob (Ceratonia siliqua) supplements can increase sperm quality. This study aimed to summarize the available evidence about the effects of carob (Ceratonia siliqua) supplements on sperm quality and reproductive hormones in infertile men. Systematic searches of five databases were conducted from inception to October 20, with the last update on November 20, 2023. Randomized clinical trials (RCTs) that compared carob (Ceratonia siliqua) supplements with nonintervention control groups on infertile man. Risk of bias and certainty of evidence were assessed by the Cochrane risk of bias tool 2. Summary effect size measures were calculated using a random-effects model estimation and are reported as standardized mean differences and 95% confidence intervals. Reporting followed the PRISMA guidelines. The analysis included four studies involving 236 infertile men. It was found that sperm motility of infertile men improved after carob intervention (MD:11.30, 95% CI:5.97 to 16.64, Z = 4.15, p < 0.00001), and there was a significant difference compared to control groups. The effect size of carob on semen quantity in infertile men was positive, and the relationship was statistically significant (MD:5.42, 95% CI:1.58 to 9.42, Z = 2.77, p = 0.006). When hormone parameters of infertile men were analyzed, the MDA (malondialdehyde) value decreased compared to the control group (MD = -4.81, 95% CI: -10.18 to 0.56, Z = 1.76, p = 0.08), and there was a significant difference between them. Carob (Ceratonia siliqua) supplements was associated with improvement in sperm quality compared with nonintervention control groups in infertile man. However, high-quality, larger RCTs are required to draw more definitive conclusions.

BACKGROUND: Dexmedetomidine plays a pivotal role in mitigating postoperative delirium and cognitive dysfunction while enhancing the overall quality of life among surgical patients. Nevertheless, the influence of dexmedetomidine on such complications in various anaesthesia techniques remains inadequately explored. As such, in the present study, a meta-analysis was conducted to comprehensively evaluate its effects on postoperative delirium and cognitive dysfunction. METHODS: A number of databases were searched for randomised controlled trials comparing intravenous dexmedetomidine to other interventions in preventing postoperative delirium and cognitive dysfunction in non-cardiac and non-neurosurgical patients. These databases included PubMed, Embase, and Cochrane Library. Statistical analysis and graphing were performed using Review Manager, STATA, the second version of the Cochrane risk-of-bias tool for randomised controlled trials, and GRADE profiler. MAIN RESULTS: This meta-analysis comprised a total of 24 randomised controlled trials, including 20 trials assessing postoperative delirium and 6 trials assessing postoperative cognitive dysfunction. Across these 24 studies, a statistically significant positive association was observed between intravenous administration of dexmedetomidine and a reduced incidence of postoperative delirium (RR: 0.55; 95% CI 0.47 to 0.64, p < 0.00001, I2 = 2%) and postoperative cognitive dysfunction (RR: 0.60; 95% CI 0.38 to 0.96, p = 0.03, I2 = 60%). Subgroup analysis did not reveal a significant difference in the incidence of postoperative delirium between the general anaesthesia and non-general anaesthesia groups, but a significant difference was observed in the incidence of postoperative cognitive dysfunction. Nonetheless, when the data were pooled, it was evident that the utilisation of dexmedetomidine was associated with an increased incidence of hypotension (RR: 1.42; 95% CI 1.08 to 1.86, p = 0.01, I2 = 0%) and bradycardia (RR: 1.66; 95% CI 1.23 to 2.26, p = 0.001, I2 = 0%) compared with other interventions. However, there was no significantly higher occurrence of hypertension in the DEX groups (RR = 1.35, 95% CI 0.81-2.24, p = 0.25, I2 = 0%). CONCLUSION: Compared with other interventions, intravenous dexmedetomidine infusion during non-cardiac and non-neurosurgical procedures may significantly reduce the risk of postoperative delirium and cognitive dysfunction. The results of subgroup analysis reveal a consistent preventive effect on postoperative delirium in both general and non-general anaesthesia groups. Meanwhile, continuous infusion during general anaesthesia was more effective in reducing the risk of cognitive dysfunction. Despite such findings, hypotension and bradycardia were more frequent in patients who received dexmedetomidine during surgery.

OBJECTIVE: To systematically assess the association of Sodium-Glucose Co-Transporter 2 Inhibitors (SGLT2I) vs. Dipeptidyl Peptidase-4 Inhibitors (DPP4I) with pneumonia, COVID-19, and adverse respiratory events in patients with type 2 diabetes mellitus (DM). METHOD: PubMed, Embase, and Cochrane Library databases were retrieved to include studies on DM patients receiving SGLT2I (exposure group) or DPP4I (control group). Stata.15.0 statistical software was employed for meta-analysis. RESULT: Ten studies were included, 10 of which were used for the qualitative review and 7 for the meta-analysis. According to the meta-analysis, patients receiving SGLT2I had lower pneumonia incidence (OR=0.62, 95% Cl, 0.51-0.74) and pneumonia risk (OR=0.63, 95% Cl, 0.60-0.68, P=0.000) compared to those receiving DPP4I. The same situation occurs in mortality rate of pneumonia (OR=0.49, 95% Cl, 0.39-0.60) and pneumonia mortality risk (OR=0.47, 95% Cl, 0.42-0.51) . Lower mortality of COVID-19 (OR=0.31, 95% Cl, 0.28 -0.34), and a lower hospitalization rate and incidence of mechanical ventilation (OR=0.61, 95% Cl, 0.56-0.68, P=0.000, OR=0.69, 95% Cl, 0.58-0.83, P=0.000) due to COVID-19 in patients with type 2 DM receiving SGLT2I. The qualitative analysis results showed that SGLT2I was associated with a lower incidence of COVID-19, lower risk of obstructive Airway disease (OAD) events, and lower hospitalization rate of healthcare-associated pneumonia (HCAP) than DPP4I. CONCLUSION: In patients with type 2 DM, SGLT2I is associated with a lower risk of pneumonia, COVID-19 and mortality rate compared to those taking DPP4I.

BACKGROUND: When it comes to pandemic response, preparation can be the key. Between 2020 and 2024, the fast-paced development of COVID-19-often compounded by pubic policies' failures to reflect the latest reality and the public's divergent reactions to the pandemic and the policies-means that society should prepare for exit strategies that can reflect the reality of the pandemic and the interests of the people. Yet oftentimes societies only have one exit strategy with limited scope. This paper investigates the dangers of having only one pandemic exit strategy for pandemics like COVID-19. METHODS: Analyses were based on a review of the literature on COVID-19 exit strategies and our own research. The PubMed literature search focused on two concepts-"COVID-19″ and "exit strategy"-and was limited to peer-reviewed papers published between 2020 and 2024 in English. RESULTS: A total of 31 articles were included in the final review. Analyses showed that existing studies on COVID-19 exit strategies often focused on using the modelling method to gauge one exit strategy. Exit strategies were often discussed in the context of implementing, easing, or lifting specific pharmaceutical or non-pharmaceutical interventions. Staged and country-wide coordinated exit strategies were also discussed in the literature, both of which were often deemed as comparatively rigorous options compared to single or stand-alone exit strategies. Drawing on the overall development of COVID-19 and our own research, we presented and discussed the importance of having multiple exit strategies that are considerate of all possible pandemic trajectories, diverse interests of the public, and the communication challenges officials might face in introducing or implementing pandemic policies. CONCLUSION: This paper underscored the importance of having multiple exit strategies for societies to prepare for pandemics. The insights of this study can help inform health policies so that they can more comprehensively and compassionately protect the needs and wants of the "public" in public health, particularly in grave times like COVID-19.

BACKGROUND: Data regarding the risk of atrial fibrillation (AF) during the post-acute phase of COVID-19 are lacking. OBJECTIVE: We assess the risk of incident AF in COVID-19 recovered patients by performing a systematic review and meta-analysis of the available data. METHODS: Following the PRIMSA guidelines, we searched Medline and Scopus to locate all articles published up to December 10, 2023, reporting the risk of AF in patients recovered from COVID-19 infection compared to non-infected patients who developed the arrhythmia over the same follow-up period. AF risk was evaluated using the Mantel-Haenszel random effects models with Hazard ratio (HR) as the effect measure with 95% confidence interval (CI) while heterogeneity was assessed using Higgins I2 statistic. RESULTS: Overall, 19,478,173 patients (mean age 56.5 years, 63.0% males), enrolled in five observational studies, were included into the analysis. Among them, 5,692,510 recovered from SARS-CoV-2 infection. Over a mean follow-up of 14.5±3.2 months, a random effect model revealed a pooled incidence of new onset AF 2.6% of cases (95% CI: 1.8-6.18%). Recovered COVID-19 patients presented a higher risk of incident AF (HR: 1.57, 95% CI: 1.24-1.99, p<0.0001, I2=77.9%) compared to non-infected patients over the same follow-up period. Sensitivity analyses confirmed yielded results. A multivariable meta-regression, including age, male sex, history of hypertension, coronary artery disease and length of follow-up was able to explain a significant part of heterogeneity (R2: 54.3%, p=0.01). CONCLUSIONS: Recovered COVID-19 patients have a higher risk of AF events compared to subjects from the general population.

Bariatric surgery is a commonly performed procedure for patients who have failed to achieve weight loss through medical and lifestyle interventions. However, the altered gastrointestinal anatomy resulting from the surgery can significantly impact the bioavailability of antidepressants in patients with generalized anxiety disorder, potentially leading to uncontrolled anxiety symptoms. This case report describes a patient with generalized anxiety disorder who underwent Roux-en-Y gastric bypass surgery and subsequently experienced increased anxiety symptoms due to poor antidepressant bioavailability. The patient's medication was adjusted to a sublingual formulation, resulting in improved anxiety control and reduced side effects. Healthcare providers should be aware of the potential impact of bariatric surgery on medication absorption and closely monitor patients with generalized anxiety disorder for potential psychiatric medication-related complications postoperatively. The use of alternative routes of administration, such as sublingual medication, may be beneficial in improving drug bioavailability and managing anxiety symptoms. Creating awareness in primary care offices about poor drug absorption and using alternatives such as the sublingual route of administration to achieve optimal systemic delivery requires a multifaceted approach involving education and training for healthcare providers as well as patient education to ensure they are informed and engaged in their own care. By implementing these strategies, primary care providers can improve patient outcomes and prevent unnecessary referrals to specialists.

CAR- CD4+ T cell lymphopenia is an emerging issue following CAR-T cell therapy. We analyzed the determinants of CD4+ T cell recovery and a possible association with survival in 31 consecutive patients treated with commercial CAR-T for diffuse large B-cell (DLBCL) or mantle cell lymphoma. Circulating immune subpopulations were characterized through multiparametric-flow cytometry. Six-month cumulative incidence of CAR- CD4+ T cell recovery (≥200 cells/μL) was 0.43 (95% confidence interval [CI]: 0.28-0.65). Among possible determinants of CD4+ T cell recovery, we recognized infusion of a 4-1BB product (tisagenlecleucel, TSA) in comparison with a CD28 (axicabtagene/brexucabtagene, AXI/BRX) (hazard ratio [HR] [95% CI]: 5.79 [1.16-24.12] p = 0.016). Higher CD4+ T cell counts resulted with TSA at month-1, -2 and -3. Moderate-to-severe infections were registered with prolonged CD4+ T cell lymphopenia. Early, month-1 CD4+ T cell recovery was associated with a worse outcome in the DLBCL cohort, upheld in a multivariate regression model for overall survival (HR: 4.46 [95% CI: 1.12-17.71], p = 0.03). We conclude that a faster CAR- CD4+ T cell recovery is associated with TSA as compared to AXI/BRX. Month-1 CAR- CD4+ T cell subset recovery could represent a "red flag" for CAR-T cell therapy failure in DLBCL patients.

Recurrent abnormalities in immune surveillance-related genes affect the progression of diffuse large B-cell lymphoma (DLBCL) and modulate the response to therapeutic interventions. CD58 interacts with the CD2 receptor on T cells and natural killer (NK) cells and is recurrently mutated and deleted in DLBCL, suggesting it may play a role in regulating antitumor immunity. Herein, we comprehensively analyzed the genomic characteristics of CD58 through targeted next-generation sequencing, RNA-sequencing, whole-exome sequencing, and single-cell RNA-sequencing in patients with newly diagnosed DLBCL. The CD58 mutation rate was 9.1%, and the copy number loss rate was 44.7% among all enrolled DLBCL patients. Notably, CD58 genetic alterations, along with low CD58 expression, significantly correlated with reduced rates of response to R-CHOP therapy and inferior progression-free and overall survival. Single-cell RNA sequencing revealed that CD58 expression in tumor cells was negatively correlated with CD8+ T cell exhaustion/dysfunction status. Insufficient T-cell activation resulting from CD58 alterations could not be attributed solely to CD2 signaling. CD58 inhibited the activity of the JAK2/STAT1 pathway by activating the Lyn/CD22/SHP1 axis, thereby limiting PD-L1 and IDO expression. Elevated PD-L1 and IDO expression in CD58 deficient DLBCL cells led to immune evasion and tumor-intrinsic resistance to CAR T-cell therapy. Direct activation of CD58-CD2 costimulatory signaling in combination with anti-PD-L1 blockade or IDO inhibitor sensitized CD58-deficient DLBCL to CAR T-cell therapy. Collectively, this work identified the multiple roles of CD58 in regulating antitumor immune responses in DLBCL.

This paper investigates the causal impact of direct cash transfers on health, well-being, and life satisfaction during the COVID-19 pandemic in Russia. Motivated by the mixed findings in the existing literature, we propose a novel hypothesis: that the effectiveness of COVID-19 cash transfers is conditional on the severity of the pandemic. Our quasi-experimental design takes advantage of a unique empirical setting at the onset of the COVID-19 pandemic in Russia, particularly of three features: 1) the introduction of unconditional COVID-19 cash transfers for children of a specific age, allowing a sharp age-discontinuity design by comparing marginally eligible and marginally ineligible adolescents; 2) the availability of an annual longitudinal survey that enables a difference-in-difference approach (by controlling for the pre-pandemic level of outcome variables); 3) the onset of the COVID-19 wave coinciding with the timing of the survey as a quasi-natural experiment randomizing the experience with the pandemic among the respondents within the same location. The main finding is a significant positive effect of cash transfers on the financial situation, life satisfaction, and self-assessed health of the transfer-eligible adolescents. Yet, these effects are conditional to the severity of pandemic outbreaks experienced by the respondents. Placebo tests confirm the validity of our results. Regarding the adult household members, we find minor positive but statistically insignificant spillover effects.

Traditional nerve conduits normally perform unsatisfactory therapeutic effects for peripheral nerve injury (PNI) because of lacking biomimetic structural design and functional modification. Recent researches demonstrated that balanced immune response and electrical stimulation were the two essential factors that could alter the microenvironment to boost neuronal regeneration. Here, a novel and potential kind of conductive nerve conduit with biomimetic structure was designed in which Ti3C2Tx /PPy was coated on the Oleanic acid (OA) loaded Poly-lactic acid (PLA) conduit with an oriented inner layer through electrostatic spraying. Physical evaluation indicated that the neural conduit had moderate hydrophilicity, enhanced tensile strength (2.01 ± 0.24Mpa) and elasticity (96.4 ± 1.1%), as well as excellent conductivity (1.28 × 10-2S/cm). In vitro evaluation showed that the weight loss rate of the conduit within 8 weeks reached 58 ± 1.35% and exhibited no obvious toxicity which was suitable for the adhesion, proliferation and migration of nerve cells in vitro. Importantly, when coupled with electrical stimulation, it might not only dramatically increase PC12 differentiation and proliferation but also quicken nerve cell regeneration. Meanwhile, the OA released by the conduit could help to repolarize pro-inflammatory macrophages into healing promoting macrophages to accelerate peripheral nerve regeneration.