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.

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.

BACKGROUND AND STUDY AIMS: Upper gastrointestinal tract (UGT) leaks are associated with severe morbidity and mortality. Endoluminal vacuum (EVAC) therapy is a promising approach for repairing effectively these defects. Our study describes the results obtained from a series of cases treated with EVAC for the management of esophageal anastomotic (EA) leak following esophagectomy for cancer, gastroenteric (GE) anastomoses leak after bariatric surgery and esophageal perforation (EP). PATIENTS AND METHODS: We retrospectively analyzed ten patients who had an EA and GE anastomoses leaks and EP treated with EVAC. We described the results of the sample in terms of treatment failure, treatment duration, and number of EVAC replacements. RESULTS: Five patients underwent esophagectomy with neoadjuvant radio-chemotherapy, one patient underwent gastrojejunal bypass bariatric surgery and there were four EP. The median size of mucosal defects was 6,9 mm. The median duration of treatment was thirteen days with 3,6 interventions performed, every three to four days. Treatment success rate was 70%. Treatment failure was 30%: two patients required surgery and in one case an endoluminal prosthesis. CONCLUSIONS: EVAC therapy is an appropriate treatment for the management of postoperative fistulas in the UGT. Longer treatments are associated with neoadjuvant chemoradiotherapy and larger fistulas.

BACKGROUND: Epigenetic age estimators (clocks) are predictive of human mortality risk. However, it is not yet known whether the epigenetic age of atherosclerotic plaques is predictive for the risk of cardiovascular events. METHODS: Whole-genome DNA methylation of human carotid atherosclerotic plaques (n=485) and of blood (n=93) from the Athero-Express endarterectomy cohort was used to calculate epigenetic age acceleration (EAA). EAA was linked to clinical characteristics, plaque histology, and future cardiovascular events (n=136). We studied whole-genome DNA methylation and bulk and single-cell transcriptomics to uncover molecular mechanisms of plaque EAA. We experimentally confirmed our in silico findings using in vitro experiments in primary human coronary endothelial cells. RESULTS: Male and female patients with severe atherosclerosis had a median chronological age of 69 years. The median epigenetic age was 65 years in females (median EAA, -2.2 [interquartile range, -4.3 to 2.2] years) and 68 years in males (median EAA, -0.3 [interquartile range, -2.9 to 3.8] years). Patients with diabetes and a high body mass index had higher plaque EAA. Increased EAA of plaque predicted future events in a 3-year follow-up in a Cox regression model (univariate hazard ratio, 1.7; P=0.0034) and adjusted multivariate model (hazard ratio, 1.56; P=0.02). Plaque EAA predicted outcome independent of blood EAA (hazard ratio, 1.3; P=0.018) and of plaque hemorrhage (hazard ratio, 1.7; P=0.02). Single-cell RNA sequencing in plaque samples from 46 patients in the same cohort revealed smooth muscle and endothelial cells as important cell types in plaque EAA. Endothelial-to-mesenchymal transition was associated with EAA, which was experimentally confirmed by TGFβ-triggered endothelial-to-mesenchymal transition inducing rapid epigenetic aging in coronary endothelial cells. CONCLUSIONS: Plaque EAA is a strong and independent marker of poor outcome in patients with severe atherosclerosis. Plaque EAA was linked to mesenchymal endothelial and smooth muscle cells. Endothelial-to-mesenchymal transition was associated with EAA, which was experimentally validated. Epigenetic aging mechanisms may provide new targets for treatments that reduce atherosclerosis complications.

Vitamin D, a fat-soluble steroid, has increasingly taken a central role due to its crucial role in human health. It is estimated that about 40% of worldwide population are vitamin D deficient. The fish industry produces significant quantities of waste daily, with consequent high environmental impact. The aim of this work is to place a first brick for the fish waste reuse as a source of vitamin D3 extracts to be used for nutraceutical purposes. For this purpose, an UV conversion method for transforming the 7-dehydrocholesterol, highly present in fish, in vitamin D3 has been optimized. The UV wavelength, exposure time, temperature, stirring, and UV intensity were optimized using a surface response design tool. The optimized treatment was applied to five fish species with different fat percentages and the results were very promising reaching vitamin D3 levels >10 times higher than the pre-treatment ones.