Targeted degradation of extracellular mitochondrial aspartyl-tRNA synthetase modulates immune responses.

The severity of bacterial pneumonia can be worsened by impaired innate immunity resulting in ineffective pathogen clearance. We describe a mitochondrial protein, aspartyl-tRNA synthetase (DARS2), which is released in circulation during bacterial pneumonia in humans and displays intrinsic innate immune properties and cellular repair properties. DARS2 interacts with a bacterial-induced ubiquitin E3 ligase subunit, FBXO24, which targets the synthetase for ubiquitylation and degradation, a process that is inhibited by DARS2 acetylation. During experimental pneumonia, Fbxo24 knockout mice exhibit elevated DARS2 levels with an increase in pulmonary cellular and cytokine levels. In silico modeling identified an FBXO24 inhibitory compound with immunostimulatory properties which extended DARS2 lifespan in cells. Here, we show a unique biological role for an extracellular, mitochondrially derived enzyme and its molecular control by the ubiquitin apparatus, which may serve as a mechanistic platform to enhance protective host immunity through small molecule discovery.

Cognitive behavioral therapy for the treatment of insomnia in patients with cardiovascular diseases: a meta-analysis with GRADE analysis.

Insomnia, as a difficulty in initiating and maintaining sleep, coupled with cardiovascular diseases (CVDs) increase the risk of aggravate daytime symptoms, mortality, and morbidity. Cognitive behavioral therapy (CBT) is thought to have a significant impact on insomnia treatment, but in patients with CVDs, there is a paucity of data. To provide a comprehensive appraisal on the impact of CBT on the treatment of insomnia in patients with CVDs. We searched Ovid, Scopus, Web of science, and Cochrane central, to randomized controlled trials (RCTs) from inception till November 2022. Outcomes of interest were insomnia severity index (ISI), Pittsburgh Sleep Quality Index (PSQI), sleep efficiency (SE), Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS), and sleep disorders questionnaire (SDQ). Pooled data were analyzed using mean difference (MD) with its 95% confidence interval (CI) in a random effect model using STATA 17 for Mac. Nine RCTs comprising 365 patients were included in the analysis. CBT significantly reduced scores of ISI (MD = - 3.22, 95%  CI - 4.46 to - 1.98, p < 0.001), PSQI (MD = - 2.33, 95%  CI - 3.23 to - 1.44, p < 0.001), DBAS (MD = - 0.94, 95%  CI - 1.3 to - 0.58, p < 0.001), SDQ (MD = - 0.38, 95%  CI - 0.56 to - 0.2, p < 0.001). Also, it increased the score of SE (MD = 6.65, 95% CI 2.54 to 10.77, p < 0.001). However, there was no difference in terms of ESS. CBT is an easy and feasible intervention with clinically significant improvement in insomnia symptoms. Further large-volume studies are needed to assess sustained efficacy.

Median nerve ultrasonography in Parkinson's disease: a systematic review and meta-analysis.

BACKGROUND: The cross-sectional area (CSA) of the median nerve in Parkinson's disease remains unclear. OBJECTIVES: This meta-analysis assesses median nerve CSA changes in Parkinson's using ultrasonography. METHODS: PubMed, Web of Science, Scopus, and EBSCO were selectively searched for literature on Parkinson's disease, Median nerve, and ultrasonography. Following full-text screening, three studies were included in this meta-analysis with 144 Parkinson's disease patients and 127 controls. The primary outcome was the cross-sectional area of the median nerve; other motor parameters were also evaluated. RESULTS: The cross-sectional area of the median nerve was significantly increased in Parkinson's patients compared to controls (p = 0.007); the standardized mean difference was 0.79 [95% CI (0.21 - 1.37)]. The standardized mean difference of the motor parameters of the median nerve, amplitude, and latency was -0.04 [95% CI (-0.85 to 0.77)] and 0.30 [95% CI (-0.04 to 0.64)], respectively, with statistically insignificant (All p > 0.05). CONCLUSION: This meta-analysis concluded that the cross-sectional area of the median nerve is increased in Parkinson's disease patients. The increase in the CSA of the median nerve might explain the higher prevalence of carpal tunnel syndrome in Parkinson's disease. Further studies are needed to quantify carpal tunnel syndrome prevalence accurately in Parkinson's. LIMITATIONS: Heterogeneity exists due to non-standardized CSA calculation methods and varied disease stages. Finger movement during ultrasound may introduce artifacts, compromising CSA measurement accuracy. Establishing a definitive CSA cut-off for carpal tunnel syndrome in Parkinson's requires further investigation.

Posterior pericardiotomy for the prevention of atrial fibrillation after cardiac surgery: a systematic review and meta-analysis of 25 randomised controlled trials.

BACKGROUND: Atrial fibrillation (AF) associated with postoperative pericardial effusion is the most commonly reported adverse event after cardiac surgery. AIMS: We aimed to determine the role of posterior pericardiotomy in preventing postoperative AF (POAF). METHODS: We searched PubMed, Scopus, Web of Science, Ovid, and EBSCO from inception until 30 June 2022. We included randomised clinical trials (RCTs) that compared posterior pericardiotomy (PP) versus control (no PP) in patients undergoing cardiac surgery. The primary endpoint was the incidence of POAF after cardiac surgery. The secondary endpoints were supraventricular arrhythmias, early/late pericardial effusion, pericardial tamponade, pleural effusion, length of hospital/intensive care unit stay, intra-aortic balloon pump use, revision surgery for bleeding, and mortality. RESULTS: Twenty-five RCTs comprising 4,467 patients were included in this systematic review and meta-analysis. The overall incidence rate of POAF was 11.7% in the PP group compared with 23.67% in the no PP or control group, with a significant decrease in the risk of POAF following PP (odds ratio [OR] 0.49, 95% confidence interval [CI]: 0.38-0.61). Compared with the control group, the risk of supraventricular tachycardia (OR 0.66, 95% CI: 0.43-0.89), early pericardial effusion (OR 0.32, 95% CI: 0.22-0.46), late pericardial effusion (OR 0.15, 95% CI: 0.09-0.25), and pericardiac tamponade (OR 0.18, 95% CI: 0.10-0.33) were lower in the PP group. CONCLUSIONS: PP is an effective intervention for reducing the risk of POAF after cardiac surgery. Also, PP is economically efficient in terms of decreasing the length of hospital stay.