The impact of weight loss after laparoscopic sleeve gastrectomy on early markers of atherosclerotic vascular disease: a prospective study

Background: Considering the emerging role of aortic propagation velocity (APV) in determining the burden of the coronary artery disease, we hypothesized that laparoscopic sleeve gastrectomy (LSG) could improve APV in morbidly obese patients. Aims: The aim of this study was to investigate the impact of LSG on surrogate markers of atherosclerotic vascular disease such as APV, carotid intima‑media thickness (CIMT), epicardial fat thickness (EFT), and ankle‑brachial index (ABI) in patients with morbid obesity. Methods: We prospectively enrolled 71 patients who were scheduled for LSG for standard indications between December 2018 and June 2019 with accordance to the international guidelines. All patients underwent transthoracic echocardiography and carotid ultrasonography. Differences in the variables measured (Δ) were calculated by subtracting 6‑month follow-up results from the baseline results. Results: Laparoscopic sleeve gastrectomy led to a significant reduction in body weight, and at 6‑month follow‑up, there was a reduction in systolic and diastolic blood pressure as well as in levels of triglycerides and low‑density lipoprotein cholesterol. Moreover, a reduction in EFT and CIMT as well as an increase in ABI and APV were noted at 6‑month follow‑up compared with the baseline measurements. The change in APV at 6-month follow-up was correlated with systolic blood pressure, diastolic blood pressure, EFT, ABI, and CIMT. Conclusions: LSG leads to a significant improvement in BMI as well as CIMT, EFT, ABI, and APV, which are the surrogate markers of atherosclerotic vascular disease, in morbidly obese patients at 6‑month follow‑up after the procedure. The improvement in APV is correlated with the improvement in BMI, CIMT, EFT, and ABI

Bi-allelic variants in HOPS complex subunit VPS41 cause cerebellar ataxia and abnormal membrane trafficking

Membrane trafficking is a complex, essential process in eukaryotic cells responsible for protein transport and processing. Deficiencies in vacuolar protein sorting (VPS) proteins, key regulators of trafficking, cause abnormal intracellular segregation of macromolecules and organelles and are linked to human disease. VPS proteins function as part of complexes such as the homotypic fusion and vacuole protein sorting (HOPS) tethering complex, composed of VPS11, VPS16, VPS18, VPS33A, VPS39 and VPS41. The HOPS-specific subunit VPS41 has been reported to promote viability of dopaminergic neurons in Parkinson's disease but to date has not been linked to human disease. Here, we describe five unrelated families with nine affected individuals, all carrying homozygous variants in VPS41 that we show impact protein function. All affected individuals presented with a progressive neurodevelopmental disorder consisting of cognitive impairment, cerebellar atrophy/hypoplasia, motor dysfunction with ataxia and dystonia, and nystagmus. Zebrafish disease modelling supports the involvement of VPS41 dysfunction in the disorder, indicating lysosomal dysregulation throughout the brain and providing support for cerebellar and microglial abnormalities when vps41 was mutated. This provides the first example of human disease linked to the HOPS-specific subunit VPS41 and suggests the importance of HOPS complex activity for cerebellar function