Physiological and Cellular Functions of Vitamin K on Cardiovascular Function

This chapter reviews the physiological and cellular functions of vitamin K in the cardiovascular system based on the latest pre-clinical and clinical evidence. Vitamin K belongs to a family of structurally similar fat-soluble vitamins, actively required by the body for the synthesis of essential proteins as well as regulate blood clotting, bone metabolism and calcium level. The authors emphasize the quintessential association between dietary vitamin K2 and cardiovascular diseases shown in various studies. The association, through the vitamin K - dependent hormones, plays a primary role in regulating calcification of different cell types, especially their role in calcification of the vascular endothelial cells. The consequences of vitamin K deficiency in the vascular system are unfavorable, shown in various clinical studies on statins - well-known inhibitors of vitamin K production in the body. New clinical insights suggest that vitamin K levels in the body and its dietary supplementation play a crucial role in cardiovascular disease prevention. There is negative influence of these antagonist’s pate in vascular composition and functions. Therefore, there is a need for prospective studies to make more in-depth exploration and increase the current understanding of this critical relationship to confidently apply such knowledge to prevent cardiovascular diseases and improve their outcomes

Gender and cytoarchitecture differences: Functional connectivity of the hippocampal sub-regions

Introduction: The hippocampus plays a significant role in learning, memory encoding, and spatial navigation. Typically, the hippocampus is investigated as a whole region of interest. However, recent work has developed fully detailed atlases based on cytoarchitecture properties of brain regions, and the hippocampus has been sub-divided into seven sub-areas that have structural differences in terms of distinct numbers of cells, neurons, and other structural and chemical properties. Moreover, gender differences are of increasing concern in neuroscience research. Several neuroscience studies have found structural and functional variations between the brain regions of females and males, and the hippocampus is one of these regions. Aim: The aim of this study to explore whether the cytoarchitecturally distinct sub-regions of the hippocampus have varying patterns of functional connectivity with different networks of the brain and how these functional connections differ in terms of gender differences. Method: This study investigated 200 healthy participants using seed-based resting-state functional magnetic resonance imaging (rsfMRI). The primary aim of this study was to explore the resting connectivity and gender distinctions associated with specific sub-regions of the hippocampus and their relationship with major functional brain networks. Results: The findings revealed that the majority of the seven hippocampal sub-regions displayed functional connections with key brain networks, and distinct patterns of functional connectivity were observed between the hippocampal sub-regions and various functional networks within the brain. Notably, the default and visual networks exhibited the most consistent functional connections. Additionally, gender-based analysis highlighted evident functional resemblances and disparities, particularly concerning the anterior section of the hippocampus. Conclusion: This study highlighted the functional connectivity patterns and involvement of the hippocampal sub-regions in major brain functional networks, indicating that the hippocampus should be investigated as a region of multiple distinct functions and should always be examined as sub-regions of interest. The results also revealed clear gender differences in functional connectivity

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

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population