Interactions of mitochondrial and skeletal muscle biology in mitochondrial myopathy

\ua9 2023 The Author(s). Mitochondrial dysfunction in skeletal muscle fibres occurs with both healthy aging and a range of neuromuscular diseases. The impact of mitochondrial dysfunction in skeletal muscle and the way muscle fibres adapt to this dysfunction is important to understand disease mechanisms and to develop therapeutic interventions. Furthermore, interactions between mitochondrial dysfunction and skeletal muscle biology, in mitochondrial myopathy, likely have important implications for normal muscle function and physiology. In this review, we will try to give an overview of what is known to date about these interactions including metabolic remodelling, mitochondrial morphology, mitochondrial turnover, cellular processes and muscle cell structure and function. Each of these topics is at a different stage of understanding, with some being well researched and understood, and others in their infancy. Furthermore, some of what we know comes from disease models. Whilst some findings are confirmed in humans, where this is not yet the case, we must be cautious in interpreting findings in the context of human muscle and disease. Here, our goal is to discuss what is known, highlight what is unknown and give a perspective on the future direction of research in this area

Gender equality related to gender differences in life expectancy across the globe gender equality and life expectancy

Life expectancy (LE) depends on the wider determinants of health, many of which have gendered effects worldwide. Therefore, this study aimed to investigate whether gender equality was associated with LE for women and men and the gender gap in LE across the globe. Gender equality in 156 countries was estimated using a modified global gender gap index (mGGGI), based on the index developed by the World Economic Forum between 2010 and 2021. Linear regression was used to investigate the association between the mGGGI and its economic, political, and education subindices and the gender gap in LE and women and men's LE. Overall, the mGGGI increased from 58% in 2010 to 62% in 2021. Globally, changes in the mGGGI and its economic and political subindexes were not associated with changes in the gender gap in LE or with LE for women and men between 2010 and 2020. Improvements in gender equality in education were associated with a longer LE for women and men and widening of the gender gap in LE. In 2021, each 10% increase in the mGGGI was associated with a 4.3-month increase in women's LE and a 3.5-month increase in men's LE, and thus with an 8-month wider gender gap. However, the direction and magnitude of these associations varied between regions. Each 10% increase in the mGGGI was associated with a 6-month narrower gender gap in high-income countries, and a 13- and 16-month wider gender gap in South and Southeast Asia and Oceania, and in Sub-Saharan Africa, respectively. Globally, greater gender equality is associated with longer LE for both women and men and a widening of the gender gap in LE. The variation in this association across world regions suggests that gender equality may change as countries progress towards socioeconomic development and gender equality

How many people will need palliative care in 2040? Past trends, future projections and implications for services.

BACKGROUND: Current estimates suggest that approximately 75% of people approaching the end-of-life may benefit from palliative care. The growing numbers of older people and increasing prevalence of chronic illness in many countries mean that more people may benefit from palliative care in the future, but this has not been quantified. The present study aims to estimate future population palliative care need in two high-income countries. METHODS: We used mortality statistics for England and Wales from 2006 to 2014. Building on previous diagnosis-based approaches, we calculated age- and sex-specific proportions of deaths from defined chronic progressive illnesses to estimate the prevalence of palliative care need in the population. We calculated annual change over the 9-year period. Using explicit assumptions about change in disease prevalence over time, and official mortality forecasts, we modelled palliative care need up to 2040. We also undertook separate projections for dementia, cancer and organ failure. RESULTS: By 2040, annual deaths in England and Wales are projected to rise by 25.4% (from 501,424 in 2014 to 628,659). If age- and sex-specific proportions with palliative care needs remain the same as in 2014, the number of people requiring palliative care will grow by 25.0% (from 375,398 to 469,305 people/year). However, if the upward trend observed from 2006 to 2014 continues, the increase will be of 42.4% (161,842 more people/year, total 537,240). In addition, disease-specific projections show that dementia (increase from 59,199 to 219,409 deaths/year by 2040) and cancer (increase from 143,638 to 208,636 deaths by 2040) will be the main drivers of increased need. CONCLUSIONS: If recent mortality trends continue, 160,000 more people in England and Wales will need palliative care by 2040. Healthcare systems must now start to adapt to the age-related growth in deaths from chronic illness, by focusing on integration and boosting of palliative care across health and social care disciplines. Countries with similar demographic and disease changes will likely experience comparable rises in need

A missing dimension in measures of vaccination impacts

Immunological protection, acquired from either natural infection or vaccination, varies among hosts, reflecting underlying biological variation and affecting population-level protection. Owing to the nature of resistance mechanisms, distributions of susceptibility and protection entangle with pathogen dose in a way that can be decoupled by adequately representing the dose dimension. Any infectious processes must depend in some fashion on dose, and empirical evidence exists for an effect of exposure dose on the probability of transmission to mumps-vaccinated hosts [1], the case-fatality ratio of measles [2], and the probability of infection and, given infection, of symptoms in cholera [3]. Extreme distributions of vaccine protection have been termed leaky (partially protects all hosts) and all-or-nothing (totally protects a proportion of hosts) [4]. These distributions can be distinguished in vaccine field trials from the time dependence of infections [5]. Frailty mixing models have also been proposed to estimate the distribution of protection from time to event data [6], [7], although the results are not comparable across regions unless there is explicit control for baseline transmission [8]. Distributions of host susceptibility and acquired protection can be estimated from dose-response data generated under controlled experimental conditions [9]–[11] and natural settings [12], [13]. These distributions can guide research on mechanisms of protection, as well as enable model validity across the entire range of transmission intensities. We argue for a shift to a dose-dimension paradigm in infectious disease science and community health

Determination of phytoextraction potential of plant species for toxic elements in soils of abandoned sulphide-mining areas

Abstract This study has determined contamination levels in soils and plants from the São Domingos mining area, Portugal, by k 0 -INAA. Total concentrations of As, Sb, Cr, Hg, Cu, Zn and Fe in soils were very high, exceeding the maximum limits in Portuguese legislation. Concentrations of toxic elements like As, Sb and Zn were highest in roots of Erica andevalensis, Juncus acutus, Agrostis castellana and Nicotiana glauca. Additionally, As, Br, Cr, Fe, Sb and Zn in all organs of most plants were above toxicity levels. Those species that accumulated relatively high concentrations of toxic elements in roots (and tops) may be cultivated for phytostabilisation of similar areas

Developmental Neurotoxicity of Pyrethroid Insecticides: Critical Review and Future Research Needs

Pyrethroid insecticides have been used for more than 40 years and account for 25% of the worldwide insecticide market. Although their acute neurotoxicity to adults has been well characterized, information regarding the potential developmental neurotoxicity of this class of compounds is limited. There is a large age dependence to the acute toxicity of pyrethroids in which neonatal rats are at least an order of magnitude more sensitive than adults to two pyrethroids. There is no information on age-dependent toxicity for most pyrethroids. In the present review we examine the scientific data related to potential for age-dependent and developmental neurotoxicity of pyrethroids. As a basis for understanding this neurotoxicity, we discuss the heterogeneity and ontogeny of voltage-sensitive sodium channels, a primary neuronal target of pyrethroids. We also summarize 22 studies of the developmental neurotoxicity of pyrethroids and review the strengths and limitations of these studies. These studies examined numerous end points, with changes in motor activity and muscarinic acetylcholine receptor density the most common. Many of the developmental neurotoxicity studies suffer from inadequate study design, problematic statistical analyses, use of formulated products, and/or inadequate controls. These factors confound interpretation of results. To better understand the potential for developmental exposure to pyrethroids to cause neurotoxicity, additional, well-designed and well-executed developmental neurotoxicity studies are needed. These studies should employ state-of-the-science methods to promote a greater understanding of the mode of action of pyrethroids in the developing nervous system

Performance Improvement for OFDM-RoF Transported 60 GHz System using Spatial Diversity and Multiplexing

60 GHz system architectures with Radio over Fiber (RoF) transport and integrated transmitters/receivers provide a comprehensive solution for future mobile systems. Since 60 GHz communication relies on line-of-sight (LoS) conditions and narrow-beam antennas to compensate the high path-loss, it has limitations in terms of coverage for multiple user locations. In this paper, performance analysis of a 60 GHz integrated transmitter and receiver system supported by RoF transport has been performed experimentally at different user locations for up to 1.5m transmission distance. Extension of experimental results to prove feasibility for longer distances has been shown with a simulation model, whose results at various shorter distances have been benchmarked against the acquired experimental results at different user locations. A modified version of the Saleh Valenzuela channel has been used to model the millimeter wave (mmW) LoS indoor experimental environment. Furthermore, as a proof of concept, we present an experimental analysis demonstrating an improvement in performance of the proposed RoF based 60 GHz system using spatial diversity and multiplexing. Channel measurements at different transmitter/receiver locations and their processing have shown that an improvement (decrease from 12.5% to 10.5%) in Error Vector Magnitude (EVM) can be achieved using the Alamouti Space Time Block Coding algorithm. Then it has been shown that a two-fold data rate increase can be obtained by combining data from two transmitter locations using the Zero Forcing algorithm