Dietary intake relative to cardiovascular disease risk factors in individuals with chronic spinal cord injury: a pilot study

BACKGROUND: The relationship between cardiovascular disease (CVD) risk factors and dietary intake is unknown among individuals with spinal cord injury (SCI). OBJECTIVE: To investigate the relationship between consumption of selected food groups (dairy, whole grains, fruits, vegetables, and meat) and CVD risk factors in individuals with chronic SCI. METHODS: A cross-sectional substudy of individuals with SCI to assess CVD risk factors and dietary intake in comparison with age-, gender-, and race-matched able-bodied individuals enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Dietary history, blood pressure, waist circumference (WC), fasting blood glucose, high-sensitivity C-reactive protein (hs-CRP), lipids, glucose, and insulin data were collected from 100 SCI participants who were 38 to 55 years old with SCI >1 year and compared to 100 matched control participants from the CARDIA study. RESULTS: Statistically significant differences between SCI and CARDIA participants were identified in WC (39.2 vs 36.2 in.; P < .001) and high-density lipoprotein cholesterol (HDL-C; 39.2 vs 47.5 mg/dL; P < .001). Blood pressure, total cholesterol, triglycerides, glucose, insulin, and hs-CRP were similar between SCI and CARDIA participants. No significant relation between CVD risk factors and selected food groups was seen in the SCI participants. CONCLUSION: SCI participants had adverse WC and HDL-C compared to controls. This study did not identify a relationship between consumption of selected food groups and CVD risk factors

Global, regional, and national burden of other musculoskeletal disorders, 1990–2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021

Background Musculoskeletal disorders include more than 150 different conditions affecting joints, muscles, bones, ligaments, tendons, and the spine. To capture all health loss from death and disability due to musculoskeletal disorders, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) includes a residual musculoskeletal category for conditions other than osteoarthritis, rheumatoid arthritis, gout, low back pain, and neck pain. This category is called other musculoskeletal disorders and includes, for example, systemic lupus erythematosus and spondylopathies. We provide updated estimates of the prevalence, mortality, and disability attributable to other musculoskeletal disorders and forecasted prevalence to 2050. Methods Prevalence of other musculoskeletal disorders was estimated in 204 countries and territories from 1990 to 2020 using data from 68 sources across 23 countries from which subtraction of cases of rheumatoid arthritis, osteoarthritis, low back pain, neck pain, and gout from the total number of cases of musculoskeletal disorders was possible. Data were analysed with Bayesian meta-regression models to estimate prevalence by year, age, sex, and location. Years lived with disability (YLDs) were estimated from prevalence and disability weights. Mortality attributed to other musculoskeletal disorders was estimated using vital registration data. Prevalence was forecast to 2050 by regressing prevalence estimates from 1990 to 2020 with Socio-demographic Index as a predictor, then multiplying by population forecasts. Findings Globally, 494 million (95% uncertainty interval 431–564) people had other musculoskeletal disorders in 2020, an increase of 123·4% (116·9–129·3) in total cases from 221 million (192–253) in 1990. Cases of other musculoskeletal disorders are projected to increase by 115% (107–124) from 2020 to 2050, to an estimated 1060 million (95% UI 964–1170) prevalent cases in 2050; most regions were projected to have at least a 50% increase in cases between 2020 and 2050. The global age-standardised prevalence of other musculoskeletal disorders was 47·4% (44·9–49·4) higher in females than in males and increased with age to a peak at 65–69 years in male and female sexes. In 2020, other musculoskeletal disorders was the sixth ranked cause of YLDs globally (42·7 million [29·4–60·0]) and was associated with 83 100 deaths (73 600–91 600). Interpretation Other musculoskeletal disorders were responsible for a large number of global YLDs in 2020. Until individual conditions and risk factors are more explicitly quantified, policy responses to this burden remain a challenge. Temporal trends and geographical differences in estimates of non-fatal disease burden should not be overinterpreted as they are based on sparse, low-quality data.publishedVersio

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

INTRODUCTION: Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system (CNS) that often presents in young adults. Over the past decade, certain elements of the genetic architecture of susceptibility have gradually emerged, but most of the genetic risk for MS remained unknown. RATIONALE: Earlier versions of the MS genetic map had highlighted the role of the adaptive arm of the immune system, implicating multiple different T cell subsets. We expanded our knowledge of MS susceptibility by performing a genetic association study in MS that leveraged genotype data from 47,429 MS cases and 68,374 control subjects. We enhanced this analysis with an in-depth and comprehensive evaluation of the functional impact of the susceptibility variants that we uncovered. RESULTS: We identified 233 statistically independent associations with MS susceptibility that are genome-wide significant. The major histocompatibility complex (MHC) contains 32 of these associations, and one, the first MS locus on a sex chromosome, is found in chromosome X. The remaining 200 associations are found in the autosomal non-MHC genome. Our genome-wide partitioning approach and large-scale replication effort allowed the evaluation of other variants that did not meet our strict threshold of significance, such as 416 variants that had evidence of statistical replication but did not reach the level of genome-wide statistical significance. Many of these loci are likely to be true susceptibility loci. The genome-wide and suggestive effects jointly explain ~48% of the estimated heritability for MS. Using atlases of gene expression patterns and epigenomic features, we documented that enrichment for MS susceptibility loci was apparent in many different immune cell types and tissues, whereas there was an absence of enrichment in tissue-level brain profiles. We extended the annotation analyses by analyzing new data generated from human induced pluripotent stem cell–derived neurons as well as from purified primary human astrocytes and microglia, observing that enrichment for MS genes is seen in human microglia, the resident immune cells of the brain, but not in astrocytes or neurons. Further, we have characterized the functional consequences of many MS susceptibility variants by identifying those that influence the expression of nearby genes in immune cells or brain. Last, we applied an ensemble of methods to prioritize 551 putative MS susceptibility genes that may be the target of the MS variants that meet a threshold of genome-wide significance. This extensive list of MS susceptibility genes expands our knowledge more than twofold and highlights processes relating to the development, maturation, and terminal differentiation of B, T, natural killer, and myeloid cells that may contribute to the onset of MS. These analyses focus our attention on a number of different cells in which the function of MS variants should be further investigated. Using reference protein-protein interaction maps, these MS genes can also be assembled into 13 communities of genes encoding proteins that interact with one another; this higher-order architecture begins to assemble groups of susceptibility variants whose functional consequences may converge on certain protein complexes that can be prioritized for further evaluation as targets for MS prevention strategies. CONCLUSION: We report a detailed genetic and genomic map of MS susceptibility, one that explains almost half of this disease’s heritability. We highlight the importance of several cells of the peripheral and brain resident immune systems—implicating both the adaptive and innate arms—in the translation of MS genetic risk into an auto-immune inflammatory process that targets the CNS and triggers a neurodegenerative cascade. In particular, the myeloid component highlights a possible role for microglia that requires further investigation, and the B cell component connects to the narrative of effective B cell–directed therapies in MS. These insights set the stage for a new generation of functional studies to uncover the sequence of molecular events that lead to disease onset. This perspective on the trajectory of disease onset will lay the foundation for developing primary prevention strategies that mitigate the risk of developing MS

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

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