Conservation and divergence in modules of the transcriptional programs of the human and mouse immune systems [preprint]

Studies in mouse have shed important light on human hematopoietic differentiation and disease. However, substantial differences between the two species often limit the translation of findings from mouse to human. Here, we compare modules of co-expressed genes in human and mouse immune cells based on compendia of genome-wide profiles. We show that the overall modular organization of the transcriptional program is conserved. We highlight modules of co-expressed genes in one species that dissolve or split in the other species. Many of the associated regulatory mechanisms - as reflected by computationally inferred trans regulators, or enriched cis-regulatory elements - are conserved between the species. Nevertheless, the degree of conservation in regulatory mechanism is lower than that of expression, suggesting that distinct regulation may underlie some of the conserved transcriptional responses

The Death Debates: A Call for Public Deliberation

In this issue of the Report, James L. Bernat proposes an innovative and sophisticated distinction to justify the introduction of permanent cessation as a valid substitute standard for irreversible cessation in death determination. He differentiates two approaches to conceptualizing and determining death: the biological concept and the prevailing medical practice standard. While irreversibility is required by the biological concept, the weaker criterion of permanence, he claims, has always sufficed in the accepted standard medical practice to declare death. Bernat argues that the medical practice standard may be acceptable on the ground that proving circulatory or brain permanence is sufficient to assure complete accuracy for death diagnosis. The topic requires public deliberation: processes to survey people's opinions and mechanisms to channel their opinions into policy-making. What is at stake is the nature of our society. Do we want an expertocracy, in which an enlightened few design policies for the greater good of the majority and exploit the lack of public knowledge to achieve compliance

Facilitated Peer Mentorship to Support Aging Research: A RE‐AIM Evaluation of the CoMPAdRE Program

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149354/1/jgs15792.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149354/2/jgs15792_am.pd

Predictive processing in depression : Increased prediction error following negative valence contexts and influence of recent mood-congruent yet irrelevant experiences

Acord transformatiu CRUE-CSICBackground: Novel theoretical models of depression have recently emerged based on an influential new perspective in neuroscience known as predictive processing. In these models, depression may be understood as an imbalance of predictive signals in the brain; more specifically, a dominance of predictions leading to a relative insensitivity to prediction error. Despite these important theoretical advances, empirical evidence remains limited, and how expectations are generated and used dynamically in individuals with depression remains largely unexplored. Methods: In this study, we induced facial expression predictions using emotion contexts in 34 individuals with depression and 34 healthy controls. Results: Compared to controls, individuals with depression perceived displayed facial expressions as less similar to their expectations (i.e., increased difference between expectations and actual sensory input) following contexts evoking negative valence emotions, indicating that depressed individuals have increased prediction error in such contexts. This effect was amplified by recent mood-congruent yet irrelevant experiences. Limitations: The clinical sample included participants with comorbid psychopathology and taking medication. Additionally, the two groups were not evaluated in the same setting, and only three emotion categories (fear, sadness, and happiness) were explored. Conclusions: Our results shed light on potential mechanisms underlying processing abnormalities regarding negative information, which has been consistently reported in depression, and may be a relevant point of departure for exploring transdiagnostic vulnerability to mental illness. Our data also has the potential to improve clinical practice through the implementation of novel diagnostic and therapeutic tools based on the assessment and modulation of predictive signals

Use of the Global Alliance for Musculoskeletal Health survey module for estimating the population prevalence of musculoskeletal pain: Findings from the Solomon Islands

Background: Musculoskeletal (MSK) conditions are common and the biggest global cause of physical disability. The objective of the current study was to estimate the population prevalence of MSK-related pain using a standardized global MSK survey module for the first time. Methods: A MSK survey module was constructed by the Global Alliance for Musculoskeletal Health Surveillance Taskforce and the Global Burden of Disease MSK Expert Group. The MSK module was included in the 2015 Solomon Islands Demographic and Health Survey. The sampling design was a two-stage stratified, nationally representative sample of households. Results: A total of 9214 participants aged 15-49 years were included in the analysis. The age-standardized four-week prevalence of activity-limiting low back pain, neck pain, and hip and/or knee pain was 16.8, 8.9, and 10.8%, respectively. Prevalence tended to increase with age, and be higher in those with lower levels of education. Conclusions: Prevalence of activity-limited pain was high in all measured MSK sites. This indicates an important public health issue for the Solomon Islands that needs to be addressed. Efforts should be underpinned by integration with strategies for other non-communicable diseases, aging, disability, and rehabilitation, and with other sectors such as social services, education, industry, and agriculture. Primary prevention strategies and strategies aimed at self-management are likely to have the greatest and most cost-effective impact

Prescribing indicators at primary health care centers within the WHO African region: a systematic analysis (1995-2015)

Abstract Background Rational medicine use is essential to optimize quality of healthcare delivery and resource utilization. We aim to conduct a systematic review of changes in prescribing patterns in the WHO African region and comparison with WHO indicators in two time periods 1995–2005 and 2006–2015. Methods Systematic searches were conducted in PubMed, Scopus, Web of science, Africa-Wide Nipad, Africa Journals Online (AJOL), Google scholar and International Network for Rational Use of Drugs (INRUD) Bibliography databases to identify primary studies reporting prescribing indicators at primary healthcare centres (PHCs) in Africa. This was supplemented by a manual search of retrieved references. We assessed the quality of studies using a 14-point scoring system modified from the Downs and Black checklist with inclusions of recommendations in the WHO guidelines. Results Forty-three studies conducted in 11 African countries were included in the overall analysis. These studies presented prescribing indicators based on a total 141,323 patient encounters across 572 primary care facilities. The results of prescribing indicators were determined as follows; average number of medicines prescribed per patient encounter = 3.1 (IQR 2.3–4.8), percentage of medicines prescribed by generic name =68.0 % (IQR 55.4–80.3), Percentage of encounters with antibiotic prescribed =46.8 % (IQR 33.7–62.8), percentage of encounters with injection prescribed =25.0 % (IQR 18.7–39.5) and the percentage of medicines prescribed from essential medicines list =88.0 % (IQR 76.3–94.1). Prescribing indicators were generally worse in private compared with public facilities. Analysis of prescribing across two time points 1995–2005 and 2006–2015 showed no consistent trends. Conclusions Prescribing indicators for the African region deviate significantly from the WHO reference targets. Increased collaborative efforts are urgently needed to improve medicine prescribing practices in Africa with the aim of enhancing the optimal utilization of scarce resources and averting negative health consequences

Evaluating the collection, comparability and findings of six global surgery indicators

BACKGROUND: In 2015, six indicators were proposed to evaluate global progress towards access to safe, affordable and timely surgical and anaesthesia care. Although some have been adopted as core global health indicators, none has been evaluated systematically. The aims of this study were to assess the availability, comparability and utility of the indicators, and to present available data and updated estimates. METHODS: Nationally representative data were compiled for all World Health Organization (WHO) member states from 2010 to 2016 through contacts with official bodies and review of the published and grey literature, and available databases. Availability, comparability and utility were assessed for each indicator: access to timely essential surgery, specialist surgical workforce density, surgical volume, perioperative mortality, and protection against impoverishing and catastrophic expenditure. Where feasible, imputation models were developed to generate global estimates. RESULTS: Of all WHO member states, 19 had data on the proportion of the population within 2h of a surgical facility, 154 had data on workforce density, 72 reported number of procedures, and nine had perioperative mortality data, but none could report data on catastrophic or impoverishing expenditure. Comparability and utility were variable, and largely dependent on different definitions used. There were sufficient data to estimate that worldwide, in 2015, there were 2 038 947 (i.q.r. 1 884 916-2 281 776) surgeons, obstetricians and anaesthetists, and 266·1 (95 per cent c.i. 220·1 to 344·4) million operations performed. CONCLUSION: Surgical and anaesthesia indicators are increasingly being adopted by the global health community, but data availability remains low. Comparability and utility for all indicators require further resolution

Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

Background Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P <1.06 x 10(- 7), of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.Peer reviewe

Isokinetic Closed Kinetic Chain Exercise における膝関節反力の筋骨格モデル解析

前十字靱帯損傷者の術後リハビリテーションとして閉運動連鎖(CKC)が注目されてきた。CKCで理想的な下肢全体の筋収縮を引き出すためにサイクロイド曲線を利用した等運動性閉運動連鎖型評価訓練機を開発した。足部が円弧状運動を行うことで股関節、膝関節に均等にトルクを分散しスムーズで安全な運動が可能となる。ロードセルによる足部出力の計測と、ビデオキャプチャーデータを同期して各関節トルクを求めることができる。この運動について筋骨格シミュレーションモデルを用いて解析し、膝関節に加わるストレスを検討した。健常人では本機により大腿四頭筋とハムストリングのバランスの良い収縮が得られ、膝関節全屈曲角度域にわたって脛骨を前方へ引き出す力はほとんど働いていないことが証明された。CYBEX などのOKC では再建靱帯に危険なストレスがかかる可能性があり、本機によるCKC での筋力評価訓練は安全かつ有用であると考える