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BMC Medicine Jan 2021The etiologies of chronic neurological diseases, which heavily contribute to global disease burden, remain far from elucidated. Despite available umbrella reviews on...
BACKGROUND
The etiologies of chronic neurological diseases, which heavily contribute to global disease burden, remain far from elucidated. Despite available umbrella reviews on single contributing factors or diseases, no study has systematically captured non-purely genetic risk and/or protective factors for chronic neurological diseases.
METHODS
We performed a systematic analysis of umbrella reviews (meta-umbrella) published until September 20th, 2018, using broad search terms in MEDLINE, SCOPUS, Web of Science, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, ProQuest Dissertations & Theses, JBI Database of Systematic Reviews and Implementation Reports, DARE, and PROSPERO. The PRISMA guidelines were followed for this study. Reference lists of the identified umbrella reviews were also screened, and the methodological details were assessed using the AMSTAR tool. For each non-purely genetic factor association, random effects summary effect size, 95% confidence and prediction intervals, and significance and heterogeneity levels facilitated the assessment of the credibility of the epidemiological evidence identified.
RESULTS
We identified 2797 potentially relevant reviews, and 14 umbrella reviews (203 unique meta-analyses) were eligible. The median number of primary studies per meta-analysis was 7 (interquartile range (IQR) 7) and that of participants was 8873 (IQR 36,394). The search yielded 115 distinctly named non-genetic risk and protective factors with a significant association, with various strengths of evidence. Mediterranean diet was associated with lower risk of dementia, Alzheimer disease (AD), cognitive impairment, stroke, and neurodegenerative diseases in general. In Parkinson disease (PD) and AD/dementia, coffee consumption, and physical activity were protective factors. Low serum uric acid levels were associated with increased risk of PD. Smoking was associated with elevated risk of multiple sclerosis and dementia but lower risk of PD, while hypertension was associated with lower risk of PD but higher risk of dementia. Chronic occupational exposure to lead was associated with higher risk of amyotrophic lateral sclerosis. Late-life depression was associated with higher risk of AD and any form of dementia.
CONCLUSIONS
We identified several non-genetic risk and protective factors for various neurological diseases relevant to preventive clinical neurology, health policy, and lifestyle counseling. Our findings could offer new perspectives in secondary research (meta-research).
Topics: Biomarkers; Diet, Mediterranean; Exercise; Humans; Hypertension; Nervous System Diseases; Protective Factors; Risk Factors
PubMed: 33435977
DOI: 10.1186/s12916-020-01873-7 -
Current Heart Failure Reports Jun 2023Infarction (MINOCA) and ischaemia (INOCA) with non-obstructive coronary disease are recent non-conventional presentations of coronary syndromes that are increasingly... (Review)
Review
PURPOSE OF REVIEW
Infarction (MINOCA) and ischaemia (INOCA) with non-obstructive coronary disease are recent non-conventional presentations of coronary syndromes that are increasingly recognised in the clinical arena, particularly with the availability of new cardiovascular imaging techniques. Both are related to heart failure (HF). MINOCA is not associated with benign outcomes, and HF is among the most prevalent events. Regarding INOCA, microvascular dysfunction has also been found to associate with HF, particularly with preserved ejection fraction (HFpEF).
RECENT FINDINGS
Regardless of the several aetiologies underlying HF in MINOCA, it is likely related to LV dysfunction, where secondary prevention is not yet clearly established. Regarding INOCA, coronary microvascular ischaemia has been associated to endothelial dysfunction leading ultimately to diastolic dysfunction and HFpEF. MINOCA and INOCA are clearly related to HF. In both, there is a lack of studies on the identification of the risk factors for HF, diagnostic workup and, importantly, the appropriate primary and secondary prevention strategies.
Topics: Humans; Heart Failure; MINOCA; Stroke Volume; Myocardial Ischemia; Risk Factors; Coronary Artery Disease
PubMed: 37198520
DOI: 10.1007/s11897-023-00605-1 -
American Journal of Public Health Sep 2018
Topics: Causality; Public Health
PubMed: 30089012
DOI: 10.2105/AJPH.2018.304614 -
Drug Discovery Today Oct 2023To discover new drugs is to seek and to prove causality. As an emerging approach leveraging human knowledge and creativity, data, and machine intelligence, causal... (Review)
Review
To discover new drugs is to seek and to prove causality. As an emerging approach leveraging human knowledge and creativity, data, and machine intelligence, causal inference holds the promise of reducing cognitive bias and improving decision-making in drug discovery. Although it has been applied across the value chain, the concepts and practice of causal inference remain obscure to many practitioners. This article offers a nontechnical introduction to causal inference, reviews its recent applications, and discusses opportunities and challenges of adopting the causal language in drug discovery and development.
Topics: Humans; Bias; Causality; Knowledge; Drug Discovery
PubMed: 37591410
DOI: 10.1016/j.drudis.2023.103737 -
Journal of Medicine and Life 2016Uterine fibroids or uterine leiomyomas are the most common benign tumors of the uterus among women of fertile age, while the etiology is still incompletely elucidated.... (Review)
Review
Uterine fibroids or uterine leiomyomas are the most common benign tumors of the uterus among women of fertile age, while the etiology is still incompletely elucidated. The occurrence and development of the fibromatosis may be related to certain risk factors and genic mechanisms, although the exact causes are not yet fully known. The development of uterine fibroids is correlated not only with the metabolism and with the level of female sexual hormones, estrogen, and progesterone, but also with the number of these hormone receptors expressed on the surface of the myometrium. Proliferative effects of estrogen and progesterone may be exercised through proinflammatory factors (TNF alpha), growth factors (IGF1, IGF2, TGFbeta3 and betaFGF) or inhibitors of apoptosis (p53 suppression). A number of predisposing factors such as ethnicity - black skin, early menarche, nulliparity, caffeine and alcohol, chronic inflammation, obesity, were also identified. Approximately 40% of the uterine fibroids are caused by the same cytogenetic alterations found in the other tumor types such as kidney, lung, or leiomyosarcoma. As part of a system dysfunction, uterine fibromatosis was connected to other disorders such as AHT (arterial hypertension), endometrium adenocarcinoma, adenomyosis, endometriosis, diabetes mellitus, breast tumors, seemingly with a common causality. The action and effect of some hormonal imbalances over the various organs depend on the histological and local expression particularities of the various receptors, being the cause for many disorders, among which the uterine fibromatosis, coexisting or accompanying the later. This article examines and summarizes the latest data refreshed literature etiopathogenesis offering indicators of uterine fibroids.
Topics: Adult; Female; Humans; Leiomyoma; Risk Factors; Uterine Neoplasms
PubMed: 27974911
DOI: No ID Found -
Deutsches Arzteblatt International Oct 2020
Topics: Causality; Humans; Neck
PubMed: 33559598
DOI: 10.3238/arztebl.2020.0735a -
Critical Care (London, England) Sep 2016Elevation in core body temperature is one of the most frequently detected abnormal signs in patients admitted to adult ICUs, and is associated with increased mortality... (Review)
Review
Elevation in core body temperature is one of the most frequently detected abnormal signs in patients admitted to adult ICUs, and is associated with increased mortality in select populations of critically ill patients. The definition of an elevated body temperature varies considerably by population and thermometer, and is commonly defined by a temperature of 38.0 °C or greater. Terms such as hyperthermia, pyrexia, and fever are often used interchangeably. However, strictly speaking hyperthermia refers to the elevation in body temperature that occurs without an increase in the hypothalamic set point, such as in response to specific environmental (e.g., heat stroke), pharmacologic (e.g., neuroleptic malignant syndrome), or endocrine (e.g., thyrotoxicosis) stimuli. On the other hand, pyrexia and fever refer to the classical increase in body temperature that occurs in response to a vast list of infectious and noninfectious aetiologies in association with an increase in the hypothalamic set point. In this review, we examine the contemporary literature investigating the incidence and aetiology of pyrexia and hyperthermia among medical and surgical patients admitted to adult ICUs with or without an acute neurological condition. A temperature greater than 41.0 °C, although occasionally observed among patients with infectious or noninfectious pyrexia, is more commonly observed in patients with hyperthermia. Most episodes of pyrexia are due to infections, but incidence estimates of infectious and noninfectious aetiologies are limited by studies with small sample size and inconsistent reporting of noninfectious aetiologies. Pyrexia commonly triggers a full septic work-up, but on its own is a poor predictor of culture-positivity. In order to improve culturing practices, and better guide the diagnostic approach to critically ill patients with pyrexia, additional research is required to provide more robust estimates of the incidence of infectious and noninfectious aetiologies, and their relationship to other clinical features (e.g., leukocytosis). In the meantime, using existing literature, we propose an approach to identifying the aetiology of pyrexia in critically ill adults.
Topics: Body Temperature; Critical Illness; Fever; Humans; Infections; Intensive Care Units; Risk Factors
PubMed: 27581757
DOI: 10.1186/s13054-016-1406-2 -
Pediatric Endocrinology, Diabetes, and... 2015Insulin resistance is the state of reduced tissue sensitivity to insulin. The frequency of this occurrence is increasing dramatically in developed countries. Both,... (Review)
Review
Insulin resistance is the state of reduced tissue sensitivity to insulin. The frequency of this occurrence is increasing dramatically in developed countries. Both, environmental and genetic factors are involved in the pathogenesis of insulin resistance. Sedentary lifestyle and the excessive calorie intake cause the substantial increase of the fat issue, leading to overweight and obesity. Insulin resistance occurs physiologically during puberty, but it is also a pathological condition predisposing children to develop abnormal glucose tolerance, diabetes, hypertension and polycystic ovary syndrome among girls. More frequent occurrence of metabolic syndrome can be observed among children born small for gestational age (SGA). The article presents the current views on risk factors, etiology, diagnosis and consequences insulin resistance and disorders of glucose tolerance.
Topics: Adolescent; Blood Glucose; Causality; Child; Child, Preschool; Diabetes Mellitus, Type 2; Female; Humans; Infant; Insulin; Insulin Resistance; Male; Obesity; Risk Factors
PubMed: 26615047
DOI: 10.18544/PEDM-20.03.0010 -
RMD Open Sep 2022Although genome-wide association studies (GWASs) have identified more than 100 loci associated with rheumatoid arthritis (RA) susceptibility, the causal genes and...
BACKGROUND
Although genome-wide association studies (GWASs) have identified more than 100 loci associated with rheumatoid arthritis (RA) susceptibility, the causal genes and biological mechanisms remain largely unknown.
METHODS
A cross-tissue transcriptome-wide association study (TWAS) using the unified test for molecular signaturestool was performed to integrate GWAS summary statistics from 58 284 individuals (14 361 RA cases and 43 923 controls) with gene-expression matrix in the Genotype-Tissue Expression project. Subsequently, a single tissue by using FUSION software was conducted to validate the significant associations. We also compared the TWAS with different gene-based methodologies, including Summary Data Based Mendelian Randomization (SMR) and Multimarker Analysis of Genomic Annotation (MAGMA). Further in silico analyses (conditional and joint analysis, differential expression analysis and gene-set enrichment analysis) were used to deepen our understanding of genetic architecture and comorbidity aetiology of RA.
RESULTS
We identified a total of 47 significant candidate genes for RA in both cross-tissue and single-tissue test after multiple testing correction, of which 40 TWAS-identified genes were verified by SMR or MAGMA. Among them, 13 genes were situated outside of previously reported significant loci by RA GWAS. Both TWAS-based and MAGMA-based enrichment analyses illustrated the shared genetic determinants among autoimmune thyroid disease, asthma, type I diabetes mellitus and RA.
CONCLUSION
Our study unveils 13 new candidate genes whose predicted expression is associated with risk of RA, providing new insights into the underlying genetic architecture of RA.
Topics: Humans; Transcriptome; Genome-Wide Association Study; Arthritis, Rheumatoid; Causality; Polymorphism, Single Nucleotide
PubMed: 37582060
DOI: 10.1136/rmdopen-2022-002529 -
Molecular Genetics & Genomic Medicine Oct 2022With the increasing availability and size of multi-omics datasets, investigating the casual relationships between molecular phenotypes has become an important aspect of... (Review)
Review
BACKGROUND
With the increasing availability and size of multi-omics datasets, investigating the casual relationships between molecular phenotypes has become an important aspect of exploring underlying biology andgenetics. There are an increasing number of methodlogies that have been developed and applied to moleular networks to investigate these causal interactions.
METHODS
We have introduced and reviewed the available methods for building large-scale causal molecular networks that have been developed and applied in the past decade.
RESULTS
In this review we have identified and summarized the existing methods for infering causality in large-scale causal molecular networks, and discussed important factors that will need to be considered in future research in this area.
CONCLUSION
Existing methods to infering causal molecular networks have their own strengths and limitations so there is no one best approach, and it is instead down to the discretion of the researcher. This review also to discusses some of the current limitations to biological interpretation of these networks, and important factors to consider for future studies on molecular networks.
Topics: Causality; Phenotype
PubMed: 36087049
DOI: 10.1002/mgg3.2055