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Endocrine Reviews Mar 2024Chronic complications of diabetes are due to myriad disorders of numerous metabolic pathways that are responsible for most of the morbidity and mortality associated with... (Review)
Review
Chronic complications of diabetes are due to myriad disorders of numerous metabolic pathways that are responsible for most of the morbidity and mortality associated with the disease. Traditionally, diabetes complications are divided into those of microvascular and macrovascular origin. We suggest revising this antiquated classification into diabetes complications of vascular, parenchymal, and hybrid (both vascular and parenchymal) tissue origin, since the profile of diabetes complications ranges from those involving only vascular tissues to those involving mostly parenchymal organs. A major paradigm shift has occurred in recent years regarding the pathogenesis of diabetes complications, in which the focus has shifted from studies on risks to those on the interplay between risk and protective factors. While risk factors are clearly important for the development of chronic complications in diabetes, recent studies have established that protective factors are equally significant in modulating the development and severity of diabetes complications. These protective responses may help explain the differential severity of complications, and even the lack of pathologies, in some tissues. Nevertheless, despite the growing number of studies on this field, comprehensive reviews on protective factors and their mechanisms of action are not available. This review thus focused on the clinical, biochemical, and molecular mechanisms that support the idea of endogenous protective factors, and their roles in the initiation and progression of chronic complications in diabetes. In addition, this review also aimed to identify the main needs of this field for future studies.
Topics: Humans; Protective Factors; Diabetic Angiopathies; Diabetes Mellitus; Risk Factors; Diabetes Mellitus, Type 2
PubMed: 37638875
DOI: 10.1210/endrev/bnad030 -
Nature Jul 2023Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that results in significant neurodegeneration in the majority of those affected and...
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that results in significant neurodegeneration in the majority of those affected and is a common cause of chronic neurological disability in young adults. Here, to provide insight into the potential mechanisms involved in progression, we conducted a genome-wide association study of the age-related MS severity score in 12,584 cases and replicated our findings in a further 9,805 cases. We identified a significant association with rs10191329 in the DYSF-ZNF638 locus, the risk allele of which is associated with a shortening in the median time to requiring a walking aid of a median of 3.7 years in homozygous carriers and with increased brainstem and cortical pathology in brain tissue. We also identified suggestive association with rs149097173 in the DNM3-PIGC locus and significant heritability enrichment in CNS tissues. Mendelian randomization analyses suggested a potential protective role for higher educational attainment. In contrast to immune-driven susceptibility, these findings suggest a key role for CNS resilience and potentially neurocognitive reserve in determining outcome in MS.
Topics: Humans; Young Adult; Aging; Brain; Brain Stem; Case-Control Studies; Cognitive Reserve; Disease Progression; Educational Status; Genome-Wide Association Study; Homozygote; Mobility Limitation; Multiple Sclerosis; Protective Factors; Time Factors
PubMed: 37380766
DOI: 10.1038/s41586-023-06250-x -
Neoplasia (New York, N.Y.) Dec 2023This study aimed to investigate the causal relationship between mitochondrial biological function and lung cancer, including its subtypes, via MR.
OBJECTIVE
This study aimed to investigate the causal relationship between mitochondrial biological function and lung cancer, including its subtypes, via MR.
METHODS
SNPs significantly associated with lung cancer and its subtypes were employed as instrumental variables. MR-Egger regression, simple mode, weighted mode, simple median, and weighted median, were utilized to determine the causal relationship between the exposure factor and the occurrence of lung cancer and its subtypes.
RESULTS
NADH dehydrogenase (ubiquinone) flavoprotein 2 and transmembrane protein 70 were found to have a causal relationship with lung adenocarcinoma, acting as protective factors. The causal relationship between mitochondrial import inner membrane translocase subunit and NADH dehydrogenase (ubiquinone) iron-sulfur protein 4 and small-cell lung cancer was established as a risk factor. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 8 exhibited a causal relationship with small-cell lung cancer, acting as a protective factor. Furthermore, NAD-dependent protein deacylase sirtuin-5 was causally linked to lung squamous cell carcinoma, serving as a protective factor. A funnel plot demonstrated the symmetrical distribution of the SNPs. Thew pleiotroy test (P > 0.05) and "leave-one-out" test validated the relative stability of the results.
CONCLUSION
This study established a causal relationship between mitochondrial biological function and lung cancer, including its subtypes.
Topics: Humans; Lung Neoplasms; Electron Transport Complex I; Mendelian Randomization Analysis; Genome-Wide Association Study; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; Polymorphism, Single Nucleotide
PubMed: 37976568
DOI: 10.1016/j.neo.2023.100950 -
Cancers Oct 2023More and more studies have focused on the associations between human papillomavirus (HPV) infection and pan-cancers. However, current evidence is largely based on...
INTRODUCTION
More and more studies have focused on the associations between human papillomavirus (HPV) infection and pan-cancers. However, current evidence is largely based on retrospective studies, which are susceptible to confounding factors and do not enable the establishment of causal relationships.
METHODS
A bidirectional two-sample Mendelian randomization (MR) design was employed to thoroughly evaluate the causal relationships between HPV and 12 site-specific cancers except cervical cancer. Single nucleoside polymers (SNPs) with strong evidence from genome-wide association studies (GWAS) were selected from HPV exposure datasets and used as instrumental variables (IVs) in this study. For the MR analysis results, MR-Egger's intercept P test, MR-PRESSO global test, Cochran's Q test and a leave-one-out test were applied for sensitivity analysis. Using HPVTIMER, we also performed immune infiltration analyses in head and neck squamous cell carcinoma (HNSCC), oropharyngeal squamous cell carcinoma (OPSCC) and vulval squamous cell carcinoma (VSCC) to evaluate the tumor-immune microenvironment.
RESULTS
Based on the evidence of MR analysis, our study conclusively identified HPV16 as a risk factor implicated in the development of bladder cancer, colorectal cancer, and breast cancer, while HPV18 was identified as a risk factor for prostate cancer, ovarian cancer, lung cancer and breast cancer. The MR results also showed that HPV16 may be a protective factor for prostate cancer, anal cancer, lung cancer and oropharyngeal cancer, while HPV18 may be a protective factor for vaginal cancer.
CONCLUSION
An HPV infection may modulate the immune microenvironment and therefore has a potential inhibitory effect on the development of certain cancers. These conclusions provided new insights into the potential mechanisms of carcinogenesis and needed further research for validation.
PubMed: 37958321
DOI: 10.3390/cancers15215147 -
Journal of Translational Autoimmunity Jun 2024Autoimmune diseases (ADs) are one of the groups of chronic illnesses that impose a significant burden of disease and health costs worldwide. Age is a crucial risk factor... (Review)
Review
Autoimmune diseases (ADs) are one of the groups of chronic illnesses that impose a significant burden of disease and health costs worldwide. Age is a crucial risk factor for the onset of ADs. Theoretically, it is inferred that with organic and immune system aging, the loss of immune tolerance and specificity of immune activity becomes more intense, the probability of autoimmunity is increasing. However, there is a group of individuals whose prevalence of ADs is very low or non-existent, despite the biological aging. This paradox in autoimmunity raises questions. Centenarians, individuals who are over 100 years old, are possibly the most successful model of biological aging in humans. Most of these individuals exhibit a favorable health phenotype. To date, primary data evidence and potential hypotheses explaining this phenomenon are lacking globally, even though this paradox could provide valuable, original, and relevant information regarding the understanding of risk or protective factors, biological drivers, and biomarkers related to autoimmunity. Herein we discuss some hypothesis that may explain the absence of ADs in centenarians, including inflammaging, immunosenescence and immune resilience, immune system hyperstimulation, proteodynamics, and genetics.
PubMed: 38468861
DOI: 10.1016/j.jtauto.2024.100237 -
Maedica Dec 2023Inguinal hernia repair is one of the most commonly performed surgical activities worldwide. Given the circumstances, understanding and identifying the risk and the...
Inguinal hernia repair is one of the most commonly performed surgical activities worldwide. Given the circumstances, understanding and identifying the risk and the protective factors is an essential step in order to prevent, diagnose and treat such a common condition. For a long time, obesity was generally considered to be a risk factor in the occurrence of an inguinal hernia. Studies have provided some unexpected data, suggesting that it might actually be a protective factor. This review aims to provide an overview on this topic, taking into account systemic aspects such as collagen distribution and metabolism. In inguinal hernia patients, the ratio between type I collagen and type III collagen is decreased, with type III collagen being responsible for the weakness of the abdominal wall. In obese patients, the extracellular matrix becomes richer in collagen, especially type I collagen, which will generate strength and stiffness. Obesity seems to be a protective factor indeed, but in order to understand the underlying mechanism and to choose the optimal surgical approach, further research is needed.
PubMed: 38348082
DOI: 10.26574/maedica.2023.18.4.692 -
Aging and Disease Aug 2023Alzheimer's disease (AD) is the most common form of dementia that remains incurable and has become a major medical, social, and economic challenge worldwide. AD is... (Review)
Review
Alzheimer's disease (AD) is the most common form of dementia that remains incurable and has become a major medical, social, and economic challenge worldwide. AD is characterized by pathological hallmarks of senile plaques (SP) and neurofibrillary tangles (NFTs) that damage the brain up to twenty years before a clinical diagnosis is made. Interestingly these pathological features have also been observed in retinal neurodegenerative diseases including age related macular degeneration (ARMD), glaucoma and diabetic retinopathy (DR). An association of AD with these diseases has been suggested in epidemiological studies and several common pathological events and risk factors have been identified between these diseases. The E4 allele of Apolipoprotein E (APOE) is a well-established genetic risk factor for late onset AD. The ApoE ε4 allele is also associated with retinal neurodegenerative diseases however in contrast to AD, it is considered protective in AMD, likewise ApoE E2 allele, which is a protective factor for AD, has been implicated as a risk factor for AMD and glaucoma. This review summarizes the evidence on the effects of ApoE in retinal neurodegenerative diseases and discusses the overlapping molecular pathways in AD. The involvement of ApoE in regulating amyloid beta (Aβ) and tau pathology, inflammation, vascular integrity, glucose metabolism and vascular endothelial growth factor (VEGF) signaling is also discussed.
PubMed: 37199411
DOI: 10.14336/AD.2023.0312-1 -
Journal of Psychiatric Research Dec 2023We conducted an umbrella review to synthesise the evidence from systematic reviews and meta-analyses that examined the risk and protective factors for self-harm in young... (Review)
Review
We conducted an umbrella review to synthesise the evidence from systematic reviews and meta-analyses that examined the risk and protective factors for self-harm in young people. We searched six different databases and used the AMSTAR-2 checklist for quality assessment. The importance of each risk and protective factor was determined based on (1) the number of times it was identified by general reviews examining any risk or protective factor, and (2) the effect sizes from meta-analyses. There were 61 systematic reviews included in this review. The most frequently identified risk factors for self-harm in young people included childhood abuse, depression/anxiety, bullying, trauma, psychiatric illnesses, substance use/abuse, parental divorce, poor family relationships, lack of friends, and exposure to self-harm behaviour in others. The risk factors with the strongest evidence for an association with self-harm were behavioural disorders, personality disorders and depression or anxiety. There was a dearth of systematic reviews examining protective factors but good family/friend relationships were most frequently identified. There was also evidence to show that non-suicidal and suicidal self-harm shared many of the same risk factors. Clinicians and other professionals who work with young people should be particularly cognisant of the psychiatric and adverse life event risk factors as well as the substance use, education-related and individual-level (e.g. being LGB) risk factors for self-harm. Knowledge of risk factors for self-harm can potentially be used to inform the design and implementation of prevention measures and further research is needed on the protective factors for self-harm.
Topics: Humans; Adolescent; Young Adult; Child; Protective Factors; Systematic Reviews as Topic; Self-Injurious Behavior; Suicidal Ideation; Risk Factors; Substance-Related Disorders
PubMed: 37972513
DOI: 10.1016/j.jpsychires.2023.10.017 -
Clinical Reviews in Allergy & Immunology Oct 2023Many potential environmental risk factors, protective factors, and biomarkers of AR have been published, but so far, the strength and consistency of their evidence are... (Review)
Review
Many potential environmental risk factors, protective factors, and biomarkers of AR have been published, but so far, the strength and consistency of their evidence are unclear. We conducted a comprehensive review of environmental risk, protective factors, and biomarkers for AR to establish the evidence hierarchy. We systematically searched Embase, PubMed, Cochrane Library, and Web of Science electronic database from inception to December 31, 2022. We calculated summary effect estimate (odds ratio (OR), relative risk (RR), hazard ratio (HR), and standardized mean difference (SMD)), 95% confidence interval, random effects p value, I statistic, 95% prediction interval, small study effects, and excess significance biases, and stratification of the level of evidence. Methodological quality was assessed by AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). We retrieved 4478 articles, of which 43 met the inclusion criteria. The 43 eligible articles identified 31 potential environmental risk factors (10,806,206 total population, two study not reported), 11 potential environmental protective factors (823,883 total population), and 34 potential biomarkers (158,716 total population) for meta-analyses. The credibility of evidence was convincing (class I) for tic disorders (OR = 2.89, 95% CI 2.11-3.95); and highly suggestive (class II) for early-life antibiotic use (OR = 3.73, 95% CI 3.06-4.55), exposure to indoor dampness (OR = 1.49, 95% CI 1.27-1.75), acetaminophen exposure (OR = 1.54, 95% CI 1.41-1.69), childhood acid suppressant use (OR = 1.40, 95% CI 1.23-1.59), exposure to indoor mold (OR = 1.66, 95% CI 1.26-2.18), coronavirus disease 2019 (OR = 0.11, 95% CI 0.06-0.22), and prolonged breastfeeding (OR = 0.72, 95% CI 0.65-0.79). This study is registered in PROSPERO (CRD42022384320).
Topics: Child; Humans; Acetaminophen; Biomarkers; COVID-19; Protective Factors; Rhinitis, Allergic; Risk Factors; Systematic Reviews as Topic
PubMed: 37490237
DOI: 10.1007/s12016-023-08964-2 -
BMC Geriatrics Sep 2023Cognitive impairment can cause social, emotional, and financial burdens on individuals, caregivers, and healthcare providers. This is especially important in settings... (Review)
Review
BACKGROUND
Cognitive impairment can cause social, emotional, and financial burdens on individuals, caregivers, and healthcare providers. This is especially important in settings such as long-term care (LTC) homes which largely consist of vulnerable older adults. Thus, the objective of this study is to review and summarize current research examining risk factors of cognitive decline in older adults within LTC.
METHODS
This scoping review includes primary observational research studies assessing within-person change in cognition over time in LTC or equivalent settings in high resource countries. A mean participant age of ≥ 65 years was required. Searches were conducted in Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PyscInfo on June 27th, 2022 and included articles published during or after the year 2000. Title, abstract, and full-text screening was performed by two independent reviewers using Covidence. Specific predictors along with their associated relation with cognitive decline were extracted by a team of reviewers into a spreadsheet.
RESULTS
Thirty-eight studies were included in this review. The mean sample size was 14 620. Eighty-seven unique predictors were examined in relation to cognitive decline. Dementia was the most studied predictor (examined by 9 of 38 studies), and the most conclusive, with eight of those studies identifying it as a risk factor for cognitive decline. Other predictors that were identified as risk factors included arterial stiffness (identified by 2 of 2 studies), physical frailty (2 of 2 studies), sub-syndromal delirium (2 of 2 studies), and undergoing the first wave of COVID-19 lockdowns (2 of 2 studies). ADL independence was the most conclusive protective factor (3 of 4 studies), followed by social engagement (2 of 3 studies). Many remaining predictors showed no association and/or conflicting results.
CONCLUSIONS
Dementia was the most common risk factor, while ADL independence was the most common protective factor associated with cognitive decline in LTC residents. This information can be used to stratify residents by risk severity and provide better personalized care for older adults through the targeted management of cognitive decline.
Topics: Humans; Aged; Long-Term Care; COVID-19; Communicable Disease Control; Cognitive Dysfunction; Dementia
PubMed: 37670246
DOI: 10.1186/s12877-023-04193-6