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Osteoarthritis and Cartilage Jun 2024Understanding the mechanisms of hip disease, such as osteoarthritis (OA), is crucial to advance their treatment. Such hip diseases often involve specific morphological... (Review)
Review
OBJECTIVE
Understanding the mechanisms of hip disease, such as osteoarthritis (OA), is crucial to advance their treatment. Such hip diseases often involve specific morphological changes. Genetic variations, called single nucleotide polymorphisms (SNPs), influence various hip morphological parameters. This study investigated the biological relevance of SNPs correlated to hip morphology in genome-wide association studies (GWAS). The SNP-associated genes were compared to genes associated with OA in other joints, aiming to see if the same genes play a role in both hip development and the risk of OA in other lower limb joints.
METHODOLOGY
A systematic literature review was conducted to identify SNPs correlated with hip morphology, based on the Population, Intervention, Comparison, Outcome, and Study (PICOS) framework. Afterwards, Gene Ontology (GO) analysis was performed, using EnrichR, on the SNP-associated genes and compared with non-hip OA-associated genes, across different databases.
RESULTS
Reviewing 49 GWAS identified 436 SNPs associated with hip joint morphology, encompassing variance in bone size, structure and shape. Among the SNP-associated genes, SOX9 plays a pivotal role in size, GDF5 impacts bone structure, and BMP7 affects shape. Overall, skeletal system development, regulation of cell differentiation, and chondrocyte differentiation emerged as crucial processes influencing hip morphology. Eighteen percent of GWAS-identified genes related to hip morphology were also associated with non-hip OA.
CONCLUSION
Our findings indicate the existence of multiple shared genetic mechanisms across hip morphology and OA, highlighting the necessity for more extensive research in this area, as in contrast to the hip, the genetic background on knee or foot morphology remains largely understudied.
PubMed: 38852879
DOI: 10.1016/j.joca.2024.05.010 -
AIDS Research and Therapy Jun 2024Despite the widespread use of pre-exposure prophylaxis (PrEP) in preventing human immunodeficiency virus (HIV) transmission, scant information on HIV drug resistance... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Despite the widespread use of pre-exposure prophylaxis (PrEP) in preventing human immunodeficiency virus (HIV) transmission, scant information on HIV drug resistance mutations (DRMs) has been gathered over the past decade. This review aimed to estimate the pooled prevalence of pre-exposure prophylaxis and its two-way impact on DRM.
METHODS
We systematically reviewed studies on DRM in pre-exposure prophylaxis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 guidelines. PubMed, Cochrane, and SAGE databases were searched for English-language primary studies published between January 2001 and December 2023. The initial search was conducted on 9 August 2021 and was updated through 31 December 2023 to ensure the inclusion of the most recent findings. The registration number for this protocol review was CRD42022356061.
RESULTS
A total of 26,367 participants and 562 seroconversion cases across 12 studies were included in this review. The pooled prevalence estimate for all mutations was 6.47% (95% Confidence Interval-CI 3.65-9.93), while Tenofovir Disoproxil Fumarate/Emtricitabine-associated drug resistance mutation prevalence was 1.52% (95% CI 0.23-3.60) in the pre-exposure prophylaxis arm after enrolment. A subgroup analysis, based on the study population, showed the prevalence in the heterosexual and men who have sex with men (MSM) groups was 5.53% (95% CI 2.55-9.40) and 7.47% (95% CI 3.80-12.11), respectively. Notably, there was no significant difference in the incidence of DRM between the pre-exposure prophylaxis and placebo groups (log-OR = 0.99, 95% CI -0.20 to 2.18, I2 = 0%; p = 0.10).
DISCUSSION
Given the constrained prevalence of DRM, the World Health Organization (WHO) advocates the extensive adoption of pre-exposure prophylaxis. Our study demonstrated no increased risk of DRM with pre-exposure prophylaxis (p > 0.05), which is consistent with these settings. These findings align with the previous meta-analysis, which reported a 3.14-fold higher risk in the pre-exposure prophylaxis group than the placebo group, although the observed difference did not reach statistical significance (p = 0.21).
CONCLUSIONS
Despite the low prevalence of DRM, pre-exposure prophylaxis did not significantly increase the risk of DRM compared to placebo. However, long-term observation is required to determine further disadvantages of extensive pre-exposure prophylaxis use. PROSPERO Number: CRD42022356061.
Topics: Humans; Pre-Exposure Prophylaxis; HIV Infections; Drug Resistance, Viral; Mutation; Anti-HIV Agents; HIV-1; Male; Administration, Oral; Female; Tenofovir; Prevalence
PubMed: 38844950
DOI: 10.1186/s12981-024-00627-2 -
Otolaryngology--head and Neck Surgery :... Jun 2024Initiating postoperative radiotherapy (PORT) within 6 weeks of surgery for head and neck squamous cell carcinoma (HNSCC) is included in the National Comprehensive Cancer... (Review)
Review
OBJECTIVE
Initiating postoperative radiotherapy (PORT) within 6 weeks of surgery for head and neck squamous cell carcinoma (HNSCC) is included in the National Comprehensive Cancer Network Clincal Practice Guidelines and is a Commission on Cancer quality metric. Factors associated with delays in starting PORT have not been systematically described nor synthesized.
DATA SOURCES
PubMed, Scopus, and CINAHL.
REVIEW METHODS
We included studies describing demographic characteristics, clinical factors, or social determinants of health associated with PORT delay (>6 weeks) in patients with HNSCC treated in the United States after 2003. Meta-analysis of odds ratios (ORs) was performed on nonoverlapping datasets.
RESULTS
Of 716 unique abstracts reviewed, 21 studies were included in the systematic review and 15 in the meta-analysis. Study sample size ranged from 19 to 60,776 patients. In the meta-analysis, factors associated with PORT delay included black race (OR, 1.46, 95% confidence interval [CI]: 1.28-1.67), Hispanic ethnicity (OR, 1.37, 95% CI, 1.17-1.60), Medicaid or no health insurance (OR, 2.01, 95% CI, 1.90-2.13), lower income (OR, 1.38, 95% CI, 1.20-1.59), postoperative admission >7 days (OR, 2.92, 95% CI, 2.31-3.67), and 30-day hospital readmission (OR, 1.37, 95% CI, 1.29-1.47).
CONCLUSION
Patients at greatest risk for a delay in initiating guideline-adherent PORT include those who are from minoritized communities, of lower socioeconomic status, and experience postoperative challenges. These findings provide the foundational evidence needed to deliver targeted interventions to enhance equity and quality in HNSCC care delivery.
PubMed: 38842034
DOI: 10.1002/ohn.835 -
Frontiers in Cellular and Infection... 2024The microbiota-gut-lung axis has elucidated a potential association between gut microbiota and idiopathic pulmonary fibrosis (IPF). However, there is a paucity of...
BACKGROUND
The microbiota-gut-lung axis has elucidated a potential association between gut microbiota and idiopathic pulmonary fibrosis (IPF). However, there is a paucity of population-level studies with providing robust evidence for establishing causality. This two-sample Mendelian randomization (MR) analysis aimed to investigate the causal relationship between the gut microbiota and IPF as well as lung function.
MATERIALS AND METHODS
Adhering to Mendel's principle of inheritance, this MR analysis utilized summary-level data from respective genome-wide association studies (GWAS) involving 211 gut microbial taxa, IPF, and lung function indicators such as FEV, FVC, and FEV/FVC. A bidirectional two-sample MR design was employed, utilizing multiple MR analysis methods, including inverse variance-weighted (IVW), weighted median, MR-Egger, and weighted mode. Multivariable MR (MVMR) was used to uncover mediating factors connecting the exposure and outcome. Additionally, comprehensive sensitivity analyses were conducted to ensure the robustness of the results.
RESULTS
The MR results confirmed four taxa were found causally associated with the risk of IPF. (OR=0.773, 95% CI: 0.610-0.979, p=0.033), (OR=0.773, 95% CI: 0.610-0.979, p=0.033), and (OR=0.793, 95% CI: 0.652-0.965, p=0.020) exerted protective effects on IPF, while (OR=1.349, 95% CI: 1.021-1.783, p=0.035) promote the development of IPF. Several taxa were causally associated with lung function, with those in , and being the most prominent beneficial microbiota, while those in , and were associated with impaired lung function. As for the reverse analysis, MR results confirmed the effects of FEV and FVC on the increased abundance of six taxa (, and ) with a boosted level of evidence. MVMR suggested monounsaturated fatty acids, total fatty acids, saturated fatty acids, and ratio of omega-6 fatty acids to total fatty acids as potential mediating factors in the genetic association between gut microbiota and IPF.
CONCLUSION
The current study suggested the casual effects of the specific gut microbes on the risk of IPF and lung function. In turn, lung function also exerted a positive role in some gut microbes. A reasonable dietary intake of lipid substances has a certain protective effect against the occurrence and progression of IPF. This study provides novel insights into the potential role of gut microbiota in IPF and indicates a possible gut microbiota-mediated mechanism for the prevention of IPF.
Topics: Humans; Mendelian Randomization Analysis; Idiopathic Pulmonary Fibrosis; Gastrointestinal Microbiome; Genome-Wide Association Study; Lung; Respiratory Function Tests; Genetic Predisposition to Disease
PubMed: 38841114
DOI: 10.3389/fcimb.2024.1348685 -
Journal of Stroke May 2024Possible differences in the prevalence of cerebral amyloid angiopathy (CAA) in East-Asian compared to Western populations have received little attention, and results so... (Review)
Review
BACKGROUND AND PURPOSE
Possible differences in the prevalence of cerebral amyloid angiopathy (CAA) in East-Asian compared to Western populations have received little attention, and results so far have been ambiguous. Our aim is to compare the prevalence of CAA neuropathology and magnetic resonance imaging markers of CAA in East-Asian and Western cohorts reflecting the general population, cognitively normal elderly, patients with Alzheimer's disease (AD), and patients with (lobar) intracerebral hemorrhage (ICH).
METHODS
We performed a systematic literature search in PubMed and Embase for original research papers on the prevalence of CAA and imaging markers of CAA published up until February 17th 2022. Records were screened by two independent reviewers. Pooled estimates were determined using random-effects models. We compared studies from Japan, China, Taiwan, South Korea (East-Asian cohorts) to studies from Europe or North America (Western cohorts) by meta-regression models.
RESULTS
We identified 12,257 unique records, and we included 143 studies on Western study populations and 53 studies on East-Asian study populations. Prevalence of CAA neuropathology did not differ between East-Asian and Western cohorts in any of the investigated patient domains. The prevalence of strictly lobar microbleeds was lower in East-Asian cohorts of population-based individuals (5.6% vs. 11.4%, P=0.020), cognitively normal elderly (2.6% vs. 11.4%, P=0.001), and patients with ICH (10.2% vs. 24.6%, P<0.0001). However, age was in general lower in the East-Asian cohorts.
CONCLUSION
The prevalence of CAA neuropathology in the general population, cognitively normal elderly, patients with AD, and patients with (lobar) ICH is similar in East-Asian and Western countries. In East-Asian cohorts reflecting the general population, cognitively normal elderly, and patients with ICH, strictly lobar microbleeds were less prevalent, likely due to their younger age. Consideration of potential presence of CAA is warranted in decisions regarding antithrombotic treatment and potential new anti-amyloid-β immunotherapy as treatment for AD in East-Asian and Western countries alike.
PubMed: 38836267
DOI: 10.5853/jos.2023.04287 -
Comprehensive Psychiatry Aug 2024Trichotillomania (TTM) and excoriation disorder (ED) are impairing obsessive-compulsive related disorders that are common in the general population and for which there...
BACKGROUND
Trichotillomania (TTM) and excoriation disorder (ED) are impairing obsessive-compulsive related disorders that are common in the general population and for which there are no clear first-line medications, highlighting the need to better understand the underlying biology of these disorders to inform treatments. Given the importance of genetics in obsessive-compulsive disorder (OCD), evaluating genetic factors underlying TTM and ED may advance knowledge about the pathophysiology of these body-focused repetitive behaviors.
AIM
In this systematic review, we summarize the available evidence on the genetics of TTM and ED and highlight gaps in the field warranting further research.
METHOD
We systematically searched Embase, PsycInfo, PubMed, Medline, Scopus, and Web of Science for original studies in genetic epidemiology (family or twin studies) and molecular genetics (candidate gene and genome-wide) published up to June 2023.
RESULTS
Of the 3536 records identified, 109 studies were included in this review. These studies indicated that genetic factors play an important role in the development of TTM and ED, some of which may be shared across the OCD spectrum, but there are no known high-confidence specific genetic risk factors for either TTM or ED.
CONCLUSIONS
Our review underscores the need for additional genome-wide research conducted on the genetics of TTM and ED, for instance, genome-wide association and whole-genome/whole-exome DNA sequencing studies. Recent advances in genomics have led to the discovery of risk genes in several psychiatric disorders, including related conditions such as OCD, but to date, TTM and ED have remained understudied.
Topics: Humans; Trichotillomania; Obsessive-Compulsive Disorder; Genome-Wide Association Study; Excoriation Disorder
PubMed: 38833896
DOI: 10.1016/j.comppsych.2024.152506 -
BJS Open May 2024Diverticulosis is a normal anatomical variant of the colon present in more than 70% of the westernized population over the age of 80. Approximately 3% will develop...
BACKGROUND
Diverticulosis is a normal anatomical variant of the colon present in more than 70% of the westernized population over the age of 80. Approximately 3% will develop diverticulitis in their lifetime. Many patients present emergently, suffer high morbidity rates and require substantial healthcare resources. Diverticulosis is the most common finding at colonoscopy and has the potential for causing a significant morbidity rate and burden on healthcare. There is a need to better understand the aetiology and pathogenesis of diverticular disease. Research suggests a genetic susceptibility of 40-50% in the formation of diverticular disease. The aim of this review is to present the hypothesized functional effects of the identified gene loci and environmental factors.
METHODS
A systematic literature review was performed using PubMed, MEDLINE and Embase. Medical subject headings terms used were: 'diverticular disease, diverticulosis, diverticulitis, genomics, genetics and epigenetics'. A review of grey literature identified environmental factors.
RESULTS
Of 995 articles identified, 59 articles met the inclusion criteria. Age, obesity and smoking are strongly associated environmental risk factors. Intrinsic factors of the colonic wall are associated with the presence of diverticula. Genetic pathways of interest and environmental risk factors were identified. The COLQ, FAM155A, PHGR1, ARHGAP15, S100A10, and TNFSF15 genes are the strongest candidates for further research.
CONCLUSION
There is increasing evidence to support the role of genomics in the spectrum of diverticular disease. Genomic, epigenetic and omic research with demographic context will help improve the understanding and management of this complex disease.
Topics: Humans; Risk Factors; Epigenesis, Genetic; Genetic Predisposition to Disease; Diverticular Diseases; Gene-Environment Interaction; Obesity
PubMed: 38831715
DOI: 10.1093/bjsopen/zrae032 -
BMC Pregnancy and Childbirth May 2024The causes of infertility have remained an important challenge. The relationship between VDR gene polymorphisms and infertility has been reported, with controversial... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The causes of infertility have remained an important challenge. The relationship between VDR gene polymorphisms and infertility has been reported, with controversial findings.
OBJECTIVE AND RATIONALE
We aimed to determine this relationship by conducting a systematic review and meta-analysis.
SEARCH METHODS
The study was started with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) declaration and the final draft was registered as a protocol in PROSPERO (ID: CRD42023416535). The international electronic databases including PubMed (Medline), Scopus, Web of Sciences, and Cumulative Index to Nursing and Allied Health Literature (CINHAL) were searched until January 30, 2023, by using appropriate keywords. The quality of the final studies was assessed using the NOS Checklist for case-control studies. The odds ratios (ORs) for each of the genetic models were pooled, and a subgroup analysis based on geographical region and types of infertility was carried out by the MetaGenyo online tool.
OUTCOMES
Case-control studies including 18 and 2 studies about infertility in women and men, respectively, and 4 miscarriage studies were entered into the meta-analysis. The VDR gene TaqI polymorphism was associated with infertility susceptibility in women in the allele contrast [OR = 1.2065, 95% CI (1.0846-1.3421); P = 0.0005], Recessive model [OR = 1.3836, 95% CI (1.1197-1.7096); P = 0.002], Dominant model [OR = 1.2146, 95% CI (0.0484-1.4072); P = 0.009], Homozygote [OR = 1.4596, 95% CI (1.1627-1.8325); P = 0.001], and TT vs. Tt [OR = 1.2853, 95% CI (1.0249-1.6117); P = 0.029. ApaI and FokI gene polymorphisms were found to be significantly protective SNPs against women and men infertility in the Dominant model [OR = 0.8379, 95% CI (0.7039- 0.9975); P = 0.046] and Recessive model [OR = 0.421, 95% CI (0.1821-0.9767); P = 0.043], respectively. Sub-group meta-analysis showed a protection association of ApaI in dominant [OR = 0.7738, 95% CI = 0.6249-0.9580; P = 0.018] and AA vs. aa [OR = 0.7404, 95 CI% (0.5860-0.9353) P = 0.011725] models in PCOS subgroup, however, a negative association with idiopathic infertility was found in AA vs. Aa [OR = 1.7063, 95% CI (1.1039-2.6375); P = 0.016187] and Aa vs. aa [OR = 0.6069, 95% CI (0.3761-0.9792); P = 0.040754]. TaqI SNP was significantly associated with infertility in the African population and BsmI was associated with the disease mostly in the Asian population.
CONCLUSION
This meta-analysis showed that the TaqI polymorphism may be linked to women's infertility susceptibility. However, ApaI and FokI might be the protective SNPs against infertility in Women and men, respectively.
Topics: Humans; Receptors, Calcitriol; Female; Genetic Predisposition to Disease; Male; Polymorphism, Genetic; Infertility, Female; Case-Control Studies; Infertility; Infertility, Male
PubMed: 38816754
DOI: 10.1186/s12884-024-06590-0 -
PloS One 2024Familial Pancreatic Cancer (FPC) presents a notable risk, with 3-10% of pancreatic adenocarcinoma cases having a family history. Studies link FPC to syndromes like HBOC,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Familial Pancreatic Cancer (FPC) presents a notable risk, with 3-10% of pancreatic adenocarcinoma cases having a family history. Studies link FPC to syndromes like HBOC, suggesting BRCA1/BRCA2 mutations play a role. BRCA gene functions in DNA repair impact FPC management, influencing sensitivity to therapies like PARP inhibitors. Identifying mutations not only aids FPC treatment but also reveals broader cancer risks. However, challenges persist in selectively applying genetic testing due to cost constraints. This Systematic Review focuses on BRCA1/BRCA2 significance in FPC, diagnostic criteria, prognostic value, and limitations.
METHOD
Original articles published from 2013 to January 2023 were sourced from databases such as Scopus, PubMed, ProQuest, and ScienceDirect. Inclusion criteria comprised observational cohort or diagnostic studies related to the role of BRCA1/2 mutation in correlation to familial pancreatic cancer (FPC), while article reviews, narrative reviews, and non-relevant content were excluded. The assessment of bias used ROBINS-I, and the results were organized using PICOS criteria in a Google spreadsheet table. The systematic review adhered to the PRISMA 2020 checklist.
RESULT
We analyzed 9 diagnostic studies encompassing 1325 families and 4267 patients from Italy, USA, and Poland. Despite the limitation of limited homogenous PICO studies, our findings effectively present evidence. BRCA1/2 demonstrates benefits in detecting first-degree relatives FPC involvement with 2.26-10 times higher risk. These mutation findings also play an important role since with the BRCA1/2 targeted therapy, Poly-ADP Ribose Polymerase inhibitors (PARP) may give better outcomes of FPC treatment. Analysis of BRCA1 and BRCA2 administration's impact on odds ratio (OR) based on six and five studies respectively. BRCA1 exhibited non-significant effects (OR = 1.26, P = 0.51), while BRCA2 showed significance (OR = 1.68, P = 0.04). No heterogeneity observed, indicating consistent results. Further research on BRCA1 is warranted.
CONCLUSION
Detecting the BRCA1/2 mutation gene offers numerous advantages, particularly in its correlation with FPC. For diagnostic and prognostic purposes, testing is strongly recommended for first-degree relatives, who face a significantly higher risk (2.26-10 times) of being affected. Additionally, FPC patients with identified BRCA1/2 mutations exhibit a more favorable prognosis compared to the non-mutated population. This is attributed to the availability of targeted BRCA1/2 therapy, which maximizes treatment outcomes.
Topics: Humans; Pancreatic Neoplasms; Germ-Line Mutation; BRCA2 Protein; BRCA1 Protein; Genetic Predisposition to Disease; Carcinoma
PubMed: 38809921
DOI: 10.1371/journal.pone.0299276 -
Sensors (Basel, Switzerland) May 2024Dizziness can be a debilitating condition with various causes, with at least one episode reported in 17% to 30% of the international adult population. Given the... (Meta-Analysis)
Meta-Analysis Review
Dizziness can be a debilitating condition with various causes, with at least one episode reported in 17% to 30% of the international adult population. Given the effectiveness of rehabilitation in treating dizziness and the recent advancements in telerehabilitation, this systematic review aims to investigate the effectiveness of telerehabilitation in the treatment of this disorder. The search, conducted across Medline, Cochrane Central Register of Controlled Trials, and PEDro databases, included randomized controlled trials assessing the efficacy of telerehabilitation interventions, delivered synchronously, asynchronously, or via tele-support/monitoring. Primary outcomes focused on dizziness frequency/severity and disability, with secondary outcomes assessing anxiety and depression measures. Seven articles met the eligibility criteria, whereas five articles contributed to the meta-analysis. Significant findings were observed regarding the frequency and severity of dizziness (mean difference of 3.01, < 0.001), disability (mean difference of -4.25, < 0.001), and anxiety (standardized mean difference of -0.16, = 0.02), favoring telerehabilitation. Telerehabilitation shows promise as a treatment for dizziness, aligning with the positive outcomes seen in traditional rehabilitation studies. However, the effectiveness of different telerehabilitation approaches requires further investigation, given the moderate methodological quality and the varied nature of existing methods and programs.
Topics: Humans; Dizziness; Telerehabilitation; Anxiety; Treatment Outcome
PubMed: 38793883
DOI: 10.3390/s24103028