-
Journal of Clinical Medicine Jul 2023While hormonal contraceptives are efficacious and available in several forms for women, perception of safety and concern over side effects are a deterrent for many.... (Review)
Review
While hormonal contraceptives are efficacious and available in several forms for women, perception of safety and concern over side effects are a deterrent for many. Existing non-hormonal contraceptives include permanent sterilization, copper intrauterine devices (IUDs), chemical/physical barriers such as spermicides and condoms, as well as traditional family planning methods including withdrawal and the rhythm method. Individuals who wish to retain their fertility in the future can achieve highest adherence and efficacy with long-acting, reversible contraceptives (LARCs), though there is only one, the copper IUD, that is non-hormonal. As rates of unintended pregnancies remain high with existing contraceptive options, it is becoming increasingly attractive to develop novel pregnancy prevention methods for both women and men. Non-hormonal contraceptives can target a variety of critical reproductive processes discussed here. This review focuses on identified non-hormonal contraceptive targets and subsequent drug candidates in development.
PubMed: 37510905
DOI: 10.3390/jcm12144791 -
Cardiovascular Diabetology Sep 2023The presence of type 1 diabetes mellitus (T1DM) has been demonstrated to pose an increased risk for developing cardiovascular diseases (CVDs). However, the causal...
BACKGROUND
The presence of type 1 diabetes mellitus (T1DM) has been demonstrated to pose an increased risk for developing cardiovascular diseases (CVDs). However, the causal relationships between T1DM and CVDs remain unclear due to the uncontrolled confounding factors and reverse causation bias of the observational studies.
METHODS
Summary statistics of T1DM and seven CVDs from the largest available genome-wide association studies (GWAS) of European ancestry and FinnGen biobank were extracted for the primary MR analysis, and the analysis was replicated using UK biobank (UKBB) for validation. Three complementary methods: inverse variance weighted (IVW), weighted median, and MR-Egger were used for the MR estimates. The potential pleiotropic effects were assessed by MR-Egger intercept and MR-PRESSO global test. Additionally, multivariable MR (MVMR) analysis was performed to examine whether T1DM has independent effects on CVDs with adjustment of potential confounding factors. Moreover, a two-step MR approach was used to assess the potential mediating effects of these factors on the causal effects between T1DM and CVDs.
RESULTS
Causal effects of T1DM on peripheral atherosclerosis (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.02-1.10; p = 0.002)] and coronary atherosclerosis (OR = 1.03, 95% CI: 1.01-1.05; p = 0.001) were found. The results were less likely to be biased by the horizontal pleiotropic effects (both p values of MR-Egger intercept and MR-PRESSO Global test > 0.05). In the following MVMR analysis, we found the causal effects of T1DM on peripheral atherosclerosis and coronary atherosclerosis remain significant after adjusting for a series of potential confounding factors. Moreover, we found that hypertension partly mediated the causal effects of T1DM on peripheral atherosclerosis (proportion of mediation effect in total effect: 11.47%, 95% CI: 3.23-19.71%) and coronary atherosclerosis (16.84%, 95% CI: 5.35-28.33%). We didn't find significant causal relationships between T1DM and other CVDs, including heart failure (HF), coronary artery disease (CAD), atrial fibrillation (AF), myocardial infarction (MI) and stroke. For the reverse MR from CVD to T1DM, no significant causal relationships were identified.
CONCLUSION
This MR study provided evidence supporting the causal effect of T1DM on peripheral atherosclerosis and coronary atherosclerosis, with hypertension partly mediating this effect.
Topics: Humans; Cardiovascular Diseases; Coronary Artery Disease; Diabetes Mellitus, Type 1; Genome-Wide Association Study; Mendelian Randomization Analysis; Hypertension; Atherosclerosis; Nonoxynol
PubMed: 37659996
DOI: 10.1186/s12933-023-01974-6 -
Sleep Aug 2023Craniofacial modification by orthodontic techniques is increasingly incorporated into the multidisciplinary management of sleep-disordered breathing in children and...
Craniofacial modification by orthodontic techniques is increasingly incorporated into the multidisciplinary management of sleep-disordered breathing in children and adolescents. With increasing application of orthodontics to this clinical population it is important for healthcare providers, families, and patients to understand the wide range of available treatments. Orthodontists can guide craniofacial growth depending on age; therefore, it is important to work with other providers for a team-based approach to sleep-disordered breathing. From infancy to adulthood the dentition and craniofacial complex change with growth patterns that can be intercepted and targeted at critical time points. This article proposes a clinical guideline for application of multidisciplinary care with emphasis on dentofacial interventions that target variable growth patterns. We also highlight how these guidelines serve as a roadmap for the key questions that will influence future research directions. Ultimately the appropriate application of these orthodontic techniques will not only provide an important therapeutic option for children and adolescents with symptomatic sleep-disordered breathing but may help also mitigate or prevent its onset.
Topics: Adolescent; Humans; Child; Nonoxynol; Sleep Apnea Syndromes
PubMed: 37014012
DOI: 10.1093/sleep/zsad095 -
Frontiers in Immunology 2023Though significant correlations between rheumatoid arthritis (RA) and hypothyroidism have been found in earlier observational studies, their underlying causal...
OBJECT
Though significant correlations between rheumatoid arthritis (RA) and hypothyroidism have been found in earlier observational studies, their underlying causal relationship is still unknown. Mendelian randomization (MR) was used in the current study to assess the bidirectional causation between RA and hypothyroidism.
METHOD
We gathered summary data from genome-wide association studies (GWASs) of RA and hypothyroidism in people of European descent. Then, using data from the FinnGen consortium, we replicated our findings. Three approaches were employed to assess the causal link between RA and hypothyroidism: MR-Egger, weighted median (WM), and inverse variance weighted (IVW). The pleiotropy and heterogeneity were examined using a variety of techniques, including the MR-Egger intercept, the MR-PRESSO approach, the leave-one-out method, and the Cochran's Q test.
RESULTS
The study looked at a bidirectional incidental relationship between RA and hypothyroidism. The risk of hypothyroidism increased with RA (IVW odds ratio (OR) = 1.28, 95% confidence interval (CI) = 1.18-1.39, = 8.30E-10), as did the risk of secondary hypothyroidism (IVW OR = 1.12, 95% CI = 1.05-1.21, = 9.64E-4). The results of reverse MR analysis revealed that hypothyroidism (IVW OR = 1.68, 95% CI = 1.51-1.88, = 4.87E-21) and secondary hypothyroidism (IVW OR = 1.74, 95% CI = 1.50-2.01, = 1.91E-13) were linked to an increased risk of RA. Additionally, we obtain the same results in the duplicated datasets as well, which makes our results even more reliable. This study revealed no evidence of horizontal pleiotropy.
CONCLUSION
The present study established a bidirectional causal link between RA and hypothyroidism. However, it differs slightly from the findings of prior observational studies, suggesting that future research should concentrate on the interaction mechanisms between RA and hypothyroidism.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Arthritis, Rheumatoid; Hypothyroidism; Nonoxynol
PubMed: 37600807
DOI: 10.3389/fimmu.2023.1146261 -
Frontiers in Endocrinology 2023Numerous observational studies have indicated a link between the composition of gut microbiota and thyroid function. Nevertheless, the precise causal relationship...
BACKGROUND
Numerous observational studies have indicated a link between the composition of gut microbiota and thyroid function. Nevertheless, the precise causal relationship between gut microbiota and thyroid function remains uncertain.
METHODS
In this two-sample Mendelian randomization study, we utilized summary data from a genome-wide association study of gut microbiota composition in 18,340 participants from 24 cohorts, as well as summary statistics on thyroid hormones and thyroid-stimulating hormone from the ThyroidOmics Consortium and summary statistics on hypothyroidism and hyperthyroidism from the FinnGen R8 release. Five different methods, including inverse variance weighting, MR-Egger, weighted median, weighted mode, and simple mode, were employed to examine the causal relationship between gut microbiota and thyroid function. Reverse Mendelian randomization analysis was conducted for taxa identified as having a causal relationship with thyroid function in the Mendelian randomization analysis. To assess the robustness of the results, sensitivity analyses were conducted employing Cochran's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis.
RESULTS
Through MR analysis of 211 microbial taxa and 4 phenotypes, we identified a total of 34 gut microbiota taxa that were associated with the outcomes. After using the bonferroni method for multiple testing correction, phylum (id.400) had a protective effect on hypothyroidism (OR=0.883, 95% CI: 0.817-0.955, =0.002), and class (id.3087) had a protective effect on hyperthyroidism (OR=0.549, 95% CI: 0.374-0.805, =0.002). According to the results of reverse MR analysis, no significant causal effect of the four phenotypes was found on gut microbiota. No significant horizontal pleiotropy was detected based on MR-Egger intercept test and MR-PRESSO global test.
CONCLUSION
Through two-sample MR analysis, we identified specific gut microbiota taxa at the genetic level that are predicted to have a causal relationship with thyroid function, which may serve as useful biomarkers for early disease diagnosis.
Topics: Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Hypothyroidism; Hyperthyroidism; Nonoxynol
PubMed: 37822602
DOI: 10.3389/fendo.2023.1240752 -
Frontiers in Immunology 2023Primary biliary cirrhosis (PBC) and psoriasis are frequently observed to co-occur in clinical settings. However, the causal associations and underlying mechanisms...
BACKGROUND
Primary biliary cirrhosis (PBC) and psoriasis are frequently observed to co-occur in clinical settings. However, the causal associations and underlying mechanisms between PBC and psoriasis remain poorly defined.
METHODS
In this study, we conducted bidirectional MR analysis to explore the causal relationship between PBC and psoriasis using four MR methods: inverse-variance weighted, MR-Egger regression, weighted median, and weighted mode. Sensitivity analyses were carried out, employing different models and testing methods for comparison to assess the influence of heterogeneity and pleiotropy on our findings and to confirm the robustness of these results.
RESULTS
A causal relationship between the risk of PBC and psoriasis was identified, as confirmed by IVW analysis (OR: 1.081, 95%CI: 1.028~1.137, <0.05). The other three MR methods also produced similar results. However, psoriasis did not have a causal effect on PBC risk (OR: 1.022, 95%CI: 0.935~1.118, >0.05). The intercept of MR-Egger regression was 0.0013 (>0.05), indicating that genetic pleiotropy did not influence the results. Additionally, the leave-one-out analysis demonstrated the robustness of our MR findings.
CONCLUSION
This study reveals a causal relationship between PBC and psoriasis, with PBC increasing the risk of psoriasis, but not the reverse. This potential causal relationship offers a new perspective on the etiology of PBC.
Topics: Humans; Liver Cirrhosis, Biliary; Mendelian Randomization Analysis; Psoriasis; Genetic Pleiotropy; Nonoxynol
PubMed: 38239358
DOI: 10.3389/fimmu.2023.1264554 -
BMC Infectious Diseases Oct 2023Previous observational studies have indicated a correlation between the gut microbiota and influenza; however, the exact nature of the bidirectional causal connection... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous observational studies have indicated a correlation between the gut microbiota and influenza; however, the exact nature of the bidirectional causal connection remains uncertain.
METHOD
A two-way, two-sample Mendelian randomization (MR) study was conducted to evaluate the possible causal connection between the gut microbiota and the two outcomes of influenza (pneumonia without influenza and influenza pneumonia). The statistical analysis of gut microbiota is derived from the information of the most extensive meta-analysis (GWAS) conducted by the MiBioGen Alliance, encompassing a sample size of 18,340.The summary statistical data for influenza (not pneumonia, n = 291,090) and influenza pneumonia (n = 342,499) are from GWAS data published by FinnGen consortium R8.Estimate and summarize Single-nucleotide polymorphisms (SNPs) using Inverse variance weighted (IVW), MR Egger, and Weighted median (WM) in bidirectional MR analysis. To assess the heterogeneity, horizontal pleiotropy, and stability of SNPs, we employed Cochran's Q test, MR Egger intercept test, and sensitivity analysis.
RESULT
The IVW analysis indicated that there was a significant association between influenza infection and five bacterial taxa. Additionally, the abundance changes of seven gut microbiota were found to be causally related to influenza infection. In addition, seven bacterial taxa showed a significant association with the occurrence of influenza pneumonia. The findings from the WM analysis largely support the outcomes of IVW, however, the results of MR egger analysis do not align with IVW. Furthermore, there is no proof to substantiate the cause-and-effect relationship between influenza pneumonia and the composition of gut microbiota.
CONCLUSION
This analysis demonstrates a possible bidirectional causal connection between the prevalence of particular gut microbiota and the occurrence of influenza infection. The presence of certain gut microbiota may potentially contribute to the development of pneumonia caused by influenza. Additional investigation into the interaction between particular bacterial communities and influenza can enhance efforts in preventing, monitoring, and treating influenza.
Topics: Humans; Gastrointestinal Microbiome; Influenza, Human; Mendelian Randomization Analysis; Nonoxynol; Pneumonia; Genome-Wide Association Study
PubMed: 37848822
DOI: 10.1186/s12879-023-08706-x -
Nutrients Nov 2023The prior observational research on the impact of polyunsaturated fatty acid (PUFA) supplementation on osteoarthritis (OA) patients had yielded inclusive outcomes. This...
The prior observational research on the impact of polyunsaturated fatty acid (PUFA) supplementation on osteoarthritis (OA) patients had yielded inclusive outcomes. This study utilized the Mendelian randomization (MR) approach to explore potential causal relationships between PUFAs and OA. The MR study was performed using GWAS summary statistics for PUFAs, encompassing omega-3 and omega-6 fatty acids, and for knee OA (KOA) and hip OA (HOA). The primary inverse-variance-weighted (IVW) method and two supplementary MR approaches were used to establish robust causality. Heterogeneity and horizontal pleiotropy were assessed using Cochrane's Q and MR-Egger intercept tests. Additionally, a range of sensitivity analyses were conducted to strengthen the precision and reliability of the results. The IVW method indicated a potential genetic association between omega-3 fatty acids and KOA risk (odd ratio (OR) = 0.94, 95% confidence interval (CI): 0.89-1.00, = 0.048). No significant correlation was found between omega-3 levels and HOA. Moreover, genetically predicted higher levels of omega-6 fatty acids were associated with a decreased risk of KOA (OR = 0. 93, 95% CI: 0.86-1.00, = 0.041) and HOA (OR = 0.89, 95% CI: 0.82-0.96; = 0.003). The MR-Egger intercept evaluation showed no horizontal pleiotropy affecting the MR analysis (all > 0.05). Our findings supported the causal relationship between PUFAs and OA susceptibility and offered a novel insight that high omega-6 fatty acids may reduce the risk of KOA and HOA. These results underscore the importance of maintaining optimal levels of PUFAs, particularly omega-6 fatty acids, in individuals with a genetic predisposition to OA. Future research is necessary to validate these findings and elucidate the underlying mechanisms involved.
Topics: Humans; Mendelian Randomization Analysis; Reproducibility of Results; Fatty Acids, Unsaturated; Fatty Acids, Omega-6; Fatty Acids, Omega-3; Osteoarthritis, Knee; Nonoxynol; Genome-Wide Association Study
PubMed: 38004181
DOI: 10.3390/nu15224787