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Medicine Jun 2024Schizophrenia (SPR) is the most devastating mental illness that causes severe deterioration in social and occupational functioning, but, the etiology remains unknown....
Schizophrenia (SPR) is the most devastating mental illness that causes severe deterioration in social and occupational functioning, but, the etiology remains unknown. The objective of this study is to explore the genetic underpinnings of novelty seeking behavior in schizophrenic family within the Korean population. By conducting a family-based genome-wide association study, we aim to identify potential genetic markers and variations associated with novelty seeking traits in the context of SPR. We have recruited 27 probands (with SPR) with their parents and siblings whenever possible. DNA was extracted from blood sampling of 58 individuals in 27 families and analyzed in an Illumina core exome single nucleotide polymorphism (SNP) array. A family-based association test (qFAM) was used to derive SNP association values across all chromosomes. Although none of the final 800,000 SNPs reached the genome-wide significant threshold of 8.45 × 10-7, the most significant 4 SNPs were within the 10-5 to 10-7. This study identifies genetic associations between novelty seeking behavior and SPR within families. RAPGEF5 emerges as a significant gene, along with other neuropsychiatric-related genes. Noteworthy genes like DRD4 and COMT did not show associations, possibly due to the focus on schizophrenic family. While shedding light on this complex relationship, larger studies are needed for robust conclusions and deeper mechanistic insights.
Topics: Humans; Genome-Wide Association Study; Schizophrenia; Male; Female; Polymorphism, Single Nucleotide; Republic of Korea; Pilot Projects; Exploratory Behavior; Adult; Middle Aged; Genetic Predisposition to Disease; Young Adult
PubMed: 38941432
DOI: 10.1097/MD.0000000000038694 -
Medicine Jun 2024Primary sclerosing cholangitis (PSC), a chronic cholestatic liver condition, is frequently associated with inflammatory bowel disease. Specific immune cells have been...
Primary sclerosing cholangitis (PSC), a chronic cholestatic liver condition, is frequently associated with inflammatory bowel disease. Specific immune cells have been implicated in PSC pathogenesis with the emergence of the "microbiota" and "gut lymphocyte homing" hypotheses, albeit their identities remain controversial. The first genome-wide association analysis leveraged nonoverlapping data from 3757 Europeans to evaluate 731 immunophenotypes. A genome-wide association analysis comprising 2871 cases and 12,019 controls yielded summary statistics for PSC. An inverse-variance weighted (IVW) analysis was performed to identify immunophenotypes causally related to PSC, and the results were validated using weighted mode, MR-Egger, and weighted median methods. Comprehensive sensitivity analyses were performed to verify the robustness, heterogeneity, and horizontal pleiotropy of the results. IVW analysis revealed 26 immune traits exhibiting causal associations with PSC. CD3 on HLA-DR+ CD4+ (IVW odds ratio [OR]: 0.904; 95% confidence interval [CI]: 0.828-0.986, P = .023) and CD3 on secreting Treg (IVW OR: 0.893; 95% CI: 0.823-0.969, P = .007) were negatively associated with PSC susceptibility and demonstrated high consistency across the 3 validation methods. Moreover, 7 other immune traits, including CD39+ resting Treg absolute cell (IVW OR = 1.083, 95% CI: 1.013-1.157, P = .019), CD39+ secreting Treg absolute cell (IVW OR = 1.063, 95% CI: 1.012-1.118, P = .015), CD3 on naive CD8br (IVW OR = 0.907, 95% CI: 0.835-0.986, P = .022), CD3 on CD39+ activated Treg (IVW OR = 0.927, 95% CI: 0.864-0.994, P = .034), CD28 on resting Treg (IVW OR = 0.724, 95% CI: 0.630-0.833, P = 5.95E-06), and CD39 on CD39+ CD4+ (IVW OR = 1.055, 95% CI: 1.001-1.112, P = .044) exhibited consistent results in the Weighted Median and Weighted Mode validation methods. Moreover, no significant heterogeneity or horizontal pleiotropy was observed across the single nucleotide polymorphisms. The leave-one-out results revealed that sequentially eliminating each single nucleotide polymorphism had no significant influence on model effect estimates or qualitative inference. This study evaluated potential causal links between 731 immune traits and PSC susceptibility. Twenty-six immune traits were identified using the IVW method. Verification across multiple methods revealed 9 immune traits with a plausible causal connection to PSC. These findings may uncover mechanistic pathways and novel therapeutic approaches.
Topics: Cholangitis, Sclerosing; Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Immunophenotyping; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide
PubMed: 38941430
DOI: 10.1097/MD.0000000000038626 -
Medicine Jun 2024Several studies have confirmed the important role of endometrial cancer (EC) in the development and progression of breast cancer (BC), and this study will explore the...
Several studies have confirmed the important role of endometrial cancer (EC) in the development and progression of breast cancer (BC), and this study will explore the causal relationship between EC and BC by 2-sample Mendelian randomization analysis. Pooled data from published genome-wide association studies were used to assess the association between EC and BC risk in women using 5 methods, namely, inverse variance weighting (IVW), MR-Egger, weighted median (WME), simple multimaximetry (SM) and weighted multimaximetry (WM) with the EC-associated genetic loci as the instrumental variables (IV) and sensitivity analyses were used to assess the robustness of the results. The statistical results showed a causal association between EC and BC (IVW: OR = 1.07, 95% CI = 1.01-1.32, P = .02; MR-Egger: OR = 1.21, 95% CI = 0.71-1.51, P = .11; weighted median: OR = 1.05, 95% CI = 0.97-1.31, P = .19; simple plurality method: OR = 0.98, 95% CI = 0.81-1.15, P = .78; weighted plurality method: OR = 0.98, 95% CI = 0.81-1.14, P = .75), and the results of the sensitivity analyses showed that there was no significant heterogeneity or multiplicity, and the results were stable. EC is associated with an increased risk of developing BC. The results of this MR analysis can be used as a guideline for screening for BC in women with EC and to help raise awareness of screening for early detection and treatment.
Topics: Humans; Mendelian Randomization Analysis; Female; Endometrial Neoplasms; Breast Neoplasms; Genome-Wide Association Study; Risk Factors; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide
PubMed: 38941373
DOI: 10.1097/MD.0000000000038732 -
PloS One 2024The study of non-communicable diseases (NCDs) in a developing country like Thailand has rarely been conducted in long-term cohorts, especially among the working-age...
Metabolic and genetic risk factors associated with pre-diabetes and type 2 diabetes in Thai healthcare employees: A long-term study from the Siriraj Health (SIH) cohort study.
BACKGROUND
The study of non-communicable diseases (NCDs) in a developing country like Thailand has rarely been conducted in long-term cohorts, especially among the working-age population. We aim to assess the prevalence and incidence of risk factors and their associations underlying NCDs, especially type-2 diabetes mellitus (T2DM) among healthcare workers enrolled in the Siriraj Health (SIH) study cohort.
METHODS
The SIH study was designed as a longitudinal cohort and conducted at Siriraj hospital, Thailand. A total of 5,011 participants (77% women) were recruited and follow-up. Physical examinations, blood biochemical analyses, family history assessments, behavior evaluations, and genetics factors were assessed.
RESULTS
The average age was 35.44±8.24 years and 51% of participants were overweight and obese. We observed that men were more likely to have a prevalence of T2DM and dyslipidemia (DLP) compared to women. Aging was significantly associated with pre-diabetes and T2DM (P<0.001). Additionally, aging, metabolic syndrome, and elevated triglycerides were associated with the development of pre-diabetes and T2DM. The minor T allele of the rs7903146(C/T) and rs4506565 (A/T) were associated with a high risk of developing pre-diabetes with odds ratios of 2.74 (95% confidence interval [CI]: 0.32-23.3) and 2.71 (95% CI: 0.32-23.07), respectively; however, these associations were statistically insignificant (P>0.05).
CONCLUSION
The findings of the SIH study provide a comprehensive understanding of the health status, risk factors, and genetic factors related to T2DM in a specific working population and highlight areas for further research and intervention to address the growing burden of T2DM and NCDs.
Topics: Humans; Diabetes Mellitus, Type 2; Male; Female; Thailand; Adult; Risk Factors; Health Personnel; Middle Aged; Prediabetic State; Longitudinal Studies; Prevalence; Genetic Predisposition to Disease; Cohort Studies; Metabolic Syndrome; Polymorphism, Single Nucleotide; Southeast Asian People
PubMed: 38941315
DOI: 10.1371/journal.pone.0303085 -
PloS One 2024A differentially methylated region (DMR) is a genomic region that has significantly different methylation patterns between biological conditions. Identifying DMRs...
A differentially methylated region (DMR) is a genomic region that has significantly different methylation patterns between biological conditions. Identifying DMRs between different biological conditions is critical for developing disease biomarkers. Although methods for detecting DMRs in microarray data have been introduced, developing methods with high precision, recall, and accuracy in determining the true length of DMRs remains a challenge. In this study, we propose a normalized kernel-weighted model to account for similar methylation profiles using the relative probe distance from "nearby" CpG sites. We also extend this model by proposing an array-adaptive version in attempt to account for the differences in probe spacing between Illumina's Infinium 450K and EPIC bead array respectively. We also study the asymptotic results of our proposed statistic. We compare our approach with a popular DMR detection method via simulation studies under large and small treatment effect settings. We also discuss the susceptibility of our method in detecting the true length of the DMRs under these two settings. Lastly, we demonstrate the biological usefulness of our method when combined with pathway analysis methods on oral cancer data. We have created an R package called idDMR, downloadable from GitHub repository with link: https://github.com/DanielAlhassan/idDMR, that allows for the convenient implementation of our array-adaptive DMR method.
Topics: DNA Methylation; Humans; CpG Islands; Oligonucleotide Array Sequence Analysis; Mouth Neoplasms; Algorithms; Software; Computer Simulation
PubMed: 38941289
DOI: 10.1371/journal.pone.0306036 -
JAMA Network Open Jun 2024Although existing research has found daily heat to be associated with dementia-related outcomes, there is still a gap in understanding the differing associations of...
IMPORTANCE
Although existing research has found daily heat to be associated with dementia-related outcomes, there is still a gap in understanding the differing associations of nighttime and daytime heat with dementia-related deaths.
OBJECTIVES
To quantitatively assess the risk and burden of dementia-related deaths associated with short-term nighttime and daytime heat exposure and identify potential effect modifications.
DESIGN, SETTING, AND PARTICIPANTS
This case-crossover study analyzed individual death records for dementia across all mainland China counties from January 1, 2013, to December 31, 2019, using a time-stratified case-crossover approach. Statistical analysis was conducted from January 1, 2013, to December 31, 2019.
EXPOSURES
Two novel heat metrics: hot night excess (HNE) and hot day excess (HDE), representing nighttime and daytime heat intensity, respectively.
MAIN OUTCOMES AND MEASURES
Main outcomes were the relative risk and burden of dementia-related deaths associated with HNE and HDE under different definitions. Analysis was conducted with conditional logistic regression integrated with the distributed lag nonlinear model.
RESULTS
The study involved 132 573 dementia-related deaths (mean [SD] age, 82.5 [22.5] years; 73 086 women [55.1%]). For a 95% threshold, the median hot night threshold was 24.5 °C (IQR, 20.1 °C-26.2 °C) with an HNE of 3.7 °C (IQR, 3.1 °C-4.3 °C), and the median hot day threshold was 33.3 °C (IQR, 29.9 °C-34.7 °C) with an HDE of 0.6 °C (IQR, 0.5 °C-0.8 °C). Both nighttime and daytime heat were associated with increased risk of dementia-related deaths. Hot nights' associations with risk of dementia-related deaths persisted for 6 days, while hot days' associations with risk of dementia-related deaths extended over 10 days. Extreme HDE had a higher relative risk of dementia-related deaths, with a greater burden associated with extreme HNE at more stringent thresholds. At a 97.5% threshold, the odds ratio for dementia-related deaths was 1.38 (95% CI, 1.22-1.55) for extreme HNE and 1.46 (95% CI, 1.27-1.68) for extreme HDE, with an attributable fraction of 1.45% (95% empirical confidence interval [95% eCI], 1.43%-1.47%) for extreme HNE and 1.10% (95% eCI, 1.08%-1.11%) for extreme HDE. Subgroup analyses suggested heightened susceptibility among females, individuals older than 75 years of age, and those with lower educational levels. Regional disparities were observed, with individuals in the south exhibiting greater sensitivity to nighttime heat and those in the north to daytime heat.
CONCLUSIONS AND RELEVANCE
Results of this nationwide case-crossover study suggest that both nighttime and daytime heat are associated with increased risk of dementia-related deaths, with a greater burden associated with nighttime heat. These findings underscore the necessity of time-specific interventions to mitigate extreme heat risk.
Topics: Humans; China; Dementia; Female; Male; Aged; Aged, 80 and over; Hot Temperature; Cross-Over Studies; Risk Factors
PubMed: 38941091
DOI: 10.1001/jamanetworkopen.2024.19250 -
Parasitology Research Jun 2024As ecosystem disruptors and intermediate hosts for various parasites, freshwater snails have significant socioeconomic impacts on human health, livestock production, and... (Review)
Review
As ecosystem disruptors and intermediate hosts for various parasites, freshwater snails have significant socioeconomic impacts on human health, livestock production, and aquaculture. Although traditional molluscicides have been widely used to mitigate these effects, their environmental impact has encouraged research into alternative, biologically based strategies to create safer, more effective molluscicides and diminish the susceptibility of snails to parasites. This review focuses on alterations in glucose metabolism in snails under the multifaceted stressors of parasitic infections, drug exposure, and environmental changes and proposes a novel approach for snail management. Key enzymes within the glycolytic pathway, such as hexokinase and pyruvate kinase; tricarboxylic acid (TCA) cycle; and electron transport chains, such as succinate dehydrogenase and cytochrome c oxidase, are innovative targets for molluscicide development. These targets can affect both snails and parasites and provide an important direction for parasitic disease prevention research. For the first time, this review summarises the reverse TCA cycle and alternative oxidase pathway, which are unique metabolic bypasses in invertebrates that have emerged as suitable targets for the formulation of low-toxicity molluscicides. Additionally, it highlights the importance of other metabolic pathways, including lactate, alanine, glycogenolysis, and pentose phosphate pathways, in snail energy supply, antioxidant stress responses, and drug evasion mechanisms. By analysing the alterations in key metabolic enzymes and their products in stressed snails, this review deepens our understanding of glucose metabolic alterations in snails and provides valuable insights for identifying new pharmacological targets.
Topics: Animals; Molluscacides; Snails; Glucose; Fresh Water
PubMed: 38940835
DOI: 10.1007/s00436-024-08274-2 -
Alternative Therapies in Health and... Jun 2024This study aimed to investigate the disease characteristics of children admitted to the hospital with high fever on an emergency basis and assess the health needs of...
OBJECTIVE
This study aimed to investigate the disease characteristics of children admitted to the hospital with high fever on an emergency basis and assess the health needs of their family members. Additionally, it aimed to analyze nursing strategies focusing on the management of chronic internal infections.
METHOD
A total of 526 children with high fever admitted between December 2020 and December 2022 were included in the study. Among them, 368 (69.96%) were aged younger than six years, and the remaining 158 were aged between (6~18 years). The main health needs of family members were assessed using a questionnaire. The children were randomly assigned to control and observation groups, each comprising 263 cases. The control group received routine emergency nursing, while the observation group received advanced chronic nursing strategies focusing on internal infections. The study compared the time taken for temperature normalization, management of depression in children, the occurrence of negative emotions among family members and nurse-patient disputes, nursing quality scores, satisfaction levels, health knowledge mastery rates, and nursing processing ability scores of family members between the two groups.
RESULTS
The observation group exhibited significantly shorter time to temperature normalization and better depression management compared to the control group. Additionally, the observation group showed lower occurrences of negative emotions among family members and nurse-patient disputes, higher nursing quality scores and satisfaction levels, and better health knowledge mastery rates and nursing processing ability scores of family members (P < .05).
CONCLUSIONS
Considering the rapid progression of conditions in emergently hospitalized children with high fever and the susceptibility of family members to various negative emotions, tailored chronic nursing strategies centered on internal infections can significantly enhance clinical diagnosis, reduce nurse-patient disputes, improve nursing quality, and elevate family nursing standards.
PubMed: 38940812
DOI: No ID Found -
Journal of Pediatric Hematology/oncology Jun 2024Programmed death-1 (PD1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) have a vital role in immune checkpoint pathways. Single nucleotide polymorphisms (SNPs)...
Relationship Between Cytotoxic T-Lymphocyte-Associated Antigen-4: Programmed Death-1 Genes Polymorphisms and Susceptibility to Pediatric B-Cell Acute Lymphoblastic Leukemia.
Programmed death-1 (PD1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) have a vital role in immune checkpoint pathways. Single nucleotide polymorphisms (SNPs) of PD1 and CTLA4 have been reported to be associated with susceptibility to certain autoimmune diseases and cancers. The potential association between SNPs in these immune checkpoint genes and risk of acute lymphoblastic leukemia (ALL) still unclear. The aim of this study is to clarify the effect of PD1 and CTLA4 SNPs on the risk of developing ALL and the prognosis of the disease. The study was performed on 100 pediatric B-ALL patients and 100 controls. The PD1 and CTLA4 SNPs were examined by RFLP technique. The study revealed that CTLA4 (rs11571316) was associated with high risk of B-ALL developments OR 1.492 (CI: 1157 to 1924) (P=0.002). PD1 (rs36084323) GA genotype was significantly associated with protective effect against nonremission (P=0.007). PD1 (rs36084323) A allele were associated with protective effect against relapse (P=0.008). CTLA4 and PD1 genotypes did not have significant impact on B-ALL patients outcome. The current study displayed for the first time that genetic variations of the CTLA-4, was associated with susceptibility to B-ALL and that PD1 (rs36084323) GA genotype was significantly associated with protective effect against nonremission, while PD1 (rs36084323) A allele was associated with protective effect against relapse.
PubMed: 38940594
DOI: 10.1097/MPH.0000000000002909 -
Medeniyet Medical Journal Jun 2024There is no test parameter with high sensitivity and specificity for the diagnosis of motion sickness. The aim of this study was to demonstrate a correlation between...
OBJECTIVE
There is no test parameter with high sensitivity and specificity for the diagnosis of motion sickness. The aim of this study was to demonstrate a correlation between vestibular function tests and motion sickness. In addition, our secondary aim is to evaluate the sensitivity of the skull vibration-induced nystagmus test (SVINT) in the diagnosis of motion sickness.
METHODS
A total of 44 young adults aged 19-25 who had no hearing loss, complaints of dizziness/vertigo, or any diagnosed neurological disease were included. According to the motion sickness susceptibility questionnaire-short form (MSSQ-SF), participants were divided into the motion sickness group (21±1.38 years) and control group (20.5±1.18 years). Mean MSSQ-SF score for the motion sickness group is 78.18±12.2 and for control group 19.09±17.08. Ocular and cervical vestibular evoked myogenic potential tests, SVINT, video head impulse test, and oculomotor tests were performed.
RESULTS
The only significant difference between the groups was in n1-p1 amplitudes in the left ocular vestibular evoked myogenic potential test (p=0.014). None of the other parameters differed between the two groups (p>0.05).
CONCLUSIONS
There was no significant relationship between motion sickness susceptibility and the results of any vestibular function test. Performing diagnostic tests for motion sickness in an environment that creates significant sensory conflict may yield different results. This study contributes to the literature in terms of evaluating the vestibular system using a comprehensive test battery and is the first to use the SVINT test in motion sickness.
PubMed: 38940460
DOI: 10.4274/MMJ.galenos.2024.08504