Association between volatile organic compounds and serum neurofilament light chain in US adults.

OBJECTIVE: This study aimed to investigate the associations between exposure to blood volatile organic compounds (VOCs) and the level of serum neurofilament light chain (NfL) in adults. METHODS: We analyzed data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES), including 2008 participants aged 20 to 75 years old. Multiple linear regression models were used to examine the associations between 28 VOCs and NfL after adjusting for multiple potential confounders. Restricted cubic spline (RCS) was used to examine the potential non-linear associations. RESULTS: The linear regression models showed that higher levels of 2,5-dimethylfuran (ß = 0.042, 95 % confidence interval [CI]: 0.001, 0.096), ethyl acetate (ß = 0.118, 95 % CI = 0.008, 0.304), and m-/p-xylene (ß = 0.043, 95%CI = 0.012, 0.074) were associated with higher NfL levels. These estimates were largely consistent after adjusting for multiple confounders. CONCLUSION: The findings of our study suggest a potential association between certain volatile organic compounds (2,5-dimethylfuran, ethyl acetate, and m-/p-xylene) and blood NfL levels, implying that they may have a role in revealing neurodegeneration and influencing neurological health.

Genetically determined telomere length and its association with chronic obstructive pulmonary disease and interstitial lung disease in biobank Japan: A Mendelian randomization study.

Importance: Chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) have been linked to shorter telomere length (TL). While understanding this association has critical clinical implications for respiratory diseases, previous studies exploring these associations were conducted in European populations. The present study aims to investigate this relationship in an Asian population. Objective: To examine the causal relationship between leukocyte TL and COPD and ILD in an Asian population. Design: Setting, and Participants: We used a genome-wide association study summary statistics-based two-sample Mendelian randomization (MR) design to investigate the association between leukocyte TL, genetically predicted by nine single-nucleotide polymorphisms and the risk of COPD and ILD. Participants were Japanese individuals enrolled in the Biobank Japan Project, including 3315 COPD patients and 806 ILD patients. Exposure: Leukocyte TL was genetically predicted by nine single-nucleotide polymorphisms. Results: The inverse-variance weighted estimates showed a significant inverse association between leukocyte TL and COPD (odds ratio [OR] = 0.78; 95 % confidence interval [CI]: 0.64, 0.95; P = 0.01) and ILD (OR = 0.29; 95 % CI: 0.14, 0.61; P = 0.001), respectively. All sensitivity analyses yielded consistent results. The MR-Egger regression intercept test showed no evidence of horizontal pleiotropy (Pintercept: COPD, 0.56; ILD: 0.70). Conclusion: and Relevance: Our findings suggest that leukocyte telomere shortening may causally increase the risk of COPD and ILD. These results highlight the potential importance of TL for these respiratory diseases.

Association between cytomegalovirus seropositivity and all-cause mortality: An original cohort study.

To examine the association between cytomegalovirus (CMV) seropositivity and all-cause mortality in a nationwide cohort of US adults. We obtained data from the National Health and Nutrition Examination Survey III (1988-1994), including 16,547 participants aged 18-90 years old with CMV serology assessments. Mortality status was ascertained until December 2019 using the National Death Index linkage data. The Cox proportional hazard model was applied to estimate the association between CMV seropositivity and mortality. During a median follow-up of 26.3 years, 6,930 deaths were recorded. CMV seropositivity was associated with a higher hazard of all-cause mortality after adjusting for attained age, sex, and ethnicity (HR: 1.22, 95% CI: 1.10, 1.36, p < 0.001). The magnitude of the association attenuated slightly after adjusting further for body mass index, family income, smoking status, diabetes, and self-reported cancer history (HR = 1.11, 95% CI: 1.00, 1.23, p = 0.04). While the association was observed for both men and women, it was only statistically significant among non-Hispanic white people (HR: 1.16, 95% CI: 1.06, 1.26, p = 0.001) but not among other ethnic populations. CMV seropositivity might be an independent risk factor for all-cause mortality among US adults. If the findings are validated in an independent population, further research is needed to unveil the biological mechanisms driving the increased mortality with CMV seropositivity.

Associations between psychological resilience and epigenetic clocks in the health and retirement study.

The aim of this study was to evaluate the associations between psychological resilience and epigenetic clocks assessed by DNA methylation age predictions. We used data from 4018 participants in the Health and Retirement Study. Multivariable linear regression models were used to estimate the association between psychological resilience and epigenetic clocks adjusted for age, sex, race, body mass index, smoking status, and years of education. Thirteen epigenetic clocks were used in our analysis and were highly correlated with one another. A higher psychological resilience score was associated with slower DNA methylation age acceleration for the majority of epigenetic clocks after multivariable adjustment. These findings imply that people with a higher level of psychological resilience may experience slower DNA methylation age acceleration and biological aging.

Association between cytomegalovirus infection and cancer­related mortality in the US adults.

PURPOSE: In a nationwide cohort of US adults, an exploration of the association between cytomegalovirus (CMV) infection and cancer­related mortality was conducted. MATERIALS AND METHODS: We acquired data from the National Health and Nutrition Examination Survey III (1988-1994), including 11,138 individuals who were aged 18-90 years at enrollment and underwent CMV serology assessments. CMV infection was determined by CMV antibody testing. Cancer­related mortality status was ascertained until December 2019 utilizing the National Death Index linkage data and determined by neoplasms. The Cox proportional hazard model was applied to estimate the potential association between CMV infection and the risk of cancer-related mortality. RESULTS: During a median follow-up of 26.1 years, 1514 cancer­related deaths were identified in the study cohort. After adjusting for age, sex, and ethnicity, CMV infection was associated with a higher hazard of cancer­related mortality (hazard ratio [HR]: 1.39, 95 % CI: 1.13, 1.70). Further adjustments for body mass index, family income, and smoking status slightly attenuated the magnitude of the association (HR: 1.24, 95 % CI: 1.00, 1.53). However, no significant interaction was observed among gender by subgroup analysis. CONCLUSIONS: CMV infection might be an independent risk factor for cancer­related mortality among US adults. Future studies could focus on the mechanisms through which CMV infection influences mortality induced by neoplasms and develop targeted interventions to reduce the risk.

Disturbance of gut microbiota aggravates cadmium-induced neurotoxicity in zebrafish larvae through V-ATPase.

Cadmium (Cd) is a harmful environmental pollutant that causes damage to the nervous system, and exposure to Cd also disrupts the gut microbiota. However, it is still unclear whether Cd-induced neurotoxicity is related to alteration of the microbiota. In this study, we first established a germ-free (GF) zebrafish model to avoid the effects of gut microbiota disturbances caused by Cd exposure, and found that Cd-induced neurotoxic effects were weak in GF zebrafish. RNA sequencing showed that expression levels of V-ATPase family genes (atp6v1g1, atp6v1b2, and atp6v0cb) were significantly decreased in Cd-treated conventionally reared (CV) zebrafish, while this inhibition could be avoided in GF zebrafish. Overexpression of atp6v0cb in the V-ATPase family could partially rescue Cd-induced neurotoxicity. Our study shows that the disturbance of gut microbiota aggravates Cd-induced neurotoxicity, and that this may be associated with the expression of several genes in the V-ATPase family.

Sex-specific non-linear associations between body mass index and impaired pulmonary ventilation function in a community-based population: Longgang COPD study.

Aim: To investigate the prevalence of pulmonary airflow limitation and its association with body mass index (BMI) in a community-based population in Shenzhen, China. Methods: Study participants were recruited from Nanlian Community in Shenzhen, China, and spirometry was performed to assess lung function including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, and FEV1 divided by predicted value. Pulmonary airflow limitation was determined by the Chinese Guideline of Pulmonary Function Examination. Multivariable logistic regression models were used to examine the association between BMI and pulmonary airflow limitation. Age, sex, educational attainment, occupation, and current cigarette smoking were used as potential confounders. Results: Of the 1206 participants, 612 (50.7%) were men and 594 (49.3%) were women with the average age being 53.7 years old. After adjusting for age, sex, educational attainment, occupation, and current cigarette smoking, higher BMI was associated with lower odds (odds ratio: 0.98, 95% confidence interval: 0.97, 0.99) of pulmonary airflow limitation by assuming a linear relationship. Further investigation of the interaction terms, we found that the magnitudes of the associations differed in men and women. A U-shaped relationship was observed in women, while the association was almost linear in men. Conclusion: The relationship between BMI and pulmonary airflow limitation was U-shaped in women and linear in men.

Trends in burden of multidrug-resistant tuberculosis in countries, regions, and worldwide from 1990 to 2017: results from the Global Burden of Disease study.

BACKGROUND: Antituberculosis-drug resistance is an important public health issue, and its epidemiological patterns has dramatically changed in recent decades. This study aimed to estimate the trends of multidrug-resistant tuberculosis (MDR-TB), which can be used to inform health strategies. METHODS: Data were collected from the Global Burden of Disease study 2017. The estimated annual percentage changes (EAPCs) were calculated to assess the trends of MDR-TB burden at global, regional, and national level from 1990 to 2017 using the linear regression model. RESULTS: Globally, the age-standardized rate (ASR) of MDR-TB burden including incidence, prevalence, death and disability-adjusted life years (DALYs) had pronounced increasing trends from 1990 to 1999, with the EAPCs were 17.63 [95% confidence interval (CI): 10.77-24.92], 17.57 (95% CI 11.51-23.95), 21.21 (95% CI 15.96-26.69), and 21.90 (95% CI 16.55-27.50), respectively. Particularly, the largest increasing trends were seen in areas and countries with low and low-middle sociodemographic index (SDI). However, the trends in incidence, prevalence, death and DALYs of MDR-TB decreased globally from 2000 to 2017, with the respective EAPCs were - 1.37 (95% CI - 1.62 to - 1.12), - 1.32 (95% CI - 1.38 to - 1.26), - 3.30 (95% CI - 3.56 to - 3.04) and - 3.32 (95% CI - 3.59 to - 3.06). Decreasing trends of MDR-TB were observed in most regions and countries, particularly that of death and DALYs in Slovenia were - 18.96 (95% CI - 20.82 to - 17.06) and -19.35 (95% CI - 21.10 to - 17.55), respectively. Whereas the pronounced increasing trends of MDR-TB occurred in Papua New Guinea, Singapore, and Australia. CONCLUSIONS: The ASR of MDR-TB showed pronounced decreasing trends from 2000 to 2017. However, the MDR-TB burden remains a substantial challenge to the TB control globally, and requires effective control strategies and healthcare systems.

[Identification of a novel mutation of GALNS gene from a Chinese pedigree with mucopolysaccharidosis type IV A].

OBJECTIVE: To study the molecular genetic mechanism of mucopolysaccharidosis type IV A(MPS IV A), and reveal the relationship between the genotype and phenotype, and provide a basis for prenatal gene diagnosis in the future. METHODS: A preliminary diagnosis was made by qualitative detection of urinary glycosaminoglycans of the suspected MPS IV A proband. Then, mutation detection was performed on the proband and her family members with PCR and direct sequencing of the PCR products. After a novel c.1567T to G mutation was detected, Xsp I restriction enzyme digestion and amplification refractory mutation system (ARMS) fast specific identification were established to analyze the sequences of exon 14 in GALNS gene, including 110 randomly selected healthy controls, the proband and other pedigree members. At the same time, bioinformatic approaches for protein secondary, tertiary structure prediction were applied to identify the novel pathologic mutation. RESULTS: The proband's urine GAGs test was a weak positive(± ), and a c.1567T to G heterozygous termination codon mutation in exon 14 and a c.374C to T heterozygous missense mutation in exon 4 were found. The proband was compound heterozygous of the two mutations, so was her younger sister. Her mother was a carrier with only a c.1567T to G heterozygous mutation in exon 14. Her father had a heterozygous mutation of c.374C to T in exon 4. After Xsp I restriction enzyme digestion, healthy controls had three bands including 28 bp, 120 bp and 399 bp, while the proband and her mother had four bands consisting of 28 bp, 120 bp, 148 bp and 399 bp. For amplification by ARMS specific primers, it was negative for the controls, while it was positive for the proband and the carrier. The results of protein secondary and tertiary structure prediction showed that the c.1567T to G mutation located in the stop codon, resulted in stop codon (TAG) changing to glutamic acid (GAG), with the peptide chain extending 92 amino acid residues, and secondary and tertiary protein structure change, which were not found in the controls. The result of enzyme assay showed that the activity of GALNS enzyme in the affected child was 8.3 nmol/17h/mg pr, which was obviously lower than the normal value (the normal range is 41.9-92.1 nmol/17h/mg pr). CONCLUSION: These results illustrate that the c.1567 T to G is a novel pathologic mutation, which is the main cause of the disease in this family.

A new mutation (1062 del 16) of iduronate-2-sulfatase gene from a Chinese patient with Hunter syndrome.

OBJECTIVE: To identify the mutations of iduronate-2-sulfatase (IDS) gene, to reveal its mutation features, and to establish a basis for genetic counseling and prenatal gene diagnosis of Hunter syndrome. METHODS: Urine glycosaminoglycans (GAGs) assay, PCR and DNA sequencing were performed to detect mutation of IDS gene of the patient and his parents. RESULTS: The result showed that the patient was: DS(++), HS(++), KS(-), CS(-), and that both of his parents were negative. A frame-shift deletion mutation (1062 del 16) was identified in exon 7 of the patient's IDS gene. His parents' genotypes were normal. CONCLUSION: The patient's mutation was not inherited by his parents but a novel one. The mutation probably altered the primary structure and tertiary structure of IDS enzyme protein remarkably and lowered the activity of IDS enzyme greatly. Therefore it is supposed to be the direct cause of the disorder.