Spatial distribution differences of cholinesterase in healthy Chinese under the influence of geographical environmental factors.

The main targets of this were to screen the factors that may influence the distribution of cholinesterase (CHE) reference value in healthy people, and further explored the geographical distribution differences of CHE reference value in China. In this study, we collected the CHE data of 17,601 healthy people from 173 cities in China to analyse the correlation between CHE and 22 geography secondary indexes through spearman regression analysis. Six indexes with significant correlation were extracted, and a ridge regression model was built, and the country's urban CHE reference value of healthy Chinese was predicted. By using the disjunctive kriging method, we obtained the geographical distribution of CHE reference values for healthy people in China. The reference value of CHE for healthy Chinese was significantly correlated with the 6 secondary indexes, namely, latitude (°), altitude (m), annual average temperature (°C), annual average relative humidity (%) and annual precipitation (mm), and topsoil sand gravel percentage (% wt). The geographical distribution of CHE values of healthy Chinese showed a trend of being higher in southeast China and lower in northwest. This study lays a foundation for further research on the mechanism of different influencing factors on the reference value of CHE index. A ridge regression model composed of significant influencing factors has been established to provide the basis for formulating reference criteria for the treatment factors of the liver damage diseases and liver cancer using CHE reference values in different regions.

Increasing Engagement of Women Veterans in Health Research.

BACKGROUND: Meaningful engagement of patients in health research has the potential to increase research impact and foster patient trust in healthcare. For the past decade, the Veterans Health Administration (VA) has invested in increasing Veteran engagement in research. OBJECTIVE: We sought the perspectives of women Veterans, VA women's health primary care providers (WH-PCPs), and administrators on barriers to and facilitators of health research engagement among women Veterans, the fastest growing subgroup of VA users. DESIGN: Semi-structured qualitative telephone interviews were conducted from October 2016 to April 2018. PARTICIPANTS: Women Veterans (N=31), WH-PCPs (N=22), and administrators (N=6) were enrolled across five VA Women's Health Practice-Based Research Network sites. APPROACH: Interviews were audio-recorded and transcribed. Consensus-based coding was conducted by two expert analysts. KEY RESULTS: All participants endorsed the importance of increasing patient engagement in women's health research. Women Veterans expressed altruistic motives as a personal determinant for research engagement, and interest in driving women's health research forward as a stakeholder or research partner. Challenges to engagement included lack of awareness about opportunities, distrust of research, competing priorities, and confidentiality concerns. Suggestions to increase engagement include utilizing VA's patient-facing portals of the electronic health record for outreach, facilitating "warm hand-offs" between researchers and clinic staff, developing an accessible research registry, and communicating the potential research impact for Veterans. CONCLUSIONS: Participants expressed support for increasing women Veterans' engagement in women's health research and identified feasible ways to foster and implement engagement of women Veterans. Given the unique healthcare needs of women Veterans, engaging them in research could translate to improved care, especially for future generations. Knowledge about how to improve women Veterans' research engagement can inform future VA policy and practice for more meaningful interventions and infrastructure.

Prevalence of Mental Health Disorders Among Immigrant, Refugee, and Nonimmigrant Children and Youth in British Columbia, Canada.

Importance: There remains limited understanding of population-level patterns of mental disorder prevalence for first- and second-generation immigrant and refugee children and youth and how such patterns may vary across mental disorders. Objective: To examine the diagnostic prevalence of conduct, attention-deficit/hyperactivity disorder (ADHD), and mood/anxiety disorders in immigrant, refugee, and nonimmigrant children and youth in British Columbia, Canada. Design, Setting, and Participants: This retrospective, population-level cohort study examined linked health administrative records of children and youth in British Columbia (birth to age 19 years) spanning 2 decades (1996-2016). Physician billings, hospitalizations, and drug dispensations were linked to immigration records to estimate time-in-British Columbia-adjusted prevalence of mental disorder diagnosis among children and youth from immigrant or refugee backgrounds compared with those from nonimmigrant backgrounds. Analyses were conducted from August 2020 to November 2021. Main Outcomes and Measures: The diagnostic prevalence of conduct, ADHD, and mood/anxiety disorders were the main outcomes. Results were stratified by migration category (immigrant, refugee, nonimmigrant), generation status (first- and second-generation), age, and sex. Results: A total of 470 464 children and youth in British Columbia were included in the study (227 217 [48.3%] female). Nonimmigrant children and youth represented 65.5% of the total study population (307 902 individuals). Among those who migrated, 142 011 (87.8%) were first- or second-generation immigrants, and 19 686 (12.2%) were first- or second-generation refugees. Diagnostic prevalence of mental disorders varied by migration category, generation status, age, and sex. Children and youth from immigrant and refugee backgrounds (both first- and second-generation), compared with nonimmigrant youth, generally had a lower prevalence of conduct disorder (eg, age 6-12 years: first-generation immigrant, 2.72% [95% CI, 2.56%-2.90%] vs nonimmigrant, 7.03% [95% CI, 6.93%-7.13%]), ADHD (eg, age 6-12 years: first-generation immigrant, 4.30% [95% CI, 4.10%-4.51%] vs nonimmigrant, 9.20% [95% CI, 9.08%-9.31%]), and mood/anxiety disorders (eg, age 13-19 years: first-generation immigrant, 11.07% [95% CI, 10.80%-11.36%] vs nonimmigrant, 24.54% [95% CI, 24.34%-24.76%]). Among immigrant children and youth, second-generation children and youth generally showed higher prevalence of conduct, ADHD, and mood/anxiety disorders than first-generation children and youth (eg, ADHD among second-generation immigrants aged 6-12 years, 5.94% [95% CI, 5.75%-6.14%]; among first-generation immigrants aged 6-12 years, 4.30% [95% CI, 4.10%-4.51%]). Second-generation refugee children had the highest diagnostic prevalence estimates for mood/anxiety in the 3-to-5-year age range relative to first- and second-generation immigrant and nonimmigrant children (eg, second-generation refugee, 2.58% [95% CI, 2.27%-2.94%] vs second-generation immigrant, 1.78% [95% CI, 1.67%-1.89%]). Mental disorder diagnoses also varied by age and sex within immigrant, refugee, and nonimmigrant groups. Conclusions and Relevance: These findings show differences in diagnostic mental disorder prevalence among first- and second-generation immigrant and refugee children and youth relative to nonimmigrant children and youth. Further investigation is required into how cultural differences and barriers in accessing health services may be contributing to these differences.

Transcriptional Analysis of Total CD8+ T Cells and CD8+CD45RA- Memory T Cells From Young and Old Healthy Blood Donors.

Memory CD8+ T cells accumulate with aging, while the naïve T cell compartment decreases, leading to an increased susceptibility to infections and a decreased vaccine efficiency. To get deeper insights into the underlying mechanisms, this study aims to determine the age-dependent expression profile of total versus memory CD8+ T cells from young and old donors. Total CD8+ and CD8+CD45RA- memory T cells isolated from young (<30 years) and old (>60 years) donors were stimulated with anti-CD3 and anti-CD28 antibodies for 48h before analyzing the cytokine secretion and activation markers by flow cytometry and changes in the expression profiles using RNA sequencing. Gene ontology (GO) term enrichment analyses were performed for up-regulated and uniquely expressed transcripts identified in the T cell populations of both age groups. Total and memory CD8+ T cells from old donors expressed significantly higher CD25 levels and have an increased cytokine secretion. While approximately 1,500 up-regulated transcripts were identified in all groups, CD8+CD45RA- memory T cells of old donors had approximately 500 more uniquely expressed transcripts. Four GO terms related to the JAK-STAT pathway were identified for up-regulated transcripts in the total CD8+ T cells of old donors, whereas CD8+CD45RA- memory T cells GO terms related to adjacent pathways, like JNK and MAPK/ERK, were found. Additionally, the unique transcripts of CD8+CD45RA- memory T cells of old donors were related to the JNK, MAPK and IL-12 pathways. For both T cell populations of the old donors, cytokine and JAK-STAT pathway transcripts were up-regulated. Thus, an age-dependent effect was observed on the transcriptomes of total and memory CD8+ T cells. The CD8+ CD45RA- memory T cells from old donors maintained the increased cytokine secretion of the total CD8+ T cell population and the increased JAK-STAT pathway transcripts, which have an impact on inflammation and senescence.

Comparison of pneumococcal colonization density among healthy children and children with respiratory symptoms using real time PCR (RT-PCR).

BACKGROUND: Nasopharyngeal colonization is considered a necessary step in the initiation of pneumococcal diseases. Real time PCR (RT-PCR) is an alternative approach for the identification and quantification of pneumococci directly from samples. OBJECTIVES: To compare pneumococcal detection rates using culture-based method versus RT-PCR direct detection and to quantify pneumococcal colonization in two study cohorts (healthy children and hospitalized children with respiratory symptoms) using quantitation through RT-PCR. METHODOLOGY: A total of 101 nasopharyngeal swabs (NPS) from healthy children and 183 NPSs from hospitalized children with respiratory symptoms were included in the study. None of the children were vaccinated. All children were between 2 months to 2 years. In parallel to routine culture and identification, a RT-PCR assay targeting the lytA gene was done. RESULTS: Considering all 284 samples tested, colonization rate by conventional culture was 41.2% (n = 117) while positive colonization using RT-PCR was 43.7% (n = 124). The colonization rate detected by RT-PCR in the healthy cohort was 33.7% (n = 34) and it was 49.2% (n = 90) in the hospitalized cohort. It was 37.6% (n = 38) and 43.2% (n = 79) for the two cohorts by culture. The mean Cq value for the healthy cohort is 29.61 (SD 2.85) and 28.93 (SD 3.62) for the hospitalized cohort. With the standard curve obtained from amplifying a dilution series of control DNA, the mean amount of genomic DNA copy numbers detected in children with respiratory symptoms was log10 7.49 (SD 1.07) while it was log10 7.30 (SD 0.23) in healthy children and the difference was not statistically significant. CONCLUSIONS: The overall colonization rate was higher when detected using RT-PCR compared to culture. However, it was lower in the healthy group when detected with RT-PCR compared to culture. Even though there was a higher detection of pneumococcal colonization density in children with respiratory symptoms, this was not significantly higher unlike many previous studies. Therefore, the use of RT-PCR to detect pneumococcal colonization needs further evaluation with careful analysis of interpretation and confounders.

Getting under the skin: Social isolation and biological markers in the National Health and Aging Trends Study.

BACKGROUND: Social isolation is a risk factor for morbidity and mortality comparable to well-established risk factors including smoking, hypertension, and a sedentary lifestyle. The specific biological mechanisms that connect social isolation to morbidity and mortality remain unclear. Interleukin-6 (IL-6) and C-reactive protein (CRP) are biological markers that are upregulated during inflammation and can have long-term negative consequences for the health of individuals as they age. METHODS: Utilizing Round 7 (2017) data from the National Health and Aging Trends Study (NHATS), we examine the relationship between social isolation and two biological markers: IL-6 and high-sensitivity CRP. This study included a nationally representative sample of 4648 Medicare beneficiaries 65 years and older who provided samples using dried blood spot (DBS) techniques. We defined social isolation utilizing a multi-domained typology that considers living arrangement, core discussion network, religious attendance, and social participation. IL-6 and CRP were obtained via DBS that were collected in Round 7 of the NHATS. We performed linear regression to examine the association between social isolation and biological markers IL-6 and CRP. RESULTS: After adjusting for age, gender, race/ethnicity, income, tobacco use, body mass index, and chronic conditions, we found that severe social isolation and social isolation were significantly associated with higher levels of IL-6 and CRP values among older adults. CONCLUSIONS: Social isolation is associated with higher levels of biological markers (IL-6 and CRP). Our findings inform the pathway between social isolation and morbidity and mortality among older adults. IL-6 or CRP could be a proximal outcome measures for future clinical and social interventions that seek to alter the trajectory of social isolation and its associated health outcomes.

Use of Facebook, Instagram, and Twitter for recruiting healthy participants in nutrition-, physical activity-, or obesity-related studies: a systematic review.

BACKGROUND: There are limited systematic reviews exploring the use of social media for recruiting participants specifically for nutrition-, physical activity-, and obesity-related studies. OBJECTIVES: The aim was to conduct a systematic review on the effectiveness of using social media (Facebook, Instagram, and Twitter) for recruiting healthy participants in nutrition-, physical activity-, or obesity-related studies. METHODS: Studies were identified from 5 databases and included if they reported the number of participants recruited by social media (Facebook, Instagram, or Twitter) vs. traditional (print, e-mail, etc.). The effectiveness of recruitment was compared between methods by study procedures (in-person vs. online procedures). The cost-effectiveness of methods was also explored. The protocol was published in the Prospero database (ID# CRD42020204414). RESULTS: Twenty-six studies were included. Among studies with both types of recruitment methods, 49% of the sample was reached through traditional methods, 40% through social media, and the rest by other methods. For in-person study procedures, the median number of participants recruited using social media was 19 (range: 3-278) and for online study procedures, it was 298 (range: 3-17,069). Median recruitment cost using social media (n = 14 studies) was $11.90 (range: $0-517) per participant, while this varied considerably for traditional methods depending on how it was calculated ($214, $18.9-$777). The ratio of participants reached vs. recruited was 0.12%; the overall ratio of participants interactions vs. recruited was 21.2%. CONCLUSIONS: For in-person study procedures, traditional recruitment methods were more effective than social media, but for online study procedures, about half reported that social media was more effective. While more potential participants were reached through social media, only 21.2% of those who interacted with ads were enrolled. With the increased use of social media, their use for recruitment may be more frequent; therefore, future reviews may show different results.

Interaction of amyloid and tau on cortical microstructure in cognitively unimpaired adults.

INTRODUCTION: Neurite orientation dispersion and density imaging (NODDI), a multi-compartment diffusion-weighted imaging (DWI) model, may be useful for detecting early cortical microstructural alterations in Alzheimer's disease prior to cognitive impairment. METHODS: Using neuroimaging (NODDI and T1-weighted magnetic resonance imaging [MRI]) and cerebrospinal fluid (CSF) biomarker data (measured using Elecsys® CSF immunoassays) from 219 cognitively unimpaired participants, we tested the main and interactive effects of CSF amyloid beta (Aß)42 /Aß40 and phosphorylated tau (p-tau) on cortical NODDI metrics and cortical thickness, controlling for age, sex, and apolipoprotein E ε4. RESULTS: We observed a significant CSF Aß42 /Aß40 × p-tau interaction on cortical neurite density index (NDI), but not orientation dispersion index or cortical thickness. The directionality of these interactive effects indicated: (1) among individuals with lower CSF p-tau, greater amyloid burden was associated with higher cortical NDI; and (2) individuals with greater amyloid and p-tau burden had lower cortical NDI, consistent with cortical neurodegenerative changes. DISCUSSION: NDI is a particularly sensitive marker for early cortical changes that occur prior to gross atrophy or development of cognitive impairment.

The association between BDNF C270T genetic variants and smoking in patients with mental disorders and in healthy controls.

Studies investigating the association between smoking and the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism have reported inconclusive results, while the studies on the association of smoking status with BDNF C270T polymorphism are missing. We aimed to determine the association of smoking and BDNF Val66Met and C270T genetic variants in control subjects and patients with mental disorders. This study included 3502 Caucasian subjects: 918 healthy controls and 2584 patients with mental disorders (519 individuals with posttraumatic stress disorder (PTSD), 419 patients with depression, 996 patients with schizophrenia, and 650 patients with alcohol dependence). The frequency of the BDNF Val66Met and C270T variants were presented in codominant, dominant and recessive models. BDNF C270T, but not BDNF Val66Met polymorphism, was significantly associated with smoking in all groups, since the presence of the C270T T allele was more frequently found in smokers compared to non-smokers. Significant predictors of smoking were sex, age and BDNF C270T genetic variants. However, after detailed analysis of the separate diagnostic entities, the significant association of BDNF C270T polymorphism was confirmed only in healthy subjects, but not in patients with mental disorders; and was not related to number of cigarettes smoked per day. In patients with alcohol dependence, the severity of smoking was significantly associated with BDNF Val66Met variants. This is a first report of the significant association between the BDNF C270T polymorphism and smoking status in the large groups of Caucasian cases/controls.

Associations between depression, oxidative stress, and semen quality among 1,000 healthy men screened as potential sperm donors.

OBJECTIVE: To explore the association between depression and semen quality and the mediating role of oxidative stress. DESIGN: Cross-sectional study with repeated measures of semen quality. SETTING: Human Sperm Bank of Hubei Province, People's Republic of China. PATIENT(S): From April 2017 to July 2018, we recruited 1,000 potential sperm donors who completed the Beck Depression Inventory questionnaire and had measures of oxidative stress biomarkers. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Severity of depression was evaluated by the Beck Depression Inventory scores (0-4, no depression; 5-13, mild depression; 14-20, moderate depression; and 21 or greater, severe depression). The urinary concentrations of 8-hydroxy-2-deoxyguanosine, 4-hydroxy-2-nonenal-mercapturic acid, and 8-iso-prostaglandin F2α (8-isoPGF2α) were measured to reflect oxidative stress status. Repeated semen quality parameters (n = 5,880) were examined by trained professional technicians according to the World Health Organization laboratory manual. Associations between depression, oxidative stress, and repeated measures of semen quality parameters were evaluated using linear or mixed-effects models with adjustment for potential confounders. Mediation analysis was performed to test the potential mediating role of oxidative stress. RESULT(S): A total of 391 (39.1%) men were classified as mild depression, 67 (6.7%) as moderate depression, and 19 (1.9%) as severe depression. Inverse dose-response relationships between severity of depression and semen quality parameters were found. Compared with men without depression (n = 523), those with severe depression had a 25.26% (95% confidence interval, -38.65%, -8.93%) lower semen volume, 37.04% (-55.37%, -11.20%) lower total sperm count, 13.57% (-23.17%, -2.78%) lower total motility, and 15.08% (-25.09%, -3.72%) lower progressive motility; men with moderate depression also had a 12.28% (-21.16%, -2.40%) lower semen volume and 23.56% (-36.50%, -7.97%) lower total sperm count. We found a positive dose-response relationship between severity of depression and urinary 8-isoPGF2α concentrations. However, we found no evidence that the associations between depression status and semen quality were mediated by oxidative stress markers. CONCLUSION(S): In the study of Chinese male sperm donors, men with depression had worse semen quality parameters, including semen volume, sperm concentration, total sperm count, total motility, and progressive motility. Although depression was positively associated with urinary 8-isoPGF2α concentrations, depression-semen quality associations were not mediated by oxidative stress.

CYP1A2 polymorphisms modify the association of habitual coffee consumption with appetite, macronutrient intake, and body mass index: results from an observational cohort and a cross-over randomized study.

BACKGROUND/OBJECTIVES: Evidence regarding the influence of coffee on appetite and weight control is equivocal and the influence of covariates, such as genetic variation in caffeine metabolism, remains unknown. Herein, we addressed the novel hypothesis that genetic variation in CYP1A2, a gene responsible for more than 95% of caffeine metabolism, differentially impacts the association of coffee consumption with appetite and BMI among individuals with different genetic predispositions to obesity. SUBJECTS/METHODS: A cross-over randomized intervention study involving 18 volunteers assessed the effects of coffee consumption on dietary intake, appetite, and levels of the appetite-controlling hormones asprosin and leptin. Data on habitual coffee intake, BMI, and perceived appetite were obtained from an observational cohort of 284 volunteers using validated questionnaires. Participants were stratified according to a validated genetic risk score (GRS) for obesity and to the -163C > A (rs762551) polymorphism of CYP1A2 as rapid (AA), intermediate (AC), or slow (CC) caffeine metabolizers. RESULTS: Coffee consumption led to lower energy and dietary fat intake and circulating asprosin levels (P for interaction of rs762551 genotype*coffee consumption=0.056, 0.039, and 0.043, respectively) as compared to slow/intermediate metabolizers. High coffee consumption was more prevalent in rapid compared to slow metabolizers (P = 0.008 after adjustment for age, sex, and BMI) and was associated with lower appetite perception and lower BMI only in rapid metabolizers (P for interaction of rs762551 genotype*coffee consumption = 0.002 and 0.048, respectively). This differential association of rs762551 genotype and coffee consumption with BMI was more evident in individuals at higher genetic risk of obesity (mean adjusted difference in BMI = -5.82 kg/m2 for rapid versus slow/intermediate metabolizers who consumed more than 14 cups of coffee per week). CONCLUSIONS: CYP1A2 rs762551 polymorphism modifies the association of habitual coffee consumption with BMI, in part by influencing appetite, energy intake and circulating levels of the orexigenic hormone asprosin. This association is more evident in subjects with high genetic predisposition to obesity. ClinicalTrials.gov: registered Clinical Trial NCT04514588.

Risk of Adverse Maternal Outcomes in Pregnant Women With Disabilities.

Importance: Women with disabilities have a higher risk of preterm birth, gestational diabetes, preeclampsia, and cesarean delivery; however, their risk of other obstetric interventions, adverse maternal outcomes, and clinical indications for increased cesarean delivery is unclear. Objective: To evaluate risk of a range of obstetric interventions and adverse maternal outcomes, including severe maternal morbidities (SMM) and mortality, among women with and without disabilities. Design, Setting, and Participants: The Consortium on Safe Labor was a retrospective cohort that included comprehensive medical chart review for deliveries between January 2002 and January 2008. Data were collected from 12 clinical sites, which included 19 hospitals across the United States. This secondary analysis was conducted in February to July 2021. Exposures: Using International Classification of Diseases, Ninth Revision, codes and a validated algorithm to define disability, participants were classified as having physical, intellectual, sensory, or any disability, and compared with women with no documented disability. Main Outcomes and Measures: The relative risk (RR) of 23 obstetric interventions and adverse maternal outcomes, including SMM and mortality, was evaluated. Results: Of the 223 385 women in the study, 9206 (4.1%) were Asian or Pacific Islander, 50 235 (22.5%) were Black, 39 039 (17.5%) were Hispanic, and 110 443 (49.4%) were White, with a mean (SD) age of 27.6 (6.2) years. There were 2074 (0.9%) women with disability and 221 311 (99.1%) without. Among women with disabilities, 1733 (83.5%) were physical, 91 (4.4%) were intellectual, and 250 (12.1%) were sensory. Compared with women with no disability, women with disabilities had higher risk of gestational diabetes, placenta previa, premature rupture of membranes, preterm premature rupture of membranes, and postpartum fever as well as maternal death (adjusted relative risk [aRR], 11.19; 95% CI, 2.40-52.19) and individual SMMs: severe preeclampsia/eclampsia (aRR, 2.15; 95% CI, 1.80-2.56), hemorrhage (aRR, 1.27; 95% CI, 1.09-1.49), and fever (aRR, 1.32; 95% CI, 1.03-1.67), with the highest risk observed for thromboembolism (aRR, 6.08; 95% CI, 4.03-9.16), cardiovascular events (aRR, 4.02; 95% CI, 2.87-5.63), and infection (aRR, 2.69; 95% CI, 1.97-3.67). Women with any disability also had higher risk of interventions, including oxytocin augmentation, operative vaginal delivery, and cesarean delivery (aRR, 1.33; 95% CI, 1.25-1.42), with the cesarean indication less likely to be medically indicated (aRR, 0.79; 95% CI, 0.70-0.89). Risk of adverse outcomes and interventions remained consistent across disability categories. Conclusions and Relevance: In this study, women with physical, intellectual, and sensory disability during pregnancy were at higher risk of adverse outcomes, including a broad range of SMM and maternal mortality.

Factors influencing serum neurofilament light chain levels in normal aging.

OBJECTIVE: Serum neurofilament light (sNfL) is a promising marker for neuro-axonal damage and it is now well known that its levels also increase with higher age. However, the effect of other determinants besides age is still poorly investigated. We therefore aimed to identify factors influencing the sNfL concentration by analysing a large set of demographical, life-style and clinical variables in a normal aging cohort. METHODS: sNfL was quantified by single molecule array (Simoa) assay in 327 neurologically inconspicuous individuals (median age 67.8±10.7 years, 192 female) who participated in the Austrian Stroke Prevention Family Study (ASPS-Fam). Random forest regression analysis was used to rank the association of included variables with sNfL in the entire cohort and in age-stratified subgroups. Linear regression then served to identify factors independently influencing sNfL concentration. RESULTS: Age (ß=0.513, p<0.001) was by far the most important factor influencing sNfL, which was mainly driven by individuals ≥60 years. In age stratified sub-groups, body mass index (BMI) (ß=-0.298, p<0.001) independently predicted sNfL in individuals aged 38-60 years. In individuals ≥60 years, age (ß=0.394, p<0.001), renal function (ß=0.376, p<0.001), blood volume (ß=-0.198, p=0.008) and high density lipoprotein (HDL) (ß=0.149, p=0.013) were associated with sNfL levels. CONCLUSIONS: Age is the most important factor influencing sNfL concentrations, getting increasingly relevant in elderly people. BMI further influences sNfL levels, especially at younger age, whereas renal function gets increasingly relevant in the elderly.

CLINICAL-METABOLIC AND HORMONAL RELATIONSHIPS BETWEEN PARATHYROID DISEASE AND OTHER NON-CANCEROUS ENDOCRINE DISORDERS IN THE CHORNOBYL NPP ACCIDENT SURVIVORS. / KLINIKO-METABOLIChNI TA GORMONAL'NI VZAIeMOZV'IaZKY MIZh PATOLOGIIeIu PRYShchYTOPODIBNYKh ZALOZ TA INShYMY NEZLOIaKISNYMY ENDOKRYNNYMY ZAKhVORIuVANNIaMY U POSTRAZhDALYKh VNASLIDOK AVARIÏ NA ChAES.

OBJECTIVE: to investigate the clinical, hormonal-metabolic and structural features of parathyroid injuries in sur-vivors exposed to ionizing radiation after the Chornobyl NPP accident in adulthood and childhood, both with theirconnections to other non-cancerous endocrine disorders, and to establish the respective interhormonal and dys-metabolic relationships. MATERIALS AND METHODS: Clinical effects of ionizing radiation on the endocrine system in persons affected by theChornobyl NPP accident (n = 224) and their descendants (n = 146), compared with the general population sample(n = 70) were the study object. All patients underwent the ultrasound thyroid and parathyroid examination. Thegenerally recognized clinical, anthropometric (body weight, height, thigh volume, body mass index), instrumental(ultrasound examination of thyroid and parathyroid glands), laboratory (biochemical, hormonal), and statisticalmethods were applied. Parametric and nonparametric statistical methods were used in data processing. The value ofp < 0.05 was considered a statistically significant. RESULTS: No significant difference was found in the incidence of carbohydrate metabolic disorders in the ChornobylNPP (ChNPP) accident consequences clean-up workers (ACCUW), evacuees from the NPP 30-km exclusion zone, res-idents of radiologically contaminated areas and in the control group in whom the parathyroid hyperplasia wasdetected. There was a significant increase in the incidence of arterial hypertension among ACCUW who had parathy-roid hyperplasia (76.9%) vs. the control group (51.2%). In cases of parathyoid hyperplasia the vitamin D levels weresignificantly lower than without it. Vitamin D insufficiency/deficiency was found in 94% of the surveyed subjects.The average level of parathyroid hormone in blood serum was significantly higher in the ACCUW of «iodine¼ period withdiagnosed parathyroid hyperplasia than in the control group: (57.2 ± 2.87) pg / ml against (32.74 ± 3.58) pg / ml,p < 0.05. Results of multivariative analysis indicated a strong association of vitamin 25(OH)D insufficiency/defi-ciency with development of thyroid disease, carbohydrate metabolic disorders, cardiovascular disease, osteo-penia/osteoporosis. parathyroid ultrasound scan was at that an effective diagnostic method for primary screeningfor parathyroid hyperplasia and regular monitoring of the treatment efficiency. When examining children bornto parents irradiated after the ChNPPA the parathyroid hyperplasia (58%) and low serum content of vitamin D(11.6 ± 3.5) nmol / l were most often found in children living on radiologically contaminated territories (RCT).A strong correlation was established between the HOMA insulin resistance index and serum content of vitamin D(r = 0.65), parathyroid hormone (r = 0.60), and free thyroxine (r = 0.68) in the group of children born to parents irra-diated after the ChNPPA, having got chronic autoimmune thyroiditis, which indicated a relationship between thy-roid function, impaired carbohydrate and fat metabolism and the state of parathyroids. CONCLUSIONS: No difference in the incidence of carbohydrate metabolic disorders was found in the ChNPP ACCUW,evacuees from the 30-km exclusion zone, and residents of radiologically contaminated territories in whom parathy-roid hyperplasia was detected vs. the control group. Patients with parathyroid hyperplasia were found to be defi-cient in vitamin D in 94% of cases, and level of latter was significantly lower than under the normal parathyroid size.There was a significant increase in the incidence of diagnosed arterial hypertension among ACCUW who had parathy-roid hyperplasia vs. the control group: (76.9 ± 3.5)% vs. (51.2 ± 3.7)%. According to multivariate analysis a strongassociation between the vitamin 25(OH)D insufficiency/deficiency and development of thyroid disease, carbohydratemetabolic disorders, cardiovascular disease, and osteopenia/osteoporosis was established. The average level of pa-rathyroid hormone in the blood serum of the ChNPP ACCUW of the «iodine¼ period with diagnosed parathyroid hyper-plasia was significantly higher (57.2 ± 2.87) pg / ml against (32.74 ± 3.58) pg / ml; p <0,05) in the control group.

Fibroblast growth factor 21 associating with serotonin and dopamine in the cerebrospinal fluid predicts impulsivity in healthy subjects.

BACKGROUND: Impulsivity is more commonly reported in subjects with mental disorders compared to healthy subjects, suggesting a potential application of impulsivity in predicting impulsivity-related mental disorders. However, no biomarker of impulsivity available so far. This study explored the association between cerebrospinal fluid (CSF) fibroblast growth factor 21 (FGF21), a key hormonal mediator of the stress response, and impulsivity in healthy subjects. METHODS: A total of 126 healthy persons subjected to surgery of anterior cruciate ligament were recruited in the present study. The impulsiveness of the subjects was evaluated by the Chinese version of the Barratt Impulsiveness Scale (BIS)-11 before surgery. CSF and blood samples of the subjects were collected before spinal anesthesia for surgery. The levels of FGF21, serotonin and dopamine in CSF and the level of FGF21 in blood of the subjects were measured by ELISA using commercial kits. RESULTS: Negative correlations were found between BIS-11 total score and either FGF21, serotonin or dopamine in CSF. However, BIS-11 total score was not correlated with FGF21 in blood. In addition, FGF21 was positively correlated with serotonin and dopamine in CSF, respectively. Multivariable linear regression models indicated that the decrease of FGF21 level associating with the decrease of serotonin and dopamine level in CSF contributed to the higher impulsivity. Furthermore, receiver operating characteristic curve (ROC) analysis indicated an important role of CSF FGF21 predicting high impulsivity. CONCLUSIONS: FGF21, serotonin and dopamine in CSF associate with impulsivity in opposite directions. The decrease of CSF FGF21 is related to higher impulsivity, and indicate that CSF FGF21 may predict impulsivity in healthy subjects.

Incidence of Impaired Kidney Function Among Adolescent Patients Hospitalized With Anorexia Nervosa.

Importance: Anorexia nervosa (AN) is a common psychiatric disorder associated with electrolyte imbalances and impaired kidney function, but their incidence and association with disease severity are unknown. Objective: To analyze kidney function in patients with AN and its association with body mass index (BMI) and physiologic parameters of disease severity. Design, Setting, and Participants: Single-center retrospective case-control study of recently hospitalized patients with a diagnosis of AN according to International Classification of Diseases, Ninth Revision. All patients were aged 9 to 18 years and hospitalized in the general pediatric ward between 2010 and 2019. BMI and estimated glomerular filtration rate (eGFR) were compared with age- and sex-matched controls hospitalized with other diagnoses. Main Outcomes and Measures: Impaired kidney function was defined as eGFR less than 90 mL/min/1.73 m2. Association between eGFR, BMI, minimal heart rate, and free triiodothyronine (T3) levels were determined using logistic regression. Results: A total of 395 patients were included in the study group (81.6% were female; mean [SD] age, 14.6 [2.2] years; median BMI percentile, 12.3 [IQR, 0.9-42.0]). Impaired kidney function was found in 36.8% (146 of 395). Mean (SD) eGFR decreased during hospitalization in the group with kidney function impairment (admission: 83 [10.9] mL/min/1.73 m2; nadir: 79.1 [8.5] mL/min/1.73 m2; latest: 97.7 [15.7] mL/min/1.73 m2; P < .001). Mean (SD) serum creatinine (SCr) to BMI ratio was higher in both anorexia groups compared with controls in impaired kidney function (4.9% [1.0%]), non-impaired kidney function (3.55% [0.84%]); and control groups (2.8 [1.1%]) (P < .001). There was no difference in admission BMI between anorexia groups with and without kidney function impairment. Mean (SD) free T3 levels (3.5 [0.2] pmol/L vs 4.08 [1.2] pmol/L; P < .001) and mean (SD) minimal heart rate (44 [11] beats per min vs 56 [16] beats per min; P < .001) were lower and hospital stay was longer (median, 13 [IQR, 6-21] days vs 8 [IQR, 4-19] days; P = .03) in the impaired kidney function group. The highest correlation was found between minimal heart rate and minimal eGFR (R = 0.53; P < .001). Conclusions and Relevance: Impaired kidney function in patients with AN is common and transiently worsens during hospitalization. SCr values probably underestimate the degree of kidney function impairment in AN. Results of this study found that patients with impaired kidney function had worse anorexia severity parameters unrelated to admission BMI. Therefore, kidney function impairment may be a better marker of anorexia severity.

Determinants of Cognitive Trajectories in Normal Aging: A Longitudinal PET-MRI Study in a Community-based Cohort.

BACKGROUND: The determinants of the progressive decrement of cognition in normal aging are still a matter of debate. Alzheimer disease (AD)-signature markers and vascular lesions, but also psychological variables such as personality factors, are thought to have an impact on the longitudinal trajectories of neuropsychological performances in healthy elderly individuals. OBJECTIVE: The current research aimed to identify the main determinants associated with cognitive trajectories in normal aging. METHODS: We performed a 4.5-year longitudinal study in 90 older community-dwellers coupling two neuropsychological assessments, medial temporal atrophy (MTA), number of cerebral microbleeds (CMB), and white matter hyperintensities (WMH) at inclusion, visual rating of amyloid and FDG PET at follow-up, and APOE genotyping. Personality factors were assessed at baseline using the NEO-PIR. Univariate and backward stepwise regression models were built to explore the association between the continuous cognitive score (CCS) and both imaging and personality variables. RESULTS: The number of strictly lobar CMB at baseline (4 or more) was related to a significant increase in the risk of cognitive decrement. In multivariable models, amyloid positivity was associated with a 1.73 unit decrease of the CCS at follow-up. MTA, WMH and abnormal FDG PET were not related to the cognitive outcome. Among personality factors, only higher agreeableness was related to better preservation of neuropsychological performances. CONCLUSION: CMB and amyloid positivity are the only imaging determinants of cognitive trajectories in this highly selected series of healthy controls. Among personality factors, higher agreeableness confers a modest but significant protection against the decline of cognitive performances.

Enhancing the Sensitivity of Memory Tests: Reference Data for the Free and Cued Selective Reminding Test and the Logical Memory Task from Cognitively Healthy Subjects with Normal Alzheimer's Disease Cerebrospinal Fluid Biomarker Levels.

BACKGROUND: Cognitive performance of a given individual should be interpreted in the context of reference standards obtained in cognitively healthy populations. Recent evidence has shown that removing asymptomatic individuals with biomarker evidence of Alzheimer's disease pathology from normative samples increases the sensitivity of norms to detect memory impairments. These kind of norms may be useful for defining subtle cognitive decline, the transitional cognitive decline between normal cognition and mild cognitive impairment. OBJECTIVE: The present study aims to provide norms for the Free and Cued Selective Reminding Test (FCSRT) and the Logical Memory subtest of the Wechsler Memory Scale-IV in a sample of individuals aged 50-70 years with normal levels of amyloid-ß and tau cerebrospinal fluid (CSF) biomarkers. METHODS: The sample was composed of 248 individuals from the ALFA+ study with negative amyloid-ß and tau CSF biomarker levels. Regression-based norms were developed, including adjustments for age, education, and sex when applicable. RESULTS: We found that education was associated with the performance in all the variables of both tests while age had a marginal effect only in the delayed free recall of the FCSRT. Sex was also related to the performance in the FCSRT, with women outperforming men. Equations to calculate z-scores and normative percentile tables were created. As compared with previously published norms the reference data presented were more sensitive but less specific, as expected. CONCLUSION: The use of the norms provided in this work, in combination with the already published conventional norms, may contribute to detecting subtle memory impairment.

Corneal endothelial cell density and morphology in ophthalmologically healthy young individuals in Japan: An observational study of 16842 eyes.

We aimed to investigate the cell density and morphology of the corneal endothelium in ophthalmologically healthy young Japanese, given the lack of normative data in literature. This observational study included eyes without ophthalmologic diseases, besides refractive errors, examined between 1996 and 2015 at Miyata Eye Hospital. Eyes with a history of ophthalmologic diseases or contact lens usage were excluded. Correlation of corneal endothelial cell density (ECD), coefficient of variation (CV), appearance rate of hexagonal cells (6A), and cell area with age were examined. Multivariate linear regression analysis was performed to determine the predictors of corneal parameters. We included 16842 eyes of 8421 individuals (19.6 ± 8.7 years). ECD was 3109.0 ± 303.7 cells/mm2 and significantly reduced with age (p < 0.001). The ECD reduction rate was 0.42%/year in the total population. On multivariate analysis, age and sex were significantly correlated with ECD, CV, 6A, and cell area (all p < 0.001). ECD, 6A, CV, and cell area are significantly associated with age in healthy young Japanese individuals. Monitoring their corneal endothelium is essential to assess the risk of endothelial damage.

Physical exercise keeps the brain connected by increasing white matter integrity in healthy controls.

ABSTRACT: Physical exercise leads to structural changes in the brain. However, it is unclear whether the initiation or continuous practice of physical exercise causes this effect and whether brain connectivity benefits from exercise. We examined the effect of 6 months of exercise on the brain in participants who exercise regularly (n = 25) and in matched healthy controls (n = 20). Diffusion tensor imaging brain scans were obtained from both groups. Our findings demonstrate that regular physical exercise significantly increases the integrity of white matter fiber tracts, especially those related to frontal function. This implies that exercise improves brain connectivity in healthy individuals, which has important implications for understanding the effect of fitness programs on the brains of healthy subjects.