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We recently reported that multiple sclerosis (MS) plasma contains IgG aggregates and induces complement-dependent neuronal cytotoxicity (Zhou et al., 2023). Using ELISA, we report herein that plasma IgG levels in the aggregates can be used as biomarkers for MS. We enriched the IgG aggregates from samples of two cohorts (190 MS and 160 controls) by collecting flow-through after plasma binding to Protein A followed by detection of IgG subclass. We show that there are significantly higher levels of IgG1, IgG3, and total IgG antibodies in MS IgG aggregates, with an AUC >90%; higher levels of IgG1 distinguish secondary progressive MS from relapsing-remitting MS (AUC = 91%). Significantly, we provided the biological rationale for MS plasma IgG biomarkers by demonstrating the strong correlation between IgG antibodies and IgG aggregate-induced neuronal cytotoxicity. These non-invasive, simple IgG-based blood ELISA assays can be adapted into clinical practice for diagnosing MS and SPMS and monitoring treatment responses. • Enriched the IgG aggregates by collecting flow-through after plasma binding to Protein A (A-FT). • Significantly higher levels of IgG1, IgG3, and total IgG antibodies in MS plasma A-FT. • Higher plasma IgG1 can distinguish secondary progressive MS (SPMS) from relapsing-remitting MS (RRMS). • Strong correlation between IgG antibodies and IgG-induced neuronal cytotoxicity. • Provided evidence for a noninvasive blood-based IgG biomarker for MS. [ABSTRACT FROM AUTHOR]

Introduction: This study examined prospective associations of perceived discrimination experience and past-week alcohol use among U.S. adults., Methods: This longitudinal study analyzed 22 biweekly surveys from the Understanding America Study during June 2020-July 2021, a nationally representative U.S. adult panel. Multivariable regressions were conducted to examine prospective associations of perceived discrimination experiences (any versus none) or mean levels of discrimination (never [0] to almost every day [4]) and past-week alcohol use frequency [days: 0-7]) or binge drinking (yes/no) 2 weeks later, after disaggregating within-person and between-person effects of discrimination regressor and adjusting for covariates. Analyses were conducted in 2024., Results: Among 8,026 participants, 18.9% reported perceived discrimination experiences. The mean of past-week alcohol drinking was 1.27 days and 9.3% reported past-week binge drinking. Within-person discrimination prevalence and levels of discrimination were associated with higher drinking frequency (IRR [95% CI]=1.05 [1.02,1.08], p=0.0003 and IRR [95% CI]=1.06 [1.02, 1.10], p=0.002, respectively), and between-person discrimination prevalence was associated with higher drinking frequency (IRR [95% CI]=1.16 [1.05, 1.30], p=0.005) and higher likelihood of binge drinking (AOR [95% CI]=1.90 [1.49, 2.42], p<0.0001). The associations of discrimination prevalence and drinking frequency differed by sex (interaction effect, p=0.02) and race/ethnicity (interaction effect of Whites versus Blacks, p=0.006), with significantly higher numbers of past-week drinking among females (AOR [95% CI]=1.10 [1.05, 1.15] and Black adults (AOR [95% CI]=1.17 [1.07, 1.28]) but not among males and Hispanic/other race adults., Conclusions: Discrimination experiences were prospectively associated with an increased risk of alcohol-drinking outcomes, and the effect was more pronounced among certain demographic groups. Efforts to mitigate the adverse effects of recurrent exposure to discrimination are critical to advance health equity., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background/Objectives : Stool-based tests, such as the fecal immunochemical test (FIT), have been widely used for increasing colorectal cancer (CRC) screening. Small media, such as printed materials or flyers, are known to be an effective intervention to increase CRC screening by fecal tests. However, more evidence is needed to determine whether such small media are effective in improving screening uptake of a mailed FIT intervention targeted at rural populations in the USA. Methods : In this randomized study, 1230 FIT kits were mailed from July to December 2022 to rural Nebraskans aged 45-74 who were not up to date on CRC screening. Half of the participants (n = 608) also received a tailored, one-page, gender-specific educational flyer created based on focus groups with rural residents. Logistic regression was used to determine predictors of returning the FIT. Results : Study participants were predominantly female (76%), non-Hispanic White (83%), and within the age group of 55-64 (43%). Overall, 192 (15.6%) kits were returned (16.1% from the flyer group; 15.1% from the no-flyer group). However, we found no significant differences between the flyer and no-flyer groups (Adjusted Odds Ratio [AOR]: 1.21; 95% CI: 0.88-1.66). Females (AOR: 1.78; 95% CI: 1.19-6.14) and the oldest (65-74) age group (AOR: 5.03; 95% CI: 2.78-8.47) were more likely to return FIT kits than males and the youngest (45-54) age group. Conclusions : A tailored educational flyer was not effective in improving the CRC-screening-rate-by-mailed-FIT approach for rural populations. Future research should explore the content, timing, and mode of delivery of educational interventions as well as other multi-component strategies to improve screening rates. Public health officials might also consider developing strategies targeted at males and younger (45-54) age groups.

Introduction: The purpose of the study was to identify barriers and facilitators of colorectal cancer (CRC) screening use among agricultural operators in Nebraska, US., Methods: The concept mapping approach was used to engage participants and enhance the generation of ideas and opinions regarding CRC screening. Two focus groups (seven women and seven men) were conducted., Results: Among women, the cost domain was most agreed upon as important, followed by experiencing symptoms, awareness, and family. Among men, the important concepts related to CRC screening were family and friend support, feeling too young to get CRC, family or personal history of CRC, and lack of awareness of the need to be screened. Some gender differences regarding barriers were observed, such as women were more concerned about the cost of screening while men were far more concerned about the embarrassment associated with CRC screening., Conclusion: These findings will be crucial to developing educational materials to increase knowledge of risk factors for CRC and of CRC screening in the agricultural population.

Grey matter pathology is central to the progression of multiple sclerosis (MS). We discovered that MS plasma immunoglobulin G (IgG) antibodies, mainly IgG1, form large aggregates (>100 nm) which are retained in the flow-through after binding to Protein A. Utilizing an annexin V live-cell apoptosis detection assay, we demonstrated six times higher levels of neuronal apoptosis induced by MS plasma IgG aggregates (n = 190, from two cohorts) compared to other neurological disorders (n = 116) and healthy donors (n = 44). MS IgG aggregate-mediated, complement-dependent neuronal apoptosis was evaluated in multiple model systems including primary human neurons, primary human astrocytes, neuroblastoma SH-SY5Y cells, and newborn mouse brain slices. Immunocytochemistry revealed the co-deposition of IgG, early and late complement activation products (C1q, C3b, and membrane attack complex C5b9), as well as active caspase 3 in treated neuronal cells. Furthermore, we found that MS plasma cytotoxic antibodies are not present in Protein G flow-through, nor in the paired plasma. The neuronal apoptosis can be inhibited by IgG depletion, disruption of IgG aggregates, pan-caspase inhibitor, and is completely abolished by digestion with IgG-cleaving enzyme IdeS. Transmission electron microscopy and nanoparticle tracking analysis revealed the sizes of MS IgG aggregates are greater than 100 nm. Our data support the pathological role of MS IgG antibodies and corroborate their connection to complement activation and axonal damage, suggesting that apoptosis may be a mechanism of neurodegeneration in MS., (© 2023. The Author(s).)

Background: Occupation is a known determinant of worker physical and behavioral health risk, yet most previous studies have focused on unemployment, underemployment, and job satisfaction to understand child maltreatment risk., Objective: This county-level study (n = 278) investigated the association between occupation and child maltreatment rates and community well-being in California, Colorado, Minnesota, Oregon, and New Mexico., Participants and Setting: States were selected due to having comparable, publicly available county-level data on substantiated child abuse and neglect rates within a five-year span between 2015 and 2020., Methods: Using US Census Bureau American Community Survey data, we collected percentages of the employed population among 13 occupations. Five additional community health indicators came from the County Health Rankings and Roadmaps. Elastic net linear regression was used for variable selection and because of explanatory variables' interrelationships. Linear regression was used to model individual industries positively associated with child abuse rates., Results: The elastic net model selected ten important variables in explaining child maltreatment rates. Important occupational sectors were agriculture, forestry, fishing (AFF), manufacturing, wholesale, retail, finance, and education. Important community indicators included housing, injury deaths, and poor mental health days. Only AFF and retail showed greater child abuse rates with increasing percentages of the workforce in these occupations in unadjusted models (AFF: β = 0.03 SE = 0.01, p = 0.02; Retail: β = 0.09 SE = 0.04, p = 0.02)., Conclusions: Our findings suggest group-level effects of counties with a larger AFF and retail presence experiencing higher child maltreatment rates. Given that numerous prior studies of county economies note the strong associations of certain employment types with cultural attitudes, educational opportunities, regional biases, and other unmeasured variables, future studies should incorporate individual level data in a multilevel framework., Competing Interests: Declaration of competing interest The authors state that they have no potential conflicts of interest with respect to the research, authorship, and/or publication of this manuscript., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The incidence of breast cancer among premenopausal women has been increasing rapidly in recent decades in East Asia. This case-control study investigated whether estrogen-DNA adducts were associated with breast cancer risk in Taiwan. The control group (n = 146) comprised healthy female volunteers and women with non-proliferative breast disease. The case group (n = 221) comprised women either with proliferative benign breast disease or breast cancer. The ratios of estrogen-DNA adducts to their respective metabolites and conjugates in plasma were analyzed using ultraperformance LC/MS-MS. The SNPs of CYP1A1, CYP1B1, and COMT were genotyped. Logistic regression model was used to compare the estrogen-DNA adduct ratios between the two groups. The estrogen-DNA adduct ratio in the case group was significantly higher than that in the control group (median ratio: 58.52 vs. 29.36, P = 0.004). A multiple logistic regression model demonstrated that a unit increase in the natural log of the estrogen-DNA adduct ratio in premenopausal women was a significant predictor of breast cancer risk, with an estimated hazard ratio of 1.718 (1.444-2.046, P < 0.001). However, the CYP1A1, CYP1B1, and COMT SNPs were not associated with the estrogen-DNA adduct ratios. In conclusion, plasma estrogen-DNA adduct ratio was associated with the presence of breast cancer or proliferating benign breast disease in premenopausal women in Taiwan., Prevention Relevance: This study provides evidence that endogenous estrogen-induced genotoxicity may contribute to the carcinogenesis of breast cancer in premenopausal Asian women. This work could have important preventive implication for the emerging disease in East Asia., (©2022 American Association for Cancer Research.)

Purpose: Tobacco use during early adolescence can harm brain development and cause adverse health outcomes. Identifying susceptibility in early adolescence before initiation presents an opportunity for tobacco use prevention., Methods: Data were drawn from the Adolescent Brain and Cognitive Development study that enrolled 9-10-year-old children in 21 US cities between 2016 and 2018 at baseline. Separate nested hierarchical models were performed to incrementally examine the associations of sociodemographic factors, psychosocial influences, parental substance use, immediate social contacts, and perceived neighborhood safety with tobacco use susceptibility among never tobacco users (n = 10,449), overall and stratified by gender., Results: A total of 16.6% of youths who have never used tobacco reported susceptibility to tobacco. Females (vs. males, adjusted odds ratio [AOR] [95% confidence interval {CI}] = 0.80 [0.70-0.91]), positive parental monitoring (AOR [95% CI] = 0.76 [0.66-0.87]) and positive school environment (AOR [95% CI] = 0.95 [0.93-0.98]) were associated with reduced susceptibility to tobacco use. Parental education level (high school, AOR [95% CI] = 1.52 [1.02-2.28]; bachelor's degree, AOR [95% CI] = 1.53 [1.03-2.28]; or postgraduate degree, AOR [95% CI] = 1.54 [1.03-2.3] vs. less than high school), youth substance ever use (AOR [95% CI] = 2.24 [1.95-2.58]), internalizing problems (AOR [95% CI] = 1.03 [1-1.06]), and high scores on negative urgency, lack of premeditation, lack of perseverance, sensation seeking, and positive urgency-impulsive behavior scale were associated with increased susceptibility to tobacco use. Stratified analysis showed that parent-perceived neighborhood safety was associated with reduced susceptibility to tobacco use among males but not among females (AOR [95% CI] = 0.89 [0.81-0.99]) vs. (AOR [95% CI] = 1.01 [0.9-1.13]). A positive school environment was associated with lower susceptibility to tobacco use among females but not among males., Discussion: Parental, environmental, and psychosocial factors influence early childhood tobacco susceptibility. Family and school-based tobacco prevention programs should consider integrating these factors into primary school curricula to reduce youth tobacco susceptibility and later initiation., (Copyright © 2022 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: The repair of unruptured intracranial aneurysms has increased since 2000. In this study, we analyzed the Nationwide Readmission Database (NRD) to determine the rate of 90-day readmission. Our objective is to examine readmission trends after unruptured aneurysm repair., Methods: This study used the 2013 and 2014 NRD. Patient data included standard demographic, comorbidity, and payer information. We selected patients who had undergone microsurgical or endovascular repair for a nonruptured aneurysm. We excluded patients who were under 18 years of age, had a subarachnoid hemorrhage, or were discharged to home the same day. Readmission was calculated by counting the number of days between the end of the index visit and earliest readmission date., Results: A total of 2180 of 29,694 patients (7.34%) were readmitted within 90 days of their initial hospitalization. They were younger (mean, 52.6 years; 95% confidence interval [CI], 51.4-53.8) than patients not readmitted (mean, 57.4 years; 95% CI, 57.1-57.8; P < 0.0001). In total, endovascular repair was more frequent than microsurgery (79.8% vs. 20.2%, respectively). Mean days to readmission was 41.8 (95% CI, 39.7-43.9) and was higher for women (P < 0.0001). The odds ratio for readmission after an endovascular repair was 1.54 (95% CI, 1.27-1.86)., Conclusions: In this study of over 28,000 patients treated for an unruptured aneurysm, the 90-day readmission rate was 7.34%. Endovascular patients had higher odds of readmission than microsurgical patients. Patients with common medical comorbidities (hypertension, obesity, renal failure, and diabetes) were less likely to be readmitted than patients without those conditions., (Copyright © 2020 Elsevier Inc. All rights reserved.)