Assessment of salivary cadmium levels and breast density in the Marin Women's Study.

BACKGROUND: We aimed to determine if salivary cadmium (Cd) levels had any association with breast density, hoping to establish a less invasive cost-effective method of stratifying Cd burden as an environmental breast cancer risk factor. METHODS: Salivary Cd levels were quantified from the Marin Women's Study, a Marin County, California population composite. Volumetric compositional breast density (BDsxa ) data were measured by single x-ray absorptiometry techniques. Digital screening mammography was performed by the San Francisco Mammography Registry. Radiologists reviewed mammograms and assigned a Breast Imaging-Reporting and Data System score. Early morning salivary Cd samples were assayed. Association analyses were then performed. RESULTS: Cd was quantifiable in over 90% of saliva samples (mean = 55.7 pg/L, SD = 29). Women with higher saliva Cd levels had a non-significant odds ratio of 1.34 with BI-RAD scores (3 or 4) (95% CI 0.75-2.39, p = 0.329). Cd levels were higher in current smokers (mean = 61.4 pg/L, SD = 34.8) than former smokers or non-smokers. These results were non-significant. Pilot data revealed that higher age and higher BMI were associated with higher BI-RAD scores (p < 0.001). CONCLUSION: Salivary Cd is a viable quantification source in large epidemiologic studies. Association analyses between Cd levels and breast density may provide additional information for breast cancer risk assessment, risk reduction plans, and future research directions. Further work is needed to demonstrate a more robust testing protocol before the extent of its usefulness can be established.

Long-term trends and spatial patterns of West Nile Virus emergence in California, 2004-2021.

AIMS: West Nile Virus (WNV) has remained a persistent source of vector-borne disease risk in California since first being identified in the state in 2003. The geographic distribution of WNV activity is relatively widespread, but varies considerably across different regions within the state. Spatial variation in human WNV infection depends upon social-ecological factors that influence mosquito populations and virus transmission dynamics. Measuring changes in spatial patterns over time is necessary for uncovering the underlying regional drivers of disease risk. METHODS AND RESULTS: In this study, we utilized statewide surveillance data to quantify temporal changes and spatial patterns of WNV activity in California. We obtained annual WNV mosquito surveillance data from 2004 through 2021 from the California Arbovirus Surveillance Program. Geographic coordinates for mosquito pools were analysed using a suite of spatial statistics to identify and classify patterns in WNV activity over time. CONCLUSIONS: We detected clear patterns of non-random WNV risk during the study period, including emerging hot spots in the Central Valley and non-random periods of oscillating WNV risk in Southern and Northern California subregions. Our findings offer new insights into 18 years of spatio-temporal variation in WNV activity across California, which may be used for targeted surveillance efforts and public health interventions.

Phased Return of Students to 77 Transitional Kindergarten-8th Grade Schools With Cohesive Mitigation Strategies Serving as Protective Factors Against the Increase of COVID-19 Cases in Marin County: September 2020-January 2021.

Background and objective Earlier uncertain implications of the coronavirus disease 2019 (COVID-19) pandemic on the pediatric population prompted the authorities to close schools worldwide under the premise that school settings would serve as drivers of an increase in the cases of COVID-19. Safe and equitable full-in-person school instruction is a critical factor in the continued educational gains of children and for their general well-being. The objective of this study was to report epidemiological trends related to the increasing percentage of students returning to in-person instruction, the suspected in-school transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, and countywide COVID-19 case rates during the first 21 weeks of school reopening in Marin County, CA, in the fall of 2020. Materials and methods The institutional review board (IRB) approval was waived for this study as it did not involve any identifiable human subjects data. Retrospective electronic reviews of countywide COVID-19 daily case count and COVID-19-related reports associated with in-person school participants from 77 schools in Marin County, CA, from September 8, 2020, to January 29, 2021, were conducted. The data were made available in collaboration with the Marin County Office of Education (MCOE) and Marin County Department of Health and Human Services (Marin HHS). Descriptive trends analyses were performed to determine whether the phased increase of students attending in-person learning was a significant contributor to countywide COVID-19 incidence rate, crude rate, and in-school COVID-19 viral transmission. This is the first long retrospective study of COVID-19 data among the reopened school population during the second half of the first pandemic year. It was conducted in a 21-week surveillance period involving an immense collaboration between Marin County's public health officials and school administrators. Results Over the 21-week observational period involving 17,639 students, 4,938 school staff, and 899,175 student days, the countywide COVID-19 crude rate decreased (from 89.9 to 35.89 per 10,000) as more students returned to in-person learning. The schools' strict adherence to public health guidance and site-specific safety plans against COVID-19 yielded a significantly reduced incidence rate of 0.84% among in-person learning participants; only nine cases were traced to suspected in-school SARS-CoV-2 transmission by way of rigorous contact tracing. The countywide COVID-19 incidence rate was 2.09%. Conclusions It is possible to minimize COVID-19 transmissions in in-person learning settings with cohesive mitigation strategies, specifically strict adherence to proper masking by students and staff while on school grounds. There is no clear correlation that the increasing phased return of students to in-person school drove an increase in countywide COVID-19 cases in Marin County, CA. Our findings revealed that schools were capable of safely resuming operations by following public health orders and recommendations. The increasing percentage of students returning to in-person school did not drive an increased COVID-19 case rate in the community. On the contrary, this analysis revealed that there was a drop in countywide COVID-19 cases as the phased student return percentage increased.

Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies.

OBJECTIVE: We investigated the association between 52 risk variants identified through genome-wide association studies and disease severity in multiple sclerosis (MS). METHODS: Ten unique MS case data sets were analyzed. The Multiple Sclerosis Severity Score (MSSS) was calculated using the Expanded Disability Status Scale at study entry and disease duration. MSSS was considered as a continuous variable and as 2 dichotomous variables (median and extreme ends; MSSS of ≤5 vs >5 and MSSS of <2.5 vs ≥7.5, respectively). Single nucleotide polymorphisms (SNPs) were examined individually and as both combined weighted genetic risk score (wGRS) and unweighted genetic risk score (GRS) for association with disease severity. Random-effects meta-analyses were conducted and adjusted for cohort, sex, age at onset, and HLA-DRB1*15:01. RESULTS: A total of 7,125 MS cases were analyzed. The wGRS and GRS were not strongly associated with disease severity after accounting for cohort, sex, age at onset, and HLA-DRB1*15:01. After restricting analyses to cases with disease duration ≥10 years, associations were null (p value ≥0.05). No SNP was associated with disease severity after adjusting for multiple testing. CONCLUSIONS: The largest meta-analysis of established MS genetic risk variants and disease severity, to date, was performed. Results suggest that the investigated MS genetic risk variants are not associated with MSSS, even after controlling for potential confounders. Further research in large cohorts is needed to identify genetic determinants of disease severity using sensitive clinical and MRI measures, which are critical to understanding disease mechanisms and guiding development of effective treatments.

Feasibility study for remote assessment of cognitive function in multiple sclerosis.

BACKGROUND: Cognitive impairment is common in multiple sclerosis (MS), and affects employment and quality of life. Large studies are needed to identify risk factors for cognitive decline. Currently, a MS-validated remote assessment for cognitive function does not exist. Studies to determine feasibility of large remote cognitive function investigations in MS have not been published. OBJECTIVE: To determine whether MS patients would participate in remote cognitive studies. We utilized the Modified Telephone Interview for Cognitive Status (TICS-M), a previously validated phone assessment for cognitive function in healthy elderly populations to detect mild cognitive impairment. We identified factors that influenced participation rates. We investigated the relationship between MS risk factors and TICS-M score in cases, and score differences between cases and control individuals. METHODS: The TICS-M was administered to MS cases and controls. Linear and logistic regression models were utilized. RESULTS: 11.5% of eligible study participants did not participate in cognitive testing. MS cases, females and individuals with lower educational status were more likely to refuse (p<0.001). Cases who did complete testing did not differ in terms of perceived cognitive deficit compared to cases that did participate. More severe disease, smoking, and being male were associated with a lower TICS-M score among cases (p<0.001). The TICS-M score was significantly lower in cases compared to controls (p=0.007). CONCLUSIONS: Our results demonstrate convincingly that a remotely administered cognitive assessment is quite feasible for conducting large epidemiologic studies in MS, and lay the much needed foundation for future work that will utilize MS-validated cognitive measures.

Genome-wide association analysis of susceptibility and clinical phenotype in multiple sclerosis.

Multiple sclerosis (MS), a chronic disorder of the central nervous system and common cause of neurological disability in young adults, is characterized by moderate but complex risk heritability. Here we report the results of a genome-wide association study performed in a 1000 prospective case series of well-characterized individuals with MS and group-matched controls using the Sentrix HumanHap550 BeadChip platform from Illumina. After stringent quality control data filtering, we compared allele frequencies for 551 642 SNPs in 978 cases and 883 controls and assessed genotypic influences on susceptibility, age of onset, disease severity, as well as brain lesion load and normalized brain volume from magnetic resonance imaging exams. A multi-analytical strategy identified 242 susceptibility SNPs exceeding established thresholds of significance, including 65 within the MHC locus in chromosome 6p21.3. Independent replication confirms a role for GPC5, a heparan sulfate proteoglycan, in disease risk. Gene ontology-based analysis shows a functional dichotomy between genes involved in the susceptibility pathway and those affecting the clinical phenotype.