Phthalates and sex steroid hormones across the perimenopausal period: A longitudinal analysis of the Midlife Women's Health Study.

BACKGROUND: The menopausal transition involves significant sex hormone changes. Environmental chemicals, such as urinary phthalate metabolites, are associated with sex hormone levels in cross-sectional studies. Few studies have assessed longitudinal associations between urinary phthalate metabolite concentrations and sex hormone levels during menopausal transition. METHODS: Pre- and perimenopausal women from the Midlife Women's Health Study (MWHS) (n = 751) contributed data at up to 4 annual study visits. We quantified 9 individual urinary phthalate metabolites and 5 summary measures (e.g., phthalates in plastics (∑Plastic)), using pooled annual urine samples. We measured serum estradiol, testosterone, and progesterone collected at each study visit, unrelated to menstrual cycling. Linear mixed-effects models and hierarchical Bayesian kernel machine regression analyses evaluated adjusted associations between individual and phthalate mixtures with sex steroid hormones longitudinally. RESULTS: We observed associations between increased concentrations of certain phthalate metabolites and lower testosterone and higher sub-ovulatory progesterone levels, e.g., doubling of monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), di-2-ethylhexyl phthalate (∑DEHP) metabolites, ∑Plastic, and ∑Phthalates concentrations were associated with lower testosterone (e.g., for ∑DEHP: -4.51%; 95% CI: -6.72%, -2.26%). For each doubling of MEP, certain DEHP metabolites, and summary measures, we observed higher mean sub-ovulatory progesterone (e.g., ∑AA (metabolites with anti-androgenic activity): 6.88%; 95% CI: 1.94%, 12.1%). Higher levels of the overall time-varying phthalate mixture were associated with lower estradiol and higher progesterone levels, especially for 2nd year exposures. CONCLUSIONS: Phthalates were longitudinally associated with sex hormone levels during the menopausal transition. Future research should assess such associations and potential health impacts during this understudied period.

Characteristics of Students Participating in Collegiate Recovery Programs and the Impact of COVID-19: An Updated National Longitudinal Study.

The goals of the present study were to describe the development of the first national longitudinal study of collegiate recovery programs (CRP) students; provide an updated characterization of CRP students' demographics, past problem severity, and current recovery-related functioning; and examine the perceived impact of COVID-19 on CRP students' recovery. Universities and community colleges with CRPs across the United States and Ontario, Canada, were invited to partner on this project. Launched in fall 2020, three cohorts of participants were recruited. All participants who completed the baseline survey (N = 334 from 43 CRPs) were invited to complete follow-up surveys. The sample was composed of mostly undergraduate, White, cisgender women averaging 29 years old at baseline. They reported challenging backgrounds, including high levels of polysubstance use, alcohol/substance problem severity, mental health challenges, and involvement with the criminal legal system. Despite such adversity, they evidenced high levels of recovery-related functioning. Recovery capital and quality of life were high. Students reported an average of nearly four years in recovery, with most having between two and four years of abstinence from their primary substance of choice. COVID-19 represented a substantial source of stress for many, impacting some students' abstinence and recovery-related functioning. Results generally parallel findings from the only other national study of CRP students conducted a decade ago, providing a much-needed update and novel insights into CRP students. Findings can inform our understanding of the CRP student population and can be used to tailor CRP design and service offerings to students' backgrounds and needs.

Within-host evolutionary dynamics and tissue compartmentalization during acute SARS-CoV-2 infection.

The global evolution of SARS-CoV-2 depends in part upon the evolutionary dynamics within individual hosts with varying immune histories. To characterize the within-host evolution of acute SARS-CoV-2 infection, we sequenced saliva and nasal samples collected daily from vaccinated and unvaccinated individuals early during infection. We show that longitudinal sampling facilitates high-confidence genetic variant detection and reveals evolutionary dynamics missed by less-frequent sampling strategies. Within-host dynamics in both unvaccinated and vaccinated individuals appeared largely stochastic; however, in rare cases, minor genetic variants emerged to frequencies sufficient for forward transmission. Finally, we detected significant genetic compartmentalization of viral variants between saliva and nasal swab sample sites in many individuals. Altogether, these data provide a high-resolution profile of within-host SARS-CoV-2 evolutionary dynamics.IMPORTANCEWe detail the within-host evolutionary dynamics of SARS-CoV-2 during acute infection in 31 individuals using daily longitudinal sampling. We characterized patterns of mutational accumulation for unvaccinated and vaccinated individuals, and observed that temporal variant dynamics in both groups were largely stochastic. Comparison of paired nasal and saliva samples also revealed significant genetic compartmentalization between tissue environments in multiple individuals. Our results demonstrate how selection, genetic drift, and spatial compartmentalization all play important roles in shaping the within-host evolution of SARS-CoV-2 populations during acute infection.

Functional delineation of the luminal epithelial microenvironment in breast using cell-based screening in combinatorial microenvironments.

Microenvironment signals are potent determinants of cell fate and arbiters of tissue homeostasis, however understanding how different microenvironment factors coordinately regulate cellular phenotype has been experimentally challenging. Here we used a high-throughput microenvironment microarray comprised of 2640 unique pairwise signals to identify factors that support proliferation and maintenance of primary human mammary luminal epithelial cells. Multiple microenvironment factors that modulated luminal cell number were identified, including: HGF, NRG1, BMP2, CXCL1, TGFB1, FGF2, PDGFB, RANKL, WNT3A, SPP1, HA, VTN, and OMD. All of these factors were previously shown to modulate luminal cell numbers in painstaking mouse genetics experiments, or were shown to have a role in breast cancer, demonstrating the relevance and power of our high-dimensional approach to dissect key microenvironmental signals. RNA-sequencing of primary epithelial and stromal cell lineages identified the cell types that express these signals and the cognate receptors in vivo. Cell-based functional studies confirmed which effects from microenvironment factors were reproducible and robust to individual variation. Hepatocyte growth factor (HGF) was the factor most robust to individual variation and drove expansion of luminal cells via cKit+ progenitor cells, which expressed abundant MET receptor. Luminal cells from women who are genetically high risk for breast cancer had significantly more MET receptor and may explain the characteristic expansion of the luminal lineage in those women. In ensemble, our approach provides proof of principle that microenvironment signals that control specific cellular states can be dissected with high-dimensional cell-based approaches.

Current and Future Habitat Suitability Models for Four Ticks of Medical Concern in Illinois, USA.

The greater U.S. Midwest is on the leading edge of tick and tick-borne disease (TBD) expansion, with tick and TBD encroachment into Illinois occurring from both the northern and the southern regions. To assess the historical and future habitat suitability of four ticks of medical concern within the state, we fit individual and mean-weighted ensemble species distribution models for Ixodes scapularis, Amblyomma americanum, Dermacentor variabilis, and a newly invading species, Amblyomma maculatum using a variety of landscape and mean climate variables for the periods of 1970-2000, 2041-2060, and 2061-2080. Ensemble model projections for the historical climate were consistent with known distributions of each species but predicted the habitat suitability of A. maculatum to be much greater throughout Illinois than what known distributions demonstrate. The presence of forests and wetlands were the most important landcover classes predicting the occurrence of all tick species. As the climate warmed, the expected distribution of all species became strongly responsive to precipitation and temperature variables, particularly precipitation of the warmest quarter and mean diurnal range, as well as proximity to forest cover and water sources. The suitable habitat for I. scapularis, A. americanum, and A. maculatum was predicted to significantly narrow in the 2050 climate scenario and then increase more broadly statewide in the 2070 scenario but at reduced likelihoods. Predicting where ticks may invade and concentrate as the climate changes will be important to anticipate, prevent, and treat TBD in Illinois.

Human biting mosquitoes and implications for West Nile virus transmission.

BACKGROUND: West Nile virus (WNV), primarily vectored by mosquitoes of the genus Culex, is the most important mosquito-borne pathogen in North America, having infected thousands of humans and countless wildlife since its arrival in the USA in 1999. In locations with dedicated mosquito control programs, surveillance methods often rely on frequent testing of mosquitoes collected in a network of gravid traps (GTs) and CO2-baited light traps (LTs). Traps specifically targeting oviposition-seeking (e.g. GTs) and host-seeking (e.g. LTs) mosquitoes are vulnerable to trap bias, and captured specimens are often damaged, making morphological identification difficult. METHODS: This study leverages an alternative mosquito collection method, the human landing catch (HLC), as a means to compare sampling of potential WNV vectors to traditional trapping methods. Human collectors exposed one limb for 15 min at crepuscular periods (5:00-8:30 am and 6:00-9:30 pm daily, the time when Culex species are most actively host-seeking) at each of 55 study sites in suburban Chicago, Illinois, for two summers (2018 and 2019). RESULTS: A total of 223 human-seeking mosquitoes were caught by HLC, of which 46 (20.6%) were mosquitoes of genus Culex. Of these 46 collected Culex specimens, 34 (73.9%) were Cx. salinarius, a potential WNV vector species not thought to be highly abundant in upper Midwest USA. Per trapping effort, GTs and LTs collected > 7.5-fold the number of individual Culex specimens than HLC efforts. CONCLUSIONS: The less commonly used HLC method provides important insight into the complement of human-biting mosquitoes in a region with consistent WNV epidemics. This study underscores the value of the HLC collection method as a complementary tool for surveillance to aid in WNV vector species characterization. However, given the added risk to the collector, novel mitigation methods or alternative approaches must be explored to incorporate HLC collections safely and strategically into control programs.

A longitudinal study examining the associations between interpersonal trauma and romantic relationships among college students.

We examined the associations between the developmental timing of interpersonal trauma exposure (IPT) and three indicators of involvement in and quality of romantic relationships in emerging adulthood: relationship status, relationship satisfaction, and partner alcohol use. We further examined whether these associations varied in a sex-specific manner. In a sample of emerging adult college students (N = 12,358; 61.5% female) assessed longitudinally across the college years, we found precollege IPT increased the likelihood of being in a relationship, while college-onset IPT decreased the likelihood. Precollege and college-onset IPT predicted lower relationship satisfaction, and college-onset IPT predicted higher partner alcohol use. There was no evidence that associations between IPT and relationship characteristics varied in a sex-specific manner. Findings indicate that IPT exposure, and the developmental timing of IPT, may affect college students' relationship status. Findings also suggest that IPT affects their ability to form satisfying relationships with prosocial partners.

Risk of Legionellosis in residential areas around farms irrigating with municipal wastewater.

The conservation of freshwater is of both global and national importance, and in the United States, agriculture is one of the largest consumers of this resource. Reduction of the strain farming puts on local surface or groundwater is vital for ensuring resilience in the face of climate change, and one possible option is to irrigate with a combination of freshwater and reclaimed water from municipal wastewater treatment facilities. However, this wastewater can contain pathogens that are harmful to human health, such as Legionella pneumophila, which is a bacterium that can survive aerosolization and airborne transportation and cause severe pneumonia when inhaled. To assess an individual adult's risk of infection with L. pneumophila from a single exposure to agricultural spray irrigation, a quantitative microbial risk assessment was conducted for a scenario of spray irrigation in central Illinois, for the growing seasons in 2017, 2018, and 2019. The assessment found that the mean risk of infection for a single exposure exceeded the safety threshold of 10-6 infections/exposure up to 1 km from a low-pressure irrigator and up to 2 km from a high-pressure irrigator, although no median risk exceeded the threshold for any distance or irrigator pressure. These findings suggest that spray irrigation with treated municipal wastewater could be a viable option for reducing freshwater consumption in Midwest farming, as long as irrigation on windy days is avoided and close proximity to the active irrigator is limited.

Nocturnal Hot Flashes, but Not Serum Hormone Concentrations, as a Predictor of Insomnia in Menopausal Women: Results from the Midlife Women's Health Study.

Background: Sleep disruptions are among the most common symptoms experienced during menopause and can be associated with depression, hot flashes, and fluctuating hormones. However, few studies have examined how such risk factors influence sleep in midlife women in a network-based approach that will establish the complex relationship between variables. Materials and Methods: We used a Bayesian network (BN) to examine the relationship between multiple factors known to influence sleep and depression in midlife women, including hormone concentrations, hot flashes, and menopause status among participants of the longitudinal Midlife Women's Health Study. In year 1, 762 women (45-54 years of age) answered questions regarding the frequency of insomnia, hot flashes, and depression; 389 of the same women answered similar questions at year 4. We measured serum hormones and calculated free estradiol index, free testosterone index, and ratios of estradiol:progesterone, and estradiol:testosterone. For our model, we calculated the change in frequency of insomnia, depression, and covariates (body mass index, menopause status, hot flashes at night, and present quality of life) from year 1 to 4. Results: Using a BN, we found that self-reported hot flashes at night, and no other factors, were direct predictors of self-reported insomnia in year 1. Surprisingly, we did not identify an association between hormone concentrations and self-reported insomnia. Frequency of insomnia in year 4 was only predicted by frequency of insomnia in year 1, whereas frequency of depression in year 4 was predicted by year 4 insomnia and frequency of depression in year 1. No other factors were direct predictors of insomnia or depression in our model. Conclusions: Therefore, hot flashes at night, previous insomnia, and depression are stronger predictors of how women will self-report frequency of sleep disruptions and treatment may reduce menopausal sleep complaints.

Annexin A2 modulates phospholipid membrane composition upstream of Arp2 to control angiogenic sprout initiation.

The intersection of protein and lipid biology is of growing importance for understanding how cells address structural challenges during adhesion and migration. While protein complexes engaged with the cytoskeleton play a vital role, support from the phospholipid membrane is crucial for directing localization and assembly of key protein complexes. During angiogenesis, dramatic cellular remodeling is necessary for endothelial cells to shift from a stable monolayer to invasive structures. However, the molecular dynamics between lipids and proteins during endothelial invasion are not defined. Here, we utilized cell culture, immunofluorescence, and lipidomic analyses to identify a novel role for the membrane binding protein Annexin A2 (ANXA2) in modulating the composition of specific membrane lipids necessary for cortical F-actin organization and adherens junction stabilization. In the absence of ANXA2, there is disorganized cortical F-actin, reduced junctional Arp2, excess sprout initiation, and ultimately failed sprout maturation. Furthermore, we observed reduced filipin III labeling of membrane cholesterol in cells with reduced ANXA2, suggesting there is an alteration in phospholipid membrane dynamics. Lipidomic analyses revealed that 42 lipid species were altered with loss of ANXA2, including an accumulation of phosphatidylcholine (16:0_16:0). We found that supplementation of phosphatidylcholine (16:0_16:0) in wild-type endothelial cells mimicked the ANXA2 knock-down phenotype, indicating that ANXA2 regulated the phospholipid membrane upstream of Arp2 recruitment and organization of cortical F-actin. Altogether, these data indicate a novel role for ANXA2 in coordinating events at endothelial junctions needed to initiate sprouting and show that proper lipid modulation is a critical component of these events.

Urinary phthalate metabolite concentrations and hot flash outcomes: Longitudinal associations in the Midlife Women's Health Study.

Midlife in women is an understudied time for environmental chemical exposures and menopausal outcomes. Recent cross-sectional research links phthalates with hot flashes, but little is known regarding such associations over time. Our objective was to estimate longitudinal associations between repeated measures of urinary phthalate metabolite concentrations and hot flash outcomes in midlife women. Using data from the Midlife Women's Health Study (MWHS), a prospective longitudinal study, we fit generalized linear mixed-effects models (GLMMs) and Cox proportional hazards regression models to repeated measures over a 4-year period. Recruitment occurred in Baltimore and surrounding counties, Maryland, USA between 2006 and 2015. Participants were premenopausal/perimenopausal women (n = 744) aged 45-54 years, who were not pregnant, not taking menopausal symptom medication or oral contraceptives, did not have hysterectomy/oophorectomy, and irrespective of hot flash experience. Baseline mean (SD) age was 48.4 (2.45), and 65% were premenopausal. Main outcome measures included adjusted odds ratios (ORs) for 4 self-reported hot flash outcomes (ever experienced, past 30 days experience, weekly/daily, and moderate/severe), and hazard ratios (HRs) for incident hot flashes. We observed mostly increased odds of certain hot flash outcomes with higher concentrations of metabolites of di (2-ethylhexyl) phthalate (DEHP), monoisobutyl phthalate (MiBP), and a molar summary measure of plasticizer phthalate metabolites (DEHP metabolites, mono-(3-carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP)). Some associations between exposures and outcomes indicated decreased odds. In conclusion, phthalate metabolites were associated with certain hot flash outcomes in midlife women. Midlife may be a sensitive period for higher phthalate metabolite concentrations with respect to menopausal symptoms.

COVID and college: how the pandemic impacted alcohol use disorder status among students.

Objective: Alcohol consumption patterns during the COVID-19 pandemic have varied notably. Participants: We examined the acute impact of the pandemic on alcohol use disorder (AUD) in a generalizable sample of college students who were surveyed pre-pandemic and re-surveyed in May 2020. Method: Items assessed pre-pandemic included DSM-5 AUD and mental health symptoms. A COVID-19 impacts questionnaire was administered, and alcohol and mental health items re-assessed. Results: AUD symptoms decreased from pre-pandemic to during the pandemic, demonstrating a change in trajectory compared to prior cohorts. Students with persistent AUD reported greater concurrent symptoms of PTSD, depression, and alcohol consumption than those with remitted AUD (ps ≤ .02), but not increased COVID-19 impact. Persistent AUD status was predicted by higher sensation seeking and alcohol consumption. Conclusions: Students with concurrent mental health problems are at continued risk for persistent AUD. Findings highlight the impact of the college environment and social context for drinking on AUD.

Knowledge, attitudes, and practices of Illinois medical professionals related to ticks and tick-borne disease.

Background: The rising incidence of tick-borne disease (TBD) underscores the importance of proficiency in TBD diagnosis. Clinicians' knowledge about vector ticks and TBDs in their area may influence whether patients are questioned about potential tick exposure and the consideration of diagnostic testing for TBDs. Objective: Our objective was to assess the knowledge, attitudes, and practices of Illinois clinicians towards ticks and TBDs. The study aimed to 1) identify predictors associated with knowledge, 2) identify knowledge gaps, and 3) evaluate attitudes and practices related to TBDs. Methods: A web-based knowledge, attitudes, and practices survey about Illinois ticks and TBDs was disseminated to physicians, mid-level practitioners, and nurses between August 2020 and February 2022. Poisson regression analysis was conducted to identify predictors of higher scores. Results: Of 346 respondents, 80% correctly identified Lyme disease as endemic to Illinois, and 95% were familiar with diagnostic testing for Lyme. Knowledge of other TBDs present in the state was highest among physicians, yet only 26% of physicians believed Rocky Mountain spotted fever (RMSF) to be present in Illinois, and only 17% believed ehrlichiosis to be endemic. Only 32% of physicians knew the cause of Alpha-gal syndrome and fewer than 18% were aware of available diagnostic testing. Tick or TBD-related education within the past two years was the most significant predictor of higher scores, increasing overall knowledge scores by 26% (RR 1.26, 95% CI 1.13-1.41) and increasing scores specific to TBDs by 42% (RR 1.42, 95% CI 1.19-1.69). Conclusion: Illinois clinicians were informed about Lyme disease but lacked knowledge of other TBDs endemic to the state, including RMSF, ehrlichiosis, and Alpha-gal syndrome. The strongest predictor of knowledge was tick/TBD training in the previous two years, highlighting the importance of frequent region-specific training on ticks and TBDs.

A multi-omic analysis of MCF10A cells provides a resource for integrative assessment of ligand-mediated molecular and phenotypic responses.

The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix proteins. While these signals are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understanding of the linkage between molecular and phenotypic changes, we generated a comprehensive dataset that catalogs the transcriptional, proteomic, epigenomic and phenotypic responses of MCF10A mammary epithelial cells after exposure to the ligands EGF, HGF, OSM, IFNG, TGFB and BMP2. Systematic assessment of the molecular and cellular phenotypes induced by these ligands comprise the LINCS Microenvironment (ME) perturbation dataset, which has been curated and made publicly available for community-wide analysis and development of novel computational methods ( synapse.org/LINCS_MCF10A ). In illustrative analyses, we demonstrate how this dataset can be used to discover functionally related molecular features linked to specific cellular phenotypes. Beyond these analyses, this dataset will serve as a resource for the broader scientific community to mine for biological insights, to compare signals carried across distinct molecular modalities, and to develop new computational methods for integrative data analysis.

Longitudinal Analysis of SARS-CoV-2 Vaccine Breakthrough Infections Reveals Limited Infectious Virus Shedding and Restricted Tissue Distribution.

Background: The global effort to vaccinate people against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during an ongoing pandemic has raised questions about how vaccine breakthrough infections compare with infections in immunologically naive individuals and the potential for vaccinated individuals to transmit the virus. Methods: We examined viral dynamics and infectious virus shedding through daily longitudinal sampling in 23 adults infected with SARS-CoV-2 at varying stages of vaccination, including 6 fully vaccinated individuals. Results: The durations of both infectious virus shedding and symptoms were significantly reduced in vaccinated individuals compared with unvaccinated individuals. We also observed that breakthrough infections are associated with strong tissue compartmentalization and are only detectable in saliva in some cases. Conclusions: Vaccination shortens the duration of time of high transmission potential, minimizes symptom duration, and may restrict tissue dissemination.

Nonspecific ileitis: Impact of histopathology and gastrointestinal ultrasound in achieving the diagnosis of Crohn's disease.

Background and Aim: Nonspecific ileitis is inflammation of the ileum without specific diagnostic features. A minority may go on to develop Crohn's disease, but optimal pathways of further investigation have not been established. This study aimed to identify a cohort of patients with nonspecific ileitis and to determine the value of ileal histology and gastrointestinal ultrasound in identifying/excluding Crohn's disease. Patients and Methods: In a retrospective analysis, all patients having nonspecific ileitis at colonoscopy from January 2010 to August 2021 were identified. Clinical associations with those subsequently diagnosed with Crohn's disease were examined with specific reference to ileal histology and gastrointestinal ultrasound. Results: Of 29 638 procedures, 147 patients (0.5%) had nonspecific ileitis. Crohn's disease was subsequently diagnosed in 8 patients (5.4%) at a median of 148 (range 27-603) days after colonoscopy. The presence of chronic inflammation on ileal biopsies was more common in those subsequently diagnosed with Crohn's disease (63% vs 20%; P = 0.0145). On gastrointestinal ultrasound, none of the 26 patients with normal bowel wall thickness (<3 mm) were subsequently diagnosed with Crohn's disease, and repeat ultrasound in 15 patients 1 year later showed no change. Of the nine patients with abnormal sonographic findings, three were diagnostic for Crohn's disease. Repeat ultrasound revealed Crohn's disease in two, while four had resolution of the abnormal findings. Conclusion: Although ileal histology was of limited value in identifying patients with nonspecific ileitis who were subsequently diagnosed with Crohn's disease, gastrointestinal ultrasound was highly informative. Prospective studies are needed to confirm the value of gastrointestinal ultrasound as a diagnostic and monitoring tool in this setting.

Knowledge, attitudes, and practices of veterinary professionals towards ticks and tick-borne diseases in Illinois.

Objective: A lack of standardized surveillance or reporting of tick-borne diseases (TBDs) in Illinois creates uncertainty for veterinarians regarding TBDs occurring within their practice geography or which TBDs may be encroaching on their area from neighboring territories. Therefore, the objective of this study was to gauge the knowledge, attitudes, and practices of veterinary professionals in Southern and Central Illinois to establish a foundation for targeting educational and outreach programs that address knowledge gaps. Sample: 72 veterinary professionals in Central and Southern Illinois. Procedures: An online knowledge, attitudes, and practices survey was distributed to veterinary professionals in Southern and Central Illinois. Poisson regression analyses were conducted to determine factors associated with knowledge scores and the estimated number of TBD cases diagnosed. Results: Knowledge scores were significantly higher among veterinary practitioners with recent (within the last 5 years) training on TBD. The number of cases of TBD diagnosed was higher among those reporting concern about TBD, and among those who routinely test for TBDs. The types of diseases diagnosed were heavily influenced by the diagnostic method used. Clinical relevance: This study paints a cohesive picture of human factors associated with diagnosing veterinary diseases and TBD prevalence in Southern and Central Illinois. Our results highlight the importance and practical value of veterinary continuing education on ticks and TBDs for both companion animals and public health. Building capacity for training veterinarians in parasitology using partnerships between academia and industry may strengthen the knowledge and understanding of ticks and tick-borne pathogens in the veterinary community.

Adherence to a priori-Defined Diet Quality Indices Throughout the Early Disease Course Is Associated With Survival in Head and Neck Cancer Survivors: An Application Involving Marginal Structural Models.

No studies, to date, have scrutinized the role of a priori dietary patterns on prognosis following a head and neck squamous cell carcinoma (HNSCC) diagnosis. The purpose of this analysis was to evaluate the associations between adherence to six a priori defined diet quality indices (including AHEI-2010, aMED, DASH, and three low-carbohydrate indices) throughout the first 3 years of observation and all-cause and cancer-specific mortalities in 468 newly diagnosed HNSCC patients from the University of Michigan Head and Neck Specialized Program of Research Excellence (UM-SPORE). The dietary intake data were measured using a food frequency questionnaire administered at three annual time points commencing at study entry. Deaths and their causes were documented throughout the study using various data sources. Marginal structural Cox proportional hazards models were used to evaluate the role of diet quality, as a time-varying covariate, on mortality. There were 93 deaths from all causes and 74 cancer-related deaths adjudicated throughout the observation period. There was a strong inverse association between adherence to the AHEI-2010, all-cause mortality (HR Q5-Q1 :0.07, 95% CI:0.01-0.43, p trend:0.04), and cancer-specific mortality (HR Q5-Q1 :0.15, 95% CI:0.02-1.07, p trend:0.04). Other more modest associations were noted for the low-carbohydrate indices. In sum, higher adherence to the AHEI-2010 and a plant-based low-carbohydrate index throughout the first 3 years since diagnosis may bolster survival and prognosis in newly diagnosed patients with HNSCC.

Daily longitudinal sampling of SARS-CoV-2 infection reveals substantial heterogeneity in infectiousness.

The dynamics of SARS-CoV-2 replication and shedding in humans remain poorly understood. We captured the dynamics of infectious virus and viral RNA shedding during acute infection through daily longitudinal sampling of 60 individuals for up to 14 days. By fitting mechanistic models, we directly estimated viral expansion and clearance rates and overall infectiousness for each individual. Significant person-to-person variation in infectious virus shedding suggests that individual-level heterogeneity in viral dynamics contributes to 'superspreading'. Viral genome loads often peaked days earlier in saliva than in nasal swabs, indicating strong tissue compartmentalization and suggesting that saliva may serve as a superior sampling site for early detection of infection. Viral loads and clearance kinetics of Alpha (B.1.1.7) and previously circulating non-variant-of-concern viruses were mostly indistinguishable, indicating that the enhanced transmissibility of this variant cannot be explained simply by higher viral loads or delayed clearance. These results provide a high-resolution portrait of SARS-CoV-2 infection dynamics and implicate individual-level heterogeneity in infectiousness in superspreading.

Deriving a Measure of Social Recovery Capital From the Important People and Activities Instrument: Construction and Psychometric Properties.

AIM: This study presents a measure of Social Recovery Capital (SRC) derived from the Important People and Activities instrument (IPA). METHODS: The sample comprised young adults who participated in the Collaborative Study on the Genetics of Alcoholism, a high-risk family study of alcohol use disorder (N = 2472). Exploratory and confirmatory factor analysis identified influential items and factor structure, adjusting for family relatedness. The final scale was tested for reliability and validity. RESULTS: Factor analysis retained 10 items loading on three factors (Network Abstinence Behaviors, Basic Network Structure and Network Importance) that together explained 42% of the variance in SRC. The total model showed adequate fit (Comparative Fit Index = 0.95; Tucker Lewis Index = 0.93; Root Mean Square Error of Approximation = 0.06; Standardized Root Mean Squared Residual = 0.05) and acceptable reliability (α = 0.60; McDonald's ω = 0.73) and correlated with validation measures mostly in the weak to moderate range. Due to variable factor scores for reliability and validity, we only recommend using the total score. CONCLUSION: The SRC-IPA is a novel measure of SRC derived from the IPA that captures social network data and has applications in research and clinical work. Secondary data analyses using the SRC-IPA in studies that collected the IPA can further demonstrate the interaction of SRC with a wide variety of clinical indicators and demographic characteristics, making it a valuable addition to other measures of SRC.