Virtual interviewing with marginalized young adult mothers: appreciating the New Norm.

BACKGROUND AND OBJECTIVE: Virtual interviewing in qualitative research may promote inclusion, diversify samples, and maximize participation, but there is limited research regarding methodological best practices for marginalized study populations. Emerging adult (ages 18-29) and young adult (through age 40) mothers have ongoing stressors and competing responsibilities that may preclude participation with in-person interviews. The purpose of this article is to describe the processes and experiences of virtual interviewing among young adult mothers living in under-resourced communities, based on their responses to specific interview questions. DESIGN AND SAMPLE: As part of an explanatory sequential mixed methods study, qualitative interviews were conducted with a sample of young adult mothers who had previously participated in randomized controlled trials testing an intensive early home visiting intervention. Thirty-one participants (M = 29.7 years, SD = 2.5) who identified as Black (39%), Hispanic (55%), and White (7%), were interviewed using Zoom. RESULTS: The overarching theme was Zoom: Appreciating the New Norm. Identified categories were Practical Benefits of Virtual Interviewing, Sharing Stories, and Drawbacks of Virtual Interviewing. CONCLUSION: Findings support virtual interviewing as a feasible and potentially ideal method for qualitative studies with emerging/young adults. Further research to examine this approach with other marginalized populations may lead to more inclusive representation in qualitative research.

Catalyst-free [2 + 2] photocycloadditions between benzils and olefins under visible light.

The catalyst-free [2 + 2] photocycloaddition between benzils and simple olefins is reported. The adoption of visible light proved essential for the transformation, as shorter wavelengths led to uncontrolled decomposition. When cyclic olefins were used, the reaction occurred smoothly to afford the expected oxetanes regio- and stereoselectively after 24 h of irradiation. In contrast, in the case of acyclic olefins, longer reaction times were typically required and small amounts (ca. 20%) of [4 + 2] photocycloadducts and by-products deriving from competitive hydrogen atom abstraction were observed. The selectivity of the transformation could be consistently improved by decreasing the reaction temperature, thus restoring the desired [2 + 2] reactivity. An overall mechanistic picture is also offered based on the chemical and photophysical quenching experiments and the stereochemical output is rationalized based on Griesbeck models.

Olive oil and risk of breast cancer: a systematic review and dose-response meta-analysis of observational studies.

Olive oil consumption has been suggested to be inversely associated with breast cancer risk, probably due to its high MUFA and polyphenol content. The purpose of this meta-analysis was to assess the association between olive oil and breast cancer risk, including assessing the potential for a dose-response association. We performed a systematic search of PubMed, Web of Science, CINAHL and Cochrane Central Register of Controlled Trials through June 2020, identifying ten observational studies (two prospective studies and eight case-control studies) for meta-analysis. We estimated summary OR and 95 % CI for the highest v. lowest olive oil intake category across studies using random effect models and assessed the dose-response relationship between olive oil and breast cancer risk using restricted cubic splines. The summary OR comparing women with the highest intake to those with the lowest category of olive oil intake was 0·48 (95 % CI 0·09, 2·70) in prospective studies and 0·76 (95 % CI 0·54, 1·06) in case-control studies, with evidence of substantial study heterogeneity (prospective I2 = 89 %, case-control I2 = 82 %). There was no significant dose-response relationship for olive oil and breast cancer risk; the OR for a 14 g/d increment was 0·93 (95 % CI 0·83, 1·04). There may be a potential inverse association between olive oil intake and breast cancer; however, since the estimates are non-significant and the certainty level is very low, additional prospective studies with better assessment of olive oil intake are needed.

Plasma B-vitamin and one-carbon metabolites and risk of breast cancer before and after folic acid fortification in the United States.

Prior epidemiologic findings for plasma folate and B-vitamins and breast cancer risk are inconsistent and have not assessed the influence of folic acid fortification. Therefore, we examined the associations of plasma folate, B12 , pyridoxal 5'-phosphate (PLP), homocysteine, cysteine and cysteinylglycine with breast cancer risk, before and after fortification. We conducted a nested case-control study within the prospective Nurses' Health Study. In 1989-1990 (pre-fortification), 32,826 women donated a blood sample and 18,743 donated an additional blood sample in 2000-2001 (post-fortification). Between the first blood collection and 2006, 1874 incident breast cancer cases with at least one blood sample and 367 with two were 1:1 matched to controls. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) adjusting for breast cancer risk factors. Overall, higher plasma folate, B12 , PLP, homocysteine, cysteine and cysteinylglycine levels were not associated with breast cancer risk. Associations did not vary by in situ/invasive, hormone receptor status, or tumor molecular subtype. Additionally, associations were null before and after fortification. For example, the RR (95% CI) for the highest versus lowest tertile of 1990 (pre-fortification) plasma folate with 1990-2000 follow-up was 0.93 (0.75-1.16) and for the 2000 plasma folate (post-fortification) with 2000-2006 follow-up the RR (95% CI) was 1.17 (0.79-1.74). Plasma folate, B12 , PLP, homocysteine, cysteine and cysteinylglycine were not significantly associated with breast cancer overall, before and after fortification, or with specific tumor molecular subtypes. However, long term associations (>8 years) after the implementation of fortification could not be examined.

Plasma B-vitamins and one-carbon metabolites and the risk of breast cancer in younger women.

PURPOSE: We examined the association of plasma B-vitamins and metabolites, and related genetic variants, with risk of breast cancer among predominantly premenopausal women. METHODS: We conducted a nested case-control study within the Nurses' Health Study II. From blood samples collected in 1996-1999 and follow-up through 2007, plasma measures were available for 610 cases and 1207 controls. Unconditional multivariable logistic regression was used to estimate relative risks (RR) of breast cancer and 95% confidence intervals (CIs). We examined whether associations varied by methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase polymorphisms, breast cancer risk factors, or tumor characteristics. RESULTS: Plasma vitamin B12 was associated with a 64% higher risk of breast cancer comparing the highest versus lowest quintile (95% CI 1.17-2.29, p-trend = 0.02). Plasma folate (comparable RR = 1.18, 95% CI 0.84-1.66), pyridoxal 5'-phosphate (RR = 1.18, 95% CI 0.85-1.64), homocysteine (RR = 0.93, 95% CI 0.67-1.28), cysteine (RR = 1.14, 95% CI 0.81-1.62), and cysteinylglycine (RR = 0.93, 95% CI 0.66-1.31) were not associated with overall breast cancer risk. Folate was significantly positively associated with invasive and estrogen receptor-positive/progesterone receptor-positive breast cancer, and this association was suggestively stronger for bloods collected post-fortification. Several nutrient/breast cancer associations varied across subgroups defined by age, smoking, alcohol, multivitamin use, and MTHFR status (p-interaction < 0.05). CONCLUSIONS: Overall, plasma B-vitamins and metabolites were not associated with lower breast cancer risk. Plasma vitamin B-12 was positively associated with higher risk of overall breast cancer, and plasma folate was positively associated with risk of invasive breast cancer. Additionally, there may be associations in subgroups defined by related genetic variants, breast cancer risk factors, and tumor factors. Further studies in younger women and in the post-fortification era are needed to confirm these findings.

Protein intake and the risk of premenstrual syndrome.

OBJECTIVE: To examine the relationship between protein intake and the risk of incident premenstrual syndrome (PMS). DESIGN: Nested case-control study. FFQ were completed every 4 years during follow-up. Our main analysis assessed protein intake 2-4 years before PMS diagnosis (for cases) or reference year (for controls). Baseline (1991) protein intake was also assessed. SETTING: Nurses' Health Study II (NHS2), a large prospective cohort study of registered female nurses in the USA.ParticipantsParticipants were premenopausal women between the ages of 27 and 44 years (mean: 34 years), without diagnosis of PMS at baseline, without a history of cancer, endometriosis, infertility, irregular menstrual cycles or hysterectomy. Incident cases of PMS (n 1234) were identified by self-reported diagnosis during 14 years of follow-up and validated by questionnaire. Controls (n 2426) were women who did not report a diagnosis of PMS during follow-up and confirmed experiencing minimal premenstrual symptoms. RESULTS: In logistic regression models adjusting for smoking, BMI, B-vitamins and other factors, total protein intake was not associated with PMS development. For example, the OR for women with the highest intake of total protein 2-4 years before their reference year (median: 103·6 g/d) v. those with the lowest (median: 66·6 g/d) was 0·94 (95 % CI 0·70, 1·27). Additionally, intakes of specific protein sources and amino acids were not associated with PMS. Furthermore, results substituting carbohydrates and fats for protein were also null. CONCLUSIONS: Overall, protein consumption was not associated with risk of developing PMS.

Intake of dietary fat and fat subtypes and risk of premenstrual syndrome in the Nurses' Health Study II.

Approximately 8-20 % of reproductive-aged women experience premenstrual syndrome (PMS), substantially impacting quality of life. Women with PMS are encouraged to reduce fat intake to alleviate symptoms; however, its role in PMS development is unclear. We evaluated the association between dietary fat intake and PMS development among a subset of the prospective Nurses' Health Study II cohort. We compared 1257 women reporting clinician-diagnosed PMS, confirmed by premenstrual symptom questionnaire and 2463 matched controls with no or minimal premenstrual symptoms. Intakes of total fat, subtypes and fatty acids were assessed via FFQ. After adjustment for age, BMI, smoking, Ca and other factors, intakes of total fat, MUFA, PUFA and trans-fat measured 2-4 years before were not associated with PMS. High SFA intake was associated with lower PMS risk (relative risk (RR) quintile 5 (median=28·1 g/d) v. quintile 1 (median=15·1 g/d)=0·75; 95 % CI 0·58, 0·98; P trend=0·07). This association was largely attributable to stearic acid intake, with women in the highest quintile (median=7·4 g/d) having a RR of 0·75 v. those with the lowest intake (median=3·7 g/d) (95 % CI 0·57, 0·97; P trend=0·03). Individual PUFA and MUFA, including n-3 fatty acids, were not associated with risk. Overall, fat intake was not associated with higher PMS risk. High intake of stearic acid may be associated with a lower risk of developing PMS. Additional prospective research is needed to confirm this finding.

Analysis of the main risk factors for gestational diabetes diagnosed with International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria in multiple pregnancies.

INTRODUCTION: The aim is to investigate the proportion of multiple pregnancies with gestational diabetes mellitus (GDM) diagnosed using the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria and to identify the impact of age, body mass index (BMI), and mode of conception on incidence of GDM. MATERIALS AND METHODS: This is a single center, retrospective cohort study on 656 multiple pregnancies screened for GDM with 75-g, 2-h oral glucose tolerance test at 24-28 weeks of gestation, between January 2010 and January 2016. The diagnosis of gestational diabetes mellitus (GDM) was reached through the IADPSG. RESULTS: The incidence of GDM in our population was 15.1%. When patients who conceived through heterologous assisted reproduction technology were compared with those who conceived spontaneously, there was a significant difference for GDM (31.1 vs 13.6%, p < 0.001, OR 2.86). A similar finding was also observed comparing egg donation IVF/ICSI patients with homologous IVF/ICSI patients (31.1 vs 14.8%, p = 0.006, OR 2.59). Incidence of GDM was significantly higher in obese than in non-obese patients (42.5 vs 14.8%, p < 0.001, OR 4.88) and in women over 35 compared to younger patients (18.4 vs 11.1%, p = 0.01, OR 1.81). Logistic regression comparing the diabetes onset with conception mode gave a p = 0.07. The calculation of the Chi-square and odds ratio for single mode of conception showed that homologous vs conceived spontaneously p = 0.90, OR 0.97, heterologous vs homologous p = 0.01 with OR 2.46, and heterologous vs conceived spontaneously p = 0.01 with OR 2.39. Logistic regression showed that age and BMI are risk factors for developing GDM, respectively, p = 0.03 with OR 1.4 and p < 0.01 and OR 1.09. DISCUSSION: The contribution our study can make is improved counseling about GDM risks for couples with multiple pregnancies. Our data support the role of age, BMI, and mode of conception as risk factors for GDM in multiple pregnancies.

The BRCA1 tumor suppressor binds to inositol 1,4,5-trisphosphate receptors to stimulate apoptotic calcium release.

The inositol 1,4,5-trisphosphate receptor (IP3R) is a ubiquitously expressed endoplasmic reticulum (ER)-resident calcium channel. Calcium release mediated by IP3Rs influences many signaling pathways, including those regulating apoptosis. IP3R activity is regulated by protein-protein interactions, including binding to proto-oncogenes and tumor suppressors to regulate cell death. Here we show that the IP3R binds to the tumor suppressor BRCA1. BRCA1 binding directly sensitizes the IP3R to its ligand, IP3. BRCA1 is recruited to the ER during apoptosis in an IP3R-dependent manner, and, in addition, a pool of BRCA1 protein is constitutively associated with the ER under non-apoptotic conditions. This is likely mediated by a novel lipid binding activity of the first BRCA1 C terminus domain of BRCA1. These findings provide a mechanistic explanation by which BRCA1 can act as a proapoptotic protein.

Real-time measurement of Plasmodium falciparum-infected erythrocyte cytoadhesion with a quartz crystal microbalance.

BACKGROUND: An important virulence mechanism of the malaria parasite Plasmodium falciparum is cytoadhesion, the binding of infected erythrocytes to endothelial cells in the second half of asexual blood stage development. Conventional methods to investigate adhesion of infected erythrocytes are mostly performed under static conditions, many are based on manual or semi-automated read-outs and are, therefore, difficult to standardize. Quartz crystal microbalances (QCM) are sensitive to nanogram-scale changes in mass and biomechanical properties and are increasingly used in biomedical research. Here, the ability of QCM is explored to measure binding of P. falciparum-infected erythrocytes to two receptors: CD36 and chondroitin sulfate A (CSA) under flow conditions. METHODS: Binding of late stage P. falciparum parasites is measured in comparison to uninfected erythrocytes to CD36- and CSA-coated quartzes by QCM observing frequency shifts. CD36-expressing cell membrane fragments and CSA polysaccharide were coated via poly-L-lysine to the quartz. The method was validated by microscopic counting of attached parasites and of erythrocytes to the coated quartzes. RESULTS: Frequency shifts indicating binding of infected erythrocytes could be observed for both receptors CD36 and CSA. The frequency shifts seen for infected and uninfected erythrocytes were strongly correlated to the microscopically counted numbers of attached cells. CONCLUSIONS: In this proof-of-concept experiment it is shown that QCM is a promising tool to measure binding kinetics and specificity of ligand-receptor interactions using viable, parasite-infected erythrocytes. The method can improve the understanding of the virulence of P. falciparum and might be used to cross-validate other methods.

Rationale, Procedures, and Response Rates for the 2015 Administration of NCI's Health Information National Trends Survey: HINTS-FDA 2015.

The National Cancer Institute (NCI) developed the Health Information National Trends Survey (HINTS) to monitor population trends in cancer communication practices, information preferences, health risk behaviors, attitudes, and cancer knowledge. The U.S. Food and Drug Administration (FDA) recognized HINTS as a unique data resource for informing its health communication endeavors and partnered with NCI to field HINTS-FDA 2015. HINTS-FDA 2015 was a self-administered paper instrument sent by mail May 29 to September 8, 2015, using a random probability-based sample of U.S. postal addresses stratified by county-level smoking rates, with an oversampling of high and medium-high smoking strata to increase the yield of current smokers responding to the survey. The response rate for HINTS-FDA 2015 was 33% (N = 3,738). The yield of current smokers (n = 495) was lower than expected, but the sampling strategy achieved the goal of obtaining more former smokers (n = 1,132). Public-use HINTS-FDA 2015 data and supporting documentation have been available for download and secondary data analyses since June 2016 at http://hints.cancer.gov . NCI and FDA encourage the use of HINTS-FDA for health communication research and practice related to tobacco-related communications, public knowledge, and behaviors as well as beliefs and actions related to medical products and dietary supplements.

Modulation of airway epithelial antiviral immunity by fungal exposure.

Multiple pathogens, such as bacteria, fungi, and viruses, have been frequently found in asthmatic airways and are associated with the pathogenesis and exacerbation of asthma. Among these pathogens, Alternaria alternata (Alt), a universally present fungus, and human rhinovirus have been extensively studied. However, their interactions have not been investigated. In the present study, we tested the effect of Alt exposure on virus-induced airway epithelial immunity using live virus and a synthetic viral mimicker, double-stranded RNA (dsRNA). Alt treatment was found to significantly enhance the production of proinflammatory cytokines (e.g., IL-6 and IL-8) induced by virus infection or dsRNA treatment. In contrast to this synergistic effect, Alt significantly repressed type I and type III IFN production, and this impairment led to elevated viral replication. Mechanistic studies suggested the positive role of NF-κB and mitogen-activated protein kinase pathways in the synergism and the attenuation of the TBK1-IRF3 pathway in the inhibition of IFN production. These opposite effects are caused by separate fungal components. Protease-dependent and -independent mechanisms appear to be involved. Thus, Alt exposure alters the airway epithelial immunity to viral infection by shifting toward more inflammatory but less antiviral responses.

Response of Central Nervous System Biomolecules and Systemic Biomarkers to Aerobic Exercise Following Concussion: A Scoping Review of Human and Animal Research.

The purpose of this study was to identify the response of biomolecules and biomarkers that are associated with the central nervous system to aerobic exercise in human and pre-clinical models of concussion or mild traumatic brain injury (TBI), and to highlight the knowledge gaps in the literature. A systematic scoping review was conducted following a search of EMBASE, MEDLINE, SCOPUS, BIOSIS, and Cochrane Libraries performed on September 8, 2023 (from data base inception). The scoping review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. Duplicates were removed and article screening was performed using an online systematic review management system. The search resulted in a total of 2,449 articles being identified, with 14 articles meeting the inclusion/exclusion criteria and having their data extracted. One study was conducted in humans, while the remainder of identified studies utilized murine models. The current literature is limited and evaluated many different biomolecules and biomarkers with brain-derived neurotrophic factor being the most researched. Further studies on this topic are needed to better understand the biomarker response to exercise after concussion and mild TBI, especially in the human population.

Impact of 8 lifestyle factors on mortality and life expectancy among United States veterans: The Million Veteran Program.

BACKGROUND: Lifestyle medicine has been proposed as a way to address the root causes of chronic disease and their associated health care costs. OBJECTIVE: This study aimed to estimate mortality risk and longevity associated with individual lifestyle factors and comprehensive lifestyle therapy. METHODS: Age- and sex-specific mortality rates were calculated on the basis of 719,147 veterans aged 40-99 y enrolled in the Veteran Affairs Million Veteran Program (2011-2019). Hazard ratios and estimated increase in life expectancy were examined among a subgroup of 276,132 veterans with complete data on 8 lifestyle factors at baseline. The 8 lifestyle factors included never smoking, physical activity, no excessive alcohol consumption, restorative sleep, nutrition, stress management, social connections, and no opioid use disorder. RESULTS: On the basis of 1.12 million person-years of follow-up, 34,247 deaths were recorded. Among veterans who adopted 1, 2, 3, 4, 5, 6, 7, and 8 lifestyle factors, the adjusted hazard ratios for mortality were 0.74 (0.60-0.90), 0.60 (95% CI: 0.49, 0.73), 0.50 (95% CI: 0.41, 0.61), 0.43 (95% CI: 0.35, 0.52), 0.35 (95% CI: 0.29, 0.43), 0.27 (95% CI: 0.22, 0.33), 0.21 (95% CI: 0.17, 0.26), and 0.13 (95% CI: 0.10, 0.16), respectively, as compared with veterans with no adopted lifestyle factors. The estimated life expectancy at age 40 y was 23.0, 26.5, 28.8, 30.8, 32.7, 35.1, 38.3, 41.3, and 47.0 y among males and 27.0, 28.8, 33.1, 38.0, 39.2, 41.4, 43.8, 46.3, and 47.5 y for females who adopted 0, 1, 2, 3, 4, 5, 6, 7, and 8 lifestyle factors, respectively. The difference in life expectancy at age 40 y was 24.0 y for male veterans and 20.5 y for female veterans when comparing adoption of 8-9 lifestyle factors. CONCLUSIONS: A combination of 8 lifestyle factors is associated with a significantly lower risk of premature mortality and an estimated prolonged life expectancy.

Developing a membrane-proximal CD33-targeting CAR T cell.

BACKGROUND: CD33 is a tractable target in acute myeloid leukemia (AML) for chimeric antigen receptor (CAR) T cell therapy, but clinical success is lacking. METHODS: We developed 3P14HLh28Z, a novel CD33-directed CD28/CD3Z-based CAR T cell derived from a high-affinity binder obtained through membrane-proximal fragment immunization in humanized mice. RESULTS: We found that immunization exclusively with the membrane-proximal domain of CD33 is necessary for identification of membrane-proximal binders in humanized mice. Compared with clinically validated lintuzumab-based CAR T cells targeting distal CD33 epitopes, 3P14HLh28Z showed enhanced in vitro functionality as well as superior tumor control and increased overall survival in both low antigen density and clinically relevant patient-derived xenograft models. Increased activation and enhanced polyfunctionality led to enhanced efficacy. CONCLUSIONS: Showing for the first time that a membrane-proximal CAR is superior to a membrane-distal one in the setting of CD33 targeting, our results demonstrate the rationale for targeting membrane-proximal epitopes with high-affinity binders. We also demonstrate the importance of optimizing CAR T cells for functionality in settings of both low antigen density and clinically relevant patient-derived models.

Norepinephrine depletion in the brain sex-dependently modulates aspects of spatial learning and memory in female and male rats.

RATIONALE: The contribution of norepinephrine on the different phases of spatial memory processing remains incompletely understood. To address this gap, this study depleted norepinephrine in the brain and then conducted a spatial learning task with multiple phases. METHODS: Male and female Wistar rats were administered 50 mg/kg/i.p. of DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) to deplete norepinephrine. After 10 days, rats were trained on a 20-hole Barnes maze spatial navigation task for 5 days. On the fifth day, animals were euthanized and HPLC was used to confirm depletion of norepinephrine in select brain regions. In Experiment 2, rats underwent a similar Barnes maze procedure that continued beyond day 5 to investigate memory retrieval and updating via a single probe trial and two reversal learning periods. RESULTS: Rats did not differ in Barnes maze acquisition between DSP-4 and saline-injected rats; however, initial acquisition differed between the sexes. HPLC analysis confirmed selective depletion of norepinephrine in dorsal hippocampus and cingulate cortex without impact to other monoamines. When retrieval was tested through a probe trial, DSP-4-improved memory retrieval in males but impaired it in females. Cognitive flexibility was transiently impacted by DSP-4 in males only. CONCLUSIONS: Despite significantly reducing levels of norepinephrine, DSP-4 had only a modest impact on spatial learning and behavioral flexibility. Memory retrieval and early reversal learning were most affected and in a sex-specific manner. These data suggest that norepinephrine has sex-specific neuromodulatory effects on memory retrieval with a lesser effect on cognitive flexibility and no impact on acquisition of learned behavior.

Influence of Intramineral Proteins on the Growth of Carbonate Crystals Using as a Scaffold Membranes of Ratite Birds and Crocodiles Eggshells.

The lack of information on structural basis where proteins are involved, as well as the biomineralization processes of different systems such as bones, diatom frustules, and eggshells, have intrigued scientists from different fields for decades. This scientific curiosity has led to the use of methodologies that help understand the mechanism involved in the formation of these complex structures. Therefore, this work focuses on the use of eggshell membranes from different species of ratites (emu and ostrich) and reptiles (two species of crocodiles) as a model to differentiate biocalcification and biosilicification by introducing calcium phosphate or silica inside the membrane fiber mantles. We performed this to obtain information about the process of eggshell formation as well as the changes that occur in the membrane during crystal formation. In order to identify and understand the early processes leading to the formation of the microstructures present in the eggshell, we decided to carry out the synthesis of silica-carbonate of calcium, barium, and strontium called biomorph in the presence of intramineral proteins. This was carried out to evaluate the influence of these proteins on the formation of specific structures. We found that the proteins on untreated membranes, present a structural growth similar to those observed in the inner part of the eggshell, while in treated membranes, the structures formed present a high similarity with those observed in the outer and intermediate part of the eggshell. Finally, a topographic and molecular analysis of the biomorphs and membranes was performed by scanning electron microscopy (SEM), Raman and Fourier-transform Infrared (FTIR) spectroscopies.

Cardiovascular Disease Risk Assessment Using Traditional Risk Factors and Polygenic Risk Scores in the Million Veteran Program.

Importance: Primary prevention of atherosclerotic cardiovascular disease (ASCVD) relies on risk stratification. Genome-wide polygenic risk scores (PRSs) are proposed to improve ASCVD risk estimation. Objective: To determine whether genome-wide PRSs for coronary artery disease (CAD) and acute ischemic stroke improve ASCVD risk estimation with traditional clinical risk factors in an ancestrally diverse midlife population. Design, Setting, and Participants: This was a prognostic analysis of incident events in a retrospectively defined longitudinal cohort conducted from January 1, 2011, to December 31, 2018. Included in the study were adults free of ASCVD and statin naive at baseline from the Million Veteran Program (MVP), a mega biobank with genetic, survey, and electronic health record data from a large US health care system. Data were analyzed from March 15, 2021, to January 5, 2023. Exposures: PRSs for CAD and ischemic stroke derived from cohorts of largely European descent and risk factors, including age, sex, systolic blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, smoking, and diabetes status. Main Outcomes and Measures: Incident nonfatal myocardial infarction (MI), ischemic stroke, ASCVD death, and composite ASCVD events. Results: A total of 79 151 participants (mean [SD] age, 57.8 [13.7] years; 68 503 male [86.5%]) were included in the study. The cohort included participants from the following harmonized genetic ancestry and race and ethnicity categories: 18 505 non-Hispanic Black (23.4%), 6785 Hispanic (8.6%), and 53 861 non-Hispanic White (68.0%) with a median (5th-95th percentile) follow-up of 4.3 (0.7-6.9) years. From 2011 to 2018, 3186 MIs (4.0%), 1933 ischemic strokes (2.4%), 867 ASCVD deaths (1.1%), and 5485 composite ASCVD events (6.9%) were observed. CAD PRS was associated with incident MI in non-Hispanic Black (hazard ratio [HR], 1.10; 95% CI, 1.02-1.19), Hispanic (HR, 1.26; 95% CI, 1.09-1.46), and non-Hispanic White (HR, 1.23; 95% CI, 1.18-1.29) participants. Stroke PRS was associated with incident stroke in non-Hispanic White participants (HR, 1.15; 95% CI, 1.08-1.21). A combined CAD plus stroke PRS was associated with ASCVD deaths among non-Hispanic Black (HR, 1.19; 95% CI, 1.03-1.17) and non-Hispanic (HR, 1.11; 95% CI, 1.03-1.21) participants. The combined PRS was also associated with composite ASCVD across all ancestry groups but greater among non-Hispanic White (HR, 1.20; 95% CI, 1.16-1.24) than non-Hispanic Black (HR, 1.11; 95% CI, 1.05-1.17) and Hispanic (HR, 1.12; 95% CI, 1.00-1.25) participants. Net reclassification improvement from adding PRS to a traditional risk model was modest for the intermediate risk group for composite CVD among men (5-year risk >3.75%, 0.38%; 95% CI, 0.07%-0.68%), among women, (6.79%; 95% CI, 3.01%-10.58%), for age older than 55 years (0.25%; 95% CI, 0.03%-0.47%), and for ages 40 to 55 years (1.61%; 95% CI, -0.07% to 3.30%). Conclusions and Relevance: Study results suggest that PRSs derived predominantly in European samples were statistically significantly associated with ASCVD in the multiancestry midlife and older-age MVP cohort. Overall, modest improvement in discrimination metrics were observed with addition of PRSs to traditional risk factors with greater magnitude in women and younger age groups.

Parenting Stress Among Adolescent Mothers: An Integrative Literature Review.

Adverse maternal and child outcomes are associated with parenting stress. Adolescent mothers may be particularly susceptible to parenting stress because of conflicting parenting and developmental demands. We performed an integrative literature review to identify risk and protective factors for parenting stress, measured by the Parenting Stress Index (PSI), among adolescent mothers. Guided by Belsky's Determinants of Parenting Model (1984) and using Whittemore and Knafl's (2005) five-stage review method, we searched CINAHL, EMBASE, PsycINFO, and MEDLINE databases to identify 786 research articles. After quality appraisal, 26 articles were included. Risk and protective factors were categorized into themes within the context of Belsky's framework, including maternal attributes (e.g. maternal self-efficacy), child characteristics (e.g. child temperament), and contextual influences (e.g. perceived social support). The new conceptual model maps risks, protective factors, and nuanced areas for parenting stress and can guide researchers and clinicians in approaches to prevent and reduce parenting stress among adolescent mothers.

A meta-analysis of experienced incivility and its correlates: Exploring the dual path model of experienced workplace incivility.

The present study proposes and examines a theoretical Dual Path Model of Experienced Workplace Incivility using meta-analytic relationships (k = 246; N = 145, 008) between experienced incivility and frequent correlates. The stress-induced mechanism was supported with perceived stress mediating the meta-analytical relationship between experienced incivility and occupational health (i.e., emotional exhaustion and somatic complaints). The commitment-induced mechanism was also supported with affective commitment to the organization mediating the relationship between experienced incivility and organizational correlates (i.e., job satisfaction and turnover intentions). However, these paths were not able to explain the strong relationship between experienced and enacted workplace incivility. Moderating analysis revealed that the experienced-enactment link is stronger between coworkers, in comparison to incivility experienced from supervisors; experienced incivility is more strongly related to organizational correlates, when incivility is enacted by supervisors in comparison to coworkers, and in human service samples when compared to samples comprised of mixed occupations. We discuss theoretical and practical implications as well as directions for future research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).