SIRIUS, Ultra-Scintillating Upconversion Breast Implant for Remote Orthotopic Photodynamic Therapy.

Present day strategies for delivery of wireless photodynamic therapy (PDT) to deep-seated targets are limited by the inadequacy of irradiance and insufficient therapeutic depth. Here we report the design and preclinical validation of a flexible wireless upconversion nanoparticle (UCNP) implant (SIRIUS) that is capable of large field, high intensity illumination for PDT of deep-seated tumors. The implant achieves this by incorporating submicrometer core-shell-shell NaYF4 UCNPs into its design, which significantly enhances upconversion efficiency and mitigates light loss from surface quenching. We demonstrate the efficacy of SIRIUS UCNP implant mediated PDT in preclinical breast cancer disease models. In our in vitro experiments, SIRIUS directed 5-Aminolevulinic Acid (5-ALA) based wireless PDT leads to significant reactive oxygen species (ROS) generation and tumor apoptosis in hormonal receptor+/HER2+ (MCF7) and triple-negative (MDA-MB-231) breast cancer cell lines. In our in vivo rodent model, SIRIUS-driven PDT is shown to be significant in regressing tumors when applied to orthotopically inoculated breast tumors. Following successful preclinical validation, we also describe a clinical prototype of UCNP breast implant with potential dual cosmetic and onco-therapeutic functions. SIRIUS is an upconversion breast implant for wireless PDT that fulfils all the design prerequisites necessary for seamless clinical translation.

Sleepless in inequality: findings from the 2018 behavioral risk factor surveillance system, a cross-sectional study.

BACKGROUND: Despite the large body of research on the adverse effects of income inequality, to date, few studies have examined its impact on sleep. The objective of this investigation is to examine the association between US state income inequality and the odds for regularly obtaining inadequate (< 7 h) and very inadequate (< 5 h) of sleep in the last 24 h. METHODS: We analysed data from 350,929 adults participating in the US 2018 Behavioral Risk Factor Surveillance System (BRFSS). Multilevel modeling was used to determine the association between state-level income inequality, as measured by the Gini coefficient, and the odds for obtaining inadequate and very inadequate sleep. We also determined if associations were heterogeneous across gender. RESULTS: A standard deviation increase in the Gini coefficient was associated with increased odds for inadequate (OR = 1.06, 95% CI: 1.00, 1.13) and very inadequate sleep (OR = 1.11, 95% CI: 1.03,1.20). Also, a cross-level Gini Coefficient X Gender interaction term was significant (OR = 1.07, 95% CI:1.01,1.13), indicating that increasing income inequality was more detrimental to women's sleep behavior. CONCLUSION: Future work should be conducted to determine whether decreasing the wide gap between incomes can alleviate the burden of income inequality on inadequate sleep in the United States.

Quality of life in Malaysian children with inflammatory bowel disease: An understudied population.

AIM: Quality of life (QoL) in children with inflammatory bowel disease (IBD) is often impaired by underlying disease. We evaluated factors affecting health-related QoL (HRQoL) in Malaysian children with IBD. METHODS: A cross-sectional study using IMPACT-III questionnaires evaluating HRQoL in children aged 8-17 years with duration of IBD of ≥6 months was conducted. IMPACT-III, a validated instrument designed to measure HRQoL in children with IBD, was used. Higher IMPACT-III (maximum = 100) score indicates better HRQoL. Impact of socio-demographic and clinical factors of IBD on the HRQoL was evaluated. Paediatric Crohn's disease (CD) and ulcerative colitis (UC) activity indices were used to classify disease severity. RESULTS: A total of 75 children (UC = 44, CD = 41; mean (SD) age at diagnosis 8.2 (3.5) years) were interviewed at mean age of 12.8 (2.7) years. Mean IMPACT-III score was significantly lower in children with more severe disease (mild: 71.8 (13.6) vs. moderate: 65.5 (10.9) vs. severe: 46.3 (14.5); P < 0.001), history of hospitalisation (yes: 64.0 (14.0) vs. none: 74.1 (12.2), P = 0.034) and a higher number of admissions (r = -0.352, P = 0.041) in preceding 6 months. Diagnosis at a younger age (r = -0.31, P = 0.007) and a longer duration of disease (r = 0.286, P = 0.013) was associated with higher score. A higher weight-for-age (r = 0.261, P = 0.023) or body mass index-for-age z-score (r = 0.235, P = 0.042) was correlated with a better body image domain score, respectively. CONCLUSIONS: In Malaysian children with IBD, HRQoL was adversely affected by a more severe disease. Better control of disease activity and maintaining long-term remission are important to improve the HRQoL in childhood IBD.

Delayed coloanal anastomosis as a stoma-sparing alternative to immediate coloanal anastomosis: A systematic review and meta-analysis.

BACKGROUND: Recent clinical trials have demonstrated favorable outcomes associated with trans-anal colonic pull-through for rectal resection followed by delayed coloanal anastomoses (DCA), resulting in a resurgence in popularity of the technique. This meta-analysis aims to review existing literature to evaluate the postoperative complications associated with DCA, and to make comparisons with immediate coloanal anastomoses (ICA) after colorectal resection to assess the suitability of DCA as an alternative form of surgical treatment. METHODS: Medline and Embase databases were reviewed from inception until 31 July 2020 in accordance with PRISMA guidelines. Single-arm studies that involved patients undergoing DCA for benign or malignant causes were selected, and meta-analysis of proportions was conducted to determine the prevalence of postoperative complications following DCA. Comparative studies comparing postoperative outcomes between DCA and ICA were also included for comparative meta-analysis. RESULTS: Patients undergoing DCA were significantly less likely to require diverting stoma construction as compared to ICA (odds ratio [OR] = 0.04; confidence interval [CI]: 0.02-0.07; P < 0.001). Overall postoperative morbidity (OR = 0.50; 95% CI: 0.23-1.12; P = 0.09) and mortality (OR = 0.49, 95% CI: 0.12-1.98; P = 0.32) was comparable between DCA and ICA groups. No significant differences in perioperative complications, such as anastomotic leakage (OR = 0.42; 95% CI: 0.11-1.64; P = 0.21), postoperative ileus, pelvic abscesses, or sepsis, were noted between DCA and ICA. CONCLUSION: Our study shows no differences in complications or functional outcomes between DCA and ICA. Pooled analysis expectedly revealed a lower rate of diverting stoma in patients undergoing DCA. DCA is thus a safe alternative to current surgical practices where avoidance of a stoma is desired.

Environmental risk factors for inflammatory bowel disease: A case control study in Southeast Asian children.

AIM: Early-life environmental exposure, which has important implications in the pathogenesis of inflammatory bowel disease (IBD), is not well understood in Asian children. We examined environmental factors prior to the development of childhood IBD in a Southeast Asian population. METHODS: We conducted a case control study in IBD diagnosed before 18 years of age and controls matched by gender, age and ethnicity. A questionnaire recording medical, family, dietary and social histories, home environment, childhood diseases and immunisation status was used. RESULTS: In a multivariate analysis involving 70 children with IBD (Crohn's disease (CD) = 38; ulcerative colitis (UC) = 32) and 140 controls, childhood acute gastroenteritis (odds ratio (OR): IBD 6.9; CD 7.8; UC 5.8) and excessive antibiotic usage in early childhood (OR: IBD 5.3; CD 4.2; UC 4.8) were significantly associated with IBD, CD and UC. Having a fish or turtle aquarium (OR 6.0), major stressful life events (OR 5.6) and attending the same school concurrently with a sibling (OR 2.9) were significant risk factors for IBD. Duration of breastfeeding >6 months (OR: IBD 0.4; UC 0.2) and safe water consumption (OR: IBD 0.2; UC 0.2) reduced the odds of having IBD and UC, respectively. Being vaccinated for rotavirus reduced the odds of developing IBD (OR 0.1). CONCLUSIONS: Several risk and protective factors were identified in this environmental risk study in Southeast Asian children with IBD. This knowledge has important implications in understanding disease aetiology and future prevention strategies to reduce the development of IBD in Southeast Asian children.

Perioperative anaphylaxis: A five-year review in a tertiary paediatric hospital.

Making a diagnosis of perioperative anaphylaxis and identifying culprit drugs are diagnostic challenges. The aim of this study is to describe the perioperative presentation of anaphylaxis and results of patients who underwent allergy evaluation. This is a retrospective review of perioperative anaphylaxis of severity Grade 2 and above based on the Australian and New Zealand Anaesthetic Allergy Group criteria from 2015 to 2019 in a tertiary paediatric hospital. Data collected were demographics, clinical features, investigations and management. Of the 35,361 cases of paediatric anaesthesia, there were 15 cases of perioperative anaphylaxis, giving an incidence of four in 10,000. The median age was seven years (interquartile range four-15 years) with a male predominance of 86.7% (13/15). The severity of anaphylaxis was Grade 2 in 33.3% (5/15) and Grade 3 in 66.7% (10/15). The commonest presenting feature was hypotension (13/15, 86.7%) while the earliest symptom was respiratory change (9/15, 60.0%). Dynamic tryptase was raised in 75% (6/8) of the patients with adequate tryptase samples. Eight patients (53.3%) completed allergy testing, of whom five patients (62.5%) had IgE-mediated anaphylaxis with skin test positive to cefazolin (n = 3), atracurium (n = 1) and rocuronium (n = 1). Three patients (25.0%) had non-IgE-mediated reactions with negative skin tests. Although only half the patients completed allergy evaluation, a culprit drug could be identified in 62.5%, with antibiotics being the commonest. This emphasises the need for appropriate evaluation in cases of suspected perioperative anaphylaxis.

Procedural myocardial injury, infarction and mortality in patients undergoing elective PCI: a pooled analysis of patient-level data.

AIMS: The prognostic importance of cardiac procedural myocardial injury and myocardial infarction (MI) in chronic coronary syndrome (CCS) patients undergoing elective percutaneous coronary intervention (PCI) is still debated. METHODS AND RESULTS: We analysed individual data of 9081 patients undergoing elective PCI with normal pre-PCI baseline cardiac troponin (cTn) levels. Multivariate models evaluated the association between post-PCI elevations in cTn and 1-year mortality, while an interval analysis evaluated the impact of the size of the myocardial injury on mortality. Our analysis was performed in the overall population and also according to the type of cTn used [52.0% had high-sensitivity cTn (hs-cTn)]. Procedural myocardial injury, as defined by the Fourth Universal Definition of MI (UDMI) [post-PCI cTn elevation ≥1 × 99th percentile upper reference limit (URL)], occurred in 52.8% of patients and was not associated with 1-year mortality [adj odds ratio (OR), 1.35, 95% confidence interval (CI) (0.84-1.77), P = 0.21]. The association between post-PCI cTn elevation and 1-year mortality was significant starting ≥3 × 99th percentile URL. Major myocardial injury defined by post-PCI ≥5 × 99th percentile URL occurred in 18.2% of patients and was associated with a two-fold increase in the adjusted odds of 1-year mortality [2.29, 95% CI (1.32-3.97), P = 0.004]. In the subset of patients for whom periprocedural evidence of ischaemia was collected (n = 2316), Type 4a MI defined by the Fourth UDMI occurred in 12.7% of patients and was strongly associated with 1-year mortality [adj OR 3.21, 95% CI (1.42-7.27), P = 0.005]. We also present our results according to the type of troponin used (hs-cTn or conventional troponin). CONCLUSION: Our analysis has demonstrated that in CCS patients with normal baseline cTn levels, the post-PCI cTn elevation of ≥5 × 99th percentile URL used to define Type 4a MI is associated with 1-year mortality and could be used to detect 'major' procedural myocardial injury in the absence of procedural complications or evidence of new myocardial ischaemia.

Maternal antioxidant treatment prevents the adverse effects of prenatal stress on the offspring's brain and behavior.

Maternal exposure to stress during pregnancy is associated with an increased risk of psychiatric disorders in the offspring in later life. The mechanisms through which the effects of maternal stress are transmitted to the fetus are unclear, however the placenta, as the interface between mother and fetus, is likely to play a key role. Using a rat model, we investigated a role for placental oxidative stress in conveying the effects of maternal social stress to the fetus and the potential for treatment using a nanoparticle-bound antioxidant to prevent adverse outcomes in the offspring. Maternal psychosocial stress increased circulating corticosterone in the mother, but not in the fetuses. Maternal stress also induced oxidative stress in the placenta, but not in the fetal brain. Blocking oxidative stress using an antioxidant prevented the prenatal stress-induced anxiety phenotype in the male offspring, and prevented sex-specific neurobiological changes, specifically a reduction in dendrite lengths in the hippocampus, as well as reductions in the number of parvalbumin-positive neurons and GABA receptor subunits in the hippocampus and basolateral amygdala of the male offspring. Importantly, many of these effects were mimicked in neuronal cultures by application of placental-conditioned medium or fetal plasma from stressed pregnancies, indicating molecules released from the placenta may mediate the effects of prenatal stress on the fetal brain. Indeed, both placenta-conditioned medium and fetal plasma contained differentially abundant microRNAs following maternal stress, and their predicted targets were enriched for genes relevant to nervous system development and psychiatric disorders. The results highlight placental oxidative stress as a key mediator in transmitting the maternal social stress effects on the offspring's brain and behavior, and offer a potential intervention to prevent stress-induced fetal programming of affective disorders.

Outcome of vaginal stripping for vaginal intraepithelial neoplasia: A 20-year observational study.

AIM: High-grade vaginal intraepithelial neoplasia (VAIN) is considered to be a premalignant lesion. We conducted a 20-year retrospective observational single-center study on the effectiveness of vaginal stripping (local excision procedure) as a treatment for high-grade VAIN. METHODS: Women diagnosed with VAIN and treated with vaginal stripping performed from 1998 to 2017 at our unit were identified using the hospital computer database. Vaginal stripping was performed for high-grade VAIN after being diagnosed by colposcopy-directed biopsies. The patients were followed every 3-6 months afterward via cytology monitoring and vaginal smear. Colposcopy-guided biopsy was repeated for high-grade abnormal cytology or persistent low-grade abnormality. The residual disease and recurrence rates were determined. Risk factors for margin positivity and residual and recurrent disease were identified. The association between margin positivity and recurrence was evaluated. RESULTS: Excluding three women whose final histology were malignant, the follow-up smears and histology (if any) were traced in the remaining 111 women. The median follow-up time was 76 months. Twenty-one of them had persistent abnormal smears (14 high-grade lesions and seven low-grade lesions) during the year following the vaginal stripping. The residual disease rate was 18.9% (21/111). The recurrence rate was 7.2%. There were five women (4%) with procedure-related complications. History of hysterectomy was identified as a risk factor for recurrence. CONCLUSIONS: Vaginal stripping is a valid treatment option for VAIN. High-grade VAIN post treatment recurred up to 5 years post treatment. Regular long-term surveillance is needed.

Laser mode locking using a single-mode-fiber coil with enhanced polarization-dependent loss.

A laser mode-locking phenomenon based on polarization-dependent loss (PDL) using a passive fiber coil is demonstrated. We propose using a fiber coil operating in low-V-number regime to achieve an enhanced bend-induced PDL and to maintain a reasonable bend loss. A mode-locked thulium doped all-fiber laser is shown using the low-V-number fiber coil. The results indicate that a moderate amount of PDL at 1 dB is sufficient to initiate and sustain a stable CW mode-locking operation. To the best of our knowledge, this is the first demonstration of a CW mode-locked fiber laser based on PDL enabled by a fiber coil.

Laws Restricting Access to Abortion Services and Infant Mortality Risk in the United States.

OBJECTIVES: Since the US Supreme Court's 1973 Roe v. Wade decision legalizing abortion, states have enacted laws restricting access to abortion services. Previous studies suggest that restricting access to abortion is a risk factor for adverse maternal and infant health. The objective of this investigation is to study the relationship between the type and the number of state-level restrictive abortion laws and infant mortality risk. METHODS: We used data on 11,972,629 infants and mothers from the US Cohort Linked Birth/Infant Death Data Files 2008-2010. State-level abortion laws included Medicaid funding restrictions, mandatory parental involvement, mandatory counseling, mandatory waiting period, and two-visit laws. Multilevel logistic regression was used to determine whether type or number of state-level restrictive abortion laws during year of birth were associated with odds of infant mortality. RESULTS: Compared to infants living in states with no restrictive laws, infants living in states with one or two restrictive laws (adjusted odds ratio (AOR) = 1.08; 95% confidence interval [CI] = 0.99-1.18) and those living in states with 3 to 5 restrictive laws (AOR = 1.10; 95% CI = 1.01-1.20) were more likely to die. Separate analyses examining the relationship between parental involvement laws and infant mortality risk, stratified by maternal age, indicated that significant associations were observed among mothers aged ≤19 years (AOR = 1.09, 95% CI = 1.00-1.19), and 20 to 25 years (AOR = 1.10, 95% CI = 1.03-1.17). No significant association was observed among infants born to older mothers. CONCLUSION: Restricting access to abortion services may increase the risk for infant mortality.

State School Policies as Predictors of Physical and Mental Health: A Natural Experiment in the REGARDS Cohort.

We used differences in state school policies as natural experiments to evaluate the joint influence of educational quantity and quality on late-life physical and mental health. Using US Census microsample data, historical measures of state compulsory schooling and school quality (term length, student-teacher ratio, and attendance rates) were combined via regression modeling on a scale corresponding to years of education (policy-predicted years of education (PPYEd)). PPYEd values were linked to individual-level records for 8,920 black and 14,605 white participants aged ≥45 years in the Reasons for Geographic and Racial Differences in Stroke study (2003-2007). Linear and quantile regression models estimated the association between PPYEd and Physical Component Summary (PCS) and Mental Component Summary (MCS) from the Short Form Health Survey. We examined interactions by race and adjusted for sex, birth year, state of residence at age 6 years, and year of study enrollment. Higher PPYEd was associated with better median PCS (ß = 1.28, 95% confidence interval (CI): 0.40, 1.49) and possibly better median MCS (ß = 0.46, 95% CI: -0.01, 0.94). Effect estimates were higher among black (vs. white) persons (PCS × race interaction, ß = 0.22, 95% CI: -0.62, 1.05, and MCS × race interaction, ß = 0.18; 95% CI: -0.08, 0.44). When incorporating both school quality and duration, this quasiexperimental analysis found mixed evidence for a causal effect of education on health decades later.

Structural Racism and Odds for Infant Mortality Among Infants Born in the United States 2010.

OBJECTIVES: While ecological studies indicate that high levels of structural racism within US states are associated with elevated infant mortality rates, studies using individual-level data are needed. To determine whether indicators of structural racism are associated with the individual odds for infant mortality among white and black infants in the US. METHODS: We used data on 2,163,096 white and 590,081 black infants from the 2010 US Cohort Linked Birth/Infant Death Data Files. Structural racism indicators were ratios of relative proportions of blacks to whites for these domains: electoral (registered to vote and voted; state legislature representation), employment (civilian labor force; employed; in management; with a bachelor's degree), and justice system (sentenced to death; incarcerated). Multilevel logistic regression was used to determine whether structural racism indicators were risk factors of infant mortality. RESULTS: Compared to the lowest tertile ratio of relative proportions of blacks to whites with a bachelor's degree or higher-indicative of low structural racism-black infants, but not whites, in states with moderate (OR = 1.12, 95% CI = 0.94, 1.32) and high tertiles (OR = 1.25, 95% CI = 1.03, 1.51) had higher odds of infant mortality. CONCLUSIONS: Educational and judicial indicators of structural racism were associated with infant mortality among blacks. Decreasing structural racism could prevent black infant deaths.

Physical activity, but not body mass index, predicts less disability before and after stroke.

OBJECTIVE: To determine whether physical activity and body mass index (BMI) predict instrumental or basic activities of daily living (I/ADL) trajectories before or after stroke compared to individuals who remained stroke-free. METHODS: Using a prospective cohort, the Health and Retirement Study, we followed adults without a history of stroke in 1998 (n = 18,117) for up to 14 years. We estimated linear regression models of I/ADL trajectories comparing individuals who remained stroke-free throughout follow-up (n = 16,264), those who survived stroke (n = 1,374), and those who died after stroke and before the next interview wave (n = 479). We evaluated whether I/ADL trajectories differed by physical activity or BMI at baseline (before stroke), adjusting for demographic and socioeconomic covariates. RESULTS: Compared to those who were physically active, stroke survivors who were physically inactive at baseline had a lower probability of independence in ADLs and IADLs 3 years after stroke (risk difference = -0.18 and -0.16 for ADLs and IADLs, respectively). However, a similar difference in the probability of independence was also present 3 years before stroke, and we observed no evidence that physical activity slowed the rate of decline in independence before or after stroke. Unlike the results for physical activity, we did not observe a consistent pattern for the probability of independence in ADLs or IADLs comparing obese stroke survivors to normal-weight or to overweight stroke survivors 3 years before stroke or 3 years after stroke. CONCLUSIONS: Physical inactivity predicts a higher risk of being dependent both before and after stroke.

Delay discounting and utility for money or weight loss.

OBJECTIVE: Obesity is related to a bias towards smaller immediate over larger delayed rewards. This bias is typically examined by studying single commodity discounting. However, weight loss often involves choices among multiple commodities. To our knowledge, no research has examined delay discounting of delayed weight loss compared with other commodities. METHODS: We examined single commodity discounting of money and cross commodity discounting of money and weight loss in a sample of 84 adults with obesity or overweight statuses interested in weight loss. The exchange rate between money and weight loss was calculated, and participants completed two delay discounting tasks: money now versus money later and money now versus weight loss later. RESULTS: Participants discounted weight loss more than money (p < 0.001). When participants were divided into those who preferred weight loss (n = 61) versus money (n = 23), those who preferred money over weight loss discounted weight loss even more than individuals that preferred weight loss (p = 0.003). CONCLUSIONS: Greater discounting of weight loss for those who preferred money suggest that idiosyncratic preferences are related to multiple commodity discounting, and greater discounting of weight loss across all participants provide insight on important challenges for weight control.

[Epigastric pain caused by a gastric wall abscess]. / Epigastrische pijn door een maagwandabces.

BACKGROUND: Gastric wall abscesses are rare, but mortality rates from this type of gastritis are high. A foreign body or mucosal damage is often the cause of the abscess. Most patients have nonspecific symptoms, including general malaise and abdominal pain, sometimes accompanied by fever and weight loss. CASE DESCRIPTION: After various tests a 45-year-old man with epigastric pain was shown to have a gastric wall abscess. After endoscopic drainage of the abscess, followed by intravenous antibiotics, he made a complete recovery. CONCLUSION: Gastric wall abscesses are rare, but should be included in the differential diagnosis in patients with epigastric pain, because of their high mortality rate. Endoscopic ultrasonography is the preferred diagnostic method. Endoscopic ultrasound-guided drainage, with or without placement of a drain, followed by intravenous antibiotics is the treatment of choice.

Generation of stretched pulses and dissipative solitons at 2 µm from an all-fiber mode-locked laser using carbon nanotube saturable absorbers.

We demonstrate for the first time, to the best of our knowledge, a thulium-doped, all-fiber, mode-locked laser using a carbon nanotube saturable absorber, operating in the dissipative-soliton regime and the stretched-pulse-soliton regime. The net dispersion of the laser cavity is adjusted by inserting different lengths of normal dispersion fiber, resulting in different mode-locking regimes. These results could serve as a foundation for the optimization of mode-locked fiber-laser cavity design at the 2 µm wavelength region.

Association of a Genetic Risk Score With Body Mass Index Across Different Birth Cohorts.

IMPORTANCE: Many genetic variants are associated with body mass index (BMI). Associations may have changed with the 20th century obesity epidemic and may differ for black vs white individuals. OBJECTIVE: Using birth cohort as an indicator for exposure to obesogenic environment, to evaluate whether genetic predisposition to higher BMI has a larger magnitude of association among adults from more recent birth cohorts, who were exposed to the obesity epidemic at younger ages. DESIGN, SETTING, AND PARTICIPANTS: Observational study of 8788 adults in the US national Health and Retirement Study who were aged 50 years and older, born between 1900 and 1958, with as many as 12 BMI assessments from 1992 to 2014. EXPOSURES: A multilocus genetic risk score for BMI (GRS-BMI), calculated as the weighted sum of alleles of 29 single nucleotide polymorphisms associated with BMI, with weights equal to the published per-allele effects. The GRS-BMI represents how much each person's BMI is expected to differ, based on genetic background (with respect to these 29 loci), from the BMI of a sample member with median genetic risk. The median-centered GRS-BMI ranged from -1.68 to 2.01. MAIN OUTCOMES AND MEASURES: BMI based on self-reported height and weight. RESULTS: GRS-BMI was significantly associated with BMI among white participants (n = 7482; mean age at first assessment, 59 years; 3373 [45%] were men; P <.001) and among black participants (n = 1306; mean age at first assessment, 57 years; 505 [39%] were men; P <.001) but accounted for 0.99% of variation in BMI among white participants and 1.37% among black participants. In multilevel models accounting for age, the magnitude of associations of GRS-BMI with BMI were larger for more recent birth cohorts. For example, among white participants, each unit higher GRS-BMI was associated with a difference in BMI of 1.37 (95% CI, 0.93 to 1.80) if born after 1943, and 0.17 (95% CI, -0.55 to 0.89) if born before 1924 (P = .006). For black participants, each unit higher GRS-BMI was associated with a difference in BMI of 3.70 (95% CI, 2.42 to 4.97) if born after 1943, and 1.44 (95% CI, -1.40 to 4.29) if born before 1924. CONCLUSIONS AND RELEVANCE: For participants born between 1900 and 1958, the magnitude of association between BMI and a genetic risk score for BMI was larger among persons born in later cohorts. This suggests that associations of known genetic variants with BMI may be modified by obesogenic environments.

Families and Disability Onset: Are Spousal Resources Less Important for Individuals at High Risk of Dementia?

OBJECTIVE: To determine whether social contacts and spousal characteristics predict incident instrumental or basic activities of daily living (I/ADL) limitations and whether effects differ for individuals with high risk of dementia. DESIGN: Cohort study. SETTING: Biennial interviews of Health and Retirement Study participants over up to 12 years. PARTICIPANTS: 4,125 participants aged 65 years and older without baseline I/ADL limitations. MEASUREMENTS: Participants' family characteristics (living arrangements, proximity to children, contacts with friends, marital status, and spouse's depression, employment, and education) and dementia probability (high versus low risk of dementia based on direct and proxy cognitive assessments) were characterized at baseline. Family characteristics and their interactions with dementia probability were used to predict incident I/ADL limitations in pooled logistic regressions. RESULTS: ADL limitation incidence was higher among the unmarried (odds ratio [OR] versus married: 1.14; 95% CI: 1.01-1.30); those married to a depressed spouse (OR versus nondepressed spouse: 1.56, 95% CI: 1.21-2.00); or whose spouse had less than high school education (OR versus spouse with high school or more: 1.29, 95% CI: 1.06-1.57). Living with someone other than a spouse compared with living with a spouse predicted higher risk of both incident ADL (OR: 1.35; 95% CI: 1.11-1.65), and IADL (OR: 1.30; 95% CI: 1.06-1.61) limitations. Effects were similar for respondents with high and low dementia probability. CONCLUSIONS: Regardless of dementia risk, older adults may receive important marriage benefits, which help delay disability. The salience of spouse's education and depression status implicate modifiable mechanisms, such as information and instrumental support, which may be amenable to interventions.