Screening mammography frequency following dense breast notification among a predominantly Hispanic/Latina screening cohort.

PURPOSE: Nationally legislated dense breast notification (DBN) informs women of their breast density (BD) and the impact of BD on breast cancer risk and detection, but consequences for screening participation are unclear. We evaluated the association of DBN in New York State (NYS) with subsequent screening mammography in a largely Hispanic/Latina cohort. METHODS: Women aged 40-60 were surveyed in their preferred language (33% English, 67% Spanish) during screening mammography from 2016 to 2018. We used clinical BD classification from mammography records from 2013 (NYS DBN enactment) through enrollment (baseline) to create a 6-category variable capturing prior and new DBN receipt (sent only after clinically dense mammograms). We used this variable to compare the number of subsequent mammograms (0, 1, ≥ 2) from 10 to 30 months after baseline using ordinal logistic regression. RESULTS: In a sample of 728 women (78% foreign-born, 72% Hispanic, 46% high school education or less), first-time screeners and women who received DBN for the first time after prior non-dense mammograms had significantly fewer screening mammograms within 30 months of baseline (Odds Ratios range: 0.33 (95% Confidence Interval (CI) 0.12-0.85) to 0.38 (95% CI 0.17-0.82)) compared to women with prior mammography but no DBN. There were no differences in subsequent mammogram frequency between women with multiple DBN and those who never received DBN. Findings were consistent across age, language, health literacy, and education groups. CONCLUSION: Women receiving their first DBN after previous non-dense mammograms have lower mammography participation within 2.5 years. DBN has limited influence on screening participation of first-time screeners and those with persistent dense mammograms.

Adherence to the Dietary Approaches to Stop Hypertension (DASH) and Serum Urate Concentrations: A Longitudinal Analysis from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND: Increased serum urate (SU) and hyperuricemia (HU) are associated with chronic noncommunicable diseases and mortality. SU concentrations are affected by several factors, including diet, and are expected to rise with age. We investigated whether the Dietary Approaches to Stop Hypertension (DASH) diet alter this trend. OBJECTIVE: The objective was to assess whether adherence to the DASH diet predicts a longitudinal change in SU concentrations and risk of HU in 8 y of follow-up. METHODS: Longitudinal analyses using baseline (2008-2010, aged 35-74 y), second (2012-2014), and third (2016-2018) visits data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). The inclusion criteria were having complete food frequency questionnaire (FFQ) and urinary sodium measurement, in addition to having SU measurement at the 1st visit and at least 1 of the 2 follow-up visits. For the HU incidence analyses, participants had also to be free from HU at baseline. The final samples included 12575 individuals for the SU change analyses and 10549 for the HU incidence analyses. Adherence to DASH diet was assessed as continuous value. HU was defined as SU>6.8 mg/dL and/or urate-lowering therapy use. Mixed-effect linear and Poisson regressions (incidence rate ratio [IRR] and 95% confidence interval [CI]) were used in the analyses, adjusted for confounders. RESULTS: The mean age was 51.4 (8.7) y, and 55.4% were females. SU means (standard deviation) were 5.4 (1.4) at 1st visit, 5.2 (1.4) at 2nd visit, and 5.1(1.3) mg/dL at 3rd visit. The HU incidence rate was 8.87 per 1000 person-y. Each additional point in adherence to the DASH diet accelerated SU decline (P< 0.01) and lowered the incidence of HU by 4.3% (IRR: 0.957; 95% CI: 0.938,0.977) in adjusted model. CONCLUSION: The present study findings reinforce the importance of encouraging the DASH diet as a healthy dietary pattern to control and reduce the SU concentrations and risk of HU.

Does physical activity and inflammation mediate the job stress-headache relationship? A sequential mediation analysis in the ELSA-Brasil study.

BACKGROUND: Evidence indicates that physical activity reduces stress and promote a myriad of health-enhancing effects through anti-inflammatory mechanisms. However, it is unknown whether these mechanisms interfere in the association between psychosocial job stress and headache disorders. OBJECTIVE: To test whether physical activity and its interplay with the systemic inflammation biomarkers high-sensitivity C-reactive protein (hs-CRP) and acute phase glycoproteins (GlycA) would mediate the associations between job stress and headache disorders. METHODS: We cross-sectionally evaluated the baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) regarding job stress (higher demand and lower control and support subscales), migraine and tension-type headache (ICHD-2 criteria), self-reported leisure-time physical activity, and plasma hs-CRP and GlycA levels. Conditional process analyses with a sequential mediation approach were employed to compute path coefficients and 95 % confidence intervals (CI) around the indirect effects of physical activity and biomarkers on the job stress-headache relationship. Separate models were adjusted for sex, age, and depression and anxiety. Further adjustments added BMI smoking status, and socioeconomic factors. RESULTS: In total, 7,644 people were included in the study. The 1-year prevalence of migraine and tension-type headache were 13.1 % and 49.4 %, respectively. In models adjusted for sex, age, anxiety, and depression, the association between job stress (lower job control) and migraine was mediated by physical activity [effect = -0.039 (95 %CI: -0.074, -0.010)] but not hs-CRP or GlycA. TTH was associated with higher job control and lower job demand, which was mediated by the inverse associations between physical activity and GlycA [Job Control: effect = 0.0005 (95 %CI: 0.0001, 0.0010); Job Demand: effect = 0.0003 (95 %CI: 0.0001, 0.0007]. Only the mediating effect of physical activity in the job stress-migraine link remained after further adjustments including socioeconomic factors, BMI, smoking, and the exclusion of major chronic diseases. CONCLUSION: In the ELSA-Brasil study, physical activity reversed the link between job stress and migraine independently of systemic inflammation, while the LTPA-mediated downregulation of GlycA was associated with lower job stress-related TTH.

RHEB/mTOR hyperactivity causes cortical malformations and epileptic seizures through increased axonal connectivity.

Hyperactivation of the mammalian target of rapamycin (mTOR) pathway can cause malformation of cortical development (MCD) with associated epilepsy and intellectual disability (ID) through a yet unknown mechanism. Here, we made use of the recently identified dominant-active mutation in Ras Homolog Enriched in Brain 1 (RHEB), RHEBp.P37L, to gain insight in the mechanism underlying the epilepsy caused by hyperactivation of the mTOR pathway. Focal expression of RHEBp.P37L in mouse somatosensory cortex (SScx) results in an MCD-like phenotype, with increased mTOR signaling, ectopic localization of neurons, and reliable generalized seizures. We show that in this model, the mTOR-dependent seizures are caused by enhanced axonal connectivity, causing hyperexcitability of distally connected neurons. Indeed, blocking axonal vesicle release from the RHEBp.P37L neurons alone completely stopped the seizures and normalized the hyperexcitability of the distally connected neurons. These results provide new evidence of the extent of anatomical and physiological abnormalities caused by mTOR hyperactivity, beyond local malformations, which can lead to generalized epilepsy.

Reprocessable Networks from Vegetable Oils, Salts, and Food Acids: A Green Polymer Outreach Demonstration for Middle School Students.

Massive amounts of mismanaged plastic waste have led to growing concerns about their adverse impacts on the environment, ecosystem, and human health. Enabling efficient plastic recycling is a key component for developing a sustainable future, which requires cohesive efforts in technology innovations, public awareness, and workforce development. Particularly, outreach activities to inform the broader community about current efforts to fabricate sustainable polymeric materials can play a central role in inspiring future generations while also improving their knowledge, viewpoints, and behaviors to address plastic waste challenges. Herein, this account demonstrates an effort to educate middle school students about a key emerging concept in polymer science for sustainable material development: reprocessable polymer networks. Background information is provided to the students about the need to transition from petroleum-based chemical feedstocks to their bioderived counterparts. We note that the materials used in this demonstration lesson are all produced from common household foods, with which students routinely interact in various applications, making them not only safe but also compelling for the middle school classroom.

Scientific uncertainty and perceived mammography benefits in women screened for breast cancer.

PURPOSE: Personal aversion to scientific uncertainty may influence how women perceive the benefits of mammography, a breast cancer screening practice with conflicting scientific opinions and guidelines. Such associations may even exist among women who participate in screening. METHODS: We evaluated the distribution of aversion to ambiguous medical information (AA-Med), using a 6-item scale capturing the level of agreement with statements about obtaining a cancer screening test with conflicting medical recommendations in 665 women (aged 40-60 years; 79.5% Hispanic) recruited during screening mammography appointments in New York City. We assessed the association of AA-Med with perceptions of benefits of mammography (breast cancer mortality reduction, worry reduction, early detection, treatment improvement) using multivariable logistic regression. RESULTS: Over a quarter of participants expressed negative reactions to medical ambiguity about a cancer screening test (e.g., fear, lower trust in experts), but a majority endorsed intention to undergo screening. AA-Med was higher in women who were U.S.-born, non-Hispanic black, and had marginal to adequate health literacy, but there were no differences by clinical factors or screening experiences (e.g., family history, prior breast biopsy). Women with higher AA-Med were more likely to perceive treatment benefits from mammography (OR = 1.37, 95% CI = 0.99-1.90), but AA-Med was not associated with other perceived mammography benefits. CONCLUSIONS: Aversion to uncertainty regarding cancer screening varies by sociodemographic characteristics but has limited associations with perceived mammography benefits in women who already participate in screening.

Hospital factors associated with maternal and neonatal outcomes of deliveries to patients with a previous cesarean delivery: an ecological study.

BACKGROUND: Recommendations for deliveries of pregnant patients with a previous cesarean delivery and the type of hospitals deemed safe for these deliveries have evolved in recent years, although no studies have examined hospital factors and associated safety. We sought to evaluate maternal and neonatal outcomes among patients with a previous cesarean delivery by hospital tier and volume. METHODS: We carried out an ecological study of singleton live births delivered at term gestation to patients with a previous cesarean delivery in all Canadian hospitals (excluding Quebec), 2013-2019. We obtained data from the Discharge Abstract Database of the Canadian Institute for Health Information. The primary outcomes were severe maternal morbidity or mortality (SMMM), and serious neonatal morbidity or mortality (SNMM). We used regression modelling to examine hospital tier (tier 4 hospitals being those that provide the highest level of care) and volume; we also identified hospitals with high rates of SMMM and SNMM using within-tier comparisons and comparisons with the overall rate. RESULTS: We included 235 442 deliveries to patients with a previous cesarean delivery; SMMM and SNMM rates were 14.6 per 1000 deliveries and 4.6 per 1000 live births, respectively. Among patients with a parity of 1, SMMM rates were lower in tier 1 hospitals (adjusted incidence rate ratio [IRR] 0.68, 95% confidence interval [CI] 0.52-0.89) and higher in tier 4 hospitals (adjusted IRR 1.41, 95% CI 1.05-1.91) than in tier 2 hospitals; SNMM rates did not differ by hospital tier. Rates of SNMM increased with increasing hospital volume (adjusted IRR 1.02, 95% CI 1.00-1.04) and increasing rates of vaginal birth after cesarean delivery (adjusted IRR 1.02, 95% CI 1.01-1.04). Most hospitals had relatively low SMMM and SNMM rates, although a few hospitals in each tier and volume category had significantly higher rates than others. INTERPRETATION: Adverse maternal and neonatal outcomes among patients with a previous cesarean delivery showed no clear pattern of decreasing SMMM and SNMM with increasing tiers of service and hospital volume. All hospitals, irrespective of tier or size, should continually review their rates of adverse maternal and neonatal outcomes.

Breast cancer worry, uncertainty, and perceived risk following breast density notification in a longitudinal mammography screening cohort.

BACKGROUND: Dense breast notification (DBN) legislation aims to increase a woman's awareness of her personal breast density and the implications of having dense breasts for breast cancer detection and risk. This information may adversely affect women's breast cancer worry, perceptions of risk, and uncertainty about screening, which may persist over time or vary by sociodemographic factors. We examined short- and long-term psychological responses to DBN and awareness of breast density (BD). METHODS: In a predominantly Hispanic New York City screening cohort (63% Spanish-speaking), ages 40-60 years, we assessed breast cancer worry, perceived breast cancer risk, and uncertainties about breast cancer risk and screening choices, in short (1-3 months)- and long-term (9-18 months) surveys following the enrollment screening mammogram (between 2016 and 2018). We compared psychological responses by women's dense breast status (as a proxy for DBN receipt) and BD awareness and examined multiplicative interaction by education, health literacy, nativity, and preferred interview language. RESULTS: In multivariable models using short-term surveys, BD awareness was associated with increased perceived risk (odds ratio (OR) 2.27, 95% confidence interval (CI) 0.99, 5.20 for high, OR 2.19, 95% CI 1.34, 3.58 for moderate, vs. low risk) in the overall sample, and with increased uncertainty about risk (OR 1.97 per 1-unit increase, 95% CI 1.15, 3.39) and uncertainty about screening choices (OR 1.73 per 1-unit increase, 95% CI 1.01, 2.9) in Spanish-speaking women. DBN was associated with decreased perceived risk among women with at least some college education (OR 0.32, 95% CI 0.11, 0.89, for high, OR 0.50, 95% CI 0.29, 0.89, for moderate vs. low risk), while those with a high school education or less experienced an increase (OR 3.01, 95% CI 1.05, 8.67 high vs. low risk). There were no associations observed between DBN or BD awareness and short-term breast cancer worry, nor with any psychological outcomes at long-term surveys. CONCLUSIONS: Associations of BD awareness and notification with breast cancer-related psychological outcomes were limited to short-term increases in perceived breast cancer risk dependent on educational attainment, and increases in uncertainty around breast cancer risk and screening choices among Spanish-speaking women.

Current regular aspirin use and mammographic breast density: a cross-sectional analysis considering concurrent statin and metformin use.

PURPOSE: The nonsteroidal anti-inflammatory drug aspirin is an agent of interest for breast cancer prevention. However, it is unclear if aspirin affects mammographic breast density (MBD), a marker of elevated breast cancer risk, particularly in the context of concurrent use of medications indicated for common cardiometabolic conditions, which may also be associated with MBD. METHODS: We used data from the New York Mammographic Density Study for 770 women age 40-60 years old with no history of breast cancer. We evaluated the association between current regular aspirin use and MBD, using linear regression for continuous measures of absolute and percent dense areas and absolute non-dense area, adjusted for body mass index (BMI), sociodemographic and reproductive factors, and use of statins and metformin. We assessed effect modification by BMI and reproductive factors. RESULTS: After adjustment for co-medication, current regular aspirin use was only positively associated with non-dense area (ß = 18.1, 95% CI: 6.7, 29.5). Effect modification by BMI and parity showed current aspirin use to only be associated with larger non-dense area among women with a BMI ≥ 30 (ß = 28.2, 95% CI: 10.8, 45.7), and with lower percent density among parous women (ß = -3.3, 95% CI: -6.4, -0.3). CONCLUSIONS: Independent of co-medication use, current regular aspirin users had greater non-dense area with stronger estimates for women with higher BMI. We found limited support for an association between current aspirin use and mammographically dense breast tissue among parous women.

Physical activity pattern and migraine according to aura symptoms in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohort: A cross-sectional study.

OBJECTIVE: To estimate the associations of physical activity (PA) levels with migraine subtypes. BACKGROUND: Physical activity has been associated with reduced migraine prevalence, but less is known about its relationship with migraine subtypes and PA levels as recommended by World Health Organization (WHO). METHODS: In this cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we estimated the odds ratios (ORs) of migraine with aura (MA) and migraine without aura (MO), compared to participants without headaches, according to PA levels in the leisure time (LTPA), commuting time (CPA), and combined PA domains. RESULTS: In total, 2773 participants provided complete data, 1556/2773 (56.1%) were women, mean (SD) age of 52.3 (9.1) years. In this study's sample, 1370/2773 (49.4%) participants had overall migraine, 480/2773 (17.3%) had MA, and 890/2773 (32.0%) had MO. In the LTPA domain, there were reduced odds of MA (OR 0.72, 95% confidence interval [CI] 0.53-0.96; p = 0.030) and MO (OR 0.71, 95% CI 0.56-0.90; p = 0.005) in participants who met the WHO PA guidelines after adjustment for confounder variables. In the analyses stratified by intensity, moderate LTPA was associated with reduced odds of MA (OR 0.56, 95% CI 0.320-0.99; p = 0.049), while vigorous LTPA was associated with reduced odds of MO (OR 0.55, 95% CI 0.395-0.77; p = 0.001). There were no significant associations between migraine subtypes and CPA or combined PA domains. In the whole migraine sample, meeting the WHO PA guidelines in the LTPA (OR 0.275, 95% CI 0.083-0.90; p = 0.034), CPA (OR 0.194, 95% CI 0.064-0.58; p = 0.004), and combined domains (OR 0.115, 95% CI 0.032-0.41; p = 0.001) was associated with reduced odds of daily migraine attack frequency. CONCLUSIONS: Meeting the WHO PA guidelines for LTPA, but not CPA or combined PA domains, is associated with lower migraine occurrence. Moderate LTPA favors MA reduction, while vigorous LTPA favors MO reduction.

Who Cares More about Chemical Defenses - the Macroalgal Producer or Its Main Grazer?

The consequences of defensive secondary metabolite concentrations and interspecific metabolite diversity on grazers have been extensively investigated. Grazers which prefer certain food sources are often found in high abundance on their host and as a result, understanding the interaction between the two is important to understand community structure. The effects of intraspecific diversity, however, on the grazer are not well understood. Within a single, localized geographic area, the Antarctic red seaweed Plocamium sp. produces 15 quantitatively and qualitatively distinct mixtures of halogenated monoterpenes ("chemogroups"). Plocamium sp. is strongly chemically defended which makes it unpalatable to most grazers, except for the amphipod Paradexamine fissicauda. We investigated differences in the feeding and growth rates of both Plocamium sp. and P. fissicauda, in addition to grazer reproductive output, in relation to different chemogroups. Some chemogroups significantly reduced the grazer's feeding rate compared to other chemogroups and a non-chemically defended control. The growth rate of Plocamium sp. did not differ between chemogroups and the growth rates of P. fissicauda also did not show clear patterns between the feeding treatments. Reproductive output, however, was significantly reduced for amphipods on a diet of algae possessing one of the chemogroups when compared to a non-chemically defended control. Hence, intraspecific chemodiversity benefits the producer since certain chemogroups are consumed at a slower rate and the grazer's reproductive output is reduced. Nevertheless, the benefits outweigh the costs to the grazer as it can still feed on its host and closely associates with the alga for protection from predation.

Incidence of excess body weight and annual weight gain in women and men: Results from the ELSA-Brasil cohort.

OBJECTIVE: To estimate annual weight gain and the incidence of overweight and obesity, stratified according to gender and socioeconomic factors. METHODS: From the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we included 13 625 women and men aged 35-74 (2008-2010) who attended a follow-up visit after a mean 3.8-years. Standardized questionnaires were used to record sociodemographic data, and height and weight were measured on all participants during in-person visits at research centers. The incidence rate to overweight was calculated among those not having excess weight at baseline, and incident obesity among those not having this condition at baseline. We evaluated the incidence of overweight and obesity in men and women, adjusted by age, through Poisson regression with robust variance. Large annual weight gain by gender was being defined as ≥90th percentile in the cohort. RESULTS: A global incidence of 7.7% for overweight and 10.6% for obesity was observed, with higher levels seen among black woman (28.5%), young men (21.1%) and woman with low educational level (35.0%). The proportions of overweight and obesity increased with age at both time points, more commonly among those with the lowest levels of per capita income and fewer years of schooling. Large annual weight gain was greater among participants with an intermediate level of education and those who self-identified as black. CONCLUSIONS: A high overall risk of becoming overweight/obese was found, especially among women. The roles of race and education level are fundamental to understanding the effects produced by social inequalities in rates of excess weight.

Sedimentary organic carbon and nitrogen stocks of intertidal seagrass meadows in a dynamic and impacted wetland: Effects of coastal infrastructure constructions and meadow establishment time.

Seagrass meadows, through their large capacity to sequester and store organic carbon in their sediments, contribute to mitigate climatic change. However, these ecosystems have experienced large losses and degradation worldwide due to anthropogenic and natural impacts and they are among the most threatened ecosystems on Earth. When a meadow is impacted, the vegetation is partial- or completely lost, and the sediment is exposed to the atmosphere or water column, resulting in the erosion and remineralisation of the carbon stored. This paper addresses the effects of the construction of coastal infrastructures on sediment properties, organic carbon, and total nitrogen stocks of intertidal seagrass meadows, as well as the size of such stocks in relation to meadow establishing time (recently and old established meadows). Three intertidal seagrass meadows impacted by coastal constructions (with 0% seagrass cover at present) and three adjacent non-impacted old-established meadows (with 100% seagrass cover at present) were studied along with an area of bare sediment and two recent-established seagrass meadows. We observed that the non-impacted areas presented 3-fold higher percentage of mud and 1.5 times higher sedimentary organic carbon stock than impacted areas. Although the impacted area was relatively small (0.05-0.07 ha), coastal infrastructures caused a significant reduction of the sedimentary carbon stock, between 1.1 and 2.2 Mg OC, and a total loss of the carbon sequestration capacity of the impacted meadow. We also found that the organic carbon stock and total nitrogen stock of the recent-established meadow were 30% lower than those of the old-established ones, indicating that OC and TN accumulation within the meadows is a continuous process, which has important consequences for conservation and restoration actions. These results contribute to understanding the spatial variability of blue carbon and nitrogen stocks in coastal systems highly impacted by urban development.

Examination of the Effectiveness of Direct Oral Anticoagulants in Comparison to Warfarin in an Obese Population.

Background: While commonly prescribed today, direct oral anticoagulants (DOACs) have historically been avoided in patients with class III obesity or a weight >120 kg due to limited literature regarding the efficacy and safety in this population. Objective: The overall objective was to examine the effectiveness of DOACs compared to warfarin in a population with obesity. Methods: Patients with a diagnosis of venous thromboembolism (VTE) or atrial fibrillation and a body mass index (BMI) ≥35 kg/m2 from August 1, 2015, to August 1, 2020, were included in this retrospective cohort study. Patients receiving a DOAC were matched in a 1:2 ratio to warfarin. The primary outcome was a composite of stroke or recurrent VTE. Secondary outcomes included the individual components of the primary outcome, hospitalization for bleed, and the primary outcome in patients with a BMI ≥40 kg/m2. Results: A total of 162 patients were included, with 54 and 108 in the DOAC and warfarin groups, respectively. Baseline BMI was similar between groups (45.7 kg/m2 for DOACs vs 43.8 kg/m2 for warfarin), with approximately 70% of patients having a BMI ≥40 kg/m2. The primary outcome occurred in 1 patient (1.9%) in the DOAC group and 2 patients (1.9%) in the warfarin group. The DOAC group had a higher, nonsignificant incidence of bleeding (5.6% vs 0.9%, P = 0.11). There was no difference between groups in incidence of deep vein thrombosis (DVT), pulmonary embolism (PE), or stroke in patients with a BMI ≥40 kg/m2. Conclusion: DOACs may be as efficacious as warfarin in the prevention of stroke or recurrent VTE in patients with a BMI of ≥35 kg/m2. Prospective, randomized trials are warranted to further assess the efficacy and safety of DOACs in this population.

Temporal dynamics of the cerebello-cortical convergence in ventro-lateral motor thalamus.

KEY POINTS: Ventrolateral thalamus (VL) integrates information from cerebellar nuclei and motor cortical layer VI. Inputs from the cerebellar nuclei evoke large-amplitude responses that depress upon repetitive stimulation while layer VI inputs from motor cortex induce small-amplitude facilitating responses. We report that the spiking of VL neurons can be determined by the thalamic membrane potential, the frequency of cerebellar inputs and the duration of pauses after cerebellar high frequency stimulation. Inputs from motor cortical layer VI shift the VL membrane potential and modulate the VL spike output in response to cerebellar stimulation.  These results help us to decipher how the cerebellar output is integrated in VL and modulated by motor cortical input. ABSTRACT: Orchestrating complex movements requires well-timed interaction of cerebellar, thalamic and cerebral structures, but the mechanisms underlying the integration of cerebro-cerebellar information in motor thalamus remain largely unknown. Here we investigated how excitatory inputs from cerebellar nuclei (CN) and primary motor cortex layer VI (M1-L6) neurons may regulate the activity of neurons in the mouse ventrolateral (VL) thalamus. Using dual-optical stimulation of the CN and M1-L6 axons and in vitro whole-cell recordings of the responses in VL neurons, we studied the individual responses as well as the effects of combined CN and M1-L6 stimulation. Whereas CN inputs evoked large-amplitude responses that were depressed upon repetitive stimulation, M1-L6 inputs elicited small-amplitude responses that were facilitated upon repetitive stimulation. Moreover, pauses in CN stimuli could directly affect VL spiking probability, an effect that was modulated by VL membrane potential. When CN and M1-L6 pathways were co-activated, motor cortical afferents increased the thalamic spike output in response to cerebellar stimulation, indicating that CN and M1 synergistically, yet differentially, control the membrane potential and spiking pattern of VL neurons.

Associations of Total Legume, Pulse, and Soy Consumption with Incident Type 2 Diabetes: Federated Meta-Analysis of 27 Studies from Diverse World Regions.

BACKGROUND: The consumption of legumes is promoted as part of a healthy diet in many countries but associations of total and types of legume consumption with type 2 diabetes (T2D) are not well established. Analyses across diverse populations are lacking despite the availability of unpublished legume consumption data in prospective cohort studies. OBJECTIVE: To examine the prospective associations of total and types of legume intake with the risk of incident T2D. METHODS: Meta-analyses of associations between total legume, pulse, and soy consumption and T2D were conducted using a federated approach without physical data-pooling. Prospective cohorts were included if legume exposure and T2D outcome data were available and the cohort investigators agreed to participate. We estimated incidence rate ratios (IRRs) and CIs of associations using individual participant data including ≤42,473 incident cases among 807,785 adults without diabetes in 27 cohorts across the Americas, Eastern Mediterranean, Europe, and Western Pacific. Random-effects meta-analysis was used to combine effect estimates and estimate heterogeneity. RESULTS: Median total legume intake ranged from 0-140 g/d across cohorts. We observed a weak positive association between total legume consumption and T2D (IRR = 1.02, 95% CI: 1.01 to 1.04) per 20 g/d higher intake, with moderately high heterogeneity (I2 = 74%). Analysis by region showed no evidence of associations in the Americas, Eastern Mediterranean, and Western Pacific. The positive association in Europe (IRR = 1.05, 95% CI: 1.01 to 1.10, I2 = 82%) was mainly driven by studies from Germany, UK, and Sweden. No evidence of associations was observed for the consumption of pulses or soy. CONCLUSIONS: These findings suggest no evidence of an association of legume intakes with T2D in several world regions. The positive association observed in some European studies warrants further investigation relating to overall dietary contexts in which legumes are consumed, including accompanying foods which may be positively associated with T2D.

Physical inactivity and headache disorders: Cross-sectional analysis in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND: Physical inactivity has been linked to headache disorders but estimates based on the current World Health Organization physical activity guidelines are unknown. OBJECTIVE: To test the associations between headache disorders and physical inactivity in the ELSA-Brasil cohort. METHODS: In a cross-sectional analysis, linear (continuous variables) and logistic regression models (categorical variables) tested the associations of physical activity levels in the leisure time, commuting time, and combined leisure time physical activity + commuting time physical activity domains with headache disorders, adjusted for the effects of sociodemographic data, cardiovascular risk variables, psychiatric disorders, and migraine prophylaxis medication. RESULTS: Of 15,105 participants, 14,847 (54.4% women) provided data on physical activity levels and headache. Higher physical activity levels (continuous values) in the leisure time physical activity domain associated with lower migraine and tension-type headache occurrence and lower headache attack frequency, while in the commuting time physical activity domain it associated with more frequent headache attacks. Compared to people who met World Health Organization physical activity levels in the leisure time physical activity or combining leisure time physical activity + commuting time physical activity domains (i.e. ≥150 min.wk-1 of moderate and/or ≥75 min.wk-1 of vigorous physical activity), physical inactivity associated with higher migraine occurrence, while somewhat active (i.e. not meeting World Health Organization recommendations) associated with higher migraine and tension-type headache occurrence. Physical inactivity in the commuting time physical activity domain associated with higher tension-type headache in men and lower migraine in women. Physical inactivity within vigorous leisure time physical activity intensity, but not moderate leisure time physical activity, associated with higher migraine, mostly in women. Finally, physical inactivity associated with higher headache attack frequency regardless headache subtype. CONCLUSION: Physical inactivity and unmet World Health Organization physical activity levels associate with primary headaches, with heterogeneous associations regarding headache subtype, sex, physical activity domain/intensity, and headache frequency in the ELSA-Brasil study.

Socio-demographic characteristics associated with emotional and social loneliness among older adults.

BACKGROUND: International studies provide an overview of socio-demographic characteristics associated with loneliness among older adults, but few studies distinguished between emotional and social loneliness. This study examined socio-demographic characteristics associated with emotional and social loneliness. METHODS: Data of 2251 community-dwelling older adults, included at the baseline measure of the Urban Health Centers Europe (UHCE) project, were analysed. Loneliness was measured with the 6-item De Jong-Gierveld Loneliness Scale. Multivariable logistic regression models were used to evaluate associations between age, sex, living situation, educational level, migration background, and loneliness. RESULTS: The mean age of participants was 79.7 years (SD = 5.6 years); 60.4% women. Emotional and social loneliness were reported by 29.2 and 26.7% of the participants; 13.6% experienced emotional and social loneliness simultaneously. Older age (OR: 1.16, 95% CI: 1.06-1.28), living without a partner (2.16, 95% CI: 1.73-2.70), and having a low educational level (OR: 1.82, 95% CI: 1.21-2.73), were associated with increased emotional loneliness. Women living with a partner were more prone to emotional loneliness than men living with a partner (OR: 1.78, 95% CI: 1.31-2.40). Older age (OR: 1.11, 95% CI: 1.00-1.22) and having a low educational level (OR: 1.77, 95% CI: 1.14-2.74) were associated with increased social loneliness. Men living without a partner were more prone to social loneliness than men living with a partner (OR: 1.94, 95% CI: 1.35-2.78). CONCLUSIONS: Socio-demographic characteristics associated with emotional and social loneliness differed regarding sex and living situation. Researchers, policy makers, and healthcare professionals should be aware that emotional and social loneliness may affect older adults with different socio-demographic characteristics.

Independent and joint cross-sectional associations of statin and metformin use with mammographic breast density.

BACKGROUND: Well-tolerated and commonly used medications are increasingly assessed for reducing breast cancer risk. These include metformin and statins, both linked to reduced hormone availability and cell proliferation or growth and sometimes prescribed concurrently. We investigated independent and joint associations of these medications with mammographic breast density (MBD), a useful biomarker for the effect of chemopreventive agents on breast cancer risk. METHODS: Using data from a cross-sectional study of 770 women (78% Hispanic, aged 40-61 years, in a mammography cohort with high cardiometabolic burden), we examined the association of self-reported "ever" use of statins and metformin with MBD measured via clinical Breast Imaging Reporting and Data System (BI-RADS) density classifications (relative risk regression) and continuous semi-automated percent and size of dense area (Cumulus) (linear regression), adjusted for age, body mass index, education, race, menopausal status, age at first birth, and insulin use. RESULTS: We observed high statin (27%), metformin (13%), and combination (9%) use, and most participants were overweight/obese (83%) and parous (87%). Statin use was associated with a lower likelihood of high density BI-RADS (RR = 0.60, 95% CI = 0.45 to 0.80), percent dense area (PD) (ß = - 6.56, 95% CI = - 9.05 to - 4.06), and dense area (DA) (ß = - 9.05, 95% CI = - 14.89 to - 3.22). Metformin use was associated with lower PD and higher non-dense area (NDA), but associations were attenuated by co-medication with statins. Compared to non-use of either medication, statin use alone or with metformin were associated with lower PD and DA (e.g., ß = - 6.86, 95% CI: - 9.67, - 4.05 and ß = - 7.07, 95% CI: - 10.97, - 3.17, respectively, for PD) and higher NDA (ß = 25.05, 95% CI: 14.06, 36.03; ß = 29.76, 95% CI: 14.55, 44.96, respectively). CONCLUSIONS: Statin use was consistently associated with lower MBD, measured both through clinical radiologist assessment and continuous relative and absolute measures, including dense area. Metformin use was associated with lower PD and higher NDA, but this may be driven by co-medication with statins. These results support that statins may lower MBD but need confirmation with prospective and clinical data to distinguish the results of medication use from that of disease.

Addressing sickness absence among adolescents and young adults: an evaluation of the Medical Advice for Sick-reported Students intervention.

BACKGROUND: Sickness absence is associated with lower school achievements and early school leaving. The Medical Advice for Sick-reported Students (MASS) intervention is a proactive school-based intervention focused primarily on early identification and reduction of sickness absence. This study used a program evaluation framework to evaluate the MASS intervention among intermediate vocational education students and Youth Health Care professionals. Outcome indicators were primarily number of sick days, education fit, and school performance, and secondarily, seven health indicators. Process indicators were dose delivered and received, satisfaction, and experience. METHODS: The MASS intervention evaluation was conducted in ten intermediate vocational education schools. Students with extensive sickness absence from school in the past three months were included in either the intervention or control condition. Students completed a baseline and a six-month follow-up self-report questionnaire. Linear and logistic regression analyses were applied. Students and Youth Health Care professionals completed an evaluation form regarding their satisfaction and experience with the intervention. RESULTS: Participants (n = 200) had a mean age of 18.6 years (SD = 2.02) and 78.5% were female. The MASS intervention showed positive results on decreasing sickness absence in days (ß = -1.13, 95% CI = -2.22;-0.05, p < 0.05) and on decreasing depressive symptoms (ß = -4.11, 95% CI = -7.06;-1.17, p < 0.05). No effects were found for other health indicators (p > 0.05). A significant interaction revealed a decline in sickness absence in males (p < 0.05) but not in females (p > 0.05). Youth Health Care professionals found the application of the MASS intervention useful (n = 35 forms). The mean rating of students for the consultation within the MASS intervention was an 8.3 (SD = 1.3) out of 10 (n = 14 forms). CONCLUSIONS: Our study provides some indication that the MASS intervention has positive effects on decreasing both sickness absence and depressive symptoms among intermediate vocational education students. The Youth Health Care professionals who provided the consultation as part of the MASS intervention considered the intervention to be useful and stated that the consultation was delivered as intended in almost all cases. Students were generally satisfied with the intervention. We recommend that future research evaluates the MASS intervention in a large randomized controlled trial with a longer follow-up. TRIAL REGISTRATION: This study was prospectively registered in the Netherlands Trial Register under number NTR5556 , in October 2015.