Trajectories of Occupational Cognitive Demands and Risk of Mild Cognitive Impairment and Dementia in Later Life: The HUNT4 70+ Study.

BACKGROUND AND OBJECTIVES: The cognitive reserve hypothesis posits that cognitively stimulating work delays the onset of mild cognitive impairment (MCI) and dementia. However, the effect of occupational cognitive demands across midlife on the risk of these conditions is unclear. METHODS: Using a cohort study design, we evaluated the association between registry-based trajectories of occupational cognitive demands from ages 30-65 years and clinically diagnosed MCI and dementia in participants in the HUNT4 70+ Study (2017-19). Group-based trajectory modeling identified trajectories of occupational cognitive demands, measured by the routine task intensity (RTI) index (lower RTI indicates more cognitively demanding occupation) from the Occupational Information Network. Multinomial regression was implemented to estimate the relative risk ratios (RRRs) of MCI and dementia, after adjusting for age, sex, education, income, baseline hypertension, obesity, diabetes, psychiatric impairment, hearing impairment, loneliness, smoking status, and physical inactivity assessed at HUNT1-2 in 1984-1986 and 1995-1997. To handle missing data, we used inverse probability weighting to account for nonparticipation in cognitive testing and multiple imputation. RESULTS: Based on longitudinal RTI scores for 305 unique occupations, 4 RTI trajectory groups were identified (n = 7,003, 49.8% women, age range 69-104 years): low RTI (n = 1,431, 20.4%), intermediate-low RTI (n = 1,578, 22.5%), intermediate-high RTI (n = 2,601, 37.1%), and high RTI (n = 1,393, 19.9%). Participants in the high RTI group had a higher risk of MCI (RRR 1.74, 95% CI 1.41-2.14) and dementia (RRR 1.37, 95% CI 1.01-1.86), after adjusting for age, sex, and education compared with participants in the low RTI group. In a sensitivity analysis, controlling for income and baseline health-related factors, the point estimates were not appreciably changed (RRR 1.66, 95% CI 1.35-2.06 for MCI, and RRR 1.31, 95% CI 0.96-1.78 for dementia). DISCUSSION: People with a history of cognitively stimulating occupations during their 30s, 40s, 50s, and 60s had a lower risk of MCI and dementia older than 70 years, highlighting the importance of occupational cognitive stimulation during midlife for maintaining cognitive function in old age. Further research is required to pinpoint the specific occupational cognitive demands that are most advantageous for maintaining later-life cognitive function.

Responsive Feeding Practices to Promote Healthy Diets: A Mixed Method Study among Low-Income Caregivers with Toddlers.

Responsive feeding (RF), the reciprocal feeding approach between caregiver and child that promotes child health, is understudied among low-income caregivers. This mixed methods study with low-income caregivers of 12-to-36-month-olds aimed to (1) assess variability in RF and associations with children's dietary intake, and (2) explore caregivers' perceptions of RF. Caregivers (n = 134) completed an online survey with RF questions (n = 25), grouped into environmental (meal environment, caregiver modeling, caregiver beliefs) and child (self-regulation, hunger/satiety cues, food for reward, food acceptance) influences scores. Children's recent food group consumption was loaded onto healthy and less healthy intake scores. In an adjusted multiple linear regression analysis, greater RF scores for environmental and child influences were associated with greater healthy intake scores (p's < 0.01). Greater scores for environmental influences were also associated with lower scores for unhealthy intake (p < 0.01). From focus groups with a separate sample of caregivers (n = 24), thematic analysis uncovered that two themes aligned (trust in child cues, positive strategies to encourage children to eat non-preferred foods) and two misaligned (lack of trust in child cues, use of force/bribery) with RF. Complementary integration of quantitative and qualitative findings can inform future interventions with low-income caregivers, encouraging trust in young children's hunger/satiety cues and positive strategies for food acceptance to improve diet quality.

Case report: Long-term follow-up of patients who received a FimCH vaccine for prevention of recurrent urinary tract infections caused by antibiotic resistant Enterobacteriaceae: a case report series.

Urinary tract infections (UTI) caused by carbapenem-resistant Enterobacteriaceae (CRE) are considered one of the most urgent health threats to humans according to the Centers for Disease Control (CDC), and the World Health Organization (WHO). A FimCH Vaccine expanded access study is being conducted in patients with a history of antibiotic resistant UTIs who are considered to be at risk for development of CRE UTI. This case series describes the clinical, safety and immunogenicity findings for four participants who received a FimCH four-vaccine series. Participants were followed for 12 months after administration of the fourth vaccine for safety, general health status and UTI occurrence. The study was later amended to allow additional follow-up of up to five years post vaccine administration to assess long-term health status, UTI occurrences and to obtain blood samples for anti-FimH antibody testing. In our population of 4 study participants, the number of symptomatic UTI occurrences caused by gram-negative bacteria in the 12-month period following peak anti-FimH antibody response were approximately 75% lower than the 12-month period preceding study enrollment. These results are consistent with the 30-patient cohort of a Phase 1 study with the same FimCH Vaccine. UTI occurrences increased during the long-term follow-up period for all 4 participants but did not reach the rate observed pre-vaccination. No new safety concerns related to the FimCH Vaccine were identified during long-term follow-up. This case series has clinical importance and public health relevance since it examines and reports on UTI frequency and recurrence following vaccination with the FimCH Vaccine in a high-risk population of patients with recurrent UTI. Additionally, participants described improved well-being following vaccination which was maintained in the long-term follow-up period.

Partial facial paralysis induced by sialolithiasis of the parotid gland: a case report.

BACKGROUND: Facial paralysis due to parotid sialolithiasis-induced parotitis is a unusual clinical phenomenon that has not been reported in prior literature. This scenario can present a diagnostic challenge due to its rarity and complex symptomatology, particularly if a patient has other potential contributing factors such as facial trauma or bilateral forehead botox injections as in this patient. This case report elucidates such a complex presentation, aiming to increase awareness and promote timely recognition among clinicians. CASE PRESENTATION: A 56-year-old male, with a medical history significant for hyperlipidemia, recurrent parotitis secondary to parotid sialolithiasis, and recent bilateral forehead cosmetic Botox injections presented to the emergency department with right lower facial drooping. This onset was about an hour after waking up and was of 4 h duration. The patient also had a history of a recent ground level fall four days prior that resulted in facial trauma to his right eyebrow without any evident neurological deficits in the region of the injury. A thorough neurological exam revealed sensory and motor deficits across the entirety of the right face, indicating a potential lesion affecting the buccal and marginal mandibular branches of the facial nerve (CN VII). Several differential diagnoses were considered for the lower motor neuron lesion, including soft tissue trauma or swelling from the recent fall, compression due to the known parotid stone, stroke, and complex migraines. An MRI of the brain was conducted to rule out a stroke, with no significant findings. A subsequent CT scan of the neck revealed an obstructed and dilated right Stensen's duct with a noticeably larger and anteriorly displaced sialolith and evidence of parotid gland inflammation. A final diagnosis of facial palsy due to parotitis secondary to sialolithiasis was made. The patient was discharged and later scheduled for a procedure to remove the sialolith which resolved his facial paralysis. CONCLUSIONS: This case emphasizes the need for a comprehensive approach to the differential diagnosis in presentations of facial palsy. It underscores the potential involvement of parotid sialolithiasis, particularly in patients with a history of recurrent parotitis or facial trauma. Prompt recognition of such uncommon presentations can prevent undue interventions, aid in timely appropriate management, and significantly contribute to the patient's recovery and prevention of long-term complications.

Urban environment in pregnancy and postpartum depression: An individual participant data meta-analysis of 12 European birth cohorts.

BACKGROUND: Urban environmental exposures associate with adult depression, but it is unclear whether they are associated to postpartum depression (PPD). OBJECTIVES: We investigated associations between urban environment exposures during pregnancy and PPD. METHODS: We included women with singleton deliveries to liveborn children from 12 European birth cohorts (N with minimum one exposure = 30,772, analysis N range 17,686-30,716 depending on exposure; representing 26-46 % of the 66,825 eligible women). We estimated maternal exposure during pregnancy to ambient air pollution with nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10), road traffic noise (Lden), natural spaces (Normalised Difference Vegetation Index; NDVI, proximity to major green or blue spaces) and built environment (population density, facility richness and walkability). Maternal PPD was assessed 3-18 months after birth using self-completed questionnaires. We used adjusted logistic regression models to estimate cohort-specific associations between each exposure and PPD and combined results via meta-analysis using DataSHIELD. RESULTS: Of the 30,772 women included, 3,078 (10 %) reported having PPD. Exposure to PM10 was associated with slightly increased odds of PPD (adjusted odd ratios (OR) of 1.08 [95 % Confidence Intervals (CI): 0.99, 1.17] per inter quartile range increment of PM10) whilst associations for exposure to NO2 and PM2.5 were close to null. Exposure to high levels of road traffic noise (≥65 dB vs. < 65 dB) was associated with an OR of 1.12 [CI: 0.95, 1.32]. Associations between green spaces and PPD were close to null; whilst proximity to major blue spaces was associated with increased risk of PPD (OR 1.12, 95 %CI: 1.00, 1.26). All associations between built environment and PPD were close to null. Multiple exposure models showed similar results. DISCUSSION: The study findings suggest that exposure to PM10, road traffic noise and blue spaces in pregnancy may increase PPD risk, however future studies should explore this causally.

Health-related Quality of Life in Idiopathic Toe Walkers: A Multicenter Prospective Cross-sectional Study.

OBJECTIVE: Despite idiopathic toe walking (ITW) being a significant source of stress and anxiety for children and parents alike, little is known about the effect on health-related quality of life (HRQoL). The primary research question for this study was "Is ITW associated with impaired HRQoL, and is the degree of equinus contracture related to the degree of impairment?" METHODS: Twelve pediatric orthopaedic centers across the United Kingdom participated in this prospective, cross-sectional observational study of children younger than 18 years with ITW. Data were collected between May 2022 and July 2022. Using a standardized, piloted proforma, data collected included: demographics, toe-walking duration, passive ankle range of motion (Silfverskiold test), associated autism spectrum disorder or attention deficit hyperactivity disorder, previous and planned treatments, and Oxford Ankle Foot Questionnaire for Children scores. Domain scores were compared with a healthy control group and correlation was made to plantarflexion contracture using standard nonparametric statistical methods. RESULTS: Data were collected from 157 children. Significant reductions in physical, school and play, and emotional domain scores were noted compared with healthy controls. A significant moderate correlation was noted between passive ankle dorsiflexion and physical domain scores. There were no significant differences in Oxford Ankle Foot Questionnaire for Children scores among patient groups by treatment. CONCLUSIONS: ITW in children is associated with an impairment in HRQoL, not only across the physical domain but also the school and play and emotional domains. The more severe the equinus contracture, the worse the physical domain scores. LEVEL OF EVIDENCE: Level II-prospective cross-sectional observational study.

More than a Nuisance: Implications of Food Marketing for Public Health Efforts to Curb Childhood Obesity.

Fifteen years ago, public health experts urged industry, governments, and advocates to take action to dramatically improve the unhealthy food-marketing environment surrounding children in order to address the global childhood obesity crisis. Since then, research has confirmed that food marketing to children has far-reaching negative effects on their diets and health, takes advantage of adolescent vulnerabilities, and contributes to health disparities. In addition, digital marketing has profoundly changed young people's engagement with brands. Moreover, reliance on industry self-regulation as a solution has proven ineffective. Government-led policies have been more successful, but they remain limited in scope and challenging to adopt and implement. New approaches are necessary to increase public and policy maker awareness that food marketing is more than a nuisance, that it threatens the long-term health of children and adolescents worldwide, and that meaningful governmental action is urgently required to curtail industry's negative impact on young people's well-being. Expected final online publication date for the Annual Review of Public Health, Volume 45 is April 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Effects of a front-of-package disclosure on accuracy in assessing children's drink ingredients: two randomised controlled experiments with US caregivers of young children.

OBJECTIVE: Test effects of a standardised front-of-package (FOP) disclosure statement (indicating added sugar, non-nutritive sweetener (NNS) and juice content) on accuracy in assessing ingredients and perceived healthfulness of children's drinks. DESIGN: In two randomised controlled experiments, the same participants viewed drink packages and indicated if products contained added sugar or NNS and percent juice and rated drink healthfulness. Experiment 1 (E1) included novel (non-US) children's drinks with a) product claims only (control), b) claims and disclosure, or c) disclosure only. Experiment 2 (E2) included existing children's drinks (with claims) with a) no disclosure (control) or b) disclosure. Both experiments evaluated sweetened (fruit drink and flavoured water) and unsweetened (100 % juice and juice/water blend) drinks. Potential individual differences (education level and race/ethnicity) in effects were explored. SETTING: Online survey. PARTICIPANTS: Six hundred and forty-eight US caregivers of young children (1-5 years). RESULTS: FOP disclosures significantly increased accuracy for most ingredients and drink types, including identifying presence or absence of NNS in sweetened drinks, no added sugar in juice/water blends, and actual percent juice in fruit drinks and juice/water blends in both experiments. Disclosures also increased recognition that the novel 100 % juice and juice/water blend did not contain NNS or added sugar (E1) and existing sweetened drinks contained added sugar (E2). Disclosures reduced perceived healthfulness of sweetened drinks but did not increase unsweetened drink healthfulness ratings. Some differences by participant socio-demographic characteristics require additional research. CONCLUSIONS: FOP disclosures on children's drink packages can increase caregivers' understanding of product ingredients and aid in selecting healthier children's drinks.

CRISPR/Cas9 Directed Reprogramming of iPSC for Accelerated Motor Neuron Differentiation Leads to Dysregulation of Neuronal Fate Patterning and Function.

Neurodegeneration causes a significant disease burden and there are few therapeutic interventions available for reversing or slowing the disease progression. Induced pluripotent stem cells (iPSCs) hold significant potential since they are sourced from adult tissue and have the capacity to be differentiated into numerous cell lineages, including motor neurons. This differentiation process traditionally relies on cell lineage patterning factors to be supplied in the differentiation media. Genetic engineering of iPSC with the introduction of recombinant master regulators of motor neuron (MN) differentiation has the potential to shorten and streamline cell developmental programs. We have established stable iPSC cell lines with transient induction of exogenous LHX3 and ISL1 from the Tet-activator regulatory region and have demonstrated that induction of the transgenes is not sufficient for the development of mature MNs in the absence of neuron patterning factors. Comparative global transcriptome analysis of MN development from native and Lhx-ISL1 modified iPSC cultures demonstrated that the genetic manipulation helped to streamline the neuronal patterning process. However, leaky gene expression of the exogenous MN master regulators in iPSC resulted in the premature activation of genetic pathways characteristic of the mature MN function. Dysregulation of metabolic and regulatory pathways within the developmental process affected the MN electrophysiological responses.

Trajectories of occupational physical activity and risk of later-life mild cognitive impairment and dementia: the HUNT4 70+ study.

Background: High levels of occupational physical activity (PA) have been linked to an increased risk of dementia. We assessed the association of trajectories of occupational PA at ages 33-65 with risk of dementia and mild cognitive impairment (MCI) at ages 70+. Methods: We included 7005 participants (49.8% were women, 3488/7005) from the HUNT4 70+ Study. Group-based trajectory modelling was used to identify four trajectories of occupational PA based on national registry data from 1960 to 2014: stable low (30.9%, 2162/7005), increasing then decreasing (8.9%, 625/7005), stable intermediate (25.1%, 1755/7005), and stable high (35.2%, 2463/7005). Dementia and MCI were clinically assessed in 2017-2019. We performed adjusted multinomial regression to estimate relative risk ratios (RRR) with 95% confidence intervals (CI) for dementia and MCI. Findings: 902 participants were diagnosed with dementia and 2407 were diagnosed with MCI. Absolute unadjusted risks for dementia and MCI were 8.8% (95% CI: 7.6-10.0) and 27.4% (25.5-29.3), respectively, for those with a stable low PA trajectory, 8.2% (6.0-10.4) and 33.3% (29.6-37.0) for those with increasing, then decreasing PA; while they were 16.0% (14.3-17.7) and 35% (32.8-37.2) for those with stable intermediate, and 15.4% (14.0-16.8) and 40.2% (38.3-42.1) for those with stable high PA trajectories. In the adjusted model, participants with a stable high trajectory had a higher risk of dementia (RRR 1.34, 1.04-1.73) and MCI (1.80, 1.54-2.11), whereas participants with a stable intermediate trajectory had a higher risk of MCI (1.36, 1.15-1.61) compared to the stable low trajectory. While not statistically significant, participants with increasing then decreasing occupational PA had a 24% lower risk of dementia and 18% higher risk of MCI than the stable low PA group. Interpretation: Consistently working in an occupation with intermediate or high occupational PA was linked to an increased risk of cognitive impairment, indicating the importance of developing strategies for individuals in physically demanding occupations to prevent cognitive impairment. Funding: This work was supported by the National Institutes of Health (R01AG069109-01) and the Research Council of Norway (296297, 262700, 288083).

A Simple Exercise Program for Patients With End-Stage Kidney Disease to Improve Strength and Quality of Life: Clinical Research Protocol.

Background: Most patients with end-stage kidney disease (ESKD) appreciate the importance of exercise and would like to increase their physical activity; however, they report a few key barriers, including (1) lack of physician advice to do so, (2) lack of safe and convenient programs (ie, appropriate for home or neighborhood), and (3) cost. Importantly, patients indicated in a previous survey that they would prefer an exercise program that improves muscle strength and symptoms, and are less interested in cardiovascular disease prevention. Objective: To test the feasibility of a simple, prescribed exercise program using Nordic walking poles in patients with ESKD treated with dialysis. Design: Randomized multicenter pilot trial of an exercise intervention that includes Nordic walking poles, personalized physician exercise prescriptions, pedometers, and access to exercise videos, compared with standard of care, in patients being treated with maintenance dialysis. Setting: Multicenter tertiary care centers in Canada. Patients: Ambulatory adult patients with ESKD treated with peritoneal dialysis or hemodialysis (HD) for at least 6 months at participating sites are potentially eligible. Inclusion criteria include ability to use Nordic walking poles (either de novo or in place of mobility aid) and to provide informed consent in English or in French. Exclusion criteria include (1) any absolute contraindication to exercise, (2) baseline step count >8000 steps/day, (3) planned living donor kidney transplant, and (4) participation in another interventional trial that may affect the results of this study. Methods: This is a randomized multicenter pilot trial of an exercise intervention that consists of a prescription to exercise using Nordic walking poles, a pedometer to track activity, and access to exercise videos, with the comparator of standard of care (dialysis unit staff encouragement to exercise) in patients being treated with maintenance dialysis. Randomization is concealed and uses a 1:1 ratio for group assignment. Our specific aims are to determine the feasibility of patient recruitment, adherence to the exercise program (verified by step counts), and efficacy of the intervention on patient-important outcomes that were assessed as a priority by patients in a prior survey-specifically strength, fatigue, and sleep. We record days spent in hospital and loss of independent living to inform sample size calculations for a definitive trial of exercise in patient with ESKD treated with dialysis. Adverse events are closely monitored. Outcomes: Primary: Our recruitment goal is 90 to 150 patients over 27 months; adherence success will be defined if >75% of randomized patients, excluding those who are transplanted or deceased, achieve >80% of their prescribed steps at 6 and 12 months. Secondary Efficacy Outcomes: (1) strength-hand grip strength and 5 times sit to stand, (2) energy-Short Form (SF)-36 vitality subscale, and (3) sleep-Pittsburg Sleep Quality Index will be assessed at baseline, 6, and 12 months. Results: Trial recruitment started before the COVID-19 pandemic and the pandemic led to many interruptions and delays. Online exercise Web sites and a tailored video were added to the protocol to encourage activity when participants were unable or reluctant to walk in public places. Limitations: This trial was designed to include ambulatory patients with ESKD and does not address the burden of disease in patients with very restricted mobility. Trial Registration: NCT03787589.

Contexte: La plupart des patients atteints d'insuffisance rénale terminale (IRT) comprennent l'importance de l'exercice physique et souhaitent augmenter leur niveau d'activité. Ils signalent toutefois quelques obstacles, notamment 1) le manque de conseils médicaux pour le faire; 2) le manque de programmes sécuritaires et faciles (c.-à-d. pouvant être suivis à la maison ou dans le quartier); et 3) les coûts. Il convient de noter que les patients avaient indiqué dans une enquête précédente préférer un programme d'exercices améliorant la force musculaire et les symptômes liés à la maladie, et être moins intéressés par la prévention des maladies cardiovasculaires. Objectif: Dans une population de patients atteints d'IRT traités par dialyse, tester la faisabilité d'un programme prescrit et simple à suivre d'exercices impliquant l'utilisation de bâtons de marche nordique. Conception: Essai pilote randomisé multicentrique mené chez des patients traités par dialyse d'entretien. L'essai compare les soins habituels à une intervention comprenant des exercices avec bâtons de marche nordique, un programme personnalisé prescrit par un médecin, un podomètre et l'accès à des vidéos d'exercices. Cadre: Plusieurs centres de soins tertiaires au Canada. Sujets: Tous les patients adultes ambulatoires atteints d'IRT traités par dialyse péritonéale ou hémodialyse depuis au moins 6 mois dans les sites participants sont potentiellement admissibles. Pour être inclus, les patients doivent pouvoir utiliser des bâtons de marche nordique (de novo ou en remplacement de l'aide à la mobilité) et fournir un consentement éclairé en anglais ou en français. Les critères d'exclusion sont : 1) toute contre-indication absolue à l'exercice; 2) le fait de marcher déjà au moins 8 000 pas/jour; 3) avoir une transplantation rénale d'un donneur vivant prévue; 4) la participation à un autre essai interventionnel susceptible d'affecter les résultats de la présente étude. Méthodologie: Il s'agit d'un essai pilote randomisé multicentrique examinant une intervention en matière d'activité physique. L'intervention consiste en une prescription d'activité physique à l'aide de bâtons de marche nordique, elle donne accès à un podomètre pour suivre l'activité, ainsi qu'à des vidéos d'exercices; le comparateur est la norme de soins (encouragement par le personnel de l'unité de dialyse à pratiquer une activité physique) pour les patients traités par dialyse d'entretien. La randomisation est masquée et utilise un ratio de 1:1 pour l'affectation aux groupes. Nous examinons la faisabilité du recrutement des patients, l'observance du programme d'exercices (vérifiée par le nombre de pas) et l'efficacité de l'intervention sur les résultats de santé ayant été jugés comme importants et prioritaires par les patients dans une enquête précédente ­ plus précisément la force, la fatigue et le sommeil. Nous enregistrons le nombre de jours passés à l'hôpital et la perte de vie autonome afin d'éclairer les calculs de la taille de l'échantillon d'un essai définitif qui portera sur l'activité physique en contexte d'HD. Les événements indésirables sont étroitement surveillés. Mesures: Primaires : nous souhaitons recruter 90 à 150 patients sur une période de 27 mois; l'observance sera jugée comme un succès si plus de 75 % des patients randomisés (excluant les patients transplantés ou décédés) atteignent plus de 80 % de leur prescription de nombres de pas/jour après 6 et 12 mois. Paramètres secondaires d'efficacité : 1) Force ­ mesure de la force de préhension et 5 fois l'exercice de se lever d'une position assise; 2) Énergie ­ sous-échelle du test de vitalité SF-36; et 3) Sommeil ­ mesure de l'Indice de la qualité du sommeil Pittsburg à l'inclusion et après 6 mois et 12 mois. Résultats: Le recrutement s'est amorcé avant la pandémie de COVID-19, puis celle-ci a entraîné de nombreuses interruptions et retards. Des sites d'exercices en ligne et une vidéo personnalisée ont été ajoutés au protocole afin d'encourager les patients à continuer de faire de l'activité physique lorsqu'ils ne pouvaient pas marcher dans des lieux publics ou étaient réticents à le faire. Limites: Cet essai a été conçu pour inclure des patients ambulatoires atteints d'IRT, il ne traite pas du fardeau de la maladie chez les patients à mobilité très restreinte.

Associations of Maternal Educational Level, Proximity to Greenspace During Pregnancy, and Gestational Diabetes With Body Mass Index From Infancy to Early Adulthood: A Proof-of-Concept Federated Analysis in 18 Birth Cohorts.

International sharing of cohort data for research is important and challenging. We explored the feasibility of multi-cohort federated analyses by examining associations between three pregnancy exposures (maternal education, exposure to green vegetation and gestational diabetes) with offspring BMI from infancy to 17 years. We used data from 18 cohorts (n=206,180 mother-child pairs) from the EU Child Cohort Network and derived BMI at ages 0-1, 2-3, 4-7, 8-13 and 14-17 years. Associations were estimated using linear regression via one-stage IPD meta-analysis using DataSHIELD. Associations between lower maternal education and higher child BMI emerged from age 4 and increased with age (difference in BMI z-score comparing low with high education age 2-3 years = 0.03 [95% CI 0.00, 0.05], 4-7 years = 0.16 [95% CI 0.14, 0.17], 8-13 years = 0.24 [95% CI 0.22, 0.26]). Gestational diabetes was positively associated with BMI from 8 years (BMI z-score difference = 0.18 [CI 0.12, 0.25]) but not at younger ages; however associations attenuated towards the null when restricted to cohorts which measured GDM via universal screening. Exposure to green vegetation was weakly associated with higher BMI up to age one but not at older ages. Opportunities of cross-cohort federated analyses are discussed.

Are U.S. food and beverage companies now advertising healthy products to children on television? An evaluation of improvements in industry self-regulation, 2017-2021.

BACKGROUND: Through the Children's Food and Beverage Advertising Initiative (CFBAI), U.S. food companies pledge to only advertise healthier products in children's television (TV) programming, but previous research shows that highly advertised products do not qualify as nutritious according to independent nutrition criteria. In 2020, the CFBAI implemented stricter nutrition criteria for products that may be advertised to children, but the potential impact of these changes has not been assessed. This observational study evaluates (1) improvements in energy and individual nutrient composition of products that companies indicated may be advertised to children (i.e., CFBAI-listed products) in 2020 versus 2017, (2) amount of advertising on children's TV for CFBAI-listed versus other products in 2021, and 3) the nutrition quality of advertised versus non-advertised CFBAI-listed products. METHODS: Data include energy, saturated fat, sodium, and sugar content and overall nutrition quality (Nutrition Profile Index [NPI] scores) of CFBAI-listed products in 2017 (n = 308) and 2020 (n = 245). Nielsen data provided total ad spending and children's exposure to ads on children's TV channels for all foods and beverages in 2021. RESULTS: From 2017 to 2021, energy, saturated fat and sugar declined for CFBAI-listed products in three of six food categories (yogurt, sweet and salty snacks). Although CFBAI-listed products accounted for 79% of food ads viewed by children on children's TV channels, just 50% of CFBAI-listed food and 36% of drink brands were advertised on children's TV. Moreover, advertised products were significantly less nutritious than non-advertised CFBAI-listed products. CONCLUSION: Despite revised nutrition standards and improvements in nutrient content of some product categories, participating companies continued to primarily advertise nutritionally poor food and beverages on children's TV. CFBAI companies have not delivered on their promises to advertise healthier products to children.

Lifestyle patterns in European preschoolers: Associations with socio-demographic factors and body mass index.

BACKGROUND: Energy balance-related behaviours (EBRBs), that is, dietary intake, screen, outdoor play and sleep, tend to combine into 'lifestyle patterns', with potential synergistic influences on health. To date, studies addressing this theme mainly focused on school children and rarely accounted for sleep, with a cross-country perspective. OBJECTIVES: We aimed at comparing lifestyle patterns among preschool-aged children across Europe, their associations with socio-demographic factors and their links with body mass index (BMI). METHODS: Harmonized data on 2-5-year-olds participating in nine European birth cohorts from the EU Child Cohort Network were used (EBRBs, socio-demographics and anthropometrics). Principal component analysis and multivariable linear and logistic regressions were performed. RESULTS: The most consistent pattern identified across cohorts was defined by at least three of the following EBRBs: discretionary consumption, high screen time, low outdoor play time and low sleep duration. Consistently, children from low-income households and born to mothers with low education level had higher scores on this pattern compared to their socioeconomically advantaged counterparts. Furthermore, it was associated with higher BMI z-scores in the Spanish and Italian cohorts (ß = 0.06, 95% CI = [0.02; 0.10], both studies). CONCLUSION: These findings may be valuable in informing early multi-behavioural interventions aimed at reducing social inequalities in health at a European scale.

Silent Conversations: Goals of Care and End-of-Life Quality in Relapsed High-Risk Leukemia.

Background: Advanced practice providers (APPs) affect high-quality health care through leadership, evidence-based practice implementation, and quality improvement projects. When planning solutions to clinical problems, leadership must solicit APP input to promote success. Hematology patients are more likely to receive poor-quality end-of-life (EOL) care than those with solid tumors. Regardless of disease, aggressive EOL care is increasing despite evidence that it is often inconsistent with patients' goals of care (GOC). Data regarding this phenomenon in hematology specifically is lacking. The distorted association of "end of life" with "goals of care" has "silenced" crucial goals discussions in patients with relapsed or refractory high-risk leukemia, which raises concerns for the provision of care that is inconsistent with patients' values and preferences. Hematologists may possess certain traits and distinct barriers leading to what one might call an aversion to GOC discussions in the inpatient setting. Aims: (1) Quantify hematologists' rate of participation in a GOC pathway initiative during two separate months. (2) Explore the hematologists' definition of and barriers to having GOC discussions. Design: This is a mixed-methods, explanatory sequential design (follow-up explanations variant). Sample: Quantitative: Hematology inpatient admissions during two nonconsecutive months in 2021. Qualitative: Eighteen leukemia hematologists from one dedicated cancer center. Results: During the 2 months, an average of 36% of admissions met the criteria for GOC pathway initiation, 19% of those had an appropriate initiation order, and < 1% had a properly documented and billed GOC discussion. Nine hematologists responded to a SurveyMonkey poll with two questions. All nine included clinical situation and communication in their definition of GOC discussions. Time limitations and prognostic uncertainty were the two most reported barriers. Discussion: The findings demonstrate that the apprehension of hematologists to have GOC conversations is similarly seen in the APPs' reluctance to initiate a pathway intended to lead to GOC conversations. The percentage of eligible inpatient admissions meeting the specified criteria was similar between the 2 months; however, the number of appropriate referrals and documented or billed GOC discussions was higher in the earlier month, demonstrating temporal decline. Further research inquiry is needed to explore causation of this phenomenon.

Inhibiting WNT secretion reduces high bone mass caused by Sost loss-of-function or gain-of-function mutations in Lrp5.

Proper regulation of Wnt signaling is critical for normal bone development and homeostasis. Mutations in several Wnt signaling components, which increase the activity of the pathway in the skeleton, cause high bone mass in human subjects and mouse models. Increased bone mass is often accompanied by severe headaches from increased intracranial pressure, which can lead to fatality and loss of vision or hearing due to the entrapment of cranial nerves. In addition, progressive forehead bossing and mandibular overgrowth occur in almost all subjects. Treatments that would provide symptomatic relief in these subjects are limited. Porcupine-mediated palmitoylation is necessary for Wnt secretion and binding to the frizzled receptor. Chemical inhibition of porcupine is a highly selective method of Wnt signaling inhibition. We treated three different mouse models of high bone mass caused by aberrant Wnt signaling, including homozygosity for loss-of-function in Sost, which models sclerosteosis, and two strains of mice carrying different point mutations in Lrp5 (equivalent to human G171V and A214V), at 3 months of age with porcupine inhibitors for 5-6 weeks. Treatment significantly reduced both trabecular and cortical bone mass in all three models. This demonstrates that porcupine inhibition is potentially therapeutic for symptomatic relief in subjects who suffer from these disorders and further establishes that the continued production of Wnts is necessary for sustaining high bone mass in these models.

Retirement age and disability status as pathways to later-life cognitive impairment: Evidence from the Norwegian HUNT Study linked with Norwegian population registers.

BACKGROUND: Research shows that retirement age is associated with later-life cognition but has not sufficiently distinguished between retirement pathways. We examined how retirement age was associated with later-life dementia and mild cognitive impairment (MCI) for people who retired via the disability pathway (received a disability pension prior to old-age pension eligibility) and those who retired via the standard pathway. METHODS: The study sample comprised 7210 participants from the Norwegian Trøndelag Health Study (HUNT4 70+, 2017-2019) who had worked for at least one year in 1967-2019, worked until age 55+, and retired before HUNT4. Dementia and MCI were clinically assessed in HUNT4 70+ when participants were aged 69-85 years. Historical data on participants' retirement age and pathway were retrieved from population registers. We used multinomial regression to assess the dementia/MCI risk for women and men retiring via the disability pathway, or early (<67 years), on-time (age 67, old-age pension eligibility) or late (age 68+) via the standard pathway. RESULTS: In our study sample, 9.5% had dementia, 35.3% had MCI, and 28.1% retired via the disability pathway. The disability retirement group had an elevated risk of dementia compared to the on-time standard retirement group (relative risk ratio [RRR]: 1.64, 95% CI 1.14-2.37 for women, 1.70, 95% CI 1.17-2.48 for men). MCI risk was lower among men who retired late versus on-time (RRR, 0.76, 95% CI 0.61-0.95). CONCLUSION: Disability retirees should be monitored more closely, and preventive policies should be considered to minimize the dementia risk observed among this group of retirees.

Quasi-dynamic breathing model of the lung incorporating viscoelasticity of the lung tissue.

We advanced a novel model to calculate viscoelastic lung compliance and airflow resistance in presence of mucus, accounting for the quasi-linear viscoelastic stress-strain response of the parenchyma (alveoli) tissue. We adapted a continuum-based numerical modeling approach for the lung, integrating the fluid mechanics of the airflow within individual generations of the bronchi and alveoli. The model accounts for elasticity of the deformable bronchioles, resistance to airflow due to the presence of mucus within the bronchioles, and subsequent mucus flow. Simulated quasi-dynamic inhalation and expiration cycles were used to characterize the net compliance and resistance of the lung, considering the rheology of the mucus and viscoelastic properties of the parenchyma tissue. The structure and material properties of the lung were identified to have an important contribution to the lung compliance and airflow resistance. The secondary objective of this work was to assess whether a higher frequency and smaller volume of harmonic air flow rate compared to a normal ventilator breathing cycle enhanced mucus outflow. Results predict, lower mucus viscosity and higher excitation frequency of breathing are favorable for the flow of mucus up the bronchi tree, towards the trachea.

Caregiver perceptions of snacks for young children: A thematic synthesis of qualitative research.

Snacks are inconsistently defined in nutrition research and dietary guidelines for young children, challenging efforts to improve diet quality. Although some guidelines suggest that snacks include at least two food groups and fit into an overall health promoting dietary pattern, snacks high in added sugars and sodium are highly marketed and frequently consumed. Understanding how caregivers perceive "snacks" for young children may aid in development of effective nutrition communications and behaviourally-informed dietary interventions for obesity prevention. We aimed to synthesize caregivers' perceptions of snacks for young children across qualitative studies. Four databases were searched for peer-reviewed qualitative articles including caregiver perceptions of "snacks" for children ≤5 years. We conducted thematic synthesis of study findings, concluding with the development of analytical themes. Data synthesis of fifteen articles from ten studies, conducted in the U.S., Europe, and Australia, revealed six analytical themes that captured food type, hedonic value, purpose, location, portion size, and time. Caregivers perceived snacks as both "healthy" and "unhealthy" foods. Less healthy snacks were described as highly liked foods, which required restriction and were consumed outside the home. Caregivers used snacks to manage behavior and curb hunger. Snack portions were described as "small", although caregivers reported various methods to estimate child portion size. Caregivers' perceptions of snacks revealed opportunities for targeted nutrition messaging, especially supporting responsive feeding and nutrient-dense food choices. In high-income countries, expert recommendations should consider caregivers' perceptions of snacks, more clearly defining nutrient-dense snacks that are enjoyable, achieve dietary requirements, reduce hunger, and promote healthy weight.