Is the frequency of breakfast consumption associated with life satisfaction in children and adolescents? A cross-sectional study with 154,151 participants from 42 countries.

BACKGROUND: The promotion of daily breakfast consumption and the importance of making appropriate breakfast choices have been underscored as significant public health messages. The aim of this study was to examine the relationship between breakfast frequency and life satisfaction in large and representative samples of school-going children and adolescents aged 10-17 years from 42 different countries. METHODS: This study used information from the 2017/2018 Health Behavior in School-aged Children study, comprising nationally representative samples of children and adolescents aged 10-17 years who were attending school. The total number of participants from the 42 countries included in the study was 155,451 (51.3% girls). The evaluation of breakfast consumption in this study involved a specific question: "How often do you typically have breakfast (more than a glass of milk or fruit juice)?". To measure life satisfaction, a subjective assessment scale was used in the form of a ladder, visually spanning from 0 to 10. On this scale, the topmost point (10) denotes the highest conceivable quality of life, whereas the bottom point (0) represents the worst imaginable quality of life. RESULTS: After adjusting for several covariates, the lowest estimated marginal mean of life satisfaction was identified in those participants who skipped breakfast (mean [M] = 5.6, 95% confidence interval [CI] 5.5 to 5.8). Conversely, the highest estimated marginal mean of life satisfaction was observed in those who had breakfast every day (M = 6.5, 95% CI 6.3 to 6.6). Overall, a nearly linear relationship between higher frequency of breakfast and greater life satisfaction in children and adolescents was identified (p-for-trend < 0.001). In addition, the highest estimated marginal mean of life satisfaction score was identified in those participants from Portugal who had breakfast every day (M = 7.7; 95% CI 6.9 to 8.5 points). Conversely, the lowest estimated marginal mean of life satisfaction was observed in those participants from Romania who no breakfast (M = 3.5; 95% CI 2.6 to 4.4 points). CONCLUSIONS: There is a nearly linear relationship between higher frequency of breakfast and greater life satisfaction in children and adolescents. Considering the potential health advantages associated with breakfast during this critical age phase, these findings imply the necessity for additional global efforts to promote increased breakfast consumption among children and adolescents.

Factors that influence participation in physical activity for people with bipolar disorder: a synthesis of qualitative evidence.

BACKGROUND: Mental health problems contribute significantly to the overall disease burden worldwide and are major causes of disability, suicide, and ischaemic heart disease. People with bipolar disorder report lower levels of physical activity than the general population, and are at greater risk of chronic health conditions including cardiovascular disease and obesity. These contribute to poor health outcomes. Physical activity has the potential to improve quality of life and physical and mental well-being. OBJECTIVES: To identify the factors that influence participation in physical activity for people diagnosed with bipolar disorder from the perspectives of service users, carers, service providers, and practitioners to help inform the design and implementation of interventions that promote physical activity. SEARCH METHODS: We searched MEDLINE, PsycINFO, and eight other databases to March 2021. We also contacted experts in the field, searched the grey literature, and carried out reference checking and citation searching to identify additional studies. There were no language restrictions. SELECTION CRITERIA: We included qualitative studies and mixed-methods studies with an identifiable qualitative component. We included studies that focused on the experiences and attitudes of service users, carers, service providers, and healthcare professionals towards physical activity for bipolar disorder. DATA COLLECTION AND ANALYSIS: We extracted data using a data extraction form designed for this review. We assessed methodological limitations using a list of predefined questions. We used the "best fit" framework synthesis based on a revised version of the Health Belief Model to analyse and present the evidence. We assessed methodological limitations using the CASP Qualitative Checklist. We used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) guidance to assess our confidence in each finding. We examined each finding to identify factors to inform the practice of health and care professionals and the design and development of physical activity interventions for people with bipolar disorder. MAIN RESULTS: We included 12 studies involving a total of 592 participants (422 participants who contributed qualitative data to an online survey, 170 participants in qualitative research studies). Most studies explored the views and experiences of physical activity of people with experience of bipolar disorder. A number of studies also reported on personal experiences of physical activity components of lifestyle interventions. One study included views from family carers and clinicians. The majority of studies were from high-income countries, with only one study conducted in a middle-income country. Most participants were described as stable and had been living with a diagnosis of bipolar disorder for a number of years. We downgraded our confidence in several of the findings from high confidence to moderate or low confidence, as some findings were based on only small amounts of data, and the findings were based on studies from only a few countries, questioning the relevance of these findings to other settings. We also had very few perspectives of family members, other carers, or health professionals supporting people with bipolar disorder. The studies did not include any findings from service providers about their perspectives on supporting this aspect of care. There were a number of factors that limited people's ability to undertake physical activity. Shame and stigma about one's physical appearance and mental health diagnosis were discussed. Some people felt their sporting skills/competencies had been lost when they left school. Those who had been able to maintain exercise through the transition into adulthood appeared to be more likely to include physical activity in their regular routine. Physical health limits and comorbid health conditions limited activity. This included bipolar medication, being overweight, smoking, alcohol use, poor diet and sleep, and these barriers were linked to negative coping skills. Practical problems included affordability, accessibility, transport links, and the weather. Workplace or health schemes that offered discounts were viewed positively. The lack of opportunity for exercise within inpatient mental health settings was a problem. Facilitating factors included being psychologically stable and ready to adopt new lifestyle behaviours. There were positive benefits of being active outdoors and connecting with nature. Achieving balance, rhythm, and routine helped to support mood management. Fitting physical activity into a regular routine despite fluctuating mood or motivation appeared to be beneficial if practised at the right intensity and pace. Over- or under-exercising could be counterproductive and accelerate depressive or manic moods. Physical activity also helped to provide a structure to people's daily routines and could lead to other positive lifestyle benefits. Monitoring physical or other activities could be an effective way to identify potential triggers or early warning signs. Technology was helpful for some. People who had researched bipolar disorder and had developed a better understanding of the condition showed greater confidence in managing their care or providing care to others. Social support from friends/family or health professionals was an enabling factor, as was finding the right type of exercise, which for many people was walking. Other benefits included making social connections, weight loss, improved quality of life, and better mood regulation. Few people had been told of the benefits of physical activity. Better education and training of health professionals could support a more holistic approach to physical and mental well-being. Involving mental health professionals in the multidisciplinary delivery of physical activity interventions could be beneficial and improve care. Clear guidelines could help people to initiate and incorporate lifestyle changes. AUTHORS' CONCLUSIONS: There is very little research focusing on factors that influence participation in physical activity in bipolar disorder. The studies we identified suggest that men and women with bipolar disorder face a range of obstacles and challenges to being active. The evidence also suggests that there are effective ways to promote managed physical activity. The research highlighted the important role that health and care settings, and professionals, can play in assessing individuals' physical health needs and how healthy lifestyles may be promoted. Based on these findings, we have provided a summary of key elements to consider for developing physical activity interventions for bipolar disorder.

Global association of secondhand smoke exposure locations and smoking behaviour among adolescents in 99 countries.

AIM: This study classified 99 countries into four income groups and then analysed the impact of secondhand smoke (SHS) exposure at home, in public places and at school, on current cigarette smoking prevalence. METHODS: We utilised data from the WHO Global Youth Tobacco Survey and a meta-analysis was conducted to evaluate the prevalence and weighted odds ratios (wORs) of adolescent smoking behaviour and SHS exposure locations. RESULTS: Both smoking behaviours increased with higher national income levels. Smoking behaviours in high and upper-middle-income countries (HICs and UMICs) exhibited an association with SHS exposure in public places (HIC: wOR, 3.50 [95% CI, 2.85-4.31]; UMIC: wOR, 2.90 [2.60-3.23]) compared to home. Low- and lower-middle-income countries (LICs and LMICs) showed an association with SHS exposure in the home (LIC: wOR, 5.33 [3.59-7.93]; LMIC: wOR, 2.71 [2.33-3.17]) than public places. The association between current cigarette smoking and SHS exposure at home increased with lower income levels, while anticipated future use of any form of tobacco with SHS exposure in public places rose in lower income countries. CONCLUSIONS: Targeted interventions based on income levels are essential, emphasising home strategies in lower income countries and public place efforts in higher income countries.

Association between self-reported visual symptoms (suggesting cataract) and self-reported fall-related injury among adults aged ≥ 65 years from five low- and middle-income countries.

BACKGROUND: Cataracts may increase risk for falls but studies on this topic from low- and middle-income countries (LMICs) are scarce. Therefore, we examined the cross-sectional association between self-reported visual symptoms (suggesting cataract) and self-reported injurious falls in nationally representative samples of adults aged ≥ 65 years from five LMICs (China, Ghana, India, Mexico, and Russia). METHODS: Data from the WHO Study on global AGEing and adult health (SAGE) were analysed. Self-reported information on past 12-month fall-related injury and cataract based on symptoms were collected. Multivariable logistic regression and meta-analyses were conducted to assess associations. RESULTS: Data on 13,101 people aged ≥ 65 years were analysed [mean (SD) age 72.5 (11.3) years; 45.2% males]. The overall prevalence of self-reported fall-related injury and visual symptoms (suggesting cataract) were 4.9% and 29.4%, respectively. There was a positive association between self-reported visual symptoms (suggesting cataract) and fall-related injury (i.e., OR > 1) in all five countries but statistical significance was reached in three: China (OR = 1.60; 95% CI = 1.08-2.35), India (OR = 1.96; 95% CI = 1.15-3.35), and Russia (OR = 3.58; 95% CI = 2.06-6.24). The pooled OR including all five countries based on a meta-analysis was OR = 1.88 (95% CI = 1.32-2.68). CONCLUSIONS: Self-reported visual symptoms (suggesting cataract) were associated with higher odds for self-reported injurious falls among older adults in LMICs. Expanding availability of cataract surgery in LMICs may also have the additional benefit of reducing falls among older people.

Need to Revise Classification of Physical Activity Intensity in Older Adults? The Use of Estimated METs, Measured METs, and V̇O2 Reserve.

BACKGROUND: Multiples of resting metabolic rate (RMR) are often used to classify physical activity intensity, a concept known as the metabolic equivalent of task (MET). However, the METs metrics may misclassify physical activity intensity in older adults because of age-related changes in RMR and maximal aerobic capacity (V˙O2max). This study aimed to (i) compare classifications of activity intensity by estimated (METsestimated) and measured (METsmeasured) METs and (ii) compare physical activity classified by absolute (METsmeasured) versus relative intensity (%V˙O2Reserve) in older adults. METHODS: Ninety-eight adults aged 75-90 years participated in the study. RMR and V˙O2 during sitting, standing, daily activities, and 6-minute walking test were measured. V˙O2Reserve was defined as the difference between V˙O2max and RMR. Moderate and vigorous intensity was classified as 3 and 6 METs and 40% and 60% of V˙O2Reserve, respectively. Paired t tests and a confusion matrix were used to investigate aims 1 and 2, respectively. RESULTS: METsmeasured was 24% lower than the standard 1 MET of 3.5 mL O2·min-1·kg-1. METsestimated underestimated the intensity during daily and walking activities when compared to METsmeasured. Nevertheless, when comparing METsmeasured to percentages of V˙O2Reserve, a mismatch was shown for moderate intensity in 47%-67% of the participants during daily activities and 21% of the participants during self-selected gait speed. CONCLUSIONS: Applying METsestimated for older adults leads to potential underestimation of physical activity intensity, suggesting that current classification metrics should be revised for older adults. V˙O2Reserve is a candidate metric for establishing precise physical activity intensity cut points for older adults. Clinical Trials Registration Number: NCT04821713.

Association between sedentary behavior and dynapenic abdominal obesity among older adults from low- and middle-income countries.

BACKGROUND: Sedentary behavior, or time spent sitting, may increase risk for dynapenic abdominal obesity (DAO), but there are currently no studies on this topic. AIMS: Therefore, we investigated the association between sedentary behaviour and DAO in a nationally representative sample of older adults from six low- and middle-income countries. METHODS: Cross-sectional data from the Study on Global AGEing and Adult Health were analysed. Dynapenia was defined as handgrip strength < 26 kg for men and < 16 kg for women. Abdominal obesity was defined as waist circumference of > 88 cm (> 80 cm for Asian countries) for women and > 102 cm (> 90 cm) for men. DAO was defined as having both dynapenia and abdominal obesity. Self-reported sedentary behavior was categorized as ≥ 8 h/day (high sedentary behaviour) or < 8 h/day. Multivariable multinomial logistic regression was conducted. RESULTS: Data on 20,198 adults aged ≥ 60 years were analyzed [mean (SD) age 69.3 (13.1) years; 54.1% females]. In the overall sample, ≥ 8 h of sedentary behavior per day (vs. <8 h) was significantly associated with 1.52 (95%CI = 1.11-2.07) times higher odds for DAO (vs. no dynapenia and no abdominal obesity), and this was particularly pronounced among males (OR = 2.27; 95%CI = 1.42-3.62). Highly sedentary behavior was not significantly associated with dynapenia alone or abdominal obesity alone. DISCUSSION: High sedentary behaviour may increase risk for DAO among older adults. CONCLUSIONS: Interventions to reduce sedentary behaviour may also lead to reduction of DAO and its adverse health outcomes, especially among males, pending future longitudinal research.

Enhanced structure/function of mTSPO translocator in lipid:surfactant mixed micelles.

TSPO is a ubiquitous transmembrane protein used as a pharmacological marker in neuroimaging. The only known atomic structure of mammalian TSPOs comes from the solution NMR of mouse TSPO (mTSPO) bound to the PK11195 ligand and in a DPC surfactant environment. No structure is available in a biomimetic environment and without PK11195 which strongly stiffens the protein. We measured the effect of different amphiphilic environments on ligand-free mTSPO to study its structure/function and find optimal solubilization conditions. By replacing the SDS surfactant, where the recombinant protein is purified, with mixed lipid:surfactant (DMPC:DPC) micelles at different ratios (0:1, 1:2, and 2:1, w:w), the α-helix content and interactions and the intrinsic tryptophan (Trp) fluorescence of mTSPO are gradually increased. Small-angle X-ray scattering (SAXS) shows a more extended mTSPO/belt complex with the addition of lipids: Dmax ∼95 Å in DPC alone versus ∼142 Å in DMPC:DPC (1:2). SEC-MALLS shows that the molecular composition of the mTSPO belt is ∼98 molecules for DPC alone and ∼58 DMPC and ∼175 DPC for DMPC:DPC (1:2). Additionally, DMPC:DPC micelles stabilize mTSPO compared to DPC alone, where the protein has a greater propensity to aggregate. These structural changes are consistent with the increased affinity of mTSPO for the PK11195 ligand in presence of lipids (Kd ∼70 µM in DPC alone versus ∼0.91 µM in DMPC:DPC, 1:2), as measured by microscale thermophoresis (MST). In conclusion, mixed lipid:surfactant micelles open new possibilities for the stabilization of membrane proteins and for their study in solution in a more biomimetic amphiphilic environment.

SARS-CoV2 Nsp1 is a metal-dependent DNA and RNA endonuclease.

Over recent years, we have been living under a pandemic, caused by the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). One of the major virulence factors of Coronaviruses is the Non-structural protein 1 (Nsp1), known to suppress the host cells protein translation machinery, allowing the virus to produce its own proteins, propagate and invade new cells. To unveil the molecular mechanisms of SARS-CoV2 Nsp1, we have addressed its biochemical and biophysical properties in the presence of calcium, magnesium and manganese. Our findings indicate that the protein in solution is a monomer and binds to both manganese and calcium, with high affinity. Surprisingly, our results show that SARS-CoV2 Nsp1 alone displays metal-dependent endonucleolytic activity towards both RNA and DNA, regardless of the presence of host ribosome. These results show Nsp1 as new nuclease within the coronavirus family. Furthermore, the Nsp1 double variant R124A/K125A presents no nuclease activity for RNA, although it retains activity for DNA, suggesting distinct binding sites for DNA and RNA. Thus, we present for the first time, evidence that the activities of Nsp1 are modulated by the presence of different metals, which are proposed to play an important role during viral infection. This research contributes significantly to our understanding of the mechanisms of action of Coronaviruses.

The structural properties of full-length annexin A11.

Annexin A11 (ANXA11) is a calcium-dependent phospholipid-binding protein belonging to the annexin protein family and implicated in the neurodegenerative amyotrophic lateral sclerosis. Structurally, ANXA11 contains a conserved calcium-binding C-terminal domain common to all annexins and a putative intrinsically unfolded N-terminus specific for ANXA11. Little is known about the structure and functions of this region of the protein. By analogy with annexin A1, it was suggested that residues 38 to 59 within the ANXA11 N-terminus could form a helical region that would be involved in interactions. Interestingly, this region contains residues that, when mutated, may lead to clinical manifestations. In the present study, we have studied the structural features of the full-length protein with special attention to the N-terminal region using a combination of biophysical techniques which include nuclear magnetic resonance and small angle X-ray scattering. We show that the N-terminus is intrinsically disordered and that the overall features of the protein are not markedly affected by the presence of calcium. We also analyzed the 38-59 helix hypothesis using synthetic peptides spanning both the wild-type sequence and clinically relevant mutations. We show that the peptides have a remarkable character typical of a native helix and that mutations do not alter the behaviour suggesting that they are required for interactions rather than being structurally important. Our work paves the way to a more thorough understanding of the ANXA11 functions.

Small-Angle X-Ray Scattering for Macromolecular Complexes.

Small angle X-ray scattering (SAXS) is a versatile technique that can provide unique insights in the solution structure of macromolecules and their complexes, covering the size range from small peptides to complete viral assemblies. Technological and conceptual advances in the last two decades have tremendously improved the accessibility of the technique and transformed it into an indispensable tool for structural biology. In this chapter we introduce and discuss several approaches to collecting SAXS data on macromolecular complexes, including several approaches to online chromatography. We include practical advice on experimental design and point out common pitfalls of the technique.

Temporal trends of carbonated soft-drink consumption among adolescents aged 12-15 years from eighteen countries in Africa, Asia and the Americas.

Carbonated soft-drink consumption is detrimental to multiple facets of adolescent health. However, little is known about temporal trends in carbonated soft-drink consumption among adolescents, particularly in non-Western countries. Therefore, we aimed to examine this trend in representative samples of school-going adolescents from eighteen countries in Africa, Asia and the Americas. Cross-sectional data from the Global School-based Student Health Survey 2009-2017 were analysed. Carbonated soft-drink consumption referred to drinking carbonated soft-drinks at least once per day in the past 30 d. The prevalence of carbonated soft-drink consumption was calculated for each survey, and crude linear trends were assessed by linear regression models. Data on 74 055 students aged 12-15 years were analysed (mean age 13·9 (sd 1·0) years; 49·2 % boys). The overall mean prevalence of carbonated soft-drink consumption was 42·1 %. Of the eighteen countries included in the study, significant decreasing, increasing and stable trends of carbonated soft-drink consumption were observed in seven, two and nine countries, respectively. The most drastic decrease was observed in Kuwait between 2011 (74·4 %) and 2015 (51·7 %). Even in countries with significant decreasing trends, the decrease was rather modest, while some countries with stable trends had very high prevalence across time (e.g. Suriname 80·5 % in 2009 and 79·4 % in 2016). The prevalence of carbonated soft-drink consumption was high in all countries included in the present analysis, despite decreasing trends being observed in some. Public health initiatives to reduce the consumption of carbonated soft-drink consumption among adolescents are urgently required.

Dynapenic Abdominal Obesity Increases Risk for Falls Among Adults Aged ≥50 Years: A Prospective Analysis of the Irish Longitudinal Study on Ageing.

BACKGROUND: There is a scarcity of studies examining the longitudinal relationship between dynapenic abdominal obesity (DAO; ie, impairment in muscle strength and high waist circumference) and future fall risk. Therefore, we aimed to investigate the prospective association between DAO at baseline and falls occurring during 2 years of follow-up in a nationally representative sample of middle-aged and older individuals from Ireland. METHODS: Data from 2 consecutive waves of the Irish Longitudinal Study on Ageing survey were analyzed. Dynapenia was defined as handgrip strength of <26 kg for men and <16 kg for women. Abdominal obesity was defined as a waist circumference of >88 cm for women and >102 cm for men. DAO was assessed at Wave 1 (2009-2011) and was defined as having both dynapenia and abdominal obesity. Falls occurring between Wave 1 and Wave 2 (2012-2013) were self-reported. Multivariable logistic regression analysis was conducted. RESULTS: Data on 5 275 individuals aged ≥50 years were analyzed (mean [standard deviation {SD}] age 63.2 [8.9] years; 48.8% males). After adjustment for potential confounders, compared to no dynapenia and no abdominal obesity at baseline, DAO was significantly associated with 1.47 (95% confidence interval [CI]: 1.14-1.89) times higher odds for falls at 2-year follow-up. Dynapenia alone (odds ratio [OR] = 1.08; 95% CI: 0.84-1.40) and abdominal obesity alone (OR = 1.09; 95% CI: 0.91-1.29) were not significantly associated with falls at follow-up. CONCLUSIONS: DAO increased the risk for falls among middle-aged and older adults in Ireland. Interventions to prevent or reverse DAO may be beneficial for fall reduction.

Prioritizing a research agenda on built environments and physical activity: a twin panel Delphi consensus process with researchers and knowledge users.

BACKGROUND: The growth of urban dwelling populations globally has led to rapid increases of research and policy initiatives addressing associations between the built environment and physical activity (PA). Given this rapid proliferation, it is important to identify priority areas and research questions for moving the field forward. The objective of this study was to identify and compare research priorities on the built environment and PA among researchers and knowledge users (e.g., policy makers, practitioners). METHODS: Between September 2022 and April 2023, a three-round, modified Delphi survey was conducted among two independent panels of international researchers (n = 38) and knowledge users (n = 23) to identify similarities and differences in perceived research priorities on the built environment and PA and generate twin 'top 10' lists of the most important research needs. RESULTS: From a broad range of self-identified issues, both panels ranked in common the most pressing research priorities including stronger study designs such as natural experiments, research that examines inequalities and inequities, establishing the cost effectiveness of interventions, safety and injuries related to engagement in active transportation (AT), and considerations for climate change and climate adaptation. Additional priorities identified by researchers included: implementation science, research that incorporates Indigenous perspectives, land-use policies, built environments that support active aging, and participatory research. Additional priorities identified by knowledge users included: built environments and PA among people living with disabilities and a need for national data on trip chaining, multi-modal travel, and non-work or school-related AT. CONCLUSIONS: Five common research priorities between the two groups emerged, including (1) to better understand causality, (2) interactions with the natural environment, (3) economic evaluations, (4) social disparities, and (5) preventable AT-related injuries. The findings may help set directions for future research, interdisciplinary and intersectoral collaborations, and funding opportunities.

Erratum: A tetracationic porphyrin with dual anti-prion activity.

[This corrects the article DOI: 10.1016/j.isci.2023.107480.].

Relationship of the SITLESS intervention on medication use in community-dwelling older adults: an exploratory study.

Background: Sedentary behavior (SB) and physical activity (PA) interventions in older adults can improve health outcomes. Problems related with aging include prevalent comorbidity, multiple non-communicable diseases, complaints, and resulting polypharmacy. This manuscript examines the relationship between an intervention aiming at reducing SB on medication patterns. Method: This manuscript presents a local sub-analysis of the SITLESS trial data on medication use. SITLESS was an exercise referral scheme (ERS) enhanced by self-management strategies (SMS) to reduce SB in community-dwelling older adults. We analyzed data from the ERS + SMS, ERS and usual care (UC) groups. Patient medication records were available at baseline and at the end of the intervention (4-month period) and were analyzed to explore the effect of SITLESS on medication patterns of use. Result: A sample of 75 participants was analyzed, mostly older overweight women with poor body composition scores and mobility limitations. There was a significant reduction of 1.6 medicines (SD = 2.7) in the ERS group (p < 0.01), but not in the UC or ERS + SMS groups. Differences were more evident in medicines used for short periods of time. Conclusion: The findings suggest that an exercise-based program enhanced by SMS to reduce SB might influence medication use for acute conditions but there is a need to further investigate effects on long-term medicine use in older adults.

Architecture of the MKK6-p38α complex defines the basis of MAPK specificity and activation.

The mitogen-activated protein kinase (MAPK) p38α is a central component of signaling in inflammation and the immune response and is, therefore, an important drug target. Little is known about the molecular mechanism of its activation by double phosphorylation from MAPK kinases (MAP2Ks), because of the challenge of trapping a transient and dynamic heterokinase complex. We applied a multidisciplinary approach to generate a structural model of p38α in complex with its MAP2K, MKK6, and to understand the activation mechanism. Integrating cryo-electron microscopy with molecular dynamics simulations, hydrogen-deuterium exchange mass spectrometry, and experiments in cells, we demonstrate a dynamic, multistep phosphorylation mechanism, identify catalytically relevant interactions, and show that MAP2K-disordered amino termini determine pathway specificity. Our work captures a fundamental step of cell signaling: a kinase phosphorylating its downstream target kinase.

Association between food insecurity and depressive symptoms among adolescents aged 12-15 years from 22 low- and middle-income countries.

Food insecurity may be a risk factor for depression in adolescents. However, data on this topic from low- and middle-income countries (LMICs) are scarce, despite food insecurity being most common in LMICs. Therefore, we aimed to examine the association between food-insecurity and depressive symptoms among school-going adolescents from 22 LMICs. Cross-sectional data from the Global school-based Student Health Survey were analyzed. Self-report measures assessed past 12-month depressive symptoms and past 30-day food insecurity (hunger). Multivariable logistic regression and meta-analysis were conducted to assess associations. Data on 48,401 adolescents aged 12-15 years were analyzed [mean (SD) age 13.8 (0.9) years; 51.4 % females]. The prevalence of depressive symptoms was 29.3 %, and those of moderate and severe food insecurity were 45.0 and 6.3 %, respectively. After adjustment for potential confounders, compared to no food insecurity, the pooled OR (95 %CI) of moderate and severe food insecurity were 1.36 (1.30-1.42) and 1.81 (1.67-1.97), respectively. The level of between-country heterogeneity was low. Food insecurity was associated with significantly higher odds for depressive symptoms among adolescents in LMICs. Policies to address food insecurity may also help prevent depression in this population, pending future longitudinal research.

Neighbourhood Walkability and Its Influence on Physical Activity and Cardiometabolic Disease: A Cross-Sectional Study in a Caribbean Small Island Developing State.

Introduction Cities and neighborhoods may provide opportunities for population-level environmental interventions to reduce physical inactivity and cardiometabolic risk. In this study, we describe the association between neighborhood walkability, physical activity (PA), and cardiometabolic outcomes, by linking data from a nationally representative survey of adults (25 years and older) collected in 2012-2013 with spatial data on built environment features in Barbados. Methods We estimated a walkability index for 45 neighborhoods using objectively measured built environment features (residential density, street connectivity, and land use mix). We used the Recent Physical Activity Questionnaire to capture time spent in outdoor walking, active commuting, moderate-to-vigorous PA (MVPA), and total PA. Our primary cardiometabolic outcome was a predicted 10-year cardiovascular risk (CVD) score, estimated using the American College of Cardiology/American Heart Association pooled cohort equation. Our secondary cardiometabolic outcomes were hypertension and diabetes. We explored the effect of neighborhood walkability on PA and cardiometabolic outcomes using several multivariable regression models (tobit and linear and logistic multi-level mixed effects), with the model choice depending on the structure of the outcome.  Results The average time spent walking weekly for any purpose among participants was 75 minutes/week, time spent on active commuting was 15 minutes/week, and MVPA was 221 minutes/week. We estimated that the average 10-year CVD risk in the study population was 11.7% (95%CI 10.9-12.5). Our confounder-adjusted analyses showed positive linear relationships between neighborhood walkability and each PA outcome (p<0.05 in all cases), and a negative relationship between walkability and predicted 10-year CVD risk (p<0.001). Conclusion In our setting, adults residing in higher walkability neighborhoods spent more time engaged in PA, had a lower predicted 10-year CVD risk, and were less likely to have diabetes. Urban planners may consider shorter-term interventions, such as those on a microscale, which may provide additional ways to increase activity in a mostly fixed macroscale environment.

A tetracationic porphyrin with dual anti-prion activity.

Prions are deadly infectious agents made of PrPSc, a misfolded variant of the cellular prion protein (PrPC) which self-propagates by inducing misfolding of native PrPC. PrPSc can adopt different pathogenic conformations (prion strains), which can be resistant to potential drugs, or acquire drug resistance, hampering the development of effective therapies. We identified Zn(II)-BnPyP, a tetracationic porphyrin that binds to distinct domains of native PrPC, eliciting a dual anti-prion effect. Zn(II)-BnPyP binding to a C-terminal pocket destabilizes the native PrPC fold, hindering conversion to PrPSc; Zn(II)-BnPyP binding to the flexible N-terminal tail disrupts N- to C-terminal interactions, triggering PrPC endocytosis and lysosomal degradation, thus reducing the substrate for PrPSc generation. Zn(II)-BnPyP inhibits propagation of different prion strains in vitro, in neuronal cells and organotypic brain cultures. These results identify a PrPC-targeting compound with an unprecedented dual mechanism of action which might be exploited to achieve anti-prion effects without engendering drug resistance.

Unclean Cooking Fuel Use and Health Outcomes in Older Adults: Potential Mechanisms, Public Health Implications, and Future Directions.

BACKGROUND: Unclean cooking fuels (ie, polluting fuels including kerosene/paraffin, and solid fuels) are a major contributor to diseases and mortality, specifically in low- and middle-income countries. METHODS: This review aimed to identify potential mechanisms, public health implications, and future directions of unclean cooking fuel use and health outcomes in older adults. RESULTS: There is an expanding body of literature to demonstrate associations between unclean cooking fuel use and multiple mental and physical health outcomes in older adults. Two key mechanisms likely driving such associations include inflammation and oxidative stress. CONCLUSIONS: Considering that inflammation and oxidative stress have been implicated in multiple other health conditions (eg, arthritis and osteoporosis) in addition to those investigated to date on this topic it would be prudent to continue investigation of unclean cooking fuel use and with yet to be studied health outcomes. Moreover, future research is indeed now required to identify pathways to eliminating unclean cooking fuel globally to better the health of an aging global population and to support the implementation of Sustainable Development Goal 7.