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In this study, a comprehensive screening and identification process to pinpoint lactic acid bacteria (LAB) strains capable of enhancing gel firmness and elevating the flavor profile in pea protein-based protein gels was conducted, aiming to demonstrate how tailored starter cultures for specific applications can provide high-quality sensory attributes in fermented plant-based cheese. Thirteen single strains were selected from a poll of 90 different LAB based on their acidification performance, contribution to gel firmness, removal of off-flavors and production of dairy-associated volatile organic compounds. They were combined in 64 different blends of five strains each and screened again for the same parameters. Fast acidifying strains were prioritized for food preservation reasons to inhibit undesirable spoilage. Fermentation of pea protein emulsions with Streptococcus thermophilus, Lactobacillus, and Lactococcus blends resulted in a significant reduction in volatile organic compounds associated with beany and green off-flavor, a production of dairy-associated compounds, and satisfactorily contributed to gel firmness.

Ultrasound haptics allows us to experience the sense of touch without contact with any physical surface. This novel "touchless" feedback can be used for various use cases but is not widely adopted nor incorporated in everyday products. The 2022 TOUCHLESS Hackathon aimed to enable novel practitioners to learn about touchless technology, generate new ideas, and implement prototypes. We invited participants to a 3-day hackathon in Copenhagen, Denmark, where we introduced touchless technology and provided novel touchless devices for prototyping use cases. Participants were joined by experts on ultrasound haptics, who helped them achieve their prototyping goals. Coming from various educational and national backgrounds, the participants approached the task in different ways and created four unique interactive prototypes. This event report introduces the TOUCHLESS Hackathon and reflects on the lessons learned.

Mediated social touch enables us to share hugs, handshakes, and caresses at a distance. Past work has focused on the experience of being touched by a remote person, but the touch initiator’s experience is underexplored. We ask whether a variation in haptic feedback can influence the touch initiator’s social experience of the interaction. In a user study participants stroked a remote person’s hand in virtual reality while feeling no haptic feedback, ultrasonic stimulation, or passive feedback from a silicone hand. In each condition, they rated the pleasantness of the interaction, the friendliness of the remote person, and their sense of co-presence. We also captured the velocity of their stroking and asked for reflections on the interaction and mediated social touch as a whole. The results show significant effects of haptic feedback on co-presence, pleasantness, and stroking velocity. The qualitative responses suggest that these results are due to the familiarity of the solid silicone hand, and the participants’ assumption that when they felt feedback, the remote person felt similar feedback.

The Gullele Botanic Garden (GBG), on the slope of the Entoto hills, adjoins the north-western limit of the city of Addis Ababa, the capital of Ethiopia. The forested area of GBG is home to a mixture of semi-natural forest and Eucalyptus plantations with Eucalyptus having been removed in the recent past. The floristic composition, species diversity and vegetative structure of the woody plant species in the forested area are here presented from 81 plots (20 × 20 m). A total of 104 woody plant species (90% native, the rest planted or naturalised) of 83 genera and 47 families are recorded; a species richness higher than what researchers have found in nearby natural forests, though the definitions of woody species have varied between studies. The number of individuals of the dominant species, Juniperus procera, decreases with increasing DBH and height class, which indicates a healthy regeneration inside the GBG; the appearance of seedlings and young plants of Juniperus after the removal of Eucalyptus is comparable to the regeneration of Juniperus forests described from East Africa after forest fires or clear-felling. Clustering analyses on the floristic data result in four partly overlapping clusters, but the distribution of the plots on clusters changes notably if data on Eucalyptus is in- or excluded. Many woody species in nearby natural or semi-natural forests, where Juniperus procera is dominant, occur also in GBG but plant communities defined for those forests are not identified in the plot data from GBG. The findings in this paper can serve as a baseline dataset to follow the regeneration of the conservation area towards natural forest, useful for future anagement and sustainable utilization of Ethiopian forest species at local and national levels.

We produced homogeneous lines of 227 pea accessions from the Nordic Genetic Resource Center via single seed descent. The genetic diversity among these, mostly Scandinavian accessions, was investigated using three microsatellite markers, A9, AC58 and AA5. The microsatellites were highly informative and separated 153 of 194 accessions on a Neighbor Joining topology. The high polymorphism information content (PIC) values between 0.87 and 0.91 indicated that the gene bank material contains a large number of pea accessions with different breeding histories. The peas were grown in the field for two years and seed protein content showed variation between 9.3% and 34.1% over the years and accessions, respectively. The mean thousand seed weight was 152.05 g. More than 10 accessions had a protein content above 28%, showing that the collection has potential as breeding nursery for high-protein pea cultivars.

The need to better care for the urban landscape as a cultural, material and regenerative resource is urgent and inevitable. From a planning and design perspective, national heritage characterisation tools currently constitute an explicit point of departure for attributing value to existing urban landscapes, which informs decisions about physical transformations. This qualitative and integrative review focuses on international recommendations and on the ability of national characterisation tools to address ‘relational character’, meaning the interconnectedness of architecture with its situated environment, people and place, atmosphere and the sensory. Although international heritage institutions pledge to include relational character, in our search of state-of-the-art and exploratory approaches to relational character both nationally and regionally, we find that few such tools incorporate relational character, and those that do provide different emphases. We conclude that heritage characterisation tools are not yet sufficiently developed to address existing urban landscapes from a relational perspective.

Computational thinking has become part of the mathematics curriculum in several countries. This has led recently available teaching resources to explicitly integrate computational thinking (CT). In this paper, we investigate and compare how curriculum resources developed in Denmark — digital teaching modules — and Sweden — printed mathematics textbooks — have incorporated CT in mathematics for grades 1–6 (age 7–12). Specifically, we identify and compare the CT and mathematical concepts, actions, and combinations in tasks within these resources. Our analysis reveals that Danish tasks are oriented toward CT concepts related to data, actions related to programming, and mathematical concepts within statistics. This is different from Swedish tasks, which are oriented toward CT concepts related to instructions and commands, actions related to following stepwise procedures, and mathematical concepts related to patterns. Moreover, what is most dominant in one country is almost or completely absent in the other. We conclude the paper by contrasting these two approaches with existing knowledge on computational thinking in school mathematics.

Consumption of traditional foods is decreasing amid a lifestyle transition in Greenland as incidence of type-2 diabetes (T2D) increases. In homozygous carriers of a TBC1D4 variant, conferring postprandial insulin resistance, the risk of developing T2D is markedly higher. We investigated the effects of traditional marine diets on glucose homeostasis and cardio-metabolic health in Greenlandic Inuit carriers and non-carriers of the variant. We conducted a randomized, crossover study consisting of two 4-week dietary interventions; Traditional (marine-based, low-carbohydrate) and Western (high in imported meats and carbohydrates). Oral glucose tolerance (OGTT, 2-h), 14-day continuous glucose and cardio-metabolic markers were assessed to investigate the effect of diet and genotype. Compared to the westernized diet, the Traditional diet reduced mean and maximum daily blood glucose by 0.17 mmol/L [95% CI;0.05, 0.29; P=0.006] and 0.26 mmol/L [95% CI;0.06, 0.46; P=0.010], respectively, with dose-dependency. Furthermore, it gave rise to a weight loss of 0.5 kg [95% CI; 0.09, 0.90; P=0.016] relative to the Western diet and 4% [95% CI;1, 9; P=0.018] lower LDL:HDL-cholesterol, which after adjustment for weight-loss appeared to be driven by HDL elevation (0.09 mmol/L [0.03, 0.15], P=0.006). A diet-gene interaction was indicated on insulin sensitivity in the OGTT (p=0.093), which seemed to reflect a non-significant increase of 1.4 [-0.6, 3.5] mmol/L in carrier 2-h glucose. A Traditional diet marginally improved daily glycaemic control and plasma lipid profile compared to a Western diet in Greenlandic Inuit. Possible adverse effects on glucose tolerance in carriers of the TBC1D4 variant warrants further studies of diet-gene interactions.

Objective: Patients with an ileostomy may experience postoperative electrolyte derangement and dehydration but are presumed to stabilise thereafter. We aimed to investigate the prevalence of sodium depletion in stable outpatients with an ileostomy and applied established methods to estimate their fluid status. Methods: We invited 178 patients with an ileostomy through a region-wide Quality-of-Life-survey to undergo outpatient evaluation of their sodium and fluid status. The patients delivered urine and blood samples, had bioelectrical impedance analysis performed and answered a questionnaire regarding dietary habits. Results: Out of 178 invitees, 49 patients with an ileostomy were included; 22 patients (45%, 95% CI, 31–59%) had unmeasurably low urinary sodium excretion (<20 mmol/L), indicative of chronic sodium depletion, and 26% (95% CI, 16–41%) had plasma aldosterone levels above the reference value. Patients with unmeasurably low urinary sodium excretion had low estimated glomerular filtration rates (median 76, IQR 63–89, mL/min/1.73m2) and low venous blood plasma CO2 (median 24, IQR 21–26, mmol/L), indicative of chronic renal impairment and metabolic acidosis. Bioelectrical impedance analysis, plasma osmolality, creatinine and sodium values were not informative in determining sodium status in this population. Conclusion: A high proportion of patients with an ileostomy may be chronically sodium depleted, indicated by absent urinary sodium excretion, secondary hyperaldosteronism and chronic renal impairment, despite normal standard biochemical tests. Sodium depletion may adversely affect longstanding renal function. Future studies should investigate methods to estimate and monitor fluid status and aim to develop treatments to improve sodium depletion and dehydration in patients with an ileostomy.

The production of reactive oxygen species (ROS) by NADPH oxidase (NOX) 2 has been linked to both insulin resistance and exercise training adaptations in skeletal muscle. This study explores the previously unexamined role of NOX2 in the interplay between diet-induced insulin resistance and exercise training (ET). Using a mouse model that harbors a point mutation in the essential NOX2 regulatory subunit, p47phox (Ncf1*), we investigated the impact of this mutation on various metabolic adaptations. Wild-type (WT) and Ncf1* mice were assigned to three groups: chow diet, 60% energy fat diet (HFD), and HFD with access to running wheels (HFD + E). After a 16-week intervention, a comprehensive phenotypic assessment was performed, including body composition, glucose tolerance, energy intake, muscle insulin signaling, redox-related proteins, and mitochondrial adaptations. The results revealed that NOX2 deficiency exacerbated the impact of HFD on body weight, body composition, and glucose intolerance. Moreover, in Ncf1* mice, ET did not improve glucose tolerance or increase muscle cross-sectional area. ET normalized body fat independently of genotype. The lack of NOX2 activity during ET reduced several metabolic adaptations in skeletal muscle, including insulin signaling and expression of Hexokinase II and oxidative phosphorylation complexes. In conclusion, these findings suggest that NOX2 mediates key beneficial effects of exercise training in the context of diet-induced obesity.

Designing cognitive experiments that allow for meaningful comparisons between different types of displays presents significant challenges. In the current study, we successfully implemented a number of solutions to conduct a virtual reality (VR) selective attention experiment with a personal computer (PC) control condition. We focused on three aspects: input hardware, multisensory experience and the perceived output, which have posed difficulties in previous research. Input hardware pertains to how users interact with the displays, multisensory experience involves the integration of senses within the experiment, and perceived output concerns the software configurations ensuring visually equivalent scenarios. A multisensory selective attention paradigm for six-seven-year-old children was developed for VR and PC environments. We found no evidence of differences in experienced task difficulty and participant distraction measured as off-task behaviours between the conditions. However, the overall reaction time was faster for the PC control condition than the VR but this reaction time difference is unlikely to impact cognitive effects of interest. There was no evidence to suggest different multisensory attentional processing between the two conditions. We demonstrate a robust approach for effectively minimising and controlling confounding technological variables inherent in the disparities between VR and PC conditions. Practical guidance for future development of PC control conditions for VR studies are provided.

When insects are introduced as a novel protein source in human diets, we need to understand the protein quality to compare their nutritional value with other foods. Protein quality assessment methods are based on evaluation of the ability of the protein to meet the amino acid (AA) requirements of the human body. Most available data comes from animal models, either in rats or pigs. The limited available data supports edible insects as a highquality protein source for human consumption. The farmed insect species considered relevant as an alternative protein source are generally of good quality, and the protein quality of the vast diversity of insect species harvested from the wild across continents are likely to be sources of good quality, though this remains to be assessed. For methodological considerations, the recommended DIAAS (digestible indispensable AA score) method relies on accurately determining the total protein content. When determining total protein based on total nitrogen (N), using the standard conversion factor of 6.25 which disregards the non-protein N in insects, the protein quality is underestimated in comparison with other animal-source foods, such as meat and dairy.

Micronutrient deficiencies and stunting are prevalent. We assessed correlates of iron, cobalamin, folate, and vitamin A biomarkers in a cross-sectional study of stunted children aged 12–59 months in eastern Uganda. The biomarkers measured were serum ferritin (S-FE), soluble transferrin receptor (S-TfR), retinol binding protein (S-RBP), plasma cobalamin (P-Cob), methylmalonic acid (P-MMA), and folate (P-Fol). Using linear regression, we assessed socio-demography, stunting severity, malaria rapid test, and inflammation as correlates of micronutrient biomarkers. Of the 750 children, the mean (SD) age was 32.0 (11.7) months, and 45% were girls. Iron stores were depleted (inflammation-corrected S-FE < 12 µg/L) in 43%, and 62% had tissue iron deficiency (S-TfR > 8.3 mg/L). P-Cob was low (<148 pmol/L) and marginal (148–221 pmol/L) in 3% and 20%, and 16% had high P-MMA (>0.75 µmol/L). Inflammation-corrected S-RBP was low (<0.7 µmol/L) in 21% and P-Fol (<14 nmol/L) in 1%. Age 24–59 months was associated with higher S-FE and P-Fol and lower S-TfR. Breastfeeding beyond infancy was associated with lower iron status and cobalamin status, and malaria was associated with lower cobalamin status and tissue iron deficiency (higher S-TfR) despite iron sequestration in stores (higher S-FE). In conclusion, stunted children have iron, cobalamin, and vitamin A deficiencies. Interventions addressing stunting should target co-existing micronutrient deficiencies.

Disturbances in terrestrial vegetation across the end-Triassic mass-extinction (ETME) and earliest Jurassic (∼201.5–201.3 Ma) have previously been linked to carbon cycle perturbations induced by the Central Atlantic Magmatic Province. Large-scale volcanic degassing has been proposed to have affected the terrestrial realm through various mechanisms. However, the effects of long-term “super greenhouse” climate variability on vegetation dynamics following the mass-extinction remain poorly understood. Based on a 10-million-year long multi-proxy record of northern Germany (Schandelah-1, Germany, paleolatitude of ∼41°N) spanning the late Rhaetian to the Sinemurian (∼201.5–190.8 Ma), we aim to assess mechanistic links between carbon cycle perturbations, climate change, and vegetation dynamics. Based on a high-resolution palynofloral record a two-phased extinction emerges, confirming extinction patterns seen in other studies. The first phase is associated with a decline in arborescent conifers, coinciding with a negative carbon isotope excursion and an influx of aquatic palynomorphs. Following this decline, we find a stepwise rise of ferns at the cost of trees during the latest Rhaetian, culminating with the extinction of tree taxa at the Triassic-Jurassic boundary. The rise in ferns is accompanied by an increase in reworked organic matter and charcoal, suggestive of erosion and wildfires. Furthermore, the Hettangian (201.3–199.3 Ma) vegetation in NW Europe shows evidence of long-term disturbance reflected by the periodic resurgence of fern taxa, similarly accompanied by increases in reworking and charcoal. This periodicity is linked to the 405-kyr eccentricity cycle indicating a biome that responded to astronomically induced variability in hydrology. A transition into an apparently more stable biome starts during the early Sinemurian, where palynofloral assemblages become dominated by bisaccate pollen taxa, mainly derived from conifers. The ETME was clear

Several proteins are implicated in transmembrane fatty acid transport. The purpose of this study was to quantify the variation in fatty acid oxidation rates during exercise explained by skeletal muscle proteins involved in fatty acid transport. Seventeen endurance-trained males underwent a (i) fasted, incremental cycling test to estimate peak whole-body fatty acid oxidation rate (PFO), (ii) resting vastus lateralis microbiopsy, and (iii) 2 h of fed-state, moderate-intensity cycling to estimate whole-body fatty acid oxidation during fed-state exercise (FO). Bivariate correlations and stepwise linear regression models of PFO and FO during 0-30 min (early FO) and 90-120 min (late FO) of continuous cycling were constructed using muscle data. To assess the causal role of transmembrane fatty acid transport in fatty acid oxidation rates during exercise, we measured fatty acid oxidation during in vivo exercise and ex vivo contractions in wild-type and CD36 knock-out mice. We observed a novel, positive association between vastus lateralis FATP1 and PFO and replicated work reporting a positive association between FABPpm and PFO. The stepwise linear regression model of PFO retained CD36, FATP1, FATP4, and FABPpm, explaining ~87% of the variation. Models of early and late FO explained ~61 and ~65% of the variation, respectively. FATP1 and FATP4 emerged as contributors to models of PFO and FO. Mice lacking CD36 had impaired whole-body and muscle fatty acid oxidation during exercise and muscle contractions, respectively. These data suggest that substantial variation in fatty acid oxidation rates during exercise can be explained by skeletal muscle proteins involved in fatty acid transport.

Objective: Medium chain fatty acids (MCFAs), which are fatty acids with chain lengths of 8 to 12 carbon atoms, have been shown to reduce food intake in rodents and humans, but the underlying mechanisms are unknown. Unlike most other fatty acids, MCFAs are absorbed from the intestine into the portal vein and enter first the liver. We thus hypothesized that MCFAs trigger the release of hepatic factors that reduce appetite.Methods: The liver transcriptome in mice that were orally administered MCFAs as C8:0 triacylglycerol (TG) was analyzed. Circulating growth/differentiation factor 15 (GDF15), tissue Gdf15 mRNA and food intake were investigated after acute oral gavage of MCFAs as C8:0 or C10:0 TG in mice. Effects of acute and subchronic administration of MCFAs as C8:0 TG on food intake and body weight were determined in mice lacking either the receptor for GDF15, GDNF Family Receptor Alpha Like (GFRAL), or GDF15.Results: Hepatic and small intestinal expression of Gdf15 and circulating GDF15 increased after MCFAs ingestion, while intake of typical dietary long-chain fatty acids (LCFAs) had no effect. Plasma GDF15 levels also increased in the portal vein with MCFA intake, indicating that in addition to the liver, the small intestine contributes to the rise in circulating GDF15. Acute oral provision of MCFAs decreased food intake over 24 hours compared with a LCFA-containing bolus, and this anorectic effect required the GDF15 receptor, GFRAL. Moreover, subchronic oral administration of MCFAs reduced body weight over 7 days, an effect that was blunted in mice lacking either GDF15 or GFRAL.Conclusions: We have identified ingestion of MCFAs as a novel nutritional approach that increases circulating GDF15 in mice and have revealed that the GDF15-GFRAL axis is required for the full anorectic effect of MCFAs.

Objective: This study (1) investigated the effect of weight loss on whole-body and tissue-specific insulin sensitivity and on intrahepatic lipid (IHL) content and composition and (2) investigated the association between weight-loss-induced changes in insulin sensitivity and IHL content in individuals with overweight or obesity. Methods: In this secondary analysis of the European SWEET project, 50 adults (age 18–65 years) with overweight or obesity (BMI ≥ 25 kg/m2) followed a low-energy diet (LED) for 2 months. At baseline and after the LED, body composition (dual-energy x-ray absorptiometry), IHL content and composition (proton magnetic resonance spectroscopy), whole-body insulin sensitivity (Matsuda index), muscle insulin sensitivity index (MISI), and hepatic insulin resistance index (HIRI) were determined (7-point oral glucose tolerance test). Results: The LED reduced body weight (p < 0.001). This was accompanied by increased Matsuda index and reduced HIRI (both p < 0.001) but no change in MISI (p = 0.260). Weight loss decreased IHL content (mean [SEM], 3.9% [0.7%] vs. 1.6% [0.5%], p < 0.001) and the hepatic saturated fatty acid fraction (41.0% [1.5%] vs. 36.6% [1.9%], p = 0.039). The reduced IHL content was associated with an improvement in HIRI (r = 0.402, p = 0.025). Conclusions: Weight loss decreased IHL content and the hepatic saturated fatty acid fraction. The decrease in IHL content was associated with weight-loss-induced improvement in hepatic insulin sensitivity in individuals with overweight or obesity.

Scope: The New Nordic Diet (NND) has been shown to promote weight loss and lower blood pressure amongst obese people. This study investigates blood plasma metabolite and lipoprotein biomarkers differentiating subjects who followed Average Danish Diet (ADD) or NND. The study also evaluates how the individual response to the diet is reflected in the metabolic differences between NND subjects who lost or maintained their pre-intervention weight.Methods: Centrally obese Danes (BMI >25) followed NND (90 subjects) or ADD (56 subjects) for 6 months. Fasting blood plasma samples, collected at three time-points during the intervention, were screened for metabolites and lipoproteins (LPs) using proton nuclear magnetic resonance spectroscopy. In total, 154 metabolites and 65 lipoproteins were analysed.Results: The NND showed a relatively small but significant effect on the plasma metabolome and lipoprotein profiles, with explained variations ranging from 0.6% for lipoproteins to 4.8% for metabolites. A total of 38 metabolites and 11 lipoproteins were found to be affected by the NND. The primary biomarkers differentiating the two diets were found to be HDL-1 cholesterol, apolipoprotein A1, phospholipids, and ketone bodies (3-hydroxybutyric acid, acetone, and acetoacetic acid). The increased levels of ketone bodies detected in the NND group inversely associated with the decrease in diastolic blood pressure of the NND subjects. The study also showed that body weight loss among the NND subjects was weakly associated with plasma levels of citrate.Conclusion: The main plasma metabolites associated with NND were acetate, methanol and 3-hydroxybutyrate. The metabolic changes associated with the NND-driven weight loss are mostly pronounced in energy and lipid metabolism.

In this study, we investigated the effects of motor practice with an emphasis on either position or force control on motor performance, motor accuracy and variability in preadolescent children. Furthermore, we investigated corticomuscular coherence and potential changes following motor practice. We designed a setup allowing discrete wrist flexions of the non-dominant hand and tested motor accuracy and variability when the task was to generate specific movement endpoints (15-75 deg) or force levels (5-25% MVC). All participants were tested in both tasks at baseline and post motor practice without augmented feedback on performance. Following baseline assessment, participants (44 children aged 9-11 years) were randomly assigned to either position (PC) or force control (FC) motor practice or a resting control group (CON). The PC and FC groups performed four blocks of 40 trials motor practice with augmented feedback on performance. Following practice, improvements in movement accuracy were significantly greater in the PC group compared to the FC and CON groups (p < 0.001). None of the groups displayed changes in force task performance indicating no benefits of force control motor practice and low transfer between tasks (p-values:0.08-0.45). Corticomuscular coherence (C4-FCR) was demonstrated during the hold phase in both tasks with no difference between tasks. Corticomuscular coherence did not change from baseline to post practice in any group. Our findings demonstrate that preadolescent children improve position control following dynamic accuracy motor practice. Contrary to previous findings in adults, preadolescent children displayed smaller or no improvements in force control following isometric motor practice, low transfer between tasks and no changes in corticomuscular coherence.

Background: Although birth weight (BW) has been associated with later cardiovascular disease and type 2 diabetes, the role of birth fat mass (BFM) and birth fat-free mass (BFFM) on cardiometabolic health is unclear.Objective: To examine associations of BW, BFM, and BFFM with later anthropometry, body composition, abdominal fat, and cardiometabolic markers.Methods: Birth cohort data on standardized exposure variables (BW, BFM, and BFFM) and follow-up information at age 10 y on anthropometry, body composition, abdominal fat, and cardiometabolic markers were included. A linear regression analysis was used to assess associations of exposures with outcome variables, adjusting for maternal and child characteristics at birth and current body size in separate models.Results: Among 353 children, mean (SD) age was 9.8 (1.0) years, and 51.5% were boys. In the fully adjusted model, 1-SD higher BW and BFFM were associated with 0.81 (95%CI: 0.21, 1.41) and 1.25 (95%CI: 0.64, 1.85) cm greater height at 10 y, respectively. The 1-SD higher BW and BFM were associated with 0.32 kg/m2 (95%CI: 0.14, 0.51 kg/m2) and 0.42 kg/m2 (95%CI: 0.25, 0.59 kg/m2) greater fat mass index at 10 y, respectively. In addition, 1-SD higher BW and BFFM were associated with 0.22 kg/m2 (95% CI: 0.09, 0.34 kg/m2) greater FFM index, whereas a 1-SD greater BFM was associated with a 0.05 cm greater subcutaneous adipose tissue (95% CI: 0.01, 0.11 cm). Furthermore, 1-SD higher BW and BFFM were associated with 10.3% (95% CI: 1.4%, 20.0%) and 8.3% (95% CI: -0.5%, 17.9%) greater insulin, respectively. Similarly, 1-SD higher BW and BFFM were associated with 10.0% (95% CI: 0.9%, 20.0%) and 8.5% (95% CI: -0.6%, 18.5%) greater homeostasis model assessment of insulin resistance, respectively.Conclusions: BW and BFFM rather than BFM are predictors of height and FFM index at 10 y. Children with

Background: Due to the complexity of human diets, it is difficult to relate single foods to health outcomes. We aimed to identify the dietary patterns and associated factors and to assess the association of dietary patterns with prediabetes/diabetes among adults living with and without HIV in Tanzania.Methods: Diet data were collected by a food frequency questionnaire (FFQ) and dietary patterns were derived by principal component analysis (PCA) and reduced rank regression (RRR). The associations between dietary patterns and associated factors as well as with prediabetes/diabetes were assessed using multinomial logistic regression and presented by marginal plots.Results: Of 572 recruited, 63% were people living with HIV. The mean (±SD) age was 42.6 (±11.7) years and 60% were females. The PCA identified two major dietary patterns, i.e., vegetable-rich pattern (VRP) and vegetable-poor pattern (VPP) whereas RRR identified one dietary pattern, i.e., carbohydrate-dense pattern (CDP). In comparison to females, males had higher adherence to VPP and CDP, but less to VRP. Higher socioeconomic status was associated with higher adherence to VRP and VPP but low adherence to CDP. Compared to HIV-negative participants, people living with HIV had higher adherence to VRP but less adherence to CDP. Compared to younger people, older people had lower adherence to VPP. High adherence to CDP or VRP was positively associated with prediabetes. Higher adherence to VRP was associated with a borderline decrease in diabetes. No association was observed between VPP with either prediabetes or diabetes.Conclusion: Our findings suggest that dietary patterns may impact the risk of prediabetes and diabetes differently. Awareness of the health benefits of VRP should be encouraged in the community, especially for men who seem to consume fewer vegetables. Longitudinal studies are needed to explore the contribution of dietary patterns to prediabetes/di

The use of non- and low-caloric sweetener(s) (NCS and LCS) as a means to prevent overweight and obesity is highly debated, as both NCS and LCS have been proposed to have a negative impact on energy homeostasis. This systematic review aimed to assess the impact of NCS and LCS on fasting and postprandial substrate oxidation, energy expenditure, and catecholamines, compared to caloric sweeteners or water, across different doses and types of NCS and LCS, acutely and in the longer-term. A total of 20 studies were eligible: 16 studies for substrate oxidation and energy expenditure and four studies for catecholamines. Most studies compared the acute effects of NCS or LCS with caloric sweeteners under non-isoenergetic conditions. These studies generally found higher fat oxidation and lower carbohydrate oxidation with NCS or LCS than with caloric sweeteners. Findings for energy expenditure were inconsistent. With the limited number of studies, no convincing pattern for the remaining outcomes and comparisons could be seen. In conclusion, drinks or meals with NCS or LCS resulted in higher fat and lower carbohydrate oxidation compared to caloric sweeteners. No other conclusions could be drawn due to insufficient or inconsistent results. Further studies in this research field are warranted.

Bsckground: Diets rich in whole grains are associated with health benefits. Yet, it remains unclear whether the benefits are mediated by changes in gut function and fermentation.Objective: We explored the effects of whole-grain vs. refined-grain diets on markers of colonic fermentation and bowel function, as well as their associations with the gut microbiome.Methods: Fifty overweight individuals with increased metabolic risk and a high habitual intake of whole grains (~69 g/day) completed a randomised cross-over trial with two 8-week dietary intervention periods comprising a whole-grain diet (≥75 g/day) and a refined-grain diet (<10 g/day), separated by a washout period of ≥6 weeks. A range of markers of colonic fermentation and bowel function were assessed before and after each intervention.Results: The whole-grain diet increased the levels of faecal butyrate (p = 0.015) and caproate (p = 0.013) compared to the refined-grain diet. No changes in other faecal SCFA, BCFA or urinary levels of microbial-derived proteolytic markers between the two interventions were observed. Similarly, faecal pH remained unchanged. Faecal pH did however increase (p = 0.030) after the refined-grain diet compared to the baseline. Stool frequency was lower at the end of the refined-grain period compared to the end of the whole-grain diet (p = 0.001). No difference in faecal water content was observed between the intervention periods, however, faecal water content increased following the whole-grain period compared to the baseline (p = 0.007). Dry stool energy density was unaffected by the dietary interventions. Nevertheless, it explained 4.7% of the gut microbiome variation at the end of the refined-grain diet, while faecal pH and colonic transit time explained 4.3 and 5%, respectively. Several butyrate-producers (e.g., Faecalibacterium, Roseburia, Butyriciococcus) were inverse

To solve the rising issue of how to feed our planet in the future, we need to enhance our knowledge of peoples' current eating patterns and analyze those in terms of their health and environmental impacts. Current studies about adherence to existing national and global dietary recommendations often lack the ability to cross-compare the results among countries. Therefore, this study aims to develop a methodology to evaluate adherence to food-based dietary guidelines (FBDGs) and the Planetary Health Diet (PHD) on a national level, which can be replicable in different countries. First, national dietary intake data was collected from surveys published by the respective responsible public institutions from five countries (Italy, Denmark, Germany, Morocco, and Poland). Second, food groups represented in the intake data and the FBDGs were mapped to establish a proposal for a new common grouping (i.e., comprehensive food groups) that enables cross-country comparison. Third, dietary intake was compared to the recommendations according to national FBDG and the PHD. The adherence to the recommended diets was assessed using an adapted version of the German Food Pyramid Index. Our results show that different ways of grouping foods may change adherence levels; when measuring adherence to the FBDGs with the food groups suggested in the FBDGs, average scores (45.5 ± 5.4) were lower than by using comprehensive food groups (46.9 ± 3.7). Higher adherence to the PHD (52.4 ± 6.1) was found also using the comprehensive food groups. Particularly the foods meats, eggs, and legumes in one group (i.e., protein equivalents) appear to influence the outcome of scores using the comprehensive food groups. This study developed a methodology to evaluate national dietary intake against national FBDGs and the PHD. Our study points out the fact that it is difficult to overcome the challenge that countries have different food grouping clusters. Yet, the combination of the methods developed enables cros

Large-scale volcanic activity during the formation of large igneous provinces (LIPs) were contemporaneous with almost every mass extinction event in Earth’s history, and LIP activity is believed to have caused or contributed to at least three, if not all, Big Five mass extinctions. However, compared to the marine fossil record, the effects of the volcanism on the terrestrial plant record is still poorly understood. Extinctions in the animal record during major biotic crises in Earth history are not mirrored by comparable major changes in land plants. Despite being sedentary organisms land plants have evolved adaptations to cope with adverse changes in the environment which may provide autecological advantages compared to animals. Despite their remarkable resilience, land plant communities were still affected in multiple ways during LIP-induced extinction events. During the end-Triassic mass extinction (201.56–201.36 million years ago) emissions of greenhouse gases, sulfur dioxide and aerosols, halocarbons, polycyclic aromatic hydrocarbons, Hg and heavy metals from magmatic activity, as well as sea-level changes, during the emplacement of the Central Atlantic Magmatic Province (CAMP) are considered to have severely stressed land plants. This is exemplified by major changes in ecosystem structure in palynological records, a rise in microscopic charcoal abundance indicating increased wildfire activity, enhanced reworking of palynomorphs indicating increased soil erosion, acid rain damages on macroplant leaves, and increased abundances of abnormal spores and pollen indicating mutagenesis from Hg-toxicity and/or ozone layer depletion. Several of these land plant responses have also been observed during other extinction events contemporaneous to LIP activity. Here, we compare and discuss some of the changes in common between different biotic crises to evaluate whether there is a common pattern or not.

The Central Atlantic Magmatic Province (CAMP) eruptions are generally regarded as the main driver of major environmental change and mass-extinction across the Triassic-Jurassic (T-J) boundary (~201.3 Ma). CAMP emissions have been invoked as the main trigger for the formation of abnormal pollen and spores during the end-Triassic crisis that may have led to forest dieback and proliferation of pioneer species. Proposed scenarios include extensive climate change leading to wildfire activity, acid rain, and increased UV-B radiation due to ozone depletion. More recently, volcanogenic mercury (Hg) has been implicated in the occurrence of mutations in fern spores. However, Hg-dynamics in deep-time remain poorly understood and require further examination. Here, we explore a new long-term (Rhaetian to Sinemurian) bulk Hg-concentration record combined with Hg-isotope data to understand the link between floral turnovers and the Hg-cycle. Shallow marine sediments sampled from the Schandelah-1 core in northern Germany contain a record of cyclical shifts in malformed fern spores coinciding with fluctuations in carbon isotopes, increased levels of weathering, and Hg-enrichments. Similarly, increased mutagenic spore abundances with accompanying Hg-isotope records confirm the volcanogenic origin of Hg at the T-J boundary, showing a sharp positive excursion in mass-independent fractionation (MIF) of odd-numbered Hg-isotopes. Hettangian cyclicity is clearly reflected in the Hg-isotopic signals, showing positive excursions in mass-dependent/independent fractionation records (d202Hg and D199Hg) during periods of sedimentary Hg-enrichment. In addition, the Hettangian Hg-isotopic signature clearly deviates from Rhaetian signatures, which hints at climate-controlled mechanisms being responsible. Atmospheric Hg-loading via volcanism can explain the synchronous enrichments of Hg concentrations at the T-J boundary interval in multiple sites across the globe. In contrast, the origin of

The ability of insulin to stimulate glucose uptake in skeletal muscle is important for whole-body glycemic control. Insulin-stimulated skeletal muscle glucose uptake is improved in the period after a single bout of exercise and accumulating evidence suggests that phosphorylation of TBC1D4 by the protein kinase AMPK is the primary mechanism responsible for this phenomenon. To investigate this, we generated a TBC1D4 knock-in mouse model with a serine-to-alanine point mutation at residue 711 that is phosphorylated in response to both insulin and AMPK activation. Female TBC1D4-S711A mice exhibited normal growth and eating behavior as well as intact wholebody glycemic control on chow and high-fat diets. Moreover, muscle contraction increased glucose uptake, glycogen utilization and AMPK activity similarly in wild-type and TBC1D4-S711A mice. In contrast, improvements in whole-body and muscle insulin sensitivity after exercise and contractions were only evident in wild-type mice and occurred concomitantly with enhanced phosphorylation of TBC1D4-S711. These results provide genetic evidence to support that TBC1D4-S711 serves as a major point of convergence for AMPK- and insulin-induced signaling that mediates the insulin-sensitizing effect of exercise and contractions on skeletal muscle glucose uptake.

Background: Airway hyperresponsiveness is a hallmark of asthma across asthma phenotypes. Airway hyperresponsiveness to mannitol specifically relates to mast cell infiltration of the airways, suggesting inhaled corticosteroids to be effective in reducing the response to mannitol, despite low levels of type 2 inflammation. Objective: We sought to investigate the relationship between airway hyperresponsiveness and infiltrating mast cells, and the response to inhaled corticosteroid treatment. Methods: In 50 corticosteroid-free patients with airway hyperresponsiveness to mannitol, mucosal cryobiopsies were obtained before and after 6 weeks of daily treatment with 1600 mg of budesonide. Patients were stratified according to baseline fractional exhaled nitric oxide (FENO) with a cutoff of 25 parts per billion. Results: Airway hyperresponsiveness was comparable at baseline and improved equally with treatment in both patients with FENO-high and FENO-low asthma: doubling dose, 3.98 (95% CI, 2.49-6.38; P < .001) and 3.85 (95% CI, 2.51-5.91; P < .001), respectively. However, phenotypes and distribution of mast cells differed between the 2 groups. In patients with FENO-high asthma, airway hyperresponsiveness correlated with the density of chymase-high mast cells infiltrating the epithelial layer (p, -0.42; P = .04), and in those with FENO-low asthma, it correlated with the density in the airway smooth muscle (p, -0.51; P = .02). The improvement in airway hyperresponsiveness after inhaled corticosteroid treatment correlated with a reduction in mast cells, as well as in airway thymic stromal lymphopoietin and IL-33. Conclusions: Airway hyperresponsiveness to mannitol is related to mast cell infiltration across asthma phenotypes, correlating with epithelial mast cells in patients with FENO-high asthma and with airway smooth muscle mast cells in patients with FENO-low a

Insect-based foods may contribute to the consumption of more sustainable diets. Acceptance strategies for children are necessary to integrate insect-based foods into normal diets and lead to significant protein replacement. This study aimed to: (1) pilot the evaluation of insect-based foods in an online classroom; and (2) investigate the effects of exposing school children to educational and tasting interventions on the perception of edible insects and insect-based foods using in-person classrooms. The online classroom (n=220) used a simple intervention design where the perception of insect-based flatbreads and dhal-inspired dish were measured after exposure to the information session and tasting. The in-person classroom intervention (n=65) was composed of a lesson, food tasting, and a question-and-answer session with designated questionnaires. The online classroom response rate decreased as the number of tasks increased during the tasting or cooking sessions. Children participating in the in-person classroom session reported positive post-intervention correlations between agreeing society needing sustainable foods and willingness to consume insects. Awareness initiatives for insect-based foods for regular consumption should advance as opinions and knowledge about sustainability change.

Objective: To compare the prognostic value of mid-upper arm circumference (MUAC), weight-for-height Z-score (WHZ) and weight-for-age Z-score (WAZ) for predicting death over periods of 1, 3 and 6 months follow-up in children.Design: Pooled analysis of twelve prospective studies examining survival after anthropometric assessment. Sensitivity and false-positive ratios to predict death within 1, 3 and 6 months were compared for three individual anthropometric indices and their combinations.Setting: Community-based, prospective studies from twelve countries in Africa and Asia.Participants: Children aged 6-59 months living in the study areas.Results: For all anthropometric indices, the receiver operating characteristic curves were higher for shorter than for longer durations of follow-up. Sensitivity was higher for death with one month follow-up compared to six months by 49% (95% CI (30-69)) for MUAC <115 mm (P<0.001), 48% (95% CI (9.4-87)) for WHZ <-3 (P<0.01) and 28% (95% CI (7.6-42)) for WAZ <-3 (P<0.005). This was accompanied by an increase in false positives of only 3% or less. For all durations of follow-up, WAZ <-3 identified more children who died and were not identified by WHZ <-3 or by MUAC <115 mm, 120 mm or 125 mm, but the use of WAZ <-3 led to an increased false-positive ratio up to 16.4% (95% CI (12.0-20.9)) compared to 3.5% (95% CI (0.4-6.5)) for MUAC <115 mm alone.Conclusions: Frequent anthropometric measurements significantly improve the identification of malnourished children with a high risk of death without markedly increasing false-positives. Combining two indices increases sensitivity but also increases false positives among children meeting case definitions.

Transfer functions with a high translational gain can increase the range of walking in virtual reality. These functions determine how much virtual movements are amplified compared to the corresponding physical movements. However, it is unclear how the design of these functions influences the user’s gait and experience when walking with high gain values. In a mixed-methods study with 20 users, we find that their best transfer functions are nonlinear and asymmetrical for starting and stopping. We use an optimization approach to determine individually optimized functions that are significantly better than a common approach of using a constant gain. Based on interviews, we also discuss what qualities of walking matter to users and how these vary across different functions. Our work shows that it is possible to create high-gain walking techniques that offer dramatically increased range of motion and speed but still feel like normal walking.

We studied the long-term effects of a multicomponent exercise training protocol (recreational team handball training, RTH) on global health status in inactive postmenopausal women. Participants (n = 45; age 65 ± 6 years, stature 157 ± 6 cm, body mass 66.2 ± 9.4 kg, fat mass 41.4 ± 5.5%, VO2peak 25.7 ± 3.6 mL/min/kg) were randomized into a control group (CG; n = 14) and a multicomponent exercise training group (EXG; n = 31, performing 2-3 weekly 60-min RTH sessions). Attendance was 2.0 ± 0.4 sessions/week (first 16 weeks) and 1.4 ± 0.5 (following 20 weeks) and mean heart rate (HR) loading was 77 and 79% of maximal HR (p = 0.002) for the first 16 and the following 20 weeks, respectively. Cardiovascular, bone, metabolic health, body composition and physical fitness markers were evaluated at baseline, and after 16 and 36 weeks. An interaction (p ≤ 0.046) was shown for the 2-h oral glucose tolerance test, HDL, Yo-Yo intermittent endurance level 1 test (YYIE1) and knee strength, in favour of EXG. At 36 weeks YYIE1 and knee strength were higher (p ≤ 0.038) for EXG vs CG. Also, within-group improvements (p ≤ 0.043) were observed after 36 weeks for EXG in VO2peak, lumbar spine bone mineral density, lumbar spine bone mineral content, P1NP, osteocalcin, total cholesterol, HDL, LDL, body mass, android fat mass, YYIE1, knee strength, handgrip strength and postural balance. At 36 comparatively to 16 weeks, EXG showed an increase (p ≤ 0.036) in fasting blood glucose, HDL, knee strength and handgrip strength, and a decrease (p ≤ 0.025) in LDL. Collectively, this multicomponent exercise training (RTH) induces beneficial changes in global health status in postmenopausal women.

Using the phenomenon of friendship as a case, the possibilities of a neurosemiotics of friendship is investigated by analysing ongoing research in cognitive social neuroscience on friendship. Neurosemiotics, both as a field dealing with particular semiosic processes that are neurobiologically based, and as an approach to the knowledge gained in neuroscience interpreting its semiosis of inquiry and dissemination, can help us better understand the construct of friendship having a neural basis. Thus, the finding that "neural similarity predict friendship", analysed as an instance of a propositional dicisign, can be true or false, depending on how prediction and friendship is interpreted.

We examined whether a semi-automated carbon monoxide (CO) rebreathing method accurately detect changes in blood volume (BV) and total hemoglobin mass (tHb). Furthermore, we investigated whether a supine position with legs raised reduced systemic CO dilution time, potentially allowing a shorter rebreathing period. Nineteen young healthy males participated. BV and tHb was quantified by a 10-min CO-rebreathing period in a supine position with legs raised before and immediately after a 900 ml phlebotomy and before and after a 900 ml autologous blood reinfusion on the same day in 16 subjects. During the first CO-rebreathing, arterial and venous blood samples were drawn every 2 min during the procedure to determine systemic CO equilibrium in all subjects. Phlebotomy decreased (P < 0.001) tHb and BV by 166 ± 24 g and 931 ± 247 ml, respectively, while reinfusion increased (P < 0.001) tHb and BV by 143 ± 21 g and 862 ± 250 ml compared to before reinfusion. After reinfusion BV did not differ from baseline levels while tHb was decreased (P < 0.001) by 36 ± 21 g. Complete CO mixing was achieved within 6 min in venous and arterial blood, respectively, when compared to the 10-min sample. On an individual level, the relative accuracy after donation for tHb and BV was 102-169% and 55-165%, respectively. The applied CO-rebreathing procedure precisely detect acute BV changes with a clinically insignificant margin of error. The 10-min CO-procedure may be reduced to 6 min with no clinical effects on BV and tHb calculation. Notwithstanding, individual differences may be of concern and should be investigated further.

Purpose: Angiotensin-converting enzyme (ACE) inhibitor treatment is widely applied, but the fact that plasma ACE activity is a potential determinant of training-induced local muscular adaptability is often neglected. Thus, we investigated the hypothesis that ACE inhibition modulates the response to systematic aerobic exercise training on leg and arm muscular adaptations.Methods: Healthy, untrained, middle-aged participants (40 ± 7 yrs) completed a randomized, double-blinded, placebo-controlled trial. Participants were randomized to placebo (PLA: CaCO3) or ACE inhibitor (ACEi: enalapril) for 8 weeks and completed a supervised, high-intensity exercise training program. Muscular characteristics in the leg and arm were extensively evaluated pre and post-intervention. Results: Forty-eight participants (nACEi = 23, nPLA = 25) completed the trial. Exercise training compliance was above 99%. After training, citrate synthase, 3-hydroxyacyl-CoA dehydrogenase and phosphofructokinase maximal activity were increased in m. vastus lateralis in both groups (all P < 0.05) without statistical differences between them (all time × treatment P > 0.05). In m. deltoideus, citrate synthase maximal activity was upregulated to a greater extent (time × treatment P < 0.05) in PLA (51 [33;69] %) than in ACEi (28 [13;43] %), but the change in 3-hydroxyacyl-CoA dehydrogenase and phosphofructokinase maximal activity was similar between groups. Finally, the training-induced changes in the platelet endothelial cell adhesion molecule-1 protein abundance, a marker of capillary density, were similar in both groups in m. vastus lateralis and m. deltoideus. Conclusion: Eight weeks of high-intensity whole-body exercise training improves markers of skeletal muscle mitochondrial oxidative capacity, glycolytic capacity and angiogenesis, with no overall effect

Context: Oral contraceptives (OCs) manipulate hormonal fluctuations of the menstrual cycle and affect physical performance. Most investigations on the effect of OCs on physical performance did not discriminate between different types of OCs. Thus, the effects of monophasic OCs (MOCs) - the most common type of OCs - on muscle strength and recovery from exercise are largely unknown.Objective: To examine the effect of MOC use on muscle strength and markers of recovery after exercise-induced muscle damage (EIMD) in premenopausal women.Data sources: Electronic databases Embase, PubMed, SportDiscus, and Web of Science were searched for studies examining the effect of MOCs on acute muscle strength and recovery.Study selection: Keywords applied for the study selection were oral contraceptive* AND muscle strength or oral contraceptive* AND muscle damage. Study design: Systematic review.Level of evidence: Lowest quality assessed for an included study in this review was serious risk of bias using ROBINS-I tool made from Cochrane for nonrandomized studies.Data extraction: A total of 104 studies on muscle strength were identified, of which 11 met the inclusion criteria. Concerning recovery, 51 studies were identified, of which 4 met the inclusion criteria.Results: Of the 11 studies included, 10 showed no effect of MOCs on acute muscle strength. Of the 4 studies on recovery, 2 found a greater decrease in muscle strength, and 3 found higher creatine kinase (CK) levels after EIMD in MOC users than in nonusers. The included studies were all rated with moderate-to-serious risk of bias.Conclusion: These findings suggest that MOCs may impair recovery from EIMD as indicated by lowered muscle strength and elevated CK levels. There is insufficient evidence to conclude whether MOCs acutely affect muscle strength. Moderate-to-serious risk of b

The purpose of this study was to investigate the importance of motivational climate for the satisfaction of psychological needs and dropout in recreational, intermediate and elite volleyball. 7936 volleyball players from all 321 volleyball clubs across Denmark were invited to participate in the study. Three thousand three thirty answered the questionnaire and 2150 were included in the analysis. Dropout from Volleyball was measured as the proportion of players that had stopped playing volleyball over the last year. The coach-created motivational climate was measured using the Motivational Climate Scale for Youth Sports. The satisfaction of players’ psychological needs was measured using an adapted version of the basic psychological needs in exercise scale. The psychometric scales were validated and showed good model fit. For volleyball players of all levels, the degree of mastery climate predicted the satisfaction of the players’ basic psychological needs satisfaction during volleyball which was in turn associated with lower dropout rates. Performance climate had a weak negative association with the satisfaction of psychological needs on the intermediate level only. When adjusting the models for the negative association between performance climate and mastery climate this negative association became nonsignificant and a weak positive association to needs satisfaction emerged for players at the elite level. Findings confirm that the coach-created mastery climate in volleyball teams is important for the satisfaction of players’ basic psychological needs and continuation within the sport across the recreational, intermediate and elite levels.

Many research questions involve time-to-event outcomes that can be prevented from occurring due to competing events. In these settings, we must be careful about the causal interpretation of classical statistical estimands. In particular, estimands on the hazard scale, such as ratios of cause specific or subdistribution hazards, are fundamentally hard to interpret causally. Estimands on the risk scale, such as contrasts of cumulative incidence functions, do have a clear causal interpretation, but they only capture the total effect of the treatment on the event of interest; that is, effects both through and outside of the competing event. To disentangle causal treatment effects on the event of interest and competing events, the separable direct and indirect effects were recently introduced. Here we provide new results on the estimation of direct and indirect separable effects in continuous time. In particular, we derive the nonparametric influence function in continuous time and use it to construct an estimator that has certain robustness properties. We also propose a simple estimator based on semiparametric models for the two cause specific hazard functions. We describe the asymptotic properties of these estimators, and present results from simulation studies, suggesting that the estimators behave satisfactorily in finite samples. Finally, we re-analyze the prostate cancer trial from Stensrud et al. (2020)., Many research questions involve time-to-event outcomes that can be prevented from occurring due to competing events. In these settings, we must be careful about the causal interpretation of classical statistical estimands. In particular, estimands on the hazard scale, such as ratios of cause-specific or subdistribution hazards, are fundamentally hard to interpret causally. Estimands on the risk scale, such as contrasts of cumulative incidence functions, do have a clear causal interpretation, but they only capture the total effect of the treatment on the event of interest; that is, effects both through and outside of the competing event. To disentangle causal treatment effects on the event of interest and competing events, the separable direct and indirect effects were recently introduced. Here we provide new results on the estimation of direct and indirect separable effects in continuous time. In particular, we derive the nonparametric influence function in continuous time and use it to construct an estimator that has certain robustness properties. We also propose a simple estimator based on semiparametric models for the two cause-specific hazard functions. We describe the asymptotic properties of these estimators and present results from simulation studies, suggesting that the estimators behave satisfactorily in finite samples. Finally, we reanalyze the prostate cancer trial from Stensrud et al. (2020)

Objective: The purpose of this study was to test the hypothesis that perfluorinated alkylate substance (PFAS) exposures are associated with body weight increases in a dietary intervention study. Methods: In the DioGenes trial, adults with obesity first lost at least 8% of their body weight and then completed at least 26 weeks on a specific diet. Concentrations of five major PFASs were assessed in plasma samples from study baseline. Results: In 381 participants with complete data, plasma concentrations averaged 2.9 ng/mL and 1.0 ng/mL for perfluorooctanoic acid (PFOA) and perfluorohexanesulfonic acid (PFHxS), respectively. A doubling in plasma PFOA was associated with an increase in weight at 26 weeks by 1.50 kg (95% CI: 0.88–2.11), with an increase of 0.91 kg (95% CI: 0.54–1.27) for PFHxS, independent of diet groups and sex. Associations for other PFASs were in the same direction and significant, although not after adjustment for PFOA and PFHxS. Weight changes associated with elevated PFAS exposures were similar to or larger than average changes ascribed to the different diet groups. Conclusions: Elevated plasma concentrations of PFOA and PFHxS were associated with increased weight gain that exceeded those related to the diets. Obesogenic PFASs may cause weight gain and thus contribute to the obesity pandemic.

Microtubules serve as tracks for long-range intracellular trafficking of glucose transporter 4 (GLUT4), but the role of this process in skeletal muscle and insulin resistance is unclear. Here, we used fixed and live-cell imaging to study microtubule-based GLUT4 trafficking in human and mouse muscle fibers and L6 rat muscle cells. We found GLUT4 localized on the microtubules in mouse and human muscle fibers. Pharmacological microtubule disruption using Nocodazole (Noco) prevented long-range GLUT4 trafficking and depleted GLUT4-enriched structures at microtubule nucleation sites in a fully reversible manner. Using a perifused muscle-on-a-chip system to enable real-time glucose uptake measurements in isolated mouse skeletal muscle fibers, we observed that Noco maximally disrupted the microtubule network after 5 min without affecting insulin-stimulated glucose uptake. In contrast, a 2h Noco treatment markedly decreased insulin responsiveness of glucose uptake. Insulin resistance in mouse muscle fibers induced either in vitro by C2 ceramides or in vivo by diet-induced obesity, impaired microtubule-based GLUT4 trafficking. Transient knockdown of the microtubule motor protein kinesin-1 protein KIF5B in L6 muscle cells reduced insulin-stimulated GLUT4 translocation while pharmacological kinesin-1 inhibition in incubated mouse muscles strongly impaired insulin-stimulated glucose uptake. Thus, in adult skeletal muscle fibers, the microtubule network is essential for intramyocellular GLUT4 movement, likely functioning to maintain an insulin-responsive cell-surface recruitable GLUT4 pool via kinesin-1 mediated trafficking.

Previous studies have shown that many children struggle with the acquisition of literacy skills and that these problems can be observed since the earliest stages of literacy learning. Embodied learning has been highlighted as a way to enhance the acquisition of early literacy skills. In addition, the use of technologies has been suggested as way of improving attentional control and motivation, which ultimately can improve learning outcomes. However, the combination of Virtual Reality (VR) and embodied learning in preschool children is yet to be explored wherefore the idea to the VR PLAYMORE study emerged. The project is designed as a three-armed randomized controlled trial with 6-7-year-old children in the Copenhagen area of Denmark. Children will be allocated to either a: 1) VR group, 2) mirror group or 3) control group throughout a 2-week intervention period. The VR group and mirror group will perform activities designed with accordance to the embodied learning theory. However, the VR group will perform the activities while wearing VR headsets whereas the mirror group will perform the activities in front of a whole-body mirror without VR headsets. The control group will continue regular teaching activities without the research group interruption. This study protocol follows the SPIRIT guidelines. Outcome measurements will include testing of literacy skills and attentional control. The study will add new knowledge to the research field of embodied learning and the use of VR technology in a school setting with focus on reading- and spelling-related skills and attentional control since this combination is yet to be explored.

Introduction: Uzbekistan is one of the countries with the highest number of diet-related chronic diseases, which is believed to be associated with high animal fat intake. Sheep meat is high in fats (~ 5% in muscle), including saturated and monounsaturated fatty acids, and it contains nearly twice the higher amounts of n-3 polyunsaturated fatty acids and conjugated linoleic acids compared to beef. Nevertheless, sheep meat is considered health promoting by the locals in Uzbekistan and it accounts for around 1/3 of red meat intake in the country.Objectives: The aim of this study was to apply a metabolomics approach to investigate if sheep meat intake frequency (SMIF) is associated with alterations in fasting blood plasma metabolites and lipoproteins in healthy Uzbek adults.Methods: The study included 263 subjects, 149 females and 114 males. For each subject a food intake questionnaire, including SMIF, was recorded and fasting blood plasma samples were collected for metabolomics. Blood plasma metabolites and lipoprotein concentrations were determined using 1H NMR spectroscopy.Results and Conclusion: The results showed that SMIF was confounded by nationality, sex, body mass index (BMI), age, intake frequency of total meat and fish in ascending order (p < 0.01). Multivariate and univariate data analyses showed differences in the levels of plasma metabolites and lipoproteins with respect to SMIF. The effect of SMIF after statistical adjustment by nationality, sex, BMI, age, intake frequency of total meat and fish decreased but remained significant. Pyruvic acid, phenylalanine, ornithine, and acetic acid remained significantly lower in the high SMIF group, whereas choline, asparagine, and dimethylglycine showed an increasing trend. Levels of cholesterol, apolipoprotein A1, as well as low- and high-density lipoprotein subfractions all displayed a decreasing trend with increased SMIF although the

The predominant source of alcohol in the diet is alcoholic beverages, including beer, wine, spirits and liquors, sweet wine, and ciders. Self-reported alcohol intakes are likely to be influenced by measurement error, thus affecting the accuracy and precision of currently established epidemiological associations between alcohol itself, alcoholic beverage consumption, and health or disease. Therefore, a more objective assessment of alcohol intake would be very valuable, which may be established through biomarkers of food intake (BFIs). Several direct and indirect alcohol intake biomarkers have been proposed in forensic and clinical contexts to assess recent or longer-term intakes. Protocols for performing systematic reviews in this field, as well as for assessing the validity of candidate BFIs, have been developed within the Food Biomarker Alliance (FoodBAll) project. The aim of this systematic review is to list and validate biomarkers of ethanol intake per se excluding markers of abuse, but including biomarkers related to common categories of alcoholic beverages. Validation of the proposed candidate biomarker(s) for alcohol itself and for each alcoholic beverage was done according to the published guideline for biomarker reviews. In conclusion, common biomarkers of alcohol intake, e.g., as ethyl glucuronide, ethyl sulfate, fatty acid ethyl esters, and phosphatidyl ethanol, show considerable inter-individual response, especially at low to moderate intakes, and need further development and improved validation, while BFIs for beer and wine are highly promising and may help in more accurate intake assessments for these specific beverages.

Background: Sweetened beverage intake may play a role in non-alcoholic fatty liver disease (NAFLD) development, but scientific evidence on their role is limited. This study examined associations between sugar-sweetened beverages (SSB), low/no-calorie beverages (LNCB) and fruit juice (FJ) intakes and NAFLD in four European studies. Methods: Data for 42,024 participants of Lifelines Cohort, NQPlus, PREDIMED-Plus and Alpha Omega Cohort were cross-sectionally analysed. NAFLD was assessed using Fatty Liver Index (FLI) (≥60). Restricted cubic spline analyses were used to visualize dose–response associations in Lifelines Cohort. Cox proportional hazard regression analyses with robust variance were performed for associations in individual cohorts; data were pooled using random effects meta-analysis. Models were adjusted for demographic, lifestyle, and other dietary factors. Results: Each additional serving of SSB per day was associated with a 7% higher FLI-defined NAFLD prevalence (95%CI 1.03–1.11). For LNCB, restricted cubic spline analysis showed a nonlinear association with FLI-defined NAFLD, with the association getting stronger when consuming ≤1 serving/day and levelling off at higher intake levels. Pooled Cox analysis showed that intake of >2 LNCB servings/week was positively associated with FLI-defined NAFLD (PR 1.38, 95% CI 1.15–1.61; reference: non-consumers). An inverse association was observed for FJ intake of ≤2 servings/week (PR 0.92, 95% CI: 0.88–0.97; reference: non-consumers), but not at higher intake levels. Theoretical replacement of SSB with FJ showed no significant association with FLI-defined NAFLD prevalence (PR 0.97, 95% CI 0.95–1.00), whereas an adverse association was observed when SSB was replaced with LNCB (PR 1.12, 95% CI 1.03–1.21). Conclusions: Pooling results of this study showed that SSB and LNCB were positively associated with FLI-defined NAFLD prevalence. Theoretical replacement of S

Inadequate intake of both macro and micronutrients is the major determinant of micronutrient deficiencies in adolescent girls. This study assessed multiple micronutrient status including vitamin D, iron, vitamin A, and urinary iodine concentration among adolescent girls through two seasonal cross-sectional surveys conducted during dry and wet seasons. Mixed-effects linear and logistic regression analysis were conducted to assess associations between micronutrient status, salinity and seasonality. The mean age of the girls was 14 years. Vitamin (OH)D insufficiency was significantly higher in freshwater areas in wet season compared to dry season (wet season: 58% and dry season: 30%, P < 0.001). In wet season, risk of vitamin (OH)D insufficiency was three times higher compared to dry season (AOR: 3.03, 95% CI 1.71, 5.37, P < 0.001). The odds of vitamin (OH)D insufficiency was 11 times higher in fresh water areas compared to high saline areas (AOR: 11.51, 95% CI 3.40, 38.93, P < 0.001). The girls had higher risk of iron deficiency in wet season. Despite the environment being enriched with micronutrient-contained aquatic food, adolescent girls in coastal areas experience different micronutrient deficiencies. The high prevalence of vitamin (OH)D insufficiency in freshwater locations and seasonal iron deficiency in high saline areas needs attention.

Branched-chain fatty acids (BCFA) are a group of lipids that are widely present in various organisms; they take part in numerous biochemical processes and affect multiple signaling pathways. However, BCFA are not well explored in terms of their effects on human health. Recently, they have been gaining interest, especially in relation to various human diseases. This review describes the occurrence of BCFA, their dietary sources, their potential health effects, and the current state of knowledge concerning their mechanism(s) of action. Many studies have been conducted so far in cellular and animal models, which reveal potent anti-cancer, lipid lowering, anti-inflammatory and neuroprotective actions. Research in humans is scarce. Therefore, further studies on animals and humans should be performed to confirm and expand these findings, and improve our understanding of the potential relevance of BCFA to human health and disease.

Many current treatment options for managing overweight and obesity consist of rather strict diet and exercise regimes that are difficult to implement as a lifelong routine. Therefore, alternative initiatives such as mindful eating and pleasure-oriented physical activity with more focus on implementation and enjoyment are needed to reverse the obesity epidemic. Mindful eating is an approach focusing on inner hunger and satiety signals. YogaDance is a novel exercise approach combining elements of yoga and dance. This study was a randomized controlled trial investigating the individual and combined effects of mindful eating and YogaDance. Participants were healthy, inactive women with overweight or obesity (body mass index ≥ 25 kg/m2 and/or waist circumference ≥ 80 cm) who were randomized to one of four groups for 8 weeks: mindful eating alone, YogaDance alone, the combination of mindful eating and YogaDance, or control. Fat mass was the primary outcome and secondary outcomes included body weight, waist circumference, and other physiological, behavioral, and quality-of-life outcomes. Sixty-one women were included in the study and randomized to mindful eating and YogaDance combined, YogaDance, mindful eating, or control. Fat mass was reduced by 1.3 kg (95% CI [-10.0, 7.3] kg; p = 0.77), 3.0 kg (95% CI [-11.1, 5.1] kg; p = 0.48), and 1.8 kg (95% CI [-10.1, 6.6] kg; p = 0.69) for the mindful eating, YogaDance, and combined mindful eating and YogaDance interventions, respectively, compared to the control, with corresponding effect sizes of 0.15, 0.34, and 0.21. In complete-case analyses, fat percent and waist circumference were reduced whereas mental quality of life and eating behavior were improved for mindful eating and mindful eating and YogaDance combined compared to the control. In conclusion, the study found modest benefits of an 8-week combination of mindful eating and YogaDance, corroborating findings in previous studies on mindfu

Objective: To examine the association of gestational weight gain (GWG) among women with pre-pregnancy overweight or obesity with infant weight and BMI z-score at birth.Methods: This study is a secondary analysis of a randomized controlled trial including data from 208 infants at birth born by mothers with pre-pregnancy BMI between 28 and 45 kg/m2 who completed the APPROACH study (randomized to a high-protein low-glycemic index diet or a moderate-protein moderate-glycemic index diet). This analysis pooled the two diet treatment groups together and data were analyzed using a linear mixed model. Results: Limiting GWG by 1 kg was associated with lower birthweight (-16 g, P = 0.003), BMI z-score (-0.03SD, P = 0.019), weight z-score (-0.03SD, P = 0.004), and infant abdominal circumference (-0.06 cm, P = 0.039). Infants born by mothers whose GWG was ≤9 kg weighed less (122 g, 95% CI: 6-249, P = 0.040), had similar BMI z-score (0.2SD, 95% CI: -0.06 to 0.55, P = 0.120), and lower incidence of emergency cesarean deliveries (11.5% vs. 23.1%, P = 0.044) compared to infants born by mothers whose GWG was >9 kg. When women were classified into GWG quartiles, women in Q1 (GWG range: -7.0 to 3.2 kg) gave birth to smaller infants (3,420 g, P = 0.015) with lower BMI z-score (-0.5SD, P = 0.041) than women in Q2 (3.3-7.1 kg), Q3 (7.2-10.9 kg) and Q4 (11.1-30.2 kg). Conclusions: Limiting GWG among women with pre-pregnancy overweight or obesity was associated with lower infant weight, BMI z-score, weight z-score, and abdominal circumference at birth. Moreover, GWG below the Institute of Medicine guideline of a maximum of 9 kg was associated with lower birthweight and fewer emergency cesarean deliveries.

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.