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Betaine supplementation has been shown to enhance hepatic lipid metabolism in obese mice and improve exercise performance in healthy populations. We examined effects of betaine supplementation, alone or in combination with treadmill exercise, on the metabolic consequences of high fat diet (HFD)-induced obesity in mice.Male C57BL/6 J mice were fed chow or HFD. After 15 weeks, HFD mice were split into: HFD, HFD with betaine (1.5% w/v), HFD with treadmill exercise, and HFD with both betaine and exercise (15 m/min for 45min, 6 days/week; n = 12/group) for 10 weeks. Compared to HFD mice, body weight was significantly reduced in exercise and exercise-betaine mice, but not in mice given betaine alone. Similarly, adiposity was reduced by exercise but not by betaine alone. HFD-induced glucose intolerance was slightly improved by exercise, but not with betaine alone. Significantly greater benefits were observed in exercise-betaine mice, compared to exercise alone, such that GTT-outcomes were similar to controls. This was associated with reduced insulin levels during ipGTT, suggesting enhanced insulin sensitivity. Modest benefits were observed in fatty acid metabolism genes in skeletal muscle, whilst limited effects were observed in the liver. HFD-induced increases in hepatic Mpc1 (mitochondrial pyruvate carrier 1) were normalized by all treatments, suggesting potential links to altered glucose metabolism.Our data show that drinking 1.5% betaine was sufficient to augment metabolic benefits of exercise in obese mice. These processes appear to be facilitated by altered glucose metabolism, with limited effects on hepatic lipid metabolism.

SCOPE: The effects of diet cycling on cognition and fecal microbiota are not well understood. METHOD AND RESULTS: Adult male Sprague-Dawley rats were cycled between a high-fat, high-sugar "cafeteria" diet (Caf) and regular chow. The impairment in place recognition memory produced by 16 days of Caf diet was reduced by switching to chow for 11 but not 4 days. Next, rats received 16 days of Caf diet in 2, 4, 8, or 16-day cycles, each separated by 4-day chow cycles. Place recognition memory declined from baseline in all groups and was impaired in the 16- versus 2-day group. Finally, rats received 24 days of Caf diet continuously or in 3-day cycles separated by 2- or 4-day chow cycles. Any Caf diet access impaired cognition and increased adiposity relative to controls, without altering hippocampal gene expression. Place recognition and adiposity were the strongest predictors of global microbiota composition. Overall, diets with higher Caf > chow ratios produced greater spatial memory impairments and larger shifts in gut microbiota species richness and beta diversity. CONCLUSION: Results suggest that diet-induced cognitive deficits worsen in proportion to unhealthy diet exposure, and that shifting to a healthy chow for at least a week is required for recovery under the conditions tested here.

Diets of children and adolescents on the autism spectrum often differ when compared to their non-autistic peers. Most dietary studies have been limited by small sample sizes and rarely assess the heterogeneity of autism. Addressing this gap, this study compared the anthropometrics, dietary composition, dietary quality, and food variety of 154 Australian children and adolescents on the spectrum and 213 non-autistic children (71 siblings and 142 unrelated controls). Beyond the case-control approach, within-group comparisons assessed the influence of autism clinical presentations and sensory processing styles on body mass index (BMI) and measures of dietary intake among those on the spectrum. In this word first study of diet that included between-group comparisons with non-autistic peers (siblings and an unrelated comparison group) and within-autism group comparisons, we found that children on the spectrum consumed limited variety and lower quality of food and non-autistic siblings also ate comparably higher levels of energy-dense, nutrient poor food, and less diary. This may be due to autistic traits influencing family's diets or shared sensory sensitivities driving dietary intake. Within the autism group, higher autistic traits were associated with lower BMIs and a specific dietary pattern higher in simple carbohydrates and lower in unprocessed protein. Contrastingly, greater sensitivity to sensory stimuli was associated with a healthier diet. Increased age was linked to more varied diets but also diets higher in saturated fats and energy-dense, nutrient poor foods. Overall, this research highlights that potential mediators of dietary intake, such as familial influences, autistic traits, sensory processing styles, age and sex, need to be considered when assessing diet in the autistic population. LAY SUMMARY: In this study of dietary differences linked to autism, children, and teenagers on the spectrum ate fewer different foods and were less likely to eat recommended amounts of fruits and vegetables when compared to non-autistic siblings and unrelated children and teenagers. There were also family differences, in that those on the spectrum and their siblings ate more unhealthy foods and less dairy. Among those on the spectrum, dietary differences were linked to age, sex, autistic traits and sensory processing styles.

Purpose Emerging evidence from rodent studies suggests that high-fat-diet (HFD)-induced obesity is characterized by increased oxidative damage in sperm and testis. However, interventions using micronutrient supplementation to mitigate oxidative damage in obesity have not been extensively studied. This study aimed to investigate the effect of an antioxidant-based micronutrient supplement (added folate, vitamin B6, choline, betaine, and zinc) on sperm and testicular oxidative damage in HFD-fed male Sprague Dawley rats. Methods Rats (3-weeks-old, 12/group) were weaned onto control (C) or HFD (H) or these diets with micronutrient supplement (CS; HS); sperm and testis were harvested at 30.5 weeks. To assess oxidative stress and antioxidant capacity in testis, levels of malondialdehyde (MDA), glutathione (GSH), folate and susceptibility index (SI) of pro-oxidative damage, mRNA expression of Nrf2, NFκB-p65, IL-6, IL-10 and TNF-α, in addition to superoxide-dismutase (SOD), catalase and glutathione-peroxidase (GPx) activities were measured. 8-hydroxy-2-deoxyguanosine (8-OHdG) were assessed in both sperm and testis. Results HFD-fed rats had significantly increased 8-OHdG content in sperm and testis, increased testicular SI, decreased testicular weight, SOD and GPx activity compared to control. Strikingly, supplementation of HFD appeared to significantly reduce 8-OHdG in sperm and testis (22% and 24.3%, respectively), reduce testicular SI and MDA content (28% and 40%, respectively), increase testicular weight (24%), SOD and GPX activity (30% and 70%, respectively) and GSH content (19%). Moreover, supplementation had significant impact to increase testicular folate content regardless of diet. Furthermore, an overall effect of supplementation to increase testicular mRNA expression of Nrf2 was observed across groups. Interestingly, testicular SI was positively correlated with sperm and testicular 8-OHdG and MDA content, suggesting a critical role of testicular antioxidant activity to combat oxidative damage in sperm and testis. Conclusion Our findings suggest that antioxidant-based micronutrient supplement has the potential to interrupt HFD-induced sperm and testicular oxidative damage by improving testicular antioxidant capacity. Graphical abstract

The leukodystrophy Hypomyelination with Brainstem and Spinal cord involvement and Leg spasticity (HBSL) is caused by recessive mutations of the DARS1 gene, which encodes the cytoplasmic aspartyl-tRNA synthetase. HBSL is a spectrum disorder with disease onset usually during early childhood and no available treatment options. Patients display regression of previously acquired motor milestones, spasticity, ataxia, seizures, nystagmus, and intellectual disabilities. Gene-function studies in mice revealed that homozygous Dars1 deletion is embryonically lethal, suggesting that successful modelling of HBSL requires the generation of disease-causing genocopies in mice. In this study, we introduced the pathogenic DARS1M256L mutation located on exon nine of the murine Dars1 locus. Despite causing severe illness in humans, homozygous Dars1M256L mice were only mildly affected. To exacerbate HBSL symptoms, we bred Dars1M256L mice with Dars1-null ‘enhancer’ mice. The Dars1M256L/− offspring displayed increased embryonic lethality, severe developmental delay, reduced body weight and size, hydrocephalus, anophthalmia, and vacuolization of the white matter. Remarkably, the Dars1M256L/− genotype affected energy metabolism and peripheral organs more profoundly than the nervous system and resulted in reduced body fat, increased respiratory exchange ratio, reduced liver steatosis, and reduced hypocellularity of the bone marrow. In summary, homozygous Dars1M256L and compound heterozygous Dars1M256L/− mutation genotypes recapitulate some aspects of HBSL and primarily manifest in developmental delay as well as metabolic and peripheral changes. These aspects of the disease might have been overlooked in HBSL patients with severe neurological deficits but could be included in the differential diagnosis of HBSL in the future.

During the COVID-19 pandemic, risk negotiation became an important precursor to in-person contact. For young adults, social planning generally occurs through computer-mediated communication. Given the importance of social connectedness for mental health and academic engagement, we sought to understand how young adults plan in-person meetups over computer-mediated communication in the context of the pandemic. We present a qualitative study that explores young adults’ risk negotiation during the COVID-19 pandemic, a period of conflicting public health guidance. Inspired by cultural probe studies, we invited participants to express their preferred precautions for one week as they planned in-person meetups. We interviewed and surveyed participants about their experiences. Through qualitative analysis, we identify strategies for risk negotiation, social complexities that impede risk negotiation, and emotional consequences of risk negotiation. Our findings have implications for AI-mediated support for risk negotiation and assertive communication more generally. We explore tensions between risks and potential benefits of such systems.

The microbiome has been implicated in the development of metabolic conditions which occur at high rates in people with schizophrenia and related psychoses. This exploratory proof-of-concept study aimed to: (i) characterize the gut microbiota in antipsychotic naïve or quasi-naïve people with first-episode psychosis, and people with established schizophrenia receiving clozapine therapy; (ii) test for microbiome changes following a lifestyle intervention which included diet and exercise education and physical activity. Participants were recruited from the Eastern Suburbs Mental Health Service, Sydney, Australia. Anthropometric, lifestyle and gut microbiota data were collected at baseline and following a 12-week lifestyle intervention. Stool samples underwent 16S rRNA sequencing to analyse microbiota diversity and composition. Seventeen people with established schizophrenia and five people with first-episode psychosis were recruited and matched with 22 age-sex, BMI and ethnicity matched controls from a concurrent study for baseline comparisons. There was no difference in α-diversity between groups at baseline, but microbial composition differed by 21 taxa between the established schizophrenia group and controls. In people with established illness pre-post comparison of α-diversity showed significant increases after the 12-week lifestyle intervention. This pilot study adds to the current literature that detail compositional differences in the gut microbiota of people with schizophrenia compared to those without mental illness and suggests that lifestyle interventions may increase gut microbial diversity in patients with established illness. These results show that microbiome studies are feasible in patients with established schizophrenia and larger studies are warranted to validate microbial signatures and understand the relevance of lifestyle change in the development of metabolic conditions in this population.

Minocycline has anti-inflammatory, antioxidant, and anti-apoptotic properties that explain the renewed interest in its use as an adjunctive treatment for psychiatric and neurological conditions. Following the completion of several new clinical trials using minocycline, we proposed an up-to-date systematic review and meta-analysis of the data available. The PICO (patient/population, intervention, comparison and outcomes) framework was used to search 5 databases aiming to identify randomized controlled trials that used minocycline as an adjunctive treatment for psychiatric and neurological conditions. Search results, data extraction, and risk of bias were performed by two independent authors for each publication. Quantitative meta-analysis was performed using RevMan software. Literature search and review resulted in 32 studies being included in this review: 10 in schizophrenia, 3 studies in depression, and 7 in stroke, with the benefit of minocycline being used in some of the core symptoms evaluated; 2 in bipolar disorder and 2 in substance use, without demonstrating a benefit for using minocycline; 1 in obsessive-compulsive disorder, 2 in brain and spinal injuries, 2 in amyotrophic lateral sclerosis, 1 in Alzheimer’s disease, 1 in multiple systems atrophy, and 1 in pain, with mixes results. For most of the conditions included in this review the data is still limited and difficult to interpret, warranting more well-designed and powered studies. On the other hand, the studies available for schizophrenia seem to suggest an overall benefit favoring the use of minocycline as an adjunctive treatment.

Background: Millennials, born between 1982­ and 2000, became the largest share of the American workforce in 2015. As of 2014, 23.9% of American occupational therapists were under the age of 30. Positive traits ascribed to millennials include: highly educated, ambitious, confident, and optimistic. However, indicators of challenges for managing millennials emerge from media and anecdotal evidence, including stereotypes of disloyalty, entitlement, dependency, and casualness. Relevant for supporting professional development is a call to understand and enhance professional communication. Method: This study analyzed how emerging millennial occupational therapists self-describe their professional communication profile and needs, compared to the perspective of managers, while aiming to describe the accuracy of communication stereotypes. Occupational therapy managers and emerging occupational therapists of the millennial generation completed an online researcher-created survey. Results: Comparison of means revealed statistically significant differences, with the most significance noted on items reflecting professional communication skills of millennial occupational therapists. Conclusion: Analysis of results suggested support for some stereotypes and inaccuracy of others, painting a unique picture of the professional communication profile of millennial occupational therapists. Results from this small-population survey study may inform professional development opportunities for academic and fieldwork educators and occupational therapy managers related to the communication profile and needs of emerging occupational therapists through the lens of generational theory.

Background Despite well-known effects of diet on gut microbiota diversity, relatively little is known about how maternal diet quality shapes the longitudinal maturation of gut microbiota in offspring. To investigate, we fed female rats standard chow (Chow) or a western-style, high-choice cafeteria diet (Caf) prior to and during mating, gestation and lactation. At weaning (3 weeks), male and female offspring were either maintained on their mother’s diet (ChowChow, CafCaf groups) or switched to the other diet (ChowCaf, CafChow). Fecal microbial composition was assessed in dams and longitudinally in offspring at 3, 7 and 14 weeks of age. Results The effect of maternal diet on maturation of offspring gut microbiota was assessed by α- and β-diversities, Deseq2/LEfSe, and SourceTracker analyses. Weanling gut microbiota composition was characterised by reduced α- and β-diversity profiles that clustered away from dams and older siblings. After weaning, offspring gut microbiota came to resemble an adult-like gut microbiota, with increased α-diversity and reduced dissimilarity of β-diversity. Similarly, Deseq2/LEfSe analyses found fewer numbers of altered operational taxonomic units (OTUs) between groups from weaning to adulthood. SourceTracker analyses indicated a greater overall contribution of Caf mothers’ microbial community (up to 20%) to that of their offspring than the contribution of Chow mothers (up to 8%). Groups maintained on the maternal diet (ChowChow, CafCaf), versus those switched to the other diet (ChowCaf, CafChow) post-weaning significantly differed from each other at 14 weeks (Permutational Multivariate Analysis of Variance), indicating interactive effects of maternal and post-weaning diet on offspring gut microbiota maturation. Nevertheless, this developmental trajectory was unaffected by sex and appeared consistent between ChowChow, CafCaf, ChowCaf and CafChow groups. Conclusions Introducing solid food at weaning triggered the maturation of offspring gut microbiota to an adult-like profile in rats, in line with previous human studies. Postweaning Caf diet exposure had the largest impact on offspring gut microbiota, but this was modulated by maternal diet history. An unhealthy maternal Caf diet did not alter the developmental trajectory of offspring gut microbiota towards an adult-like profile, insofar as it did not prevent the age-associated increase in α-diversity and reduction in β-diversity dissimilarity.

Constipation and REM sleep behaviour disorder (RBD) are the earliest non-motor manifestations of Parkinson’s disease (PD). Among non-motor symptoms of PD, it is unclear whether constipation and RBD at early stages of PD are related to cognitive outcomes at later stages. Herein, this study aims to investigate whether the presence of constipation and RBD have an impact on future cognitive outcomes in PD. Access to Parkinson’s Progression Markers Initiative (PPMI) database of 360 PD patients with longitudinal observation was requested. Constipation, probable RBD (pRBD) and neuropsychological task scores of PD patients were assessed at baseline and after 5 years. Linear mixed-effects modelling, controlling for gender, age, years of education and LEDD was used to evaluate the association between baseline constipation, pRBD and cognitive performance on follow-up. Gender differences in neuropsychological test performances were found, with men having worse global cognition, speed-attention processing, verbal learning and memory than women at early stages of the disease. We found constipation and pRBD are strongly associated with future decline in some cognitive measures among PD patients, more prominently in men. Our data suggest that early assessment of pRBD and constipation may allow better understanding of the progression of cognitive changes in later phases of PD.

Media coverage of research on phones and social media over the last decade has prompted widespread concern and one-size-fits-all guidance to limit screen time. Recognizing the limitations of screen time as a metric, researchers are now studying technology use in terms of affordances, individual differences, and longitudinal patterns. The current review examines technology use by parents, caregivers, couples, and clinicians. Individuals in these roles navigate risks, such as privacy violations, with benefits such as improved communication, empathy, and progress toward shared goals. Successful approaches vary by relationship type but have commonalities such as engaging with the technologies used by the other person to open up sensitive conversations, negotiate conflict, and illuminate patterns that would otherwise be hard to detect. To enhance relationships, some individuals depart from the intended use of technologies, for example, adapting connected devices for emotional communication or drawing on games to cope with social anxiety. One promising way in which individuals adapt technology to improve communication involves sharing technologies that were designed for personal use. This review highlights the importance of context, motivation, and the nuances of use to understand how technologies can be optimally used in personal and clinical relationships. .Durante la última década, la cobertura mediática de la investigación sobre teléfonos celulares y redes sociales ha generado una gran preocupación y el consejo uniforme de limitar el tiempo de uso de la pantalla. Al reconocer las limitaciones que tiene la medición solo del tiempo de pantalla, los investigadores ahora están estudiando el empleo de la tecnología en términos de accesibilidad, diferencias individuales y patrones longitudinales. Esta revisión examina la utilización de la tecnología por parte de padres, cuidadores, parejas y clínicos. En estos roles las personas se desenvuelven con riesgos (violaciones de la privacidad), y con beneficios (mejor comunicación, mayor empatía y mayor progreso hacia objetivos comunes). Los puntos comunes de una práctica exitosa, además de la variabilidad del tipo de relación, se basan en la adopción de las tecnologías utilizadas por el otro para iniciar conversaciones sensibles, negociar conflictos y resaltar modelos de funcionamiento que de otro modo hubieran sido difíciles de identificar. Para mejorar las relaciones, algunas personas se apartan del uso previsto de las tecnologías, por ejemplo, adaptando los dispositivos conectados para una comunicación emocional o recurriendo a juegos para enfrentar la ansiedad social. Es alentador observar cómo las personas se apropian de estas tecnologías originalmente diseñadas para uso personal y las comparten, con el objetivo de mejorar la comunicación. En esta revisión se destaca la importancia del contexto, la motivación y los matices del empleo de las tecnologías para comprender cómo se pueden utilizar de manera óptima en las relaciones personales y clínicas.Ces dix dernières années, la couverture médiatique de la recherche sur les téléphones portables et les réseaux sociaux a suscité une inquiétude généralisée et la diffusion de conseils uniformisés sur la limitation du temps d'écran. La mesure du temps passé devant l'écran ayant depuis été reconnue comme une donnée limitée, les chercheurs étudient aujourd’hui l'utilisation de la technologie en termes d'accessibilité, de différences individuelles et de modèles longitudinaux. Cet article examine l’usage qu’en font les parents, les soignants, les couples et les médecins. Ces utilisateurs font face à des risques, tels que la violation de la vie privée, mais profitent aussi d’une amélioration dans la communication, une plus grande empathie et progressent vers des objectifs communs. Les points communs d’une pratique réussie, hors variabilité relationnelle, reposent sur l’adoption des technologies utilisées par l'autre pour engager des échanges sensibles, négocier des conflits et mettre en lumière des schémas de fonctionnement qui auraient été difficiles à identifier autrement. Pour améliorer leurs relations aux autres, certains détournent ces outils technologiques, par exemple en se servant d’appareils connectés pour une communication émotionnelle ou en ayant recours à des jeux pour gérer leur anxiété sociale. Il est encourageant de constater que les individus s’approprient ces technologies conçues initialement pour un usage personnel et les partagent dans le but d’améliorer leur communication. Cette étude souligne l'importance du contexte, de la motivation et des nuances d'utilisation pour comprendre comment les technologies peuvent être utilisées de manière optimale dans les relations personnelles et cliniques.

Diets rich in sugar and saturated fat are associated with cognitive impairments in both humans and rodents with several potential mechanisms proposed. To test the involvement of diet-induced pro-inflammatory signaling, we exposed rats to a high-fat, high-sugar cafeteria diet, and administered the anti-inflammatory antibiotic minocycline. In the first experiment minocycline was coadministered across the diet, then in a second, independent cohort it was introduced following 4 weeks of cafeteria diet. Cafeteria diet impaired novel place recognition memory throughout the study. Minocycline not only prevented impairment in spatial recognition memory but also reversed impairment established in rats following 4 weeks cafeteria diet. Further, minocycline normalized diet-induced increases in hippocampal pro-inflammatory gene expression. No effects of minocycline were seen on adiposity or dietary intake across the experiments. Cafeteria diet and minocycline treatment significantly altered microbiome composition. The relative abundance of Desulfovibrio_OTU31, uniquely enriched in vehicle-treated cafeteria-fed rats, negatively and significantly correlated with spatial recognition memory. We developed a statistical model that accurately predicts spatial recognition memory based on Desulfovibrio_OTU31 relative abundance and fat mass. Thus, our results show that minocycline prevents and reverses a dietary-induced diet impairment in spatial recognition memory, and that spatial recognition performance is best predicted by changes in body composition and Desulfovibrio_OTU31, rather than changes in pro-inflammatory gene expression.