A cortico-cerebellar loop for motor planning.

Persistent and ramping neural activity in the frontal cortex anticipates specific movements1-6. Preparatory activity is distributed across several brain regions7,8, but it is unclear which brain areas are involved and how this activity is mediated by multi-regional interactions. The cerebellum is thought to be primarily involved in the short-timescale control of movement9-12; however, roles for this structure in cognitive processes have also been proposed13-16. In humans, cerebellar damage can cause defects in planning and working memory13. Here we show that persistent representation of information in the frontal cortex during motor planning is dependent on the cerebellum. Mice performed a sensory discrimination task in which they used short-term memory to plan a future directional movement. A transient perturbation in the medial deep cerebellar nucleus (fastigial nucleus) disrupted subsequent correct responses without hampering movement execution. Preparatory activity was observed in both the frontal cortex and the cerebellar nuclei, seconds before the onset of movement. The silencing of frontal cortex activity abolished preparatory activity in the cerebellar nuclei, and fastigial activity was necessary to maintain cortical preparatory activity. Fastigial output selectively targeted the behaviourally relevant part of the frontal cortex through the thalamus, thus closing a cortico-cerebellar loop. Our results support the view that persistent neural dynamics during motor planning is maintained by neural circuits that span multiple brain regions17, and that cerebellar computations extend beyond online motor control13-15,18.

Prevalence and risk factors associated with low bone mineral density in Asian adolescents with anorexia nervosa and atypical anorexia nervosa.

OBJECTIVE: This retrospective study aimed to evaluate the prevalence and risk factors for low bone mineral density (BMD) at diagnosis in Asian adolescent females with anorexia nervosa (AN) and atypical AN. METHOD: We analyzed the BMD results for 213 patients between 10 and 18 years of age, with AN and atypical AN receiving care at a pediatric hospital in Singapore. We used linear regression analyses to determine if type of eating disorder, premorbid weight, and duration of amenorrhea were risk factors for low BMD. For a subset of patients with repeat BMD evaluation, we used paired t-tests to assess the impact of weight or menstrual restoration on the change in BMD. RESULTS: The prevalence of BMD height-for-age Z-scores <-2 at presentation was higher in patients with AN (13.0%) than atypical AN (2.3%) (p = .034). In multivariate regression, a diagnosis of atypical AN was protective against low BMD at the lumbar spine (B = 0.394, p = .009) and total body less head (B = 0.774, p = .010). Duration of amenorrhea was not associated with BMD across all sites. For those with repeat BMD measures, there was significantly less deterioration in the BMD Z-scores for patients with weight or menstrual restoration (R = -0.22 ± 0.59, NR = -0.69 ± 0.43, p = .029). CONCLUSIONS: Duration of amenorrhea was not associated with BMD in this sample. A diagnosis of AN was correlated with lower BMD than atypical AN. Further research is needed to better understand the relationship between amenorrhea, weight status, and bone health in Asian adolescents with eating disorders. PUBLIC SIGNIFICANCE: In this sample, 13% of Asian adolescents with AN and 2.3% of Asian adolescents with atypical AN have low BMD. In our study population, duration of amenorrhea was not correlated with BMD. Among adolescents with AN, a history of being underweight at the highest pre-morbid BMI, is correlated with low BMD. It is important for physicians to take a thorough weight history in evaluating bone health in this population.

A nutritional biomarker score of the Mediterranean diet and incident type 2 diabetes: Integrated analysis of data from the MedLey randomised controlled trial and the EPIC-InterAct case-cohort study.

BACKGROUND: Self-reported adherence to the Mediterranean diet has been modestly inversely associated with incidence of type 2 diabetes (T2D) in cohort studies. There is uncertainty about the validity and magnitude of this association due to subjective reporting of diet. The association has not been evaluated using an objectively measured biomarker of the Mediterranean diet. METHODS AND FINDINGS: We derived a biomarker score based on 5 circulating carotenoids and 24 fatty acids that discriminated between the Mediterranean or habitual diet arms of a parallel design, 6-month partial-feeding randomised controlled trial (RCT) conducted between 2013 and 2014, the MedLey trial (128 participants out of 166 randomised). We applied this biomarker score in an observational study, the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, to assess the association of the score with T2D incidence over an average of 9.7 years of follow-up since the baseline (1991 to 1998). We included 22,202 participants, of whom 9,453 were T2D cases, with relevant biomarkers from an original case-cohort of 27,779 participants sampled from a cohort of 340,234 people. As a secondary measure of the Mediterranean diet, we used a score estimated from dietary-self report. Within the trial, the biomarker score discriminated well between the 2 arms; the cross-validated C-statistic was 0.88 (95% confidence interval (CI) 0.82 to 0.94). The score was inversely associated with incident T2D in EPIC-InterAct: the hazard ratio (HR) per standard deviation of the score was 0.71 (95% CI: 0.65 to 0.77) following adjustment for sociodemographic, lifestyle and medical factors, and adiposity. In comparison, the HR per standard deviation of the self-reported Mediterranean diet was 0.90 (95% CI: 0.86 to 0.95). Assuming the score was causally associated with T2D, higher adherence to the Mediterranean diet in Western European adults by 10 percentiles of the score was estimated to reduce the incidence of T2D by 11% (95% CI: 7% to 14%). The study limitations included potential measurement error in nutritional biomarkers, unclear specificity of the biomarker score to the Mediterranean diet, and possible residual confounding. CONCLUSIONS: These findings suggest that objectively assessed adherence to the Mediterranean diet is associated with lower risk of T2D and that even modestly higher adherence may have the potential to reduce the population burden of T2D meaningfully. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12613000602729 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363860.

COVID-19 virtual patient cohort suggests immune mechanisms driving disease outcomes.

To understand the diversity of immune responses to SARS-CoV-2 and distinguish features that predispose individuals to severe COVID-19, we developed a mechanistic, within-host mathematical model and virtual patient cohort. Our results suggest that virtual patients with low production rates of infected cell derived IFN subsequently experienced highly inflammatory disease phenotypes, compared to those with early and robust IFN responses. In these in silico patients, the maximum concentration of IL-6 was also a major predictor of CD8+ T cell depletion. Our analyses predicted that individuals with severe COVID-19 also have accelerated monocyte-to-macrophage differentiation mediated by increased IL-6 and reduced type I IFN signalling. Together, these findings suggest biomarkers driving the development of severe COVID-19 and support early interventions aimed at reducing inflammation.

Challenges and opportunities for using natural history collections to estimate insect population trends.

Natural history collections (NHC) provide a wealth of information that can be used to understand the impacts of global change on biodiversity. As such, there is growing interest in using NHC data to estimate changes in species' distributions and abundance trends over historic time horizons when contemporary survey data are limited or unavailable. However, museum specimens were not collected with the purpose of estimating population trends and thus can exhibit spatiotemporal and collector-specific biases that can impose severe limitations to using NHC data for evaluating population trajectories. Here we review the challenges associated with using museum records to track long-term insect population trends, including spatiotemporal biases in sampling effort and sparse temporal coverage within and across years. We highlight recent methodological advancements that aim to overcome these challenges and discuss emerging research opportunities. Specifically, we examine the potential of integrating museum records and other contemporary data sources (e.g. collected via structured, designed surveys and opportunistic citizen science programs) in a unified analytical framework that accounts for the sampling biases associated with each data source. The emerging field of integrated modelling provides a promising framework for leveraging the wealth of collections data to accurately estimate long-term trends of insect populations and identify cases where that is not possible using existing data sources.

Disentangling direct and indirect effects of extreme events on coastal wetland communities.

One of the primary ways in which climate change will impact coastal freshwater wetlands is through changes in the frequency, intensity, timing and distribution of extreme weather events. Disentangling the direct and indirect mechanisms of population- and community-level responses to extreme events is vital to predicting how species composition of coastal wetlands will change under future conditions. We extended static structural equation modelling approaches to incorporate system dynamics in a multi-year multispecies occupancy model to quantify the effects of extreme weather events on a coastal freshwater wetland system. We used data from an 8-year study (2009-2016) on St. Marks National Wildlife Refuge in Florida, USA, to quantify species-specific and community-level changes in amphibian and fish occupancy associated with two flooding events in 2012 and 2013. We examine how physical changes to the landscape, including potential changes in salinity and increased wetland connectivity, may have contributed to or exacerbated the effects of these extreme weather events on the biota of isolated coastal wetlands. We provide evidence that the primary effects of flooding on the amphibian community were through indirect mechanisms via changes in the composition of the sympatric fish community that may have had lethal (i.e. through direct predation) or non-lethal (i.e. through direct or indirect competitive interactions) effects. In addition, we have shown that amphibian species differed in their sensitivity to direct flooding effects and indirect changes in the fish community and wetland-specific conductance, which led to variable responses across the community. These effects led to the overall decline in amphibian species richness from 2009 to 2016, suggesting that wetland-breeding amphibian communities on St. Marks National Wildlife Refuge may not be resilient to predicted changes in coastal disturbance regimes because of climate change. Understanding both direct and indirect effects, as well as species interactions, is important for predicting the effects of a changing climate on individual species, communities and ecosystems.

Integrated community models: A framework combining multispecies data sources to estimate the status, trends and dynamics of biodiversity.

Data deficiencies among rare or cryptic species preclude assessment of community-level processes using many existing approaches, limiting our understanding of the trends and stressors for large numbers of species. Yet evaluating the dynamics of whole communities, not just common or charismatic species, is critical to understanding and the responses of biodiversity to ongoing environmental pressures. A recent surge in both public science and government-funded data collection efforts has led to a wealth of biodiversity data. However, these data collection programmes use a wide range of sampling protocols (from unstructured, opportunistic observations of wildlife to well-structured, design-based programmes) and record information at a variety of spatiotemporal scales. As a result, available biodiversity data vary substantially in quantity and information content, which must be carefully reconciled for meaningful ecological analysis. Hierarchical modelling, including single-species integrated models and hierarchical community models, has improved our ability to assess and predict biodiversity trends and processes. Here, we highlight the emerging 'integrated community modelling' framework that combines both data integration and community modelling to improve inferences on species- and community-level dynamics. We illustrate the framework with a series of worked examples. Our three case studies demonstrate how integrated community models can be used to extend the geographic scope when evaluating species distributions and community-level richness patterns; discern population and community trends over time; and estimate demographic rates and population growth for communities of sympatric species. We implemented these worked examples using multiple software methods through the R platform via packages with formula-based interfaces and through development of custom code in JAGS, NIMBLE and Stan. Integrated community models provide an exciting approach to model biological and observational processes for multiple species using multiple data types and sources simultaneously, thus accounting for uncertainty and sampling error within a unified framework. By leveraging the combined benefits of both data integration and community modelling, integrated community models can produce valuable information about both common and rare species as well as community-level dynamics, allowing for holistic evaluation of the effects of global change on biodiversity.

#EatingDisorderRecovery: a qualitative content analysis of eating disorder recovery-related posts on Instagram.

PURPOSE: Limited research has evaluated the role of Social Networking Sites (SNS) in eating disorder (ED) recovery. While research has demonstrated the deleterious effects of pro-ED SNS content, less is known regarding SNS content documenting ED recovery. This study evaluates orientation towards help-seeking, ongoing ED warning signs and recovery themes on ED recovery SNS hashtags. METHODS: 600 Instagram posts were retrieved from two popular hashtags: #EDrecovery and #EatingDisorderRecovery. They were categorized into four thematic concerns: Food, Quotes, People or Others. Posts were analysed for behavioural and psychological signs of ED based on the Mental Health First Aid Eating Disorders Guidelines, and whether they encouraged seeking professional help. Thematic qualitative analysis to evaluate themes posted on recovery hashtags was conducted. RESULTS: Of the 600 posts, 405 were used for analysis. The majority of posts were on Food (49.6%), Quotes (24.2%) and People (22.7%). Behavioural and psychological signs suggestive of EDs were present in 18.0% and 22.5% of images, respectively. Only 9.4% of posts encouraged seeking professional help. Important themes that emerged from the qualitative analysis included the recovery journey, increased awareness and stigma for EDs and the development of a supportive community. CONCLUSIONS: Despite identifying with ED recovery, posts had a high prevalence of ongoing ED behaviour and low prevalence of help-seeking. Thematic analysis emphasized the role of recovery as a journey and the role of stigma and community in recovery. These findings suggest that SNSs could potentially be leveraged as a platform to improve help-seeking and encourage recovery for users with eating disorders. LEVEL OF EVIDENCE: Level V, descriptive study.

First presentation of restrictive early onset eating disorders in Asian children.

OBJECTIVE: This study aims to describe the spectrum of children with restrictive early onset eating disorders (EOEDs), defined as below 13 years of age, presenting to a tertiary institution in Asia and comparing them with older adolescents with eating disorders. METHODS: This is a retrospective case review of Asian children who were treated in an eating disorder center. Baseline characteristics and inpatient management at first presentation of children younger than 13 years of age (EOED) were compared to those in older adolescents. RESULTS: A total of 288 patients with restrictive eating disorders were analyzed with 53 (18%) patients having onset younger than age 13 at initial presentation. There were no significant differences in percentage weight loss and hospitalization rates between the two age groups. Patients with EOED presented with significantly shorter duration of symptoms, and lower rates of secondary amenorrhea. More patients with EOED required phosphate supplementation compared to those in older age group. CONCLUSION: Despite having a shorter duration of illness, Asian children with EOED had similar percentage weight loss and rates of admission due to malnutrition as those in older Asian adolescent patients. This study underlined the severity of EOEDs and the need for early recognition and medical assessment.

Implementation of family-based treatment for Asian adolescents with anorexia nervosa: A consecutive cohort examination of outcomes.

OBJECTIVE: This study describes the implementation of family-based treatment (FBT) in an eating disorder program in Asia as well as clinical outcomes of Asian adolescents with anorexia nervosa (AN) treated with FBT. METHOD: This retrospective consecutive cohort study of 147 Asian adolescents with AN was compared between those in FBT (n = 65) versus treatment as usual (TAU) (n = 82). Variables associated with weight restoration were analyzed between groups. RESULTS: Participants' mean age was 14.2 (SD = 1.5) years and 93% were female. Mean presenting %mBMI was 74.0 (SD = 7.8) and average illness duration was 7.7 (SD = 6.1) months. The two groups' baseline characteristics were not significantly different. Weight restoration rates in the FBT group were significantly higher than the TAU group at 6-, 12-, and 24-month time points. A linear mixed model showed the mean %mBMI was significantly higher at 0, 6, 12, and 24 months in the FBT group. The median time to weight restoration for patients on FBT was shorter (FBT: 7.0 months, TAU: 19.0 months; 95% CI [14.5, 23.5] χ2 = 15.84, p < .001). Within the FBT group, those that completed ≥9 FBT sessions had significantly higher rates of weight restoration at 12 months. Across all participants, those with a lower starting %mBMI were less likely to achieve weight restoration by 12 months. CONCLUSION: FBT can be effectively implemented in a multidisciplinary eating disorder program managing Asian adolescents with AN with improved rates of weight restoration. Further research is needed to understand the predictors and moderators of remission using FBT in Asian adolescents with AN.

Outcomes of a higher calorie inpatient refeeding protocol in Asian adolescents with anorexia nervosa.

OBJECTIVE: This study aims to compare the outcomes of higher calorie refeeding (HCR) and a lower calorie refeeding (LCR) methods among a diverse sample of young Asian adolescents admitted to a tertiary institution in Asia for management of anorexia nervosa (AN). METHOD: This is a retrospective case control study of Asian adolescents who were managed using an inpatient HCR protocol (2016-2017) and an LCR protocol (2010-2014). Baseline characteristics, daily change in percent median body mass index (%mBMI), and rates of refeeding hypophosphatemia were analyzed between groups. RESULTS: A total of 125 adolescents with AN were analyzed with 61 (52%) patients in the HCR group. Mean age was 14.0 years (SD =1.5) and mean presenting %mBMI was 73.2 (SD =6.9) with mean length of stay of 11.9 days (SD = 6.6). Patients in the HCR group had significantly increased rate of change of %mBMI (M = 0.39, SD = 0.31) than patients in the LCR group (M = 0.12, SD = 0.43) (p < .001). There was an increased rate of mild hypophosphatemia in the HCR group (HCR: 46%, LCR: 22%, p = .007) but no difference in rates of moderate hypophosphatemia and no cases of severe hypophosphataemia. Lower presenting %mBMI significantly predicted the phosphate levels (p = .004). DISCUSSION: In a sample of Asian adolescents with AN, use of an HCR protocol was associated with improved rate of inpatient weight gain. There was increased risk of mild hypophosphataemia, but not moderate to severe hypophosphataemia, suggesting that an HCR protocol can be used safely with close monitoring of phosphate levels.

Use of a Mobile Lifestyle Intervention App as an Early Intervention for Adolescents With Obesity: Single-Cohort Study.

BACKGROUND: Effective, resource-efficient treatment is urgently needed to address the high rates of pediatric and adolescent obesity. This need has been accelerated by the COVID-19 pandemic. The use of a mobile health tool as an early intervention before a clinic-based multidisciplinary weight management program could be an effective treatment strategy that is appropriate during a pandemic. OBJECTIVE: This study aims to assess the effectiveness of and adolescent engagement with a mobile app-based lifestyle intervention program as an early intervention before enrollment in a clinic-based multidisciplinary weight management program. METHODS: This prospective single-cohort study involved adolescents, aged 10-16 years, who were overweight and obese (defined as BMI percentile above the 85th percentile). Participants used the mobile Kurbo app as an early intervention before enrolling in a clinic-based multidisciplinary weight management program. Kurbo's health coaches provided weekly individual coaching informed by a model of supportive accountability via video chat, and participants self-monitored their health behavior. The implementation of Kurbo as an early intervention was evaluated using the reach, effectiveness, adoption, implementation, and maintenance framework by reach (number who consented to participate out of all patients approached), implementation (Kurbo engagement and evaluation), and effectiveness as measured by the primary outcome of the BMI z-score at 3 months. Secondary outcome measures included changes in body fat percentage, nutrition and physical activity levels, and quality of life at 3 months. Maintenance was defined as the outcome measures at 6-month follow-up. RESULTS: Of the 73 adolescents who were approached for enrollment, 40 (55%) of adolescents were recruited. The mean age was 13.8 (SD 1.7) years, and the mean BMI z-score was 2.07 (SD 0.30). In the multiethnic Asian sample, 83% (33/40) of the participants had household incomes below the national median. Kurbo engagement was high, with 83% (33/40) of participants completing at least 7 coaching sessions. In total, 78% (18/23) of participants rated the app as good to excellent and 70% (16/23) stated that they would recommend it to others. There were no statistically significant changes in BMI z-scores at 3 months (P=.19) or 6 months (P=.27). Participants showed statistically significant improvements in measured body fat percentage, self-reported quality of life, and self-reported caloric intake from the 3-day food diaries at 3 and 6 months. CONCLUSIONS: The use of Kurbo before enrollment in an outpatient multidisciplinary clinical care intervention is a feasible strategy to expand the reach of adolescent obesity management services to a low-income and racially diverse population. Although there was no significant change in BMI z-scores, the use of Kurbo as an early intervention could help to improve quality of life and reduce body fat percentage and total caloric intake.

An evaluation of a medical student international service-learning experience in Southeast Asia.

Background: International service-learning trips (ISLTs) are structured experiences in a different country where students interact and engage in cross-cultural dialog with others. Month-long ISLTs originating from North American or European medical schools enhance clinical acumen, cultural awareness, and global health familiarity. The impact of experiences shorter than 1 month or those that originate from Asia is unknown. We aimed to determine the impact of a short-term ISLT on medical students' clinical and cultural competence. Methods: At Duke-National University Singapore, we developed an ISLT incorporating peer-assisted learning and a 1-week on-site experience delivering supervised primary care, health screening, and health education in an underserved Southeast Asian community. Using a prospective controlled design, we assessed its impact on medical students' clinical and cultural competency using validated surveys. We compared medical students who participated in the ISTL (intervention group) to a control group of students before and after the ISTL experience. We analyzed responses using univariate analysis and the Kruskal-Wallis test. Results: : Sixty-six students responded to the survey (100%). After the ISTL, the intervention group (n = 32) showed an increase in their ratings of clinical competency (preexperience mean = 3.39, postexperience mean = 3.81, P < 0.01) as well as an increase in their cultural competency domains (preexperience mean = 3.61, postexperience mean = 4.12, P < 0.01). Post the ISTL, students in the intervention group rated their clinical and cultural competency higher than the control group (n = 34) (clinical: intervention postexperience mean = 3.81, control postexperience mean = 3.30, P < 0.01; cultural: intervention postexperience mean = 4.12, control postexperience mean = 3.50, P < 0.01). After the ISTL, the intervention group reported increased ratings of self-efficacy (pre mean = 3.99, post mean = 4.29, P = 0.021), which were higher than the control group (pre mean = 4.29, post mean = 3.57, P < 0.01). Discussion: : This short-term ISLT in an Asian medical school improved students' clinical and cultural competency and self-efficacy. Our findings suggest a positive impact of short-term ISLTs if designed and implemented with a student learning focus.

Approval of Cancer Drugs With Uncertain Therapeutic Value: A Comparison of Regulatory Decisions in Europe and the United States.

Policy Points Regulatory agencies may have limited evidence on the clinical benefits and harms of new drugs when deciding whether new therapeutic agents are allowed to enter the market and under which conditions, including whether approval is granted under special regulatory pathways and obligations to address knowledge gaps through postmarketing studies are imposed. In a matched comparison of marketing applications for cancer drugs of uncertain therapeutic value reviewed by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), we found frequent discordance between the two agencies on regulatory outcomes and the use of special regulatory pathways. Both agencies often granted regular approval, even when the other agency judged there to be substantial uncertainty about drug benefits and risks that needed to be resolved through additional studies in the postmarketing period. Postmarketing studies imposed by regulators under special approval pathways to address remaining questions of efficacy and safety may not be suited to deliver timely, confirmatory evidence due to shortcomings in study design and delays, raising questions over the suitability of the FDA's Accelerated Approval and the EMA's Conditional Marketing Authorization as tools for allowing early market access for cancer drugs while maintaining rigorous regulatory standards. CONTEXT: Regulatory agencies are increasingly required to make market approval decisions for new drugs on the basis of limited clinical evidence, a situation commonly encountered in cancer. We aimed to investigate how regulators manage uncertainty in the benefit-risk profiles of new cancer drugs by comparing decisions for the world's two largest regulatory bodies-the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA)-over a 5-year period. METHODS: We systematically identified a set of cancer drug-indication pairs for which data on efficacy and safety was less complete than that required for regular approval at time of market entry from 2009 to 2013, as determined by the FDA's use of Accelerated Approval (AA) or the EMA's use of Conditional Marketing Authorization (CMA) pathways, and matched these across the two agencies. Using publicly available information, we compared regulatory pathways and outcomes, final approved indications, and postmarketing obligations imposed by the agencies. FINDINGS: We identified 21 cancer drug-indication pairs that received FDA AA, EMA CMA, or both. Although most applications relied on identical pivotal trials across the FDA and the EMA, regulatory pathways often differed; 57% of indications received either FDA AA or EMA CMA, and regular approval by the other agency. After approval, the EMA more often accepted single-arm studies to confirm clinical benefit compared to the FDA (75% vs. 29% of indications), and the FDA more commonly requested randomized controlled trials (85% vs. 50%). Forty-one percent of confirmatory trials after FDA AA were conducted in different populations than the approved indication, compared to 13% after EMA CMA. Both agencies relied primarily on surrogate measures of patient benefit for postmarketing obligations. After a median follow-up of 7.25 years, 40% of FDA and 61% of EMA postmarketing obligations after AA and CMA, respectively, were delayed. CONCLUSIONS: US and European regulators often deemed early and less complete evidence on benefit-risk profiles of cancer drugs sufficient to grant regular approval, raising questions over regulatory standards for the approval of new medicines. Even when imposing confirmatory studies in the postmarketing period through special approval pathways, meaningful evidence may not materialize due to shortcomings in study design and delays in conducting required studies with due diligence.

Serotonin type-3 receptors differentially modulate anxiety and aggression during withdrawal from adolescent anabolic steroid exposure.

Male Syrian hamsters (Mesocricetus auratus) administered anabolic/androgenic steroids during adolescent development display increased aggression and decreased anxious behavior during the adolescent exposure period. Upon withdrawal from anabolic/androgenic steroids, this neurobehavioral relationship shifts and hamsters exhibit decreased aggression and increased anxious behavior. This study investigated the hypothesis that alterations in anterior hypothalamic signaling through serotonin type-3 receptors modulate the behavioral shift between adolescent anabolic/androgenic steroid-induced aggressive and anxious behaviors during the withdrawal period. To test this, hamsters were administered anabolic/androgenic steroids during adolescence then withdrawn from drug exposure for 21 days and tested for aggressive and anxious behaviors following direct pharmacological manipulation of serotonin type-3 receptor signaling within the latero-anterior hypothalamus. Blockade of latero-anterior hypothalamic serotonin type-3 receptors both increased aggression and decreased anxious behavior in steroid-treated hamsters, effectively reversing the pattern of behavioral responding normally observed during anabolic/androgenic steroid withdrawal. These findings suggest that the state of serotonin neural signaling within the latero-anterior hypothalamus plays an important role in behavioral shifting between aggressive and anxious behaviors following adolescent exposure to anabolic/androgenic steroids.

A Mediterranean diet supplemented with dairy foods improves mood and processing speed in an Australian sample: results from the MedDairy randomized controlled trial.

Background The Mediterranean diet has been linked to improved cognitive function and reduced risk of dementia. However, a traditional Mediterranean diet may not meet calcium requirements for older non-Mediterranean populations, which could limit long-term sustainability in Western countries. The current study therefore aimed to determine the cognitive and psychological effects of a Mediterranean diet with adequate calcium for an ageing Australian population. Method: A randomized controlled cross-over design trial compared a Mediterranean diet with 3-4 daily serves of dairy food (MedDairy) with a low-fat (LF) control diet. Forty-one participants aged ≥45 years with systolic blood pressure ≥120 mm Hg and at least two other risk factors for cardiovascular disease completed each dietary intervention for 8 weeks, with an 8-week washout period separating interventions. Attention, processing speed, memory and planning were assessed at the start and end of each intervention using the Cambridge Automated Neuropsychological Test Battery. Mood and health-related quality of life were evaluated using the Profile of Mood States (POMS) and Short-Form Health Survey (SF-36). Dementia risk was also measured using the Framingham Vascular Risk and CAIDE scores. Results Significant improvements were observed for processing speed (P = .04), Total Mood Disturbance (P = .01), Tension (P = .03), Depression (P = .03), Anger (P = .02), and Confusion (P = .004) following the MedDairy intervention. No significant effects were found for attention, memory and planning, or measures of dementia risk. Conclusion Our study provides evidence that a Mediterranean diet supplemented with dairy foods may benefit cognitive function and psychological well-being in an ageing population at risk of dementia.

Effects of Mediterranean diet supplemented with lean pork on blood pressure and markers of cardiovascular risk: findings from the MedPork trial.

The Mediterranean diet offers a range of health benefits. However, previous studies indicate that the restricted consumption of red meat in the diet may affect long-term sustainability in non-Mediterranean countries. A 24-week randomised controlled parallel cross-over design compared a Mediterranean diet supplemented with 2-3 serves per week of fresh, lean pork (MedPork) with a low-fat control diet (LF). Thirty-three participants at risk of CVD followed each intervention for 8 weeks, with an 8-week washout period separating interventions. The primary outcome was home-measured systolic blood pressure. Secondary outcomes included diastolic blood pressure, fasting lipids, glucose, insulin, C-reactive protein (CRP), body composition and dietary adherence. During the MedPork intervention, participants achieved high adherence to dietary guidelines. Compared with the MedPork intervention, the LF intervention led to greater reductions in weight (Δ = -0·65; 95 % CI -0·04, -1·25 kg, P = 0·04), BMI (Δ = -0·25; 95 % CI -0·03, -0·47 kg/m2, P = 0·01) and waist circumference (Δ = -1·40; 95 % CI -0·45, -2·34 cm, P < 0·01). No significant differences were observed for blood pressure, lipids, glucose, insulin or CRP. These findings indicate that Australians are capable of adhering to a Mediterranean diet with 2-3 weekly serves of fresh, lean pork. Larger intervention studies are now required to demonstrate clinical efficacy of the diet in populations with elevated blood pressure.

Ecological correlates of the spatial co-occurrence of sympatric mammalian carnivores worldwide.

The composition of local mammalian carnivore communities has far-reaching effects on terrestrial ecosystems worldwide. To better understand how carnivore communities are structured, we analysed camera trap data for 108 087 trap days across 12 countries spanning five continents. We estimate local probabilities of co-occurrence among 768 species pairs from the order Carnivora and evaluate how shared ecological traits correlate with probabilities of co-occurrence. Within individual study areas, species pairs co-occurred more frequently than expected at random. Co-occurrence probabilities were greatest for species pairs that shared ecological traits including similar body size, temporal activity pattern and diet. However, co-occurrence decreased as compared to other species pairs when the pair included a large-bodied carnivore. Our results suggest that a combination of shared traits and top-down regulation by large carnivores shape local carnivore communities globally.

Regulatory scientists' work has important ramifications for public health and should be open to public scrutiny.

The Swedish Medical Products Agency (MPA) objects to the fact that we occasionally refer to one of its senior ex-employees by name. However, names of individual MPA assessors, Food and Drug Administration (FDA) reviewers, and European Medicines Agency rapporteurs and co-rapporteurs are cited in regulatory documents and are a matter of public record. In our paper (Health Res Policy Syst 15:93, 2017), we in no way suggest that regulatory decisions were left to individual reviewers or assessors, although we do emphasise that individual MPA and FDA employees' scientific assessments and benefit-risk evaluations are critical to the decision-making process. In this response to the MPA, we raise a further issue - one in which the question of personal identification of individuals is relevant - and this pertains to the accountability of influential scientists and experts who contribute to public policy decisions with important ramifications for public health. In our view, it is important that interested observers are able to identify those influential individuals, and entirely appropriate that their work should be open to public scrutiny.