Case Report: PAFAH1B1 Mutation and Posterior Band Heterotopia With Focal Temporal Lobe Epilepsy Treated by Responsive Neurostimulation

Subcortical band heterotopia (SBH), also known as double cortex syndrome, is a malformation of cortical development caused by inherited or somatic gene variants. We present a case of a young adult with posterior SBH and electroclinical features of focal neocortical temporal lobe epilepsy. Genomic blood analysis identified a pathogenic somatic mosaicism duplication variant of the PAFAH1B1 gene. Despite bilateral cortical MRI abnormalities, the interictal and ictal EEG findings indicated a focal epileptogenic region in the left posterior temporal region. Chronic responsive cortical neurostimulation across two four-contact depth electrodes placed 5mm on either side of the maximal interictal spiking identified during intraoperative electrocorticography resulted in a consistent 28%reduction in duration of electrographic seizures and as well as constricted propagation. Although electrographic seizures continued, the family reported no clinical seizures and a marked improvement in resistant behaviors. This observation supports that focal neocortical neuromodulation can control clinical seizures of consistently localized origin despite genetic etiology, bilateral structural brain abnormalities, and continuation of non-propagating electrographic seizures. We propose that a secondary somatic mutation may be the cause of the focal neocortical temporal lobe epilepsy

Reviews and contestability: new directions for Defence

Overview: The First Principles Review of Defence is arguably the most significant review of the defence establishment since the 1973 re-organisation led by Sir Arthur Tange. This Strategic Insights brings together a series of contributions to ASPI’s blog The Strategist written by ten experts with long experience and broad knowledge of Australia’s defence bureaucracy. They bring a wealth of different perspectives and point to significant challenges ahead for Defence if the reforms proposed by the First Principles Review are to succeed

Sustainable Tiny Home

As housing prices and environmental concerns continue to increase, many people are looking for cheaper and more sustainable ways to live. A solution to both problems is building homes with smaller footprints which incorporate renewable energy and water-reclamation systems. In addition, adding a roof pond system to the dwelling also reduces the need for heating and cooling. The roof pond system uses a water bladder on the roof which acts as a heat-sink and moveable insulation panels. This document contains the process for our final design along with results from testing the verification prototype

Physical Activity/Exercise and Diabetes: A Position Statement of the American Diabetes Association

The adoption and maintenance of physical activity are critical foci for blood glucose management and overall health in individuals with diabetes and prediabetes. Recommendations and precautions vary depending on individual characteristics and health status. In this Position Statement, we provide a clinically oriented review and evidence-based recommendations regarding physical activity and exercise in people with type 1 diabetes, type 2 diabetes, gestational diabetes mellitus, and prediabetes. Physical activity includes all movement that increases energy use, whereas exercise is planned, structured physical activity. Exercise improves blood glucose control in type 2 diabetes, reduces cardiovascular risk factors, contributes to weight loss, and improves well-being (1,2). Regular exercise may prevent or delay type 2 diabetes development (3). Regular exercise also has considerable health benefits for people with type 1 diabetes (e.g., improved cardiovascular fitness, muscle strength, insulin sensitivity, etc.) (4). The challenges related to blood glucose management vary with diabetes type, activity type, and presence of diabetes-related complications (5,6). Physical activity and exercise recommendations, therefore, should be tailored to meet the specific needs of each individual

Psychedelics Promote Structural and Functional Neural Plasticity.

Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders

Mothers after Gestational Diabetes in Australia (MAGDA): A Randomised Controlled Trial of a Postnatal Diabetes Prevention Program

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background Gestational diabetes mellitus (GDM) is an increasingly prevalent risk factor for type 2 diabetes. We evaluated the effectiveness of a group-based lifestyle modification program in mothers with prior GDM within their first postnatal year. Methods and Findings In this study, 573 women were randomised to either the intervention (n = 284) or usual care (n = 289). At baseline, 10% had impaired glucose tolerance and 2% impaired fasting glucose. The diabetes prevention intervention comprised one individual session, five group sessions, and two telephone sessions. Primary outcomes were changes in diabetes risk factors (weight, waist circumference, and fasting blood glucose), and secondary outcomes included achievement of lifestyle modification goals and changes in depression score and cardiovascular disease risk factors. The mean changes (intention-to-treat [ITT] analysis) over 12 mo were as follows: −0.23 kg body weight in intervention group (95% CI −0.89, 0.43) compared with +0.72 kg in usual care group (95% CI 0.09, 1.35) (change difference −0.95 kg, 95% CI −1.87, −0.04; group by treatment interaction p = 0.04); −2.24 cm waist measurement in intervention group (95% CI −3.01, −1.42) compared with −1.74 cm in usual care group (95% CI −2.52, −0.96) (change difference −0.50 cm, 95% CI −1.63, 0.63; group by treatment interaction p = 0.389); and +0.18 mmol/l fasting blood glucose in intervention group (95% CI 0.11, 0.24) compared with +0.22 mmol/l in usual care group (95% CI 0.16, 0.29) (change difference −0.05 mmol/l, 95% CI −0.14, 0.05; group by treatment interaction p = 0.331). Only 10% of women attended all sessions, 53% attended one individual and at least one group session, and 34% attended no sessions. Loss to follow-up was 27% and 21% for the intervention and control groups, respectively, primarily due to subsequent pregnancies. Study limitations include low exposure to the full intervention and glucose metabolism profiles being near normal at baseline. Conclusions Although a 1-kg weight difference has the potential to be significant for reducing diabetes risk, the level of engagement during the first postnatal year was low. Further research is needed to improve engagement, including participant involvement in study design; it is potentially more effective to implement annual diabetes screening until women develop prediabetes before offering an intervention. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN1261000033806

Acute effects of breaking up prolonged sitting on fatigue and cognition: a pilot study.

OBJECTIVES: To compare the acute effects of uninterrupted sitting with sitting interrupted by brief bouts of light-intensity walking on self-reported fatigue, cognition, neuroendocrine biomarkers and cardiometabolic risk markers in overweight/obese adults. DESIGN: Randomised two-condition crossover trial. SETTING: Laboratory study conducted in Melbourne, Australia. PARTICIPANTS: 19 overweight/obese adults (45-75 years). INTERVENTIONS: After an initial 2 h period seated, participants consumed a meal-replacement beverage and completed (on 2 days separated by a 6-day washout period) each condition over the next 5 h: uninterrupted sitting (sedentary condition) or sitting with 3 min bouts of light-intensity walking every 30 min (active condition). PRIMARY OUTCOME MEASURES: Self-reported fatigue, executive function and episodic memory at 0 h, 4 h and 7 h. SECONDARY OUTCOME MEASURES: Neuroendocrine biomarkers and cardiometabolic risk markers (blood collections at 0 h, 4 h and 7 h, blood pressure and heart rate measured hourly and interstitial glucose measured using a continuous glucose monitoring system). RESULTS: During the active condition, fatigue levels were lower at 4 h (-13.32 (95% CI -23.48 to -3.16)) and at 7 h (-10.73 (95% CI -20.89 to -0.58)) compared to the sedentary condition. Heart rate was higher at 4 h (4.47 (95% CI 8.37 to 0.58)) and at 7 h (4.32 (95% CI 8.21 to 0.42)) during the active condition compared to the sedentary condition. There were no significant differences between conditions by time for other variables. In the sedentary condition, changes in fatigue scores over time correlated with a decrease in heart rate and plasma dihydroxyphenylalanine (DOPA) and an increase in plasma dihydroxyphenylglycol (DHPG). CONCLUSIONS: Interrupting prolonged sitting with light-intensity walking breaks may be an effective fatigue countermeasure acutely. Fatigue levels corresponded with the heart rate and neuroendocrine biomarker changes in uninterrupted sitting in this pilot study. Further research is needed to identify potential implications, particularly for the occupational health context. TRIAL REGISTRATION NUMBER: ACTRN12613000137796; Results

Towards a new paradigm of care: the International Declaration on Youth Mental Health.

A recent and growing body of evidence on young people\u27s mental health has pointed to the need for an international response to the increasing and concerning rates of mental ill-health among young people.[1, 2] The periods of adolescence and emerging adulthood[3] are considered the peak periods for the onset of mental ill-health[4] with 75% of all adult diagnoses of mental ill-health having had an onset before the age of 25 years.[5] In an era when the physical health of young people has never been better,[6] their psychological and mental health has never been worse.[7] This leaves young people vulnerable to developing potentially intractable and enduring mental health difficulties with the inevitable personal, familial, social and vocational consequences that accompany the experience of mental ill-health.[4, 8] In spite of growing concerns about young people\u27s mental health, service provision for young people remains largely inadequate and unsuited to their needs. A number of systemic factors can be implicated in insufficient and unsuitable mental health service provision for young people. Internationally, there has been an endemic failure to invest in mental health across the lifespan with an average global spend on mental health of less than $US3 per capita per year.[9] This global underinvestment brings with it particular challenges in relation to the level of priority afforded to youth mental health and the concurrent commitment needed to respond to the scale of young people\u27s mental health needs. Even in developed countries where mental health services exist, there are widespread problems with services targeting young people. Primary care and other front line community agencies can struggle to respond to high levels of need, often with little support from specialist mental health services. Specialist mental health services have traditionally followed a paediatric-adult split, with child and adolescent services offering intervention until the largely arbitrary ages of 16 or 18 years and adult services taking all young people 18 years and older.[1] In many instances, there have been gaps in service provision between the ages of 16 and 18 years.[10] This has resulted in many young people being unable to access specialist mental health support during these critical years along with high rates of attrition and dissatisfaction by young people during this transitional period.[11, 12] With a recognition that, in many sociocultural contexts, the transition from adolescence to adulthood is a variable one that spans a period from the mid-teens to the mid- to late-20s,[13] both young people and youth mental health advocates have called for a reorganization of mental health services to mirror this extended developmental period for young people.[2] Not surprisingly, there has been a trend of poor help seeking and engagement by young people in mental health services.[14, 15] A key challenge remains in supporting young people to reach out for help when they need it and early evidence suggests that factors such as ease of access, the physical environment, location, atmosphere, branding and peer influence can promote help seeking among young people.[12] It must be noted, however, that even when services are youth friendly and appropriate to their needs, individual and psychological factors strongly influence help-seeking behaviour among young people experiencing emotional or psychological distress.[16, 17] From both an economic[18] and a human impact perspective, there is a strong rationale to invest in efforts to tackle the reality of mental ill-health among the youth population.[2] Efforts to establish a new youth mental health paradigm have already begun and are gaining momentum internationally, reflected most recently in the establishment of a new International Association for Youth Mental Health (http://www.iaymh.org). The first International Youth Mental Health Conference was held in Melbourne, Australia, in 2010 and the second is being held in 2013 in Brighton, the UK (http://www.iaymh2013.com). Those involved in the youth mental health movement recognize that positively impacting on young people\u27s mental health trajectories requires transformative change. Along with a need for early promotion, detection and intervention, stemming the tide of mental ill-health among young people requires a fundamental change in how we think about young people and their mental health. It demands that we challenge traditional approaches to service development and delivery and replace them with approaches that are inclusive and empowering for young people and their families. Young people and their families need to be involved in designing and implementing more creative, responsive, accessible and youth-friendly mental health services that have the capacity to meet their needs

Impact of rapid near-patient STI testing on service delivery outcomes in an integrated sexual health service in the United Kingdom:a controlled interrupted time series study

OBJECTIVES: To evaluate the impact of a new clinic-based rapid sexually transmitted infection testing, diagnosis and treatment service on healthcare delivery and resource needs in an integrated sexual health service. DESIGN: Controlled interrupted time series study. SETTING: Two integrated sexual health services (SHS) in UK: Unity Sexual Health in Bristol, UK (intervention site) and Croydon Sexual Health in London (control site). PARTICIPANTS: Electronic patient records for all 58 418 attendances during the period 1 year before and 1 year after the intervention. INTERVENTION: Introduction of an in-clinic rapid testing system for gonorrhoea and chlamydia in combination with revised treatment pathways. OUTCOME MEASURES: Time-to-test notification, staff capacity, cost per episode of care and overall service costs. We also assessed rates of gonorrhoea culture swabs, follow-up attendances and examinations. RESULTS: Time-to-notification and the rate of gonorrhoea swabs significantly decreased following implementation of the new system. There was no evidence of change in follow-up visits or examination rates for patients seen in clinic related to the new system. Staff capacity in clinics appeared to be maintained across the study period. Overall, the number of episodes per week was unchanged in the intervention site, and the mean cost per episode decreased by 7.5% (95% CI 5.7% to 9.3%). CONCLUSIONS: The clear improvement in time-to-notification, while maintaining activity at a lower overall cost, suggests that the implementation of clinic-based testing had the intended impact, which bolsters the case for more widespread rollout in sexual health services