BDNF and TRiC-inspired reagent rescue cortical synaptic deficits in a mouse model of Huntington's disease.

Synaptic changes are early manifestations of neuronal dysfunction in Huntington's disease (HD). However, the mechanisms by which mutant HTT protein impacts synaptogenesis and function are not well understood. Herein we explored HD pathogenesis in the BACHD mouse model by examining synaptogenesis and function in long term primary cortical cultures. At DIV14 (days in vitro), BACHD cortical neurons showed no difference from WT neurons in synaptogenesis as revealed by colocalization of a pre-synaptic (Synapsin I) and a post-synaptic (PSD95) marker. From DIV21 to DIV35, BACHD neurons showed progressively reduced colocalization of Synapsin I and PSD95 relative to WT neurons. The deficits were effectively rescued by treatment of BACHD neurons with BDNF. The recombinant apical domain of CCT1 (ApiCCT1) yielded a partial rescuing effect. BACHD neurons also showed culture age-related significant functional deficits as revealed by multielectrode arrays (MEAs). These deficits were prevented by BDNF, whereas ApiCCT1 showed a less potent effect. These findings are evidence that deficits in BACHD synapse and function can be replicated in vitro and that BDNF or a TRiC-inspired reagent can potentially be protective against these changes in BACHD neurons. Our findings support the use of cellular models to further explicate HD pathogenesis and potential treatments.

Environmental safety of second and third generation bioplastics in the context of the circular economy.

Bioplastics derived from organic materials other than crude oil are often suggested as sustainable solutions for tackling end-of-life plastic waste, but little is known of their ecotoxicity to aquatic species. Here, we investigated the ecotoxicity of second and third generation bioplastics toward the freshwater zooplankton Daphnia magna. In acute toxicity tests (48 h), survival was impacted at high concentrations (g.L-1 range), within the range of salinity-induced toxicity. Macroalgae-derived bioplastic induced hormetic responses under chronic exposure (21 d). Most biological traits were enhanced from 0.06 to 0.25 g.L-1 (reproduction rate, body length, width, apical spine, protein concentration), while most of these traits returned to controls level at 0.5 g.L-1. Phenol-oxidase activity, indicative of immune function, was enhanced only at the lowest concentration (0.06 g.L-1). We hypothesise these suggested health benefits were due to assimilation of carbon derived from the macroalgae-based bioplastic as food. Polymer identity was confirmed by infra-red spectroscopy. Chemical analysis of each bioplastic revealed low metal abundance whilst non target exploration of organic compounds revealed trace amounts of phthalates and flame retardants. The macroalgae-bioplastic disintegrated completely in compost and biodegraded up to 86 % in aqueous medium. All bioplastics acidified the test medium. In conclusion, the tested bioplastics were classified as environmentally safe. Nonetheless, a reasonable end-of-life management of these safer-by-design materials is advised to ensure the absence of harmful effects at high concentrations, depending on the receiving environment.

Usability survey of an inpatient electronic clinical communication platform at a large New Zealand tertiary hospital.

BACKGROUND: Internationally, there is significant published literature indicating low levels of clinical satisfaction with the digital electronic clinical record. Many New Zealand hospitals are currently undergoing a process of digitisation. The aim of the current study was to determine the usability of the inpatient clinical documentation and communication platform known as Cortex approximately one year after full deployment at Christchurch Hospital. METHODS: Te Whatu Ora - Health New Zealand Waitaha Canterbury staff were invited via their work email to complete an online questionnaire. It was comprised of the System Usability Scale (SUS) survey (industry standard mean scores: 50-69 marginal, and ≥70 acceptable) and one additional question about the participant's clinical profession within the organisation. RESULTS: A total of 144 responses were received during the study period. The median SUS score was 75 with an interquartile range (IQR) of 60-87.5. The median IQR SUS scores did not significantly differ among the different occupation groups: 78 (65-90) for doctors; 70 (57.5-82.5) for nurses; and 73 (55.6-84.4) for allied health staff (p=0.268). Additionally, 70 qualitative responses were recorded. Three themes were identified through the analysis of the participants' responses. These were: the need for integration with other electronic systems; implementation issues; and fine-tuning the functionality of Cortex. CONCLUSIONS: The current study revealed good usability of Cortex. The user experience was equivalent among the various professions of the study's participants (doctors, nurses, and allied health staff). The present study provides a useful benchmark for Cortex at a point-of-time, and it sets up potential to periodically repeat this survey to see how new functionality has added to (or detracted from) its usability.

Increase of Human Milk Fat Inducing Nutritional Ketosis in Exclusively Breastfed Infant, Brought About by Treating the Mother With Ketogenic Dietary Therapy.

INTRODUCTION: Medicalized Ketogenic Therapy is commonly used to treat refractory epilepsy. Patients have varying degrees of seizure or symptom relief, responding at individual levels of ketone production. Typically, initiating the therapy necessitates the discontinuation of breastfeeding. Our case study mother was keen to continue breastfeeding if possible. We were able to achieve this by placing the healthy mother on a ketogenic diet and altering the composition of the mother's own milk. MAIN LACTATION ISSUE: Pediatric Medicalized Ketogenic Therapy is delivered through a ketogenic diet consisting of up to 90% fat, measuring of ingredients to 0.1 g matching a food prescription of fat, protein, and carbohydrate. We placed the mother on a less stringent ketogenic diet achieving 61% fat and measured both infant and mother's blood sugar levels and ketones. The hypothesis was that changes would occur in the mother's own milk fat content, and/or ketones would be passed directly to the infant. If therapeutic levels of ketones were reached in the infant and a reduction in seizures observed, breastfeeding could continue. MANAGEMENT OVERVIEW: Over 3 months we achieved a calorific increase of the mother's mature milk by an additional 134%. The infant was successfully put into nutritional ketosis and visible seizures eliminated. CONCLUSION: Medicalized Ketogenic Therapy can be safely used to treat seizures of breastfeeding infants diagnosed with epilepsy, through management of the mother on a ketogenic diet. Significantly increasing the mature mothers own milk fat component could have implications for other areas, including faltering growth.

Quality of delivery of "right@home": Implementation evaluation of an Australian sustained nurse home visiting intervention to improve parenting and the home learning environment.

BACKGROUND: Home visiting programs are implemented in high income countries to improve outcomes for families with young children. Significant resources are invested in such programs and high quality evaluations are important. In the context of research trials, implementation quality is often poorly reported and, when reported, is variable. This paper presents the quality of implementation of the right@home program, a sustained nurse home visiting intervention trialled in Australia, and delivered in a 'real world' context through usual child and family health services. right@home is structured around the core Maternal Early Childhood Sustained Home-visiting (MECSH) program, which is a salutogenic, child focused prevention model. METHOD: At each visit right@home practitioners completed a checklist detailing the client unique identifier, date of contact and activities undertaken. These checklists were collated to provide data on intervention dose, retention to program completion at child age 2 years, and visit content, which were compared with the program schedule. Quality of family-provider relationship was measured using the Session Rating Scale. Exploratory factor analysis was conducted to identify clusters of activities and allow qualitative assessment of concordance between program aims and program delivery. RESULTS: Of 363 intervention families offered the program, 352 (97·0%) commenced the program and 304 (87·3%) completed the program to child age 2 years. 253 of 352 (71·9%) families who commenced the program received more than 75 percent of scheduled visits including at least one antenatal visit. Families rated the participant-practitioner relationship highly (mean 39.4/40). The factor analysis identified six antenatal and six postnatal components which were concordant with the program aims. CONCLUSIONS: The right@home program was delivered with higher adherence to program dose, schedule and content, and retention than usually reported in other home visiting research. Program compliance may have resulted from program design (visit schedule, dose, content and delivery flexibility) that was consistent with family aims.

A brief survey to identify pregnant women experiencing increased psychosocial and socioeconomic risk.

PROBLEM: Identifying pregnant women whose children are at risk of poorer development in a rapid, acceptable and feasible way. BACKGROUND: A range of antenatal psychosocial and socioeconomic risk factors adversely impact children's health, behaviour and cognition. AIM: Investigate whether a brief, waiting room survey of risk factors identifies women experiencing increased antenatal psychosocial and socioeconomic risk when asked in a private, in-home interview. METHODS: Brief 10-item survey (including age, social support, health, smoking, stress/anxious mood, education, household income, employment) collected from pregnant women attending 10 Australian public birthing hospitals, used to determine eligibility (at least 2 adverse items) for the "right@home" trial. 735 eligible women completed a private, in-home interview (including mental health, wellbeing, substance use, domestic violence, housing problems). Regression models tested for dose-response trends between the survey risk factor count and interview measures. FINDINGS: 38%, 31%, 15% and 16% of women reported a survey count of 2, 3, 4 and 5 or more adverse risk factors, respectively. Dose-response relationships were evident between the survey count and interview measures, e.g. of women with a survey count of 2, 8% reported ever having a drug problem, 4% experienced domestic violence in the last year and 10% experienced housing problems, contrasting with 31%, 31% and 26%, respectively, for women reporting a survey count of 5 or more. DISCUSSION/CONCLUSIONS: A brief, waiting room survey of psychosocial and socioeconomic risk factors concurs with a private antenatal risk factor interview, and could help health professionals quickly identify which women would benefit from more support.

Nurse Home Visiting for Families Experiencing Adversity: A Randomized Trial.

OBJECTIVES: Nurse home visiting (NHV) may redress inequities in children's health and development evident by school entry. We tested the effectiveness of an Australian NHV program (right@home), offered to pregnant women experiencing adversity, hypothesizing improvements in (1) parent care, (2) responsivity, and (3) the home learning environment at child age 2 years. METHODS: A randomized controlled trial of NHV delivered via universal child and family health services was conducted. Pregnant women experiencing adversity (≥2 of 10 risk factors) with sufficient English proficiency were recruited from antenatal clinics at 10 hospitals across 2 states. The intervention comprised 25 nurse visits to child age 2 years. Researchers blinded to randomization assessed 13 primary outcomes, including Home Observation of the Environment (HOME) Inventory (6 subscales) and 25 secondary outcomes. REULTS: Of 1427 eligible women, 722 (50.6%) were randomly assigned; 306 of 363 (84%) women in the intervention and 290 of 359 (81%) women in the control group provided 2-year data. Compared with women in the control group, those in the intervention reported more regular child bedtimes (adjusted odds ratio 1.76; 95% confidence interval [CI] 1.25 to 2.48), increased safety (adjusted mean difference [AMD] 0.22; 95% CI 0.07 to 0.37), increased warm parenting (AMD 0.09; 95% CI 0.02 to 0.16), less hostile parenting (reverse scored; AMD 0.29; 95% CI 0.16 to 0.41), increased HOME parental involvement (AMD 0.26; 95% CI 0.14 to 0.38), and increased HOME variety in experience (AMD 0.20; 95% CI 0.07 to 0.34). CONCLUSIONS: The right@home program improved parenting and home environment determinants of children's health and development. With replicability possible at scale, it could be integrated into Australian child and family health services or trialed in countries with similar child health services.