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.

Functional behavioral analysis and social scripting for the older patient with schizophrenia: a staff development program.

Executive functioning is the ability to plan, strategize, organize, and focus on details. Impaired executive functioning plays a significant role in behavior disturbances. Lack of inhibition, impaired abstract reasoning, thought perseverance, rigidity in routine, and lack of insight disrupt social skills and daily life. Autism and schizophrenia present some similar behaviors, including impaired executive functioning, often resulting in pharmacological management as many healthcare professionals receive limited training in executive functioning. Non-pharmacological tools used in autism for behavior management include functional behavioral analysis and social scripting, which help to identify causes of behavior and teach more appropriate behavioral responses. Described here is an educational program for healthcare workers in a long-term care skilled nursing facility, to help them understand the basis for behaviors in individuals with impaired executive function, to use these same tools for behavioral modification techniques, and to help patients learn more appropriate social skills. Program evaluation suggested the educational program was successful in increasing the staff's knowledge and comfort level in addressing the behavioral issues that arise with this population and staff also reported less use of medication as first-line treatment for behavioral issues.

Chromatin remodeler BRG1 recruits huntingtin to repair DNA double-strand breaks in neurons.

Persistent DNA double-strand breaks (DSBs) are enigmatically implicated in neurodegenerative diseases including Huntington's disease (HD), the inherited late-onset disorder caused by CAG repeat elongations in Huntingtin (HTT). Here we combine biochemistry, computation and molecular cell biology to unveil a mechanism whereby HTT coordinates a Transcription-Coupled Non-Homologous End-Joining (TC-NHEJ) complex. HTT joins TC-NHEJ proteins PNKP, Ku70/80, and XRCC4 with chromatin remodeler Brahma-related Gene 1 (BRG1) to resolve transcription-associated DSBs in brain. HTT recruitment to DSBs in transcriptionally active gene- rich regions is BRG1-dependent while efficient TC-NHEJ protein recruitment is HTT-dependent. Notably, mHTT compromises TC-NHEJ interactions and repair activity, promoting DSB accumulation in HD tissues. Importantly, HTT or PNKP overexpression restores TC-NHEJ in a Drosophila HD model dramatically improving genome integrity, motor defects, and lifespan. Collective results uncover HTT stimulation of DSB repair by organizing a TC-NHEJ complex that is impaired by mHTT thereby implicating dysregulation of transcription-coupled DSB repair in mHTT pathophysiology. Highlights: BRG1 recruits HTT and NHEJ components to transcriptionally active DSBs.HTT joins BRG1 and PNKP to efficiently repair transcription related DSBs in brain.Mutant HTT impairs the functional integrity of TC-NHEJ complex for DSB repair.HTT expression improves DSB repair, genome integrity and phenotypes in HD flies.

Maintenance of response to ketogenic diet therapy for drug-resistant epilepsy post diet discontinuation: A multi-centre case note review.

PURPOSE: There is limited research on the proportion of individuals with epilepsy who maintain response to ketogenic diet therapy (KDT) after discontinuing treatment. We aimed to determine the proportion of individuals who did / did not maintain response post KDT and explore factors that may influence the likelihood of maintaining response. METHODS: Retrospective data were collected from 97 individuals from 9 KDT centres. Individuals had achieved ≥50 % seizure reduction on KDT for at least 12 months, with seizure frequency data available at 3 months+ post diet. Outcome 1 was: recurrence of seizures or increase in seizure frequency post diet; outcome 2: recurrence of seizures, increase in seizure frequency or an additional anti-seizure treatment started post diet. RESULTS: 61/97 (62.9 %) individuals maintained response at latest follow-up (mean 2.5[2.0] years since stopping KDT). Approximately one third maintained response without further anti-seizure treatments. One quarter of individuals had an increase in frequency or recurrence of seizures within 6 months (95 %CI 4, 12) for outcome 1 and within 3 months (3, 6) for outcome 2. Individuals who did not achieve seizure freedom on diet were significantly more likely to have an increase in seizures or to require additional anti-seizure treatments post diet compared to those who were seizure-free on diet (hazard ratio 4.02, 95 %CI (1.46, 11.16) p < 0.01). CONCLUSION: Our findings should help guide clinical teams with the information they provide patients and their families regarding likelihood of long-term seizure response to KDT. Realistic costings for KDT services may need to be considered.

Transition to an electronic professional nurse portfolio: part II.

Part I, published last month, described the background and purpose for a professional portfolio that showcases accomplishments supporting professional goals, scholarship, service, and competency in one's professional nursing practice. This column reviews the benefits, options, and issues to consider when developing a professional portfolio online.

Transition to an electronic professional nurse portfolio: part I.

This column describes the background and purpose for a professional portfolio that showcases accomplishments supporting professional goals, scholarship, service, and competency in one's professional nursing practice. Part II will review the benefits, options, and issues to consider when developing a professional portfolio online.

The flipped classroom for professional development: part II. making podcasts and videos.

As described in Part I, podcasts and videos are educational technologies used to flip the classroom. This column describes the technology options for creating podcasts and videos and offers tips on developing podcasts and videos.

The flipped classroom for professional development: part I. Benefits and strategies.

Individualizing the educational encounter is supported by flipping the classroom experience. This column offers an overview and describes the benefits of flipping the classroom. Part II will explore the practicalities and pedagogy of lecture capture using podcasts and videos, a technology strategy used in flipping the classroom.

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.

Harnessing mobile devices in the classroom.

This column describes the use of mobile devices in the classroom to support nurses' competency in information literacy. Nurses, as knowledge workers, require competency in information literacy and mobile technology to access accurate and current information promptly in practice settings.

Assessment and planning for a dedicated education unit.

This pilot project describes the use of the Revised Professional Practice Environment scale to identify inpatient acute care units suitable for implementation of dedicated education units. Staff development professionals may use the suggested model to assess and plan phases of a dedicated education unit.

Facilitators and barriers to success among ethnic minority students enrolled in a predominately white baccalaureate nursing program.

This study identified facilitators and barriers to academic success among ethnic minority students enrolled in a BSN program. The following research questions were asked: What factors (a) facilitate academic performance; (b) are barriers to academic performance; (c) influence the college experience and academic success; (d) within the nursing department, influence academic success; (e) What is the impact of socialization on academic performance; (f) What were facilitators of academic success identified among study participants; and, (g) Which facilitators, identified by subjects, were most common among those participants? A retrospective-descriptive study design consisted of a sample of all minority students who were enrolled in clinical at a baccalaureate nursing program between 2005 and the fall of 2010. Bandura's theory on self-efficacy was used. Loftus and Duty's Survey of Factors Influencing Student Retention and Academic Success was adapted. Data were analyzed using SPSS 19.0 with ANOVA to determine if a significant difference in responses existed.

A high anisotropy barrier in a sulfur-bridged organodysprosium single-molecule magnet.

The sulfur-bridged dimers [{Cp'(2)Ln(µ-SSiPh(3))}(2)] (Ln=Gd (1), Dy (2); Cp'=η(5)-C(5)H(4)Me) were synthesized by the transmetalation reactions between [Cp'(3)Ln] and Ph(3)SiSLi. Compound 2 is a single-molecule magnet with slow relaxation of magnetization up to 40 K and an anisotropy barrier of U(eff) =133 cm(-1). Insight into the SMM properties of 2 and closely related SMMs has been obtained using ab initio calculations.

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.

Low-loss hollow-core silica/air photonic bandgap fibre.

Photonic bandgap structures use the principle of interference to reflect radiation. Reflection from photonic bandgap structures has been demonstrated in one, two and three dimensions and various applications have been proposed. Early work in hollow-core photonic bandgap fibre technology used a hexagonal structure surrounding the air core; this fibre was the first demonstration of light guided inside an air core of a photonic bandgap fibre. The potential benefits of guiding light in air derive from lower Rayleigh scattering, lower nonlinearity and lower transmission loss compared to conventional waveguides. In addition, these fibres offer a new platform for studying nonlinear optics in gases. Owing largely to challenges in fabrication, the early air-core fibres were only available in short lengths, and so systematic studies of loss were not possible. More recently, longer lengths of fibre have become available with reported losses of 1,000 dB km(-1). We report here the fabrication and characterization of long lengths of low attenuation photonic bandgap fibre. Attenuation of less than 30 dB km(-1) over a wide transmission window is observed with minimum loss of 13 dB km(-1) at 1,500 nm, measured on 100 m of fibre. Coupling between surface and core modes of the structure is identified as an important contributor to transmission loss in hollow-core photonic bandgap fibres.

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.

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.

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.