Impact and process evaluation of a primary-school Food Education and Sustainability Training (FEAST) program in 10-12-year-old children in Australia: pragmatic cluster non-randomized controlled trial.

BACKGROUND: Environmentally sustainable food initiatives accompanying nutrition education, such as the Food Education and Sustainability Training (FEAST) program, have gained traction in school settings. The aim of this trial was to conduct an impact and process evaluation of FEAST, to evaluate its effect on children's fruit and vegetable (F&V) intakes, and secondary outcomes: F&V variety consumed, nutrition knowledge, food preparation/cooking skills, self-efficacy and behaviours, food waste knowledge and behaviours, and food production knowledge. METHODS: FEAST was a 10-week curriculum-aligned program, designed to educate children about healthy eating, food waste, and sustainability, while teaching cooking skills. It was implemented by classroom teachers, face-to-face and online, during COVID-19 school closures, in Australia in 2021. A custom designed survey was used to collect baseline and post-intervention data from students. Generalised linear mixed models (GLMM) estimated group differences in pre-post changes for primary and secondary outcomes. Surveys were also administered to students and teachers to evaluate intervention implementation. RESULTS: Twenty schools participated and self-selected to be either intervention schools (n = 10) or wait-list control (WLC) schools (n = 10). A total of 977, 5th and 6th grade children participated in the trial with a mean age of 11.1 years (SD ± 0.7). The FEAST intervention, compared to WLC, did not result in significant increases in primary outcomes nor secondary outcomes. The process evaluation revealed FEAST was well-received by students and teachers, but COVID-19 school closures hindered implementation fidelity with a less intense program delivered under the constraints of pandemic lockdowns. CONCLUSIONS: This is the first cluster non-randomized controlled trial designed to independently evaluate FEAST in the primary-school setting. No evidence was found for improved F&V intakes in children, nor secondary outcomes. However, the positive process evaluation results suggest that further trials of the program are warranted. If implemented as originally designed (pre-pandemic), with increased duration and complemented by supporting school policies, such programs have the potential to improve children's daily F&V intakes, cooking skills and food waste behaviours. This would support the Australian curriculum and contribute to: health promotion within schools and sustainable schools initiatives, the national agenda to reduce food waste and sustainable development goals. AUSTRALIAN AND NEW ZEALAND CLINICAL TRIALS REGISTRY: [ACTRN12620001347954]- Registered prospectively on 14/12/2020.

The Impacts of the Molecular Education and Research Consortium in Undergraduate Computational Chemistry on the Careers of Women in Computational Chemistry.

The Molecular Education and Research Consortium in Undergraduate Computational Chemistry (MERCURY) has supported a diverse group of faculty and students for over 20 years by providing computational resources as well as networking opportunities and professional support. The consortium comprises 38 faculty (42% women) at 34 different institutions, who have trained nearly 900 undergraduate students, more than two-thirds of whom identify as women and one-quarter identify as students of color. MERCURY provides a model for the support necessary for faculty to achieve professional advancement and career satisfaction. The range of experiences and expertise of the consortium members provides excellent networking opportunities that allow MERCURY faculty to support each other's teaching, research, and service needs, including generating meaningful scientific advancements and outcomes with undergraduate researchers as well as being leaders at the departmental, institutional, and national levels. While all MERCURY faculty benefit from these supports, the disproportionate number of women in the consortium, relative to their representation in computational sciences generally, produces a sizable impact on advancing women in the computational sciences. In this report, the women of MERCURY share how the consortium has benefited their careers and the careers of their students.

A disordered encounter complex is central to the yeast Abp1p SH3 domain binding pathway.

Protein-protein interactions are involved in a wide range of cellular processes. These interactions often involve intrinsically disordered proteins (IDPs) and protein binding domains. However, the details of IDP binding pathways are hard to characterize using experimental approaches, which can rarely capture intermediate states present at low populations. SH3 domains are common protein interaction domains that typically bind proline-rich disordered segments and are involved in cell signaling, regulation, and assembly. We hypothesized, given the flexibility of SH3 binding peptides, that their binding pathways include multiple steps important for function. Molecular dynamics simulations were used to characterize the steps of binding between the yeast Abp1p SH3 domain (AbpSH3) and a proline-rich IDP, ArkA. Before binding, the N-terminal segment 1 of ArkA is pre-structured and adopts a polyproline II helix, while segment 2 of ArkA (C-terminal) adopts a 310 helix, but is far less structured than segment 1. As segment 2 interacts with AbpSH3, it becomes more structured, but retains flexibility even in the fully engaged state. Binding simulations reveal that ArkA enters a flexible encounter complex before forming the fully engaged bound complex. In the encounter complex, transient nonspecific hydrophobic and long-range electrostatic contacts form between ArkA and the binding surface of SH3. The encounter complex ensemble includes conformations with segment 1 in both the forward and reverse orientation, suggesting that segment 2 may play a role in stabilizing the correct binding orientation. While the encounter complex forms quickly, the slow step of binding is the transition from the disordered encounter ensemble to the fully engaged state. In this transition, ArkA makes specific contacts with AbpSH3 and buries more hydrophobic surface. Simulating the binding between ApbSH3 and ArkA provides insight into the role of encounter complex intermediates and nonnative hydrophobic interactions for other SH3 domains and IDPs in general.

Evaluating OzHarvest's primary-school Food Education and Sustainability Training (FEAST) program in 10-12-year-old children in Australia: protocol for a pragmatic cluster non-randomized controlled trial.

BACKGROUND: The promotion of healthy eating is a public health priority. Poor dietary behaviours, including low fruit and vegetable (F&V) consumption are of particular concern among children. Novel nutrition promotion strategies are needed to improve F&V consumption. Sustainability education could be used to support nutrition education within the school context. The purpose of this paper is to report the protocol for impact and process evaluation of the school-based Food Education and Sustainability Training (FEAST) program, designed to educate children about sustainability, food waste and nutrition, using hands-on cooking activities. METHODS: A pragmatic, parallel, cluster non-randomized controlled trial with pre- and post-measures, will be implemented among 20 primary schools (10 intervention vs 10 wait-list-control) within NSW, Australia, involving children in Grades 5-6. FEAST is a curriculum-aligned program, delivered as a 1.5-h lesson/week, for a 10-week unit of inquiry, incorporating theory and cooking. FEAST was developed using theoretical frameworks which included Social Cognitive Theory and the Precede-Proceed Planning model. Primary outcomes include children's self-reported F&V intakes (serves/day). Food literacy constructs such as: nutrition knowledge, food preparation and cooking skills, self-efficacy and behaviours, food waste knowledge and behaviours and food production knowledge, will be assessed as secondary outcomes. Process evaluation will assess program reach, adoption, implementation, maintenance, satisfaction and perceived benefits by teachers and students. An online survey (including quantitative and qualitative questions) was developed for administration at baseline (impact evaluation) and immediately post-intervention (impact and process evaluation). Intervention effects on quantitative study outcomes will be estimated with ​generalised linear mixed models, including random effects and will follow the intention-to-treat principles. Open-ended questions embedded within the surveys will be analysed qualitatively using content and thematic analyses. DISCUSSION: Results from this trial will provide valuable information on the value of adding environmental sustainability strategies to nutrition education in schools. Results will inform the design of future research and programs focused on primary-school children's nutrition, sustainability-related behaviours and experiential school-based interventions. TRIAL REGISTRATION: Trial registered 14th December 2020 with the Australian and New Zealand Clinical Trials Registry ( ACTRN12620001347954 ).

Conformational Dynamics of the HIV-Vif Protein Complex.

Human immunodeficiency virus-1 viral infectivity factor (Vif) is an intrinsically disordered protein responsible for the ubiquitination of the APOBEC3 (A3) antiviral proteins. Vif folds when it binds Cullin-RING E3 ligase 5 and the transcription cofactor CBF-ß. A five-protein complex containing the substrate receptor (Vif, CBF-ß, Elongin-B, Elongin-C (VCBC)) and Cullin5 (CUL5) has a published crystal structure, but dynamics of this VCBC-CUL5 complex have not been characterized. Here, we use molecular dynamics (MD) simulations and NMR to characterize the dynamics of the VCBC complex with and without CUL5 and an A3 protein bound. Our simulations show that the VCBC complex undergoes global dynamics involving twisting and clamshell opening of the complex, whereas VCBC-CUL5 maintains a more static conformation, similar to the crystal structure. This observation from MD is supported by methyl-transverse relaxation-optimized spectroscopy NMR data, which indicates that the VCBC complex without CUL5 is dynamic on the µs-ms timescale. Our NMR data also show that the VCBC complex is more conformationally restricted when bound to the antiviral APOBEC3F (one of the A3 proteins), consistent with our MD simulations. Vif contains a flexible linker region located at the hinge of the VCBC complex, which changes conformation in conjunction with the global dynamics of the complex. Like other substrate receptors, VCBC can exist alone or in complex with CUL5 and other proteins in cells. Accordingly, the VCBC complex could be a good target for therapeutics that would inhibit full assembly of the ubiquitination complex by stabilizing an alternate VCBC conformation.

A pilot intervention to reduce postpartum weight retention and central adiposity in first-time mothers: results from the mums OnLiNE (Online, Lifestyle, Nutrition & Exercise) study.

BACKGROUND: Postpartum weight retention (PPWR) increases the risk for obesity and complications during subsequent pregnancies. Few interventions have been successful in limiting PPWR in mothers. The present study assessed the effectiveness of the mums OnLiNE (Online, Lifestyle, Nutrition & Exercise) intervention with respect to reducing PPWR and improving diet, physical activity and sedentary behaviour. METHODS: A subsample of first-time mothers enrolled in the Extended Melbourne Infant Feeding Activity and Nutrition Trial (InFANT Extend) completed the nonrandomised mums OnLiNE intervention. Women in the intervention (I) group (n = 28) received access to an online calorie tracking program, smartphone app, three telephone counselling calls with a dietitian and written material. Women in two comparison groups (CI and C2) (n = 48; n = 43) were from the control (C1) and intervention (C2) arms of InFANT Extend and received no additional support. Weight and waist circumference were measured objectively. Written surveys assessed diet and physical activity. Sedentary behaviour was self-reported. Linear and logistic regression assessed changes in outcomes between groups from 9 to 18 months postpartum. RESULTS: Mean PPWR decreased in the (I) group (-1.2 kg) and the C2 group (-1.2 kg), although the changes were not significant. Mean waist circumference for all groups exceeded recommendations at baseline but decreased to below recommendations for women in the (I) group (78.3 cm) and significantly for the (I) group (-6.4 cm) compared to C1 (-1.1 cm; P = 0.002) and C2 (-3.3 cm; P = 0.001). Changes in diet, physical activity or sedentary behaviour were not significant. CONCLUSIONS: The online intervention reported in the present study shows promise with respect to reducing waist circumference in postpartum women. Further evidence of strategies that may improve weight and related behaviours in this target group is needed.

Validity of an ultra-wideband local positioning system to measure locomotion in indoor sports.

The validity of an Ultra-wideband (UWB) positioning system was investigated during linear and change-of-direction (COD) running drills. Six recreationally-active men performed ten repetitions of four activities (walking, jogging, maximal acceleration, and 45º COD) on an indoor court. Activities were repeated twice, in the centre of the court and on the side. Participants wore a receiver tag (Clearsky T6, Catapult Sports) and two reflective markers placed on the tag to allow for comparisons with the criterion system (Vicon). Distance, mean and peak velocity, acceleration, and deceleration were assessed. Validity was assessed via percentage least-square means difference (Clearsky-Vicon) with 90% confidence interval and magnitude-based inference; typical error was expressed as within-subject standard deviation. The mean differences for distance, mean/peak speed, and mean/peak accelerations in the linear drills were in the range of 0.2-12%, with typical errors between 1.2 and 9.3%. Mean and peak deceleration had larger differences and errors between systems. In the COD drill, moderate-to-large differences were detected for the activity performed in the centre of the court, increasing to large/very large on the side. When filtered and smoothed following a similar process, the UWB-based positioning system had acceptable validity, compared to Vicon, to assess movements representative of indoor sports.

A pilot investigation on the effects of combination transcranial direct current stimulation and speed of processing cognitive remediation therapy on simulated driving behavior in older adults with HIV.

Cognitive impairments seen in people living with HIV (PLWH) are associated with difficulties in everyday functioning, specifically driving. This study utilized speed of processing cognitive remediation therapy (SOP-CRT) with transcranial direct current stimulation (tDCS) to gauge the feasibility and impact on simulated driving. Thirty PLWH (M age = 54.53, SD = 3.33) were randomly assigned to either: sham tDCS SOP-CRT or active tDCS SOP-CRT. Seven indicators of simulated driving performance and safety were obtained. Repeated measures ANOVAs controlling for driver's license status (valid and current license or expired/no license) revealed a large training effect on average driving speed. Participants who received active tDCS SOP-CRT showed a slower average driving speed (p = 0.020, d = 0.972) than those who received sham tDCS SOP-CRT. Non-significant small-to-medium effects were seen for driving violations, collisions, variability in lane positioning, and lane deviations. Combination tDCS SOP-CRT was found to increase indices of cautionary simulated driving behavior. Findings reveal a potential avenue of intervention and rehabilitation for improving driving safety among vulnerable at-risk populations, such as those aging with chronic disease.

Non-degradative Ubiquitination of Protein Kinases.

Growing evidence supports other regulatory roles for protein ubiquitination in addition to serving as a tag for proteasomal degradation. In contrast to other common post-translational modifications, such as phosphorylation, little is known about how non-degradative ubiquitination modulates protein structure, dynamics, and function. Due to the wealth of knowledge concerning protein kinase structure and regulation, we examined kinase ubiquitination using ubiquitin remnant immunoaffinity enrichment and quantitative mass spectrometry to identify ubiquitinated kinases and the sites of ubiquitination in Jurkat and HEK293 cells. We find that, unlike phosphorylation, ubiquitination most commonly occurs in structured domains, and on the kinase domain, ubiquitination is concentrated in regions known to be important for regulating activity. We hypothesized that ubiquitination, like other post-translational modifications, may alter the conformational equilibrium of the modified protein. We chose one human kinase, ZAP-70, to simulate using molecular dynamics with and without a monoubiquitin modification. In Jurkat cells, ZAP-70 is ubiquitinated at several sites that are not sensitive to proteasome inhibition and thus may have other regulatory roles. Our simulations show that ubiquitination influences the conformational ensemble of ZAP-70 in a site-dependent manner. When monoubiquitinated at K377, near the C-helix, the active conformation of the ZAP-70 C-helix is disrupted. In contrast, when monoubiquitinated at K476, near the kinase hinge region, an active-like ZAP-70 C-helix conformation is stabilized. These results lead to testable hypotheses that ubiquitination directly modulates kinase activity, and that ubiquitination is likely to alter structure, dynamics, and function in other protein classes as well.

A mobile health intervention promoting healthy gestational weight gain for women entering pregnancy at a high body mass index: the txt4two pilot randomised controlled trial.

OBJECTIVE: To determine the feasibility and effectiveness of an mHealth intervention promoting healthy diet, physical activity and gestational weight gain in pregnant women. DESIGN: Randomised controlled trial (RCT). SETTING: Australian tertiary obstetric hospital. POPULATION: One hundred pregnant women who were overweight or obese prior to pregnancy. METHODS: Women recruited at the first antenatal clinic visit were randomised to either an intervention or a control group. The intervention consisted of a tailored suite of strategies delivered (from first antenatal visit until 36 weeks' gestation) via multiple modalities available on mobile devices. MAIN OUTCOME MEASURES: The primary outcome was intervention feasibility and secondary outcomes were objectively measured changes in gestational weight gain (GWG) and self-reported dietary intake and physical activity. RESULTS: Ninety-one women completed the study. Delivery to protocol provides evidence of program feasibility. Most women engaged regularly with the program, with the majority (97.6%) reporting that the intervention was helpful. Secondary outcomes demonstrated a significantly lower GWG in the intervention group (7.8 kg ± 4.7 versus 9.7 kg ± 3.9; P =0.041) compared with the control group at intervention completion. Intervention group women reported significantly smaller reductions in total, light- and moderate-intensity physical activity from baseline to completion of the intervention (P = 0.001) compared with the control group, but no differences in consumption frequencies of key food groups. CONCLUSION: An intervention that aimed to deliver healthy diet, physical activity and GWG guidance utilising innovative technology can be feasibly implemented and produce positive physical activity and GWG outcomes. TWEETABLE ABSTRACT: txt4two mHealth study improved gestational weight gain and physical activity in pregnant women with high BMIs.

Translating an early childhood obesity prevention program for local community implementation: a case study of the Melbourne InFANT Program.

BACKGROUND: While there is a growing interest in the field of research translation, there are few published examples of public health interventions that have been effectively scaled up and implemented in the community. This paper provides a case study of the community-wide implementation of the Melbourne Infant, Feeding, Activity and Nutrition Trial (InFANT), an obesity prevention program for parents with infants aged 3-18 months. The study explored key factors influencing the translation of the Program into routine practice and the respective role of policy makers, researchers and implementers. METHODS: Case studies were conducted of five of the eight prevention areas in Victoria, Australia who implemented the Program. Cases were selected on the basis of having implemented the Program for 6 months or more. Data were collected from January to June 2015 and included 18 individual interviews, one focus group and observation of two meetings. A total of 28 individuals, including research staff (n = 4), policy makers (n = 2) and implementers (n = 22), contributed to the data collected. Thematic analysis was conducted using cross case comparisons and key themes were verified through member checking. RESULTS: Key facilitators of implementation included availability of a pre-packaged evidence based program addressing a community need, along with support and training provided by research staff to local implementers. Partnerships between researchers and policy makers facilitated initial program adoption, while local partnerships supported community implementation. Community partnerships were facilitated by local coordinators through alignment of program goals with existing policies and services. Workforce capacity for program delivery and administration was a challenge, largely overcome by embedding the Program into existing roles. Adapting the Program to fit local circumstance was critical for feasible and sustainable delivery, however balancing this with program fidelity was a critical issue. The lack of ongoing funding to support translation activities was a barrier for researchers continued involvement in community implementation. CONCLUSION: Policy makers, researchers and practitioners have important and complementary roles to play in supporting the translation of effective research interventions into practice. New avenues need to be explored to strengthen partnerships between researchers and end users to support the integration of effective public health research interventions into practice.

Trends in body mass index according to educational attainment for urban Australian adults between 1980 and 2007.

BACKGROUND: We have previously demonstrated that between the years 1980 and 2000, the mean body mass index (BMI) of the urban Australian population increased, with greater increases observed with increasing BMI. The current study aimed to quantify trends over time in BMI according to level of education between 1980 and 2007. METHODS: We compared data from the 1980, 1983 and 1989 National Heart Foundation Risk Factor Prevalence Studies, 1995 National Nutrition Survey, 2000 Australian Diabetes, Obesity and Lifestyle Study and the 2007 National Health Survey. For survey comparability, analyses were restricted to urban Australian residents aged 25-64 years. BMI was calculated from measured height and weight. The education variable was dichotomised at completion of secondary school. Four age-standardised BMI indicators were compared over time by sex and education: mean BMI, mean BMI of the top 5% of the BMI distribution, prevalence of obesity (BMI⩾30 kg m(-)(2)), prevalence of class II(+) obesity (BMI⩾35 kg m(-)(2)). RESULTS: Between 1980 and 2007, the mean BMI among men increased by 2.5 and 1.7 kg m(-)(2) for those with low and high education levels, respectively, corresponding to increases in obesity prevalence of 20 (from 12-32%) and 11 (10-21%) %-points. Among women, mean BMI increased by 2.9 and 2.4 kg m(-)(2) for those with low and high education levels, respectively, corresponding to increases in obesity prevalence of 16 (12-28%) and 12 (7-19%) %-points. The prevalence of class II(+) obesity among men increased by 9 (1-10%) and 4 (1-5%) %-points for those with low and high education levels, and among women increased by 8 (4-12%) and 4 (2-6%) %-points. Absolute and relative differences between education groups generally increased over time. CONCLUSIONS: Educational differences in BMI have persisted among urban Australian adults since 1980 without improvement. Obesity prevention policies will need to be effective in those with greatest socio-economic disadvantage if we are to equitably and effectively address the population burden of obesity and its corollaries.

A facile method for expression and purification of (15)N isotope-labeled human Alzheimer's ß-amyloid peptides from E. coli for NMR-based structural analysis.

Alzheimer's disease (AD) is a progressive neurodegenerative disease affecting millions of people worldwide. AD is characterized by the presence of extracellular plaques composed of aggregated/oligomerized ß-amyloid peptides with Aß42 peptide representing a major isoform in the senile plaques. Given the pathological significance of Aß42 in the progression of AD, there is considerable interest in understanding the structural ensembles for soluble monomer and oligomeric forms of Aß42. This report describes an efficient method to express and purify high quality (15)N isotope-labeled Aß42 for structural studies by NMR. The protocol involves utilization of an auto induction system with (15)N isotope labeled medium, for high-level expression of Aß42 as a fusion with IFABP. After the over-expression of the (15)N isotope-labeled IFABP-Aß42 fusion protein in the inclusion bodies, pure (15)N isotope-labeled Aß42 peptide is obtained following a purification method that is streamlined and improved from the method originally developed for the isolation of unlabeled Aß42 peptide (Garai et al., 2009). We obtain a final yield of ∼ 6 mg/L culture for (15)N isotope-labeled Aß42 peptide. Mass spectrometry and (1)H-(15)N HSQC spectra of monomeric Aß42 peptide validate the uniform incorporation of the isotopic label. The method described here is equally applicable for the uniform isotope labeling with (15)N and (13)C in Aß42 peptide as well as its other variants including any Aß42 peptide mutants.

Obesity prevention in early life: an opportunity to better support the role of Maternal and Child Health Nurses in Australia.

BACKGROUND: Because parents with young children access primary health care services frequently, a key opportunity arises for Maternal and Child Health (MCH) nurses to actively work with families to support healthy infant feeding practices and lifestyle behaviours. However, little is known regarding the extent to which MCH nurses promote obesity prevention practices and how such practices could be better supported. METHODS: This mixed methods study involved a survey of 56 MCH nurses (response rate 84.8 %), 16 of whom participated in semi-structured qualitative interviews. Both components aimed to examine the extent to which nurses addressed healthy infant feeding practices, healthy eating, active play and limiting sedentary behavior during routine consultations with young children 0-5 years. Key factors influencing such practices and how they could be best supported were also investigated. All data were collected from September to December 2013. Survey data were analysed descriptively and triangulated with qualitative interview findings, the analysis of which was guided by grounded theory principles. RESULTS: Although nurses reported measuring height/length and weight in most consultations, almost one quarter (22.2 %) reported never/rarely using growth charts to identify infants or children at risk of overweight or obesity. This reflected a reluctance to raise the issue of weight with parents and a lack of confidence in how to address it. The majority of nurses reported providing advice on aspects of infant feeding relevant to obesity prevention at most consultations, with around a third (37 %) routinely provided advice on formula preparation. Less than half of nurses routinely promoted active play and only 30 % discussed limiting sedentary behaviour such as TV viewing. Concerns about parental receptiveness and maintaining rapport were key barriers to more effective implementation. CONCLUSION: While MCH nurses are well placed to address obesity prevention in early life, there is currently a missed public health opportunity. Improving nurse skills in behaviour change counseling will be key to increasing their confidence in raising sensitive lifestyle issues with parents to better integrate obesity prevention practices into normal MCH service delivery.

Efficient derivation of cortical glutamatergic neurons from human pluripotent stem cells: a model system to study neurotoxicity in Alzheimer's disease.

Alzheimer's disease (AD) is among the most prevalent forms of dementia affecting the aging population, and pharmacological therapies to date have not been successful in preventing disease progression. Future therapeutic efforts may benefit from the development of models that enable basic investigation of early disease pathology. In particular, disease-relevant models based on human pluripotent stem cells (hPSCs) may be promising approaches to assess the impact of neurotoxic agents in AD on specific neuronal populations and thereby facilitate the development of novel interventions to avert early disease mechanisms. We implemented an efficient paradigm to convert hPSCs into enriched populations of cortical glutamatergic neurons emerging from dorsal forebrain neural progenitors, aided by modulating Sonic hedgehog (Shh) signaling. Since AD is generally known to be toxic to glutamatergic circuits, we exposed glutamatergic neurons derived from hESCs to an oligomeric pre-fibrillar forms of Aß known as "globulomers", which have shown strong correlation with the level of cognitive deficits in AD. Administration of such Aß oligomers yielded signs of the disease, including cell culture age-dependent binding of Aß and cell death in the glutamatergic populations. Furthermore, consistent with previous findings in postmortem human AD brain, Aß-induced toxicity was selective for glutamatergic rather than GABAeric neurons present in our cultures. This in vitro model of cortical glutamatergic neurons thus offers a system for future mechanistic investigation and therapeutic development for AD pathology using human cell types specifically affected by this disease.

Efficacy of gallium maltolate against Lawsonia intracellularis infection in a rabbit model.

Antimicrobial efficacy against Lawsonia intracellularis is difficult to evaluate in vitro, thus, the effects of gallium maltolate's (GaM) were investigated in a rabbit model for equine proliferative enteropathy (EPE). Juvenile (5-6-week-old) does were infected with 3.0 × 10(8) L. intracellularis/rabbit and allocated into three groups (n = 8). One week postinfection, one group was treated with GaM, 50 mg/kg; one, with doxycycline, 5 mg/kg; and one with a sham-treatment (control). Feces and blood were collected daily and weekly, respectively, to verify presence of L. intracellularis fecal shedding using qPCR, and seroconversion using immunoperoxidase monolayer assay. Rabbits were sacrificed after 1 week of treatment to collect intestinal tissues focusing on EPE-affected sections. Intestinal lesions were confirmed via immunohistochemistry. No difference was noted between treatments regarding EPE-lesions in jejunum (P = 0.51), ileum (P = 0.74), and cecum (P = 0.35), or in L. intracellularis fecal shedding (P = 0.64). GaM and doxycycline appear to have similar efficacy against EPE in infected rabbits.

Pharmacokinetics of gallium maltolate in Lawsonia intracellularis-infected and uninfected rabbits.

Oral gallium maltolate (GaM) pharmacokinetics (PK) and intestinal tissue (IT) concentrations of elemental gallium ([Ga]) and iron ([Fe]) were investigated in a rabbit model of equine proliferative enteropathy (EPE). New Zealand white does (uninfected controls and EPE-infected, n = 6/group) were given a single oral GaM dose (50 mg/kg). Serial blood samples were collected from 0 to 216 h post-treatment (PT) and IT samples after euthanasia. Serology, qPCR, and immunohistochemistry confirmed, or excluded, EPE. Blood and IT [Ga] and [Fe] were determined using inductively coupled plasma-mass spectrometry. PK parameters were estimated through noncompartmental approaches. For all statistical comparisons on [Ga] and [Fe] α = 5%. The Ga log-linear terminal phase rate constant was lower in EPE rabbits vs. uninfected controls [0.0116 ± 0.004 (SD) vs. 0.0171 ± 0.0028 per hour; P = 0.03]; but half-life (59.4 ± 24.0 vs. 39.4 ± 10.8 h; P = 0.12); Cmax (0.50 ± 0.21 vs. 0.59 ± 0.42 µg/mL; P = 0.45); tmax (1.75 ± 0.41 vs. 0.9 ± 0.37 h; P = 0.20); and oral clearance (6.743 ± 1.887 vs. 7.208 ± 2.565 L/h; P = 0.74) were not. IT's [Ga] and [Fe] were higher (P < 0.0001) in controls. In conclusion, although infection reduces IT [Ga] and [Fe], a 48 h GaM dosing interval is appropriate for multidose studies in EPE rabbits.

Differences in ß-strand populations of monomeric Aß40 and Aß42.

Using homonuclear (1)H NOESY spectra, with chemical shifts, (3)JH(N)H(α) scalar couplings, residual dipolar couplings, and (1)H-(15)N NOEs, we have optimized and validated the conformational ensembles of the amyloid-ß 1-40 (Aß40) and amyloid-ß 1-42 (Aß42) peptides generated by molecular dynamics simulations. We find that both peptides have a diverse set of secondary structure elements including turns, helices, and antiparallel and parallel ß-strands. The most significant difference in the structural ensembles of the two peptides is the type of ß-hairpins and ß-strands they populate. We find that Aß42 forms a major antiparallel ß-hairpin involving the central hydrophobic cluster residues (16-21) with residues 29-36, compatible with known amyloid fibril forming regions, whereas Aß40 forms an alternative but less populated antiparallel ß-hairpin between the central hydrophobic cluster and residues 9-13, that sometimes forms a ß-sheet by association with residues 35-37. Furthermore, we show that the two additional C-terminal residues of Aß42, in particular Ile-41, directly control the differences in the ß-strand content found between the Aß40 and Aß42 structural ensembles. Integrating the experimental and theoretical evidence accumulated over the last decade, it is now possible to present monomeric structural ensembles of Aß40 and Aß42 consistent with available information that produce a plausible molecular basis for why Aß42 exhibits greater fibrillization rates than Aß40.

High-intensity re-warm-ups enhance soccer performance.

The effects of high-intensity, short-duration, re-warm-ups on team-sport-related performance were investigated. In a randomised, cross-over study, participants performed 2×26-min periods of an intermittent activity protocol (IAP) on a non-motorized treadmill, interspersed by 15-min of passive recovery (CON); 3-min small-sided game (SSG); or a 5RM leg-press. Measures included counter-movement jump, repeated-sprint, the Loughborough soccer passing test (LSPT), blood lactate concentration, heart-rate, and perceptual measures. Data were analyzed using effect size (90% confidence intervals), and percentage change; determining magnitudes of effects. A 5RM re-warm-up improved flight-time to contraction-time ratio when compared to SSG (9.8%, ES; 0.5±0.3) and CON (ES: 9.4%, 0.7±0.5) re-warm-ups, remaining higher following the second IAP (8.8%, ES; 0.5±0.3 and 10.2%, ES; 0.6±0.6, respectively). Relative-maximum rate-of-force development was greater in the 5RM condition following the second IAP compared to SSG (29.3%, ES; 0.7±0.5) and CON (16.2%, ES; 0.6±0.6). Repeated-sprint ability during the second IAP improved in the 5RM re-warm-up; peak velocity, mean velocity, and acceleration were 4, 3, and 18% greater, respectively. Within groups, the SSG re-warm-up improved LSPT performance post-intervention; 6.4% (ES: 0.6±0.8) and following the second IAP 6.2% (ES: 0.6±0.6), compared to pre-intervention. A 5RM leg-press re-warm-up improved physical performance, while a SSG re-warm-up enhanced skill execution following standardized intermittent exercise.

What helps children to be more active and less sedentary? Perceptions of mothers living in disadvantaged neighbourhoods.

BACKGROUND: Increasing children's participation in physical activity and decreasing time spent in sedentary behaviours is of great importance to public health. Despite living in disadvantaged neighbourhoods, some children manage to engage in health-promoting physical activity and avoid high levels of screen-based activities (i.e. watching TV, computer use and playing electronic games). Understanding how these children manage to do well and whether there are unique features of their home or neighbourhood that explain their success is important for informing strategies targeting less active and more sedentary children. The aim of this qualitative study was to gain in-depth insights from mothers regarding their child's resilience to low physical activity and high screen-time. METHODS: Semi-structured face-to-face interviews were conducted with 38 mothers of children who lived in disadvantaged neighbourhoods in urban and rural areas of Victoria, Australia. The interviews were designed to gain in-depth insights about perceived individual, social and physical environmental factors influencing resilience to low physical activity and high screen-time. RESULTS: Themes relating to physical activity that emerged from the interviews included: parental encouragement, support and modelling; sports culture in a rural town; the physical home and neighbourhood environment; child's individual personality; and dog ownership. Themes relating to screen-time behaviours encompassed: parental control; and child's individual preferences. CONCLUSIONS: The results offer important insights into potential avenues for developing 'resilience' and increasing physical activity and reducing screen-time among children living in disadvantaged neighbourhoods. In light of the negative effects of low physical activity and high levels of screen-time on children's health, this evidence is urgently needed.