Introducing First-Year Undergraduate Students the Fundamentals of Antibiotic Sensitivity Testing through a Combined Computer Simulation and Face-to-Face Laboratory Session.

Determining the antibiotic sensitivity of disease-causing microorganisms is a fundamental process in a clinical microbiology laboratory. With the continued use of antibiotics, the emergence of antibiotic resistance has become a significant health issue. However, the principles and laboratory testing to determine antibiotic sensitivity are generally not taught to first-year undergraduate students. This is partly due to the limited time to cover the fundamental biology of microorganisms and the mechanism of action of antibiotics in an introductory course. We overcame these limitations by teaching first-year students the fundamental principles of antibiotic sensitivity using an online data generator/simulation. Using the Kirby-Bauer disk diffusion test, students replicated the effects of antibiotic dose on bacterial growth and determined the antimicrobial susceptibility testing of their allocated bacterium. After 2-3 weeks, the antimicrobial sensitivity testing was replicated in an authentic face-to-face laboratory setting over 2 days. The impact of the intervention on student learning was assessed using a written laboratory report and a short questionnaire containing Likert and free-text questions. Student self-reported understanding of the content rose significantly, with nearly all students passing the written assessment. The approach was found to be enjoyable and interactive and facilitated authentic learning in first-year students. This cohort of students will continue to use more advanced versions of this simulation in future years, allowing for the long-term benefits of this approach to be assessed.

Scalable Science Education via Online Cooperative Questioning.

A critical goal for science education is to design and implement learning activities that develop a deep conceptual understanding, are engaging for students, and are scalable for large classes or those with few resources. Approaches based on peer learning and online technologies show promise for scalability but often lack a grounding in cognitive learning principles relating to conceptual understanding. Here, we present a novel design for combining these elements in a principled way. The design centers on having students author multiple-choice questions for their peers using the online platform PeerWise, where beneficial forms of cognitive engagement are encouraged via a series of supporting activities. We evaluated an implementation of this design within a cohort of 632 students in an undergraduate biochemistry course. Our results show a robust relationship between the quality of question authoring and relevant learning outcomes, even after controlling for the confounding influence of prior grades. We conclude by discussing practical and theoretical implications.

Peppy: A virtual reality environment for exploring the principles of polypeptide structure.

A key learning outcome for undergraduate biochemistry classes is a thorough understanding of the principles of protein structure. Traditional approaches to teaching this material, which include two-dimensional (2D) images on paper, physical molecular modeling kits, and projections of 3D structures into 2D, are unable to fully capture the dynamic 3D nature of proteins. We have built a virtual reality application, Peppy, aimed at facilitating teaching of the principles of protein secondary structure. Rather than attempt to model molecules with the same fidelity to the underlying physical chemistry as existing, research-oriented molecular modelling approaches, we took the more straightforward approach of harnessing the Unity video game physics engine. Indeed, the simplicity and limitations of our model are strengths in a teaching context, provoking questions and thus deeper understanding. Peppy allows exploration of the relative effects of hydrogen bonding (and electrostatic interactions more generally), backbone φ/ψ angles, basic chemical structure, and steric effects on a polypeptide structure in an accessible format that is novel, dynamic, and fun to use. Apart from describing the implementation and use of Peppy, we discuss the outcomes of deploying Peppy in undergraduate biochemistry courses.

Validation of the e-NutLit, an Electronic Tool to Assess Nutrition Literacy.

OBJECTIVE: To validate an electronic nutrition literacy assessment tool (e-NutLit). DESIGN: Cross-sectional. SETTING: An Australian teaching hospital obesity clinic (clinical cohort) and university (dietetic cohort). PARTICIPANTS: A convenience sample of patients with obesity (body mass index > 35 kg m-2) (obese participants [OP]) and dietetic interns (DI). INTERVENTIONS: The e-NutLit was administered to OP and scores were compared with performance on the Newest Vital Sign and e-NutLit scores of the DI to establish construct validity. A subset of OP completed the e-NutLit again to examine instrument temporal stability. Internal consistency was assessed using Cronbach α. MAIN OUTCOME MEASURES: Construct validity, temporal stability, and internal consistency. ANALYSIS: Parametric and nonparametric tests and general linear modeling were used as appropriate. RESULTS: A total of 103 participants completed the study (OP: n = 59; 64.4% female; DI: n = 44; 86.4% female). Newest Vital Sign and e-NutLit scores were significantly and positively associated (rs = 0.66; P <.001). The DI performed significantly better than the OP (OP: 59.7 ± 13.1 percentage points; DI: 83.9 ±â€¯5.5 percentage points; P <.001), further supporting construct validity. The e-NutLit Cronbach α was >0.9 indicating a good level of internal consistency. The OP test and retest scores were not significantly different, supporting instrument temporal stability. CONCLUSION AND IMPLICATIONS: The results support the validity of the e-NutLit, for both clinicians and researchers.

Development of an Athlete Diet Index for Rapid Dietary Assessment of Athletes.

Food-based diet indices provide a practical, rapid, and inexpensive way of evaluating dietary intake. Rather than nutrients, diet indices assess the intake of whole foods and dietary patterns, and compare these with nutrition guidelines. An athlete-specific diet index would offer an efficient and practical way to assess the quality of athletes' diets, guide nutrition interventions, and focus sport nutrition support. This study describes the development and validation of an Athlete Diet Index (ADI). Item development was informed by a review of existing diet indices, relevant literature, and in-depth focus groups with 20 sports nutritionists (median of 11 years' professional experience) from four elite athlete sporting institutes. Focus group data were analyzed (NVivo 11 Pro; QSR International Pty. Ltd., 2017, Melbourne, Australia), and key themes were identified to guide the development of athlete-relevant items. A modified Delphi survey in a subgroup of sports nutritionists (n = 9) supported item content validation. Pilot testing with athletes (n = 15) subsequently informed face validity. The final ADI (n = 68 items) was categorized into three sections. Section A (n = 45 items) evaluated usual intake, special diets or intolerances, dietary habits, and culinary skills. Section B (n = 15 items) assessed training load, nutrition supporting training, and sports supplement use. Section C (n = 8 items) captured the demographic details, sporting type, and caliber. All of the athletes reported the ADI as easy (40%) or very easy (60% of participants) to use and rated the tool as relevant (37%) or very relevant (63% of participants) to athletes. Further evaluation of the ADI, including the development of a scoring matrix and validation compared with established dietary methodology, is warranted.

A method for investigating the cellular response to cyclic tension or compression in three-dimensional culture.

We have an interest in the cellular response to mechanical stimuli, and here describe an in-vitro method to examine the response of cells cultured in a three-dimensional matrix to mechanical compressive and tensile stress. Synthetic aliphatic polyester scaffolds coated with 45S5 bioactive glass were seeded with human dental follicular cells (HDFC), and attached to well inserts and magnetic endplates in six well palates. Scaffolds were subjected to either cyclic 10% tensile deformation, or 8% compression, at 1 Hz and 2 Hz respectively for 6, 24 or 48 h, by uniaxial motion of magnetically-coupled endplates. It was possible to isolate high quality mRNA from cells in these scaffolds, as demonstrated by high RNA integrity numbers scores, and ability to perform meaningful cRNA microarray analysis, in which 669 and 727 genes were consistently upregulated, and 662 and 518 genes down regulated at all times studied under tensile and compressive loading conditions respectively. MetaCore analysis revealed the most regulated gene ontogenies under both loading conditions to be for: cytoskeletal remodelling; cell adhesion-chemokines and adhesion; cytoskeleton remodelling-TGF WNT and cytoskeletal remodelling pathways. We believe the method here described will be of value for analysis of the cellular response to cyclic loading.

Microglia have a more extensive and divergent response to interferon-α compared with astrocytes.

Type I interferons (IFN-I) are crucial for effective antimicrobial defense in the central nervous system (CNS) but also can cause severe neurological disease (termed cerebral interferonopathy) as exemplified by Aicardi-Goutières Syndrome. In the CNS, microglia and astrocytes have essential roles in host responses to infection and injury, with both cell types responding to IFN-I. While the IFN-I signaling pathways are the same in astrocytes and microglia, the extent to which the IFN-I responses of these cells differ, if at all, is unknown. Here we determined the global transcriptional responses of astrocytes and microglia to the IFN-I, IFN-α. We found that under basal conditions, each cell type has a unique gene expression pattern reflective of its developmental origin and biological function. Following stimulation with IFN-α, astrocytes and microglia also displayed a common core response that was characterized by the increased expression of genes required for pathogen detection and elimination. Compared with astrocytes, microglia had a more extensive and diverse response to IFN-α with significantly more genes with expression upregulated (282 vs. 141) and downregulated (81 vs. 3). Further validation was documented for selected IFN-I-regulated genes in a murine model of cerebral interferonopathy. In all, the findings highlight not only overlapping but importantly divergent responses to IFN-I by astrocytes versus microglia. This suggests specialized roles for these cells in host defense and in the development of cerebral interferonopathy.

Effect of a high-egg diet on cardiometabolic risk factors in people with type 2 diabetes: the Diabetes and Egg (DIABEGG) Study-randomized weight-loss and follow-up phase.

Background: Some country guidelines recommend that people with type 2 diabetes (T2D) limit their consumption of eggs and cholesterol. Our previously published 3-mo weight-maintenance study showed that a high-egg (≥12 eggs/wk) diet compared with a low-egg diet (<2 eggs/wk) did not have adverse effects on cardiometabolic risk factors in adults with T2D. Objective: The current study follows the previously published 3-mo weight-maintenance study and assessed the effects of the high-egg compared with the low-egg diets as part of a 3-mo weight-loss period, followed by a 6-mo follow-up period for a total duration of 12 mo. Design: Participants with prediabetes or T2D (n = 128) were prescribed a 3-mo daily energy restriction of 2.1 MJ and a macronutrient-matched diet and instructed on specific types and quantities of foods to be consumed, with an emphasis on replacing saturated fats with monounsaturated and polyunsaturated fats. Participants were followed up at the 9- and 12-mo visits. Results: From 3 to 12 mo, the weight loss was similar (high-egg compared with low-egg diets: -3.1 ± 6.3 compared with -3.1 ± 5.2 kg; P = 0.48). There were no differences between groups in glycemia (plasma glucose, glycated hemoglobin, 1,5-anhydroglucitol), traditional serum lipids, markers of inflammation (high-sensitivity C-reactive protein, interleukin 6, soluble E-selectin), oxidative stress (F2-isoprostanes), or adiponectin from 3 to 12 mo or from 0 to 12 mo. Conclusions: People with prediabetes or T2D who consumed a 3-mo high-egg weight-loss diet with a 6-mo follow-up exhibited no adverse changes in cardiometabolic markers compared with those who consumed a low-egg weight-loss diet. A healthy diet based on population guidelines and including more eggs than currently recommended by some countries may be safely consumed. This trial is registered at http://www.anzctr.org.au/ as ACTRN12612001266853.

Improving large class performance and engagement through student-generated question banks.

Disciplines such as Biochemistry and Molecular Biology, which involve concepts not included in the high-school curriculum, are very challenging for many first year university students. These subjects are particularly difficult for students accustomed to surface learning strategies involving memorization and recall of facts, as a deeper understanding of the relationship between concepts is needed for successful transfer to related areas and subsequent study. In this article, we explore an activity in a very large first year Molecular Biology course, in which students create multiple-choice questions related to targeted learning outcomes, and then answer and evaluate one another's questions. This activity encompasses elements of both self- and peer-assessment and the generative tasks of creating questions and producing written feedback may contribute to a deeper understanding of the material. We make use of a free online platform to facilitate all aspects of the process and analyze the effect of student engagement with the task on overall course performance. When compared to previous semester's cohorts, we observe a pronounced improvement in class performance on exam questions targeting similar concepts to the student-generated questions. In addition, those students that engage to a greater extent with the activity perform significantly better on the targeted exam questions than those who are less active, yet all students perform similarly on a set of isolated control questions appearing on the same exam. © 2018 by The International Union of Biochemistry and Molecular Biology, 46:306-317, 2018.

A Qualitative Investigation to Underpin the Development of an Electronic Tool to Assess Nutrition Literacy in Australians Adults.

Nutrition literacy is linked to health via its influence on dietary intake. There is a need for a tool to assess nutrition literacy in research and dietetic practice. We sought guidance from nutrition professionals on topic areas and features of an electronic nutrition literacy assessment tool for Australian adults. 28 experienced nutrition professionals engaged in a range of nutrition and dietetic work areas participated in six focus groups using a semi-structured interview schedule. Data were analysed using an inductive approach using NVivo 10 (QSR International, Pty Ltd., Doncaster, Australia, 2012). Key areas identified to assess nutrition literacy included specific nutrients versus foods, labels and packaging, construction of the diet, knowledge of the Australian Dietary Guidelines and Australian Guide to Healthy Eating, understanding of serve and portion sizes, ability to select healthier foods, and demographics such as belief systems and culture. Exploitation of electronic features to enhance visual and auditory displays, including interactive animations such as "drag and drop" and virtual reality situations, were discussed. This study provided insight into the most relevant topic areas and presentation format to assess the nutrition literacy of adult Australians. The visual, auditory, and interactive capacity of the available technology could enhance the assessment of nutrition literacy.

Left Ventricular Fibrosis and Systolic Hypertension Persist in a Repaired Aortic Coarctation Model.

BACKGROUND: Despite successful repair in early life, patients with coarctation of the aorta (CoA) are predisposed to several cardiovascular complications in later life related to systemic hypertension or left ventricular (LV) dysfunction, or both, the pathogenesis of which is unclear. METHODS: Three-week-old Sprague-Dawley rats underwent transverse aortic constriction (TAC) or a sham operation, with release of the constriction 3 weeks later. Twenty-five weeks after the repair operation, animals underwent hemodynamic assessment, LV gene profiling, and histologic analysis. RESULTS: Animals with repaired aortic constriction exhibited a significantly elevated central systolic pressure (116 ± 5 mm Hg vs 103 ± 4 mm Hg; p < 0.05) despite the absence of any significant pressure gradient across the former constriction site compared with shams (5 ± 4 mm Hg vs 0 ± 2 mm Hg; p = 0.2). They also had more than a 2-fold increase in LV collagen deposition (4.86% ± 0.24% vs 2.40% ± 0.18%; p < 0.001). However, no significant differences were noted between the groups in maximum LV pressure (116 ± 3 mm Hg vs 107 ± 3 mm Hg; p = 0.1), LV mass indexed to tibial length (p = 0.07), or myocyte size. There was no significant differential expression of hypertrophy or fibrosis-related genes in the left ventricles of the repaired animals compared with shams. CONCLUSIONS: Despite successful early relief of simulated CoA in early life, relative hypertension and LV fibrosis were demonstrable late consequences in this animal model. This abnormal fibrosis persists in the absence of altered LV hemodynamics and gene expression.

Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells.

Memory T cells exhibit transcriptional memory and "remember" their previous pathogenic encounter to increase transcription on re-infection. However, how this transcriptional priming response is regulated is unknown. Here we performed global FAIRE-seq profiling of chromatin accessibility in a human T cell transcriptional memory model. Primary activation induced persistent accessibility changes, and secondary activation induced secondary-specific opening of previously less accessible regions associated with enhanced expression of memory-responsive genes. Increased accessibility occurred largely in distal regulatory regions and was associated with increased histone acetylation and relative H3.3 deposition. The enhanced re-stimulation response was linked to the strength of initial PKC-induced signalling, and PKC-sensitive increases in accessibility upon initial stimulation showed higher accessibility on re-stimulation. While accessibility maintenance was associated with ETS-1, accessibility at re-stimulation-specific regions was linked to NFAT, especially in combination with ETS-1, EGR, GATA, NFκB, and NR4A. Furthermore, NFATC1 was directly regulated by ETS-1 at an enhancer region. In contrast to the factors that increased accessibility, signalling from bHLH and ZEB family members enhanced decreased accessibility upon re-stimulation. Interplay between distal regulatory elements, accessibility, and the combined action of sequence-specific transcription factors allows transcriptional memory-responsive genes to "remember" their initial environmental encounter.

Type I interferon-regulated gene expression and signaling in murine mixed glial cells lacking signal transducers and activators of transcription 1 or 2 or interferon regulatory factor 9.

Type I interferons (IFN-I) are critical in antimicrobial and antitumor defense. Although IFN-I signal via the interferon-stimulated gene factor 3 (ISGF3) complex consisting of STAT1, STAT2, and IRF9, IFN-I can mediate significant biological effects via ISGF3-independent pathways. For example, the absence of STAT1, STAT2, or IRF9 exacerbates neurological disease in transgenic mice with CNS production of IFN-I. Here we determined the role of IFN-I-driven, ISGF3-independent signaling in regulating global gene expression in STAT1-, STAT2-, or IRF9-deficient murine mixed glial cell cultures (MGCs). Compared with WT, the expression of IFN-α-stimulated genes (ISGs) was reduced in number and magnitude in MGCs that lacked STAT1, STAT2, or IRF9. There were significantly fewer ISGs in the absence of STAT1 or STAT2 versus in the absence of IRF9. The majority of ISGs regulated in the STAT1-, STAT2-, or IRF9-deficient MGCs individually were shared with WT. However, only a minor number of ISGs were common to WT and STAT1-, STAT2-, and IRF9-deficient MGCs. Whereas signal pathway activation in response to IFN-α was rapid and transient in WT MGCs, this was delayed and prolonged and correlated with increased numbers of ISGs expressed at 12 h versus 4 h of IFN-α exposure in all three IFN-I signaling-deficient MGCs. In conclusion, 1) IFN-I can mediate ISG expression in MGCs via ISGF3-independent signaling pathways but with reduced efficiency, with delayed and prolonged kinetics, and is more dependent on STAT1 and STAT2 than IRF9; and 2) signaling pathways not involving STAT1, STAT2, or IRF9 play a minor role only in mediating ISG expression in MGCs.

The effect of a novel probiotic on metabolic biomarkers in adults with prediabetes and recently diagnosed type 2 diabetes mellitus: study protocol for a randomized controlled trial.

BACKGROUND: Shifts in the gastrointestinal microbiome have been shown to contribute to the progression of metabolic diseases including prediabetes and type 2 diabetes mellitus. Research suggests that in-vivo modulation of the gut microbiome by specific probiotic microorganisms may improve insulin sensitivity and blood sugar management, preventing or delaying the development of type 2 diabetes mellitus. However, further research is needed to understand the effect of probiotics as a therapy for the treatment of metabolic diseases. An evidence-based multi-species probiotic was developed to encourage a shift in the gastrointestinal bacterial cohort from a disease-prone to a balanced state with the aim of improving metabolic markers associated with type 2 diabetes mellitus. METHODS: Sixty adults with a body mass index ≥25 kg/m2 with prediabetes or type 2 diabetes mellitus (diagnosed within the previous 12 months) will be enrolled in a double-blind, placebo-controlled pilot study. Participants will be randomized to a multi-species probiotic or placebo for 12 weeks. Both groups will receive lifestyle and nutritional advice. The primary outcome measure is the change between groups in fasting plasma glucose levels from baseline to 12 weeks. Secondary outcome measures include, but are not limited to, the change in lipid profile, systemic inflammation, gut permeability, and faecal microbial and metabolomic profiles. Blood and stool samples are collected at baseline and 12 weeks after treatment. DISCUSSION: Intentional manipulation of gastrointestinal microbial profiles may be useful for preventing and controlling type 2 diabetes mellitus and its associated metabolic complications. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12613001378718 . Registered on 16 December 2013.

Examining mindfulness as a predictor of weight loss - Findings from the DIABEGG study.

OBJECTIVE: Identifying individuals who are less likely to respond to a weight loss intervention allows better allocation or focus of resources to achieve better weight loss results. The current study investigated whether baseline levels of mindfulness would predict weight loss during a 12-month diet and exercise intervention. METHODS: The Five Facet Mindfulness Questionnaire (FFMQ) was administered and body weight measured, at baseline, three, six and 12 months in 140 participants with pre-diabetes or type 2 diabetes mellitus and a body mass index of ≥25kg/m2. 137 of 140 participants completed the FFMQ at baseline and were included in this study. RESULTS: There was no correlation between baseline mindfulness scores and weight loss. Mean baseline total FFMQ score was 112.2 [95% confidence interval: 109.4, 115.1] which did not change over the course of the study. Mean baseline body weight was 95.1kg (standard deviation (19.1kg)). There was a significant decrease in weight at month 12 (-3.8kg (±standard deviation 5.8kg)). This is comparable to the weight loss achieved by participants in other interventions of the same duration. CONCLUSIONS: The findings suggest that baseline dispositional mindfulness does not predict the amount of weight loss in a lifestyle (diet and exercise) intervention.

The primary immune response to Vaccinia virus vaccination includes cells with a distinct cytotoxic effector CD4 T-cell phenotype.

BACKGROUND: Smallpox was eradicated by a global program of inoculation with Vaccinia virus (VV). Robust VV-specific CD4 T-cell responses during primary infection are likely essential to controlling VV replication. Although there is increasing interest in cytolytic CD4 T-cells across many viral infections, the importance of these cells during acute VV infection is unclear. METHODS: We undertook a detailed functional and genetic characterization of CD4 T-cells during acute VV-infection of humans. VV-specific T-cells were identified by up-regulation of activation markers directly ex vivo and through cytokine and co-stimulatory molecule expression. At day-13-post primary inoculation with VV, CD38highCD45RO+ CD4 T-cells were purified by cell sorting, RNA isolated and analysed by microarray. Differential expression of up-regulated genes in activated CD4 T-cells was confirmed at the mRNA and protein levels. We compared analyses of VV-specific CD4 T-cells to studies on 12 subjects with primary HIV infection (PHI). VV-specific T-cells lines were established from PBMCs collected post vaccination and checked for cytotoxicity potential. RESULTS: A median 11.9% CD4 T-cells were CD38highCD45RO+ at day-13 post-VV inoculation, compared to 3.0% prior and 10.4% during PHI. Activated CD4 T-cells had an up-regulation of genes related to cytolytic function, including granzymes K and A, perforin, granulysin, TIA-1, and Rab27a. No difference was seen between CD4 T-cell expression of perforin or TIA-1 to VV and PHI, however granzyme k was more dominant in the VV response. At 25:1 effector to target ratio, two VV-specific T-cell lines exhibited 62% and 30% cytotoxicity respectively and CD107a degranulation. CONCLUSIONS: We show for the first time that CD4 CTL are prominent in the early response to VV. Understanding the role of CD4 CTL in the generation of an effective anti-viral memory may help develop more effective vaccines for diseases such as HIV.

Randomized Controlled Trial Investigating the Effects of a Low-Glycemic Index Diet on Pregnancy Outcomes in Women at High Risk of Gestational Diabetes Mellitus: The GI Baby 3 Study.

OBJECTIVE: Dietary interventions can improve pregnancy outcomes in women with gestational diabetes mellitus (GDM). We compared the effect of a low-glycemic index (GI) versus a conventional high-fiber (HF) diet on pregnancy outcomes, birth weight z score, and maternal metabolic profile in women at high risk of GDM. RESEARCH DESIGN AND METHODS: One hundred thirty-nine women [mean (SD) age 34.7 (0.4) years and prepregnancy BMI 25.2 (0.5) kg/m(2)] were randomly assigned to a low-GI (LGI) diet (n = 72; target GI ∼50) or a high-fiber, moderate-GI (HF) diet (n = 67; target GI ∼60) at 14-20 weeks' gestation. Diet was assessed by 3-day food records and infant body composition by air-displacement plethysmography, and pregnancy outcomes were assessed from medical records. RESULTS: The LGI group achieved a lower GI than the HF group [mean (SD) 50 (5) vs. 58 (5); P < 0.001]. There were no differences in glycosylated hemoglobin, fructosamine, or lipids at 36 weeks or differences in birth weight [LGI 3.4 (0.4) kg vs. HF 3.4 (0.5) kg; P = 0.514], birth weight z score [LGI 0.31 (0.90) vs. HF 0.24 (1.07); P = 0.697], ponderal index [LGI 2.71 (0.22) vs. HF 2.69 (0.23) kg/m(3); P = 0.672], birth weight centile [LGI 46.2 (25.4) vs. HF 41.8 (25.6); P = 0.330], % fat mass [LGI 10 (4) vs. HF 10 (4); P = 0.789], or incidence of GDM. CONCLUSIONS: In intensively monitored women at risk for GDM, a low-GI diet and a healthy diet produce similar pregnancy outcomes.

Injury-Dependent and Disability-Specific Lumbar Spinal Gene Regulation following Sciatic Nerve Injury in the Rat.

Allodynia, hyperalgesia and spontaneous pain are cardinal sensory signs of neuropathic pain. Clinically, many neuropathic pain patients experience affective-motivational state changes, including reduced familial and social interactions, decreased motivation, anhedonia and depression which are severely debilitating. In earlier studies we have shown that sciatic nerve chronic constriction injury (CCI) disrupts social interactions, sleep-wake-cycle and endocrine function in one third of rats, a subgroup reliably identified six days after injury. CCI consistently produces allodynia and hyperalgesia, the intensity of which was unrelated either to the altered social interactions, sleep-wake-cycle or endocrine changes. This decoupling of the sensory consequences of nerve injury from the affective-motivational changes is reported in both animal experiments and human clinical data. The sensory changes triggered by CCI are mediated primarily by functional changes in the lumbar dorsal horn, however, whether lumbar spinal changes may drive different affective-motivational states has never been considered. In these studies, we used microarrays to identify the unique transcriptomes of rats with altered social behaviours following sciatic CCI to determine whether specific patterns of lumbar spinal adaptations characterised this subgroup. Rats underwent CCI and on the basis of reductions in dominance behaviour in resident-intruder social interactions were categorised as having Pain & Disability, Pain & Transient Disability or Pain alone. We examined the lumbar spinal transcriptomes two and six days after CCI. Fifty-four 'disability-specific' genes were identified. Sixty-five percent were unique to Pain & Disability rats, two-thirds of which were associated with neurotransmission, inflammation and/or cellular stress. In contrast, 40% of genes differentially regulated in rats without disabilities were involved with more general homeostatic processes (cellular structure, transcription or translation). We suggest that these patterns of gene expression lead to either the expression of disability, or to resilience and recovery, by modifying local spinal circuitry at the origin of ascending supraspinal pathways.

The effect of a high-egg diet on cardiovascular risk factors in people with type 2 diabetes: the Diabetes and Egg (DIABEGG) study-a 3-mo randomized controlled trial.

BACKGROUND: Previously published research that examined the effects of high egg consumption in people with type 2 diabetes (T2D) produced conflicting results leading to recommendations to limit egg intake. However, people with T2D may benefit from egg consumption because eggs are a nutritious and convenient way of improving protein and micronutrient contents of the diet, which have importance for satiety and weight management. OBJECTIVE: In this randomized controlled study, we aimed to determine whether a high-egg diet (2 eggs/d for 6 d/wk) compared with a low-egg diet (<2 eggs/wk) affected circulating lipid profiles, in particular high-density lipoprotein (HDL) cholesterol, in overweight or obese people with prediabetes or T2D. DESIGN: A total of 140 participants were randomly assigned to one of the 2 diets as part of a 3-mo weight maintenance study. Participants attended the clinic monthly and were instructed on the specific types of foods and quantities to be consumed. RESULTS: There was no significant difference in the change in HDL cholesterol from screening to 3 mo between groups; the mean difference (95% CI) between high- and low-egg groups was +0.02 mmol/L (-0.03, 0.08 mmol/L; P = 0.38). No between-group differences were shown for total cholesterol, low-density lipoprotein cholesterol, triglycerides, or glycemic control. Both groups were matched for protein intake, but the high-egg group reported less hunger and greater satiety postbreakfast. Polyunsaturated fatty acid (PUFA) and monounsaturated fatty acid (MUFA) intakes significantly increased from baseline in both groups. CONCLUSIONS: High egg consumption did not have an adverse effect on the lipid profile of people with T2D in the context of increased MUFA and PUFA consumption. This study suggests that a high-egg diet can be included safely as part of the dietary management of T2D, and it may provide greater satiety. This trial was registered at the Australia New Zealand Clinical Trials Registry (http://www.anzctr.org.au/) as ACTRN12612001266853.

Reduced ß­2­glycoprotein І inhibits hypoxia­induced retinal angiogenesis in neonatal mice through the vascular endothelial growth factor pathway.

ß­2­glycoprotein I (ß2GPI), also known as apolipoprotein H, is a phospholipid­binding plasma protein consisting of five homologous repeated units. ß2GPI downregulates vascular endothelial growth factor (VEGF) signaling pathways and inhibits angiogenesis in vitro. However, the in vivo roles and effectors of reduced ß2GPI and ß2GPI in retinal angiogenesis are still not fully understood. In this study, an oxygen­induced retinopathy model was used to investigate the effects of reduced ß2GPI and ß2GPI, and to monitor the expression of VEGF, VEGF receptor (VEGFR) 1, VEGFR­2 and hypoxia­inducible factor 1 (HIF­1) mRNA and the phosphorylation of extracellular signal­regulated kinase (ERK) and Akt. The data showed that both ß2GPI and reduced ß2GPI inhibited retinal angiogenesis and suppressed the expression of VEGF, VEGFR­1, VEGFR­2, HIF­1, phosphorylated- (p­) ERK and p­Akt. The effects of reduced ß2GPI were significantly stronger than those of ß2GPI. In conclusion, this study showed that ß2GPI and reduced ß2GPI could inhibit retinal angiogenesis by downregulating the expression of VEGF and its downstream targets. This suggests that ß2GPI and reduced ß2GPI may have potential anti­angiogenic activity in vivo.