Molecular mimicry: Can epitope mimicry induce autoimmune disease?

Mimicry of host antigens by infectious agents may induce cross-reactive autoimmune responses to epitopes within host proteins which, in susceptible individuals, may tip the balance of immunological response versus tolerance toward response and subsequently lead to autoimmune disease. Epitope mimicry may indeed be involved in the pathogenesis of several diseases such as post-viral myocarditis or Chagas disease, but for many other diseases in which it has been implicated, such as insulin-dependent diabetes mellitis or rheumatoid arthritis, convincing evidence is still lacking. Even if an epitope mimic can support a cross-reactive T or B cell response in vitro, its ability to induce an autoimmune disease in vivo will depend upon the appropriate presentation of the mimicked host antigen in the target tissue and, in the case of T cell mimics, the ability of the mimicking epitope to induce a proliferative rather than anergizing response upon engagement of the MHC-peptide complex with the T cell receptor. B cell presentation of mimicking foreign antigen to T cells is a possible mechanism for instigating an autoimmune response to self antigens that in turn can lead to autoimmune disease under particular conditions of antigen presentation, secondary signalling and effector cell repertoire. In this review evidence in support of epitope mimicry is examined in the light of the necessary immunological considerations of the theory.

The effects of osteoporosis on osseointegration in the rat maxilla

The study investigated the effects of oestrogen deficiency on dental implant in a rat model. An osteoporosis rat model was successfully established for dental implant research and it was noted that bone cells functioned differently in osteoporotic condition during the healing of dental implant. The study further demonstrated that implant surface roughness could stimulate bone formation, therefore, improve the bone healing in osteoporotic condition.

Effect of age, gender and mannose-binding lectin (MBL) status on the inflammatory profile in peripheral blood plasma of Australian blood donors

Transfusion of blood components has been associated with poor patient outcomes and, an overall increase in morbidity and mortality. Differences in the blood components arising from donor health, age and immune status may impact on outcomes of transfusion and transfusion-related immune modulation in recipients. The aim of this study was to investigate differences in inflammatory profile in donors and association with parameters including age, gender and deficiency status of pattern recognition molecule mannose-binding lectin (MBL). MBL level was determined by ELISA. Serum levels of interleukin (IL)-1α, IL-1β, IL-6, IL-8, IL-10, IL-12, tumour necrosis factor (TNF)-α, macrophage inflammatory protein (MIP)-1α, monocyte chemoattractant protein (MCP)-1, interferon (IFN)-α, and IFN-γ were examined by cytometric bead array (CBA). C-reactive protein (CRP) and rheumatoid factor (RF) were examined by immunoturbidimetry. This study demonstrated age was a parameter associated with the immune profile of blood donors, with significant increases in MCP-1 (p < 0.05) and RF (p < 0.05) and decreases in IL-1α evident in the older donors (61–76 years). Significant gender-associated differences in MCP-1, IL-12 and CRP plasma levels in the blood donor cohort were also reported. There was no significant difference in the level of any inflammatory markers studied according to MBL status. This study demonstrated that age and gender are associated with inflammatory profile in donors. These differences may be a factor impacting on outcomes of transfusion.

Health-related quality of life of individuals with transfemoral amputation fitted with the Transcutaneous Bone Anchoring Prosthesis following the OGAAP

Background The benefits and safety transcutaneous bone anchored prosthesis relying on a screw fixation are well reported.[1-17] However, most of the studies on press-fit implants and joint replacement technology have focused on surgical techniques.[3, 18-23] One European centre using this technique has reported on health related quality of life (HRQOL) for a group of individuals with transfemoral amputation (TFA).[3] Data from other centres are needed to assess the effectiveness of the technique in different settings. Aim This study aimed at reporting HRQOL data at baseline and up to 2-year follow-up for a group of TFAs treated by Osseointegration Group of Australia who followed the Osseointegration Group of Australia Accelerated Protocol (OGAAP), in Sydney between 08/12/2011 and 09/04/2014. Method A total of 16 TFAs (7 females and 9 males, age 51 ± 12 y, height 1.73 ± 0.12 m, weight 83 ±18 kg) participated in this study. The cause of amputation was trauma or congenital limb deficiency for 11 (69%) and 5 (31%) participants, respectively. A total of 12 (75%) participants were prosthetic users while 4(25%) were wheelchair bound prior the surgery. The HRQOL were obtained from Questionnaire for Persons with Transfemoral Amputation (Q-TFA) using the four main scales (i.e., Prosthetic use, Mobility, Problem, Global) one year before and between 6.5 and 24 months after the Stage 1 of the surgeries for the baseline and follow-up, respectively. Results The lapse of time before and after Stage 1 was -6.19±3.54 and 10.83±3.58 months respectively. The raw score and percentage of improvement are presented in Figures 1 and 2, respectively. Discussion & Conclusion The average results demonstrated an improvement in each domain, particularly in the reduction of problems and an increase in global state. Furthermore, 56%, 75%, 94% and 69% of the participants reported an improvement in Prosthetic use, Mobility, Problem, Global scales, respectively. These results were comparable to previous studies relying of screwed fixation confirming that press-fit implantation is a viable alternative for bone-anchored prostheses.[1, 7, 8]

Serum vitamin D levels are lower in Australian children and adolescents with type 1 diabetes than in children without diabetes

Vitamin D is synthesised in the skin through the action of UVB radiation (sunlight), and 25-hydroxy vitamin D (25OHD) measured in serum as a marker of vitamin D status. Several studies, mostly conducted in high latitudes, have shown an association between type 1 diabetes mellitus (T1DM) and low serum 25OHD. We conducted a case-control study to determine whether, in a sub-tropical environment with abundant sunlight (latitude 27.5°S), children with T1DM have lower serum vitamin D than children without diabetes. Fifty-six children with T1DM (14 newly diagnosed) and 46 unrelated control children participated in the study. Serum 25OHD, 1,25-dihydroxy vitamin D (1,25(OH)2D) and selected biochemical indices were measured. Vitamin D receptor (VDR) polymorphisms Taq1, Fok1, and Apa1 were genotyped. Fitzpatrick skin classification, self-reported daily hours of outdoor exposure, and mean UV index over the 35d prior to blood collection were recorded. Serum 25OHD was lower in children with T1DM (n=56) than in controls (n=46) [mean (95%CI)=78.7 (71.8-85.6) nmol/L vs. 91.4 (83.5-98.7) nmol/L, p=0.02]. T1DM children had lower self-reported outdoor exposure and mean UV exposure, but no significant difference in distribution of VDR polymorphisms. 25OHD remained lower in children with T1DM after covariate adjustment. Children newly diagnosed with T1DM had lower 1,25(OH)2D [median (IQR)=89 (68-122) pmol/L] than controls [121 (108-159) pmol/L, p=0.03], or children with established diabetes [137 (113-153) pmol/L, p=0.01]. Children with T1DM have lower 25OHD than controls, even in an environment of abundant sunlight. Whether low vitamin D is a risk factor or consequence of T1DM is unknown. © 2012 John Wiley & Sons A/S.

Long-term growth and anthropometry after childhood liver transplantation

Objectives: To describe longitudinal height, weight, and body mass index changes up to 15 years after childhood liver transplantation. Study design: Retrospective chart review of patients who underwent liver transplant from 1985-2004 was performed. Subjects were age <18 years at transplant, survived ≥5 years, with at least 2 recorded measurements, of which one was ≥5 years post-transplant. Measurements were recorded pre-transplant, 1, 5, 10, and 15 years later. Results: Height and weight data were available in 98 and 104 patients, respectively; 47% were age <2 years at transplant; 58% were Australian, and the rest were from Japan. Height recovery continued for at least 10 years to reach the 26th percentile (Z-score -0.67) 15 years after transplant. Australians had better growth recovery and attained 47th percentile (Z-score -0.06) at 15 years. Weight recovery was most marked in the first year and continued for 15 years even in well-nourished children. Growth impaired and malnourished children at transplant exhibited the best growth, but remained significantly shorter and lighter even 15 years later. No effect of sex or age at transplant was noted on height or weight recovery. Post-transplant factors significantly impact growth recovery and likely caused the dichotomous growth recovery between Australian and Japanese children; 9% (9/98) of patients were overweight on body mass index calculations at 10-15 years but none were obese. Conclusions: After liver transplant, children can expect ongoing height and weight recovery for at least 10-15 years. Growth impairment at transplant and post-transplant care significantly impact long-term growth recovery. Copyright © 2013 Mosby Inc. All rights reserved.

Risedronate in adults with osteogenesis imperfecta type I: Increased bone mineral density and decreased bone turnover, but high fracture rate persists

Summary Bisphosphonates can increase bone mineral density (BMD) in children with osteogenesis imperfecta (OI). In this study of adults with OI type I, risedronate increased BMD at lumbar spine (but not total hip) and decreased bone turnover. However, the fracture rate in these patients remained high. Introduction Intravenous bisphosphonates given to children with OI can increase BMD and reduce fracture incidence. Oral and/or intravenous bisphosphonates may have similar effects in adults with OI. We completed an observational study of the effect of risedronate in adults with OI type I. Methods Thirty-two adults (mean age, 39 years) with OI type I were treated with risedronate (total dose, 35 mg weekly) for 24 months. Primary outcome measures were BMD changes at lumbar spine (LS) and total hip (TH). Secondary outcome measures were fracture incidence, bone pain, and change in bone turnover markers (serum procollagen type I aminopropeptide (P1NP) and bone ALP). A meta-analysis of published studies of oral bisphosphonates in adults and children with OI was performed. Results Twenty-seven participants (ten males and seventeen females) completed the study. BMD increased at LS by 3.9% (0.815 vs. 0.846 g/cm 2, p=0.007; mean Z-score, -1.93 vs. -1.58, p=0.002), with no significant change at TH. P1NP fell by 37% (p=0.00041), with no significant change in bone ALP (p=0.15). Bone pain did not change significantly (p=0.6). Fracture incidence remained high, with 25 clinical fractures and 10 major fractures in fourteen participants (0.18 major fractures per person per year), with historical data of 0.12 fractures per person per year. The meta-analysis did not demonstrate a significant difference in fracture incidence in patients with OI treated with oral bisphosphonates. Conclusions Risedronate in adults with OI type I results in modest but significant increases in BMD at LS, and decreased bone turnover. However, this may be insufficient to make a clinically significant difference to fracture incidence.

Disorganizing educational tropes: Conceptions of dis/ability and curriculum

A study examined the politics of dis/ability and curriculum. Data were obtained from a review of the new disability studies literature, focusing on the areas of history, sociology, anthropology, and critical legal theory. The results indicate that this new literature challenges popular psychoeducational models that assume disability as an objective medical, individual, and pathological deficiency, effectively restricting the systematic study of dis/ability as relational, external, shifting, and socially constituted. The findings suggest ways in which perceptions of “school problems” have to be adjusted to understand how the constant refiguration of normativities in everyday activities creates perceptions of disability-negative ontologies, generates experiences that incite efforts to modify those perceptions in multiple ways, and produces unintended effects from well-intended approaches that in the end remain irreducible to simplistic definitions for the one “ethical” or “politically correct” strategy.

The nature of malnutrition in children with end-stage liver disease awaiting orthotopic liver transplantation

To evaluate malnutrition in chronic liver disease, and its relationship to nutrient deficiencies and hepatic dysfunction. 27 children with end-stage liver disease were studied. Mean protein-energy intakes were 70% of recommended daily intakes. The patients were underweight and stunted with reduced mean triceps and subscapular skinfold thicknesses and midupper arm circumference. Mean total body potassium was only 63 ± 18% of that expected for age and sex. Deficiency of essential fatty acids (32%), and low concentrations of fat-soluble vitamins (A, 92%; E, 32%), iron (32%), zinc (42%), and selenium (13%) were common. Serum ammonia concentrations were raised in all patients, and increased methionine, tyrosine, and glutamic acid, and reduced glutamine concentrations were noted. There was no correlation between the degree of malnutrition and the degree of liver synthetic function, the degree of cholestasis, or the degree of liver injury. We suggest that potentially correctable factors in addition to liver failure (eg, inadequate absorbed intake) were important determinants of malnutrition in these patients.

Exercise improves quality of life in ADT-treated prostate cancer: Systematic review of RCTs

Men receiving androgen deprivation therapy (ADT) for prostate cancer (PCa) are likely to develop metabolic conditions such as diabetes, cardiovascular disease, abdominal obesity and osteoporosis. Other treatment-related side effects adversely influence quality of life (QoL) including vasomotor distress, depression, anxiety, mood swings, poor sleep quality and compromised sexual function. The objective of this study was to systematically review the nature and effects of dietary and exercise interventions on QoL, androgen deprivation symptoms and metabolic risk factors in men with PCa undergoing ADT. An electronic search of CINAHL, CENTRAL, Medline, PsychINFO and reference lists was performed to identify peer-reviewed articles published between January 2004 and December, 2014 in English. Eligible study designs included randomised controlled trials with pre- and post-intervention data. Data extraction and assessment of methodological quality with the Cochrane approach was conducted by two independent reviewers. Seven exercise studies were identified. Exercise significantly improved QoL, but showed no effect on metabolic risk factors (weight, waist circumference, lean or fat mass, blood pressure, lipid profile). Two dietary studies were identified, both of which tested soy supplements. Soy supplementation did not improve any outcomes. No dietary counselling studies were identified. No studies evaluated androgen-deficiency symptoms (libido, erectile function, sleep quality, mood swings, depression, anxiety, bone mineral density). Evidence from RCTs indicates that exercise enhances health- and disease-specific QoL in men with PCa undergoing ADT. Further studies are required to evaluate the effect of exercise and dietary interventions on QoL, androgen deprivation symptoms and metabolic risk factors in this cohort.

Inverse Correlation between Vitamin D and C-Reactive Protein in Newborns

Some studies suggested that adequate vitamin D might reduce inflammation in adults. However, little is known about this association in early life. We aimed to determine the relationship between cord blood 25-hydroxyvitamin D (25(OH)D) and C-reactive protein (CRP) in neonates. Cord blood levels of 25(OH)D and CRP were measured in 1491 neonates in Hefei, China. Potential confounders including maternal sociodemographic characteristics, perinatal health status, lifestyle, and birth outcomes were prospectively collected. The average values of cord blood 25(OH)D and CRP were 39.43 nmol/L (SD = 20.35) and 6.71 mg/L (SD = 3.07), respectively. Stratified by 25(OH)D levels, per 10 nmol/L increase in 25(OH)D, CRP decreased by 1.42 mg/L (95% CI: 0.90, 1.95) among neonates with 25(OH)D <25.0 nmol/L, and decreased by 0.49 mg/L (95% CI: 0.17, 0.80) among neonates with 25(OH)D between 25.0 nmol/L and 49.9 nmol/L, after adjusting for potential confounders. However, no significant association between 25(OH)D and CRP was observed among neonates with 25(OH)D ≥50 nmol/L. Cord blood 25(OH)D and CRP levels showed a significant seasonal trend with lower 25(OH)D and higher CRP during winter-spring than summer-autumn. Stratified by season, a significant linear association of 25(OH)D with CRP was observed in neonates born in winter-spring (adjusted β = −0.11, 95% CI: −0.13, −0.10), but not summer-autumn. Among neonates born in winter-spring, neonates with 25(OH)D <25 nmol/L had higher risk of CRP ≥10 mg/L (adjusted OR = 3.06, 95% CI: 2.00, 4.69), compared to neonates with 25(OH)D ≥25 nmol/L. Neonates with vitamin D deficiency had higher risk of exposure to elevated inflammation at birth.

A visual profile of Queensland Indigenous children

Purpose Little is known about the prevalence of refractive error, binocular vision, and other visual conditions in Australian Indigenous children. This is important given the association of these visual conditions with reduced reading performance in the wider population, which may also contribute to the suboptimal reading performance reported in this population. The aim of this study was to develop a visual profile of Queensland Indigenous children. Methods Vision testing was performed on 595 primary schoolchildren in Queensland, Australia. Vision parameters measured included visual acuity, refractive error, color vision, nearpoint of convergence, horizontal heterophoria, fusional vergence range, accommodative facility, AC/A ratio, visual motor integration, and rapid automatized naming. Near heterophoria, nearpoint of convergence, and near fusional vergence range were used to classify convergence insufficiency (CI). Results Although refractive error (Indigenous, 10%; non-Indigenous, 16%; p = 0.04) and strabismus (Indigenous, 0%; non-Indigenous, 3%; p = 0.03) were significantly less common in Indigenous children, CI was twice as prevalent (Indigenous, 10%; non-Indigenous, 5%; p = 0.04). Reduced visual information processing skills were more common in Indigenous children (reduced visual motor integration [Indigenous, 28%; non-Indigenous, 16%; p < 0.01] and slower rapid automatized naming [Indigenous, 67%; non-Indigenous, 59%; p = 0.04]). The prevalence of visual impairment (reduced visual acuity) and color vision deficiency was similar between groups. Conclusions Indigenous children have less refractive error and strabismus than their non-Indigenous peers. However, CI and reduced visual information processing skills were more common in this group. Given that vision screenings primarily target visual acuity assessment and strabismus detection, this is an important finding as many Indigenous children with CI and reduced visual information processing may be missed. Emphasis should be placed on identifying children with CI and reduced visual information processing given the potential effect of these conditions on school performance

Children’s personal exposure to air pollution in rural villages in Bhutan

Exposure assessment studies conducted in developing countries have been based on fixed-site monitoring to date. This is a major deficiency, leading to errors in estimating the actual exposures, which are a function of time spent and pollutant concentrations in different microenvironments. This study quantified school children’s daily personal exposure to ultrafine particles (UFP) using real-time monitoring, as well as volatile organic compounds (VOCs) and NO2 using passive sampling in rural Bhutan in order to determine the factors driving the exposures. An activity diary was used to track children’s time activity patterns, and difference in mean exposure levels across sex and indoor/outdoor were investigated with ANOVA. 82 children, attending three primary schools participated in this study; S1 and S2 during the wet season and S3 during the dry season. Mean daily UFP exposure (cm-3) was 1.08 × 104 for children attending S1, 9.81 × 103 for S2, and 4.19 × 104 for S3. The mean daily NO2 exposure (µg m-3) was 4.27 for S1, 3.33 for S2 and 5.38 for S3 children. Likewise, children attending S3 also experienced higher daily exposure to a majority of the VOCs than those attending S1 and S2. Time-series of UFP personal exposures provided detailed information on identifying sources of these particles and quantifying their contributions to the total daily exposures for each microenvironment. The highest UFP exposure resulted from cooking/eating, contributing to 64% of the daily exposure, due to firewood combustion in houses using traditional mud cookstoves. The lowest UFP exposures were during the hours that children spent outdoors at school. The outcomes of this study highlight the significant contributions of lifestyle and socio-economic factors in personal exposures and have applications in environmental risk assessment and household air pollution mitigation in Bhutan.

Abstract concepts made real: A pilot study examining pedagogical approaches in thermodynamics tutorials

BACKGROUND OR CONTEXT Thermodynamics is a core concept for mechanical engineers yet notoriously difficult. Evidence suggests students struggle to understand and apply the core fundamental concepts of thermodynamics with analysis indicating a problem with student learning/engagement. A contributing factor is that thermodynamics is a ‘science involving concepts based on experiments’ (Mayhew 1990) with subject matter that cannot be completely defined a priori. To succeed, students must engage in a deep-holistic approach while taking ownership of their learning. The difficulty in achieving this often manifests itself in students ‘not getting’ the principles and declaring thermodynamics ‘hard’. PURPOSE OR GOAL Traditionally, students practice and “learn” the application of thermodynamics in their tutorials, however these do not consider prior conceptions (Holman & Pilling 2004). As ‘hands on’ learning is the desired outcome of tutorials it is pertinent to study methods of improving their efficacy. Within the Australian context, the format of thermodynamics tutorials has remained relatively unchanged over the decades, relying anecdotally on a primarily didactic pedagogical approach. Such approaches are not conducive to deep learning (Ramsden 2003) with students often disengaged from the learning process. Evidence suggests (Haglund & Jeppsson 2012), however, that a deeper level and ownership of learning can be achieved using a more constructivist approach for example through self generated analogies. This pilot study aimed to collect data to support the hypothesis that the ‘difficulty’ of thermodynamics is associated with the pedagogical approach of tutorials rather than actual difficulty in subject content or deficiency in students. APPROACH Successful application of thermodynamic principles requires solid knowledge of the core concepts. Typically, tutorial sessions guide students in this application. However, a lack of deep and comprehensive understanding can lead to student confusion in the applications resulting in the learning of the ‘process’ of application without understanding ‘why’. The aim of this study was to gain empirical data on student learning of both concepts and application, within thermodynamic tutorials. The approach taken for data collection and analysis was: - 1 Four concurrent tutorial streams were timetabled to examine student engagement/learning in traditional ‘didactic’ (3 weeks) and non-traditional (3 weeks). In each week, two of the selected four sessions were traditional and two non-traditional. This provided a control group for each week. - 2 The non-traditional tutorials involved activities designed to promote student-centered deep learning. Specific pedagogies employed were: self-generated analogies, constructivist, peer-to-peer learning, inquiry based learning, ownership of learning and active learning. - 3 After a three-week period, teaching styles of the selected groups was switched, to allow each group to experience both approaches with the same tutor. This also acted to mimimise any influence of tutor personality / style on the data. - 4 At the conclusion of the trial participants completed a ‘5 minute essay’ on how they liked the sessions, a small questionnaire, modelled on the modified (Christo & Hoang, 2013)SPQ designed by Biggs (1987) and a small formative quiz to gauge the level of learning achieved. DISCUSSION Preliminary results indicate that overall students respond positively to in class demonstrations (inquiry based learning), and active learning activities. Within the active learning exercises, the current data suggests students preferred individual rather than group or peer-to-peer activities. Preliminary results from the open-ended questions such as “What did you like most/least about this tutorial” and “do you have other comments on how this tutorial could better facilitate your learning”, however, indicated polarising views on the nontraditional tutorial. Some student’s responded that they really like the format and emphasis on understanding the concepts, while others were very vocal that that ‘hated’ the style and just wanted the solutions to be presented by the tutor. RECOMMENDATIONS/IMPLICATIONS/CONCLUSION Preliminary results indicated a mixed, but overall positive response by students with more collaborative tutorials employing tasks promoting inquiry based, peer-to-peer, active, and ownership of learning activities. Preliminary results from student feedback supports evidence that students learn differently, and running tutorials focusing on only one pedagogical approached (typically didactic) may not be beneficial to all students. Further, preliminary data suggests that the learning / teaching style of both students and tutor are important to promoting deep learning in students. Data collection is still ongoing and scheduled for completion at the end of First Semester (Australian academic calendar). The final paper will examine in more detail the results and analysis of this project.

Mice lacking the serotonin Htr2B receptor gene present an antipsychotic-sensitive schizophrenic-like phenotype

Impulsivity and hyperactivity share common ground with numerous mental disorders, including schizophrenia. Recently, a population-specific serotonin 2B (5-HT2B) receptor stop codon (ie, HTR2B Q20*) was reported to segregate with severely impulsive individuals, whereas 5-HT2B mutant (Htr2B−/−) mice also showed high impulsivity. Interestingly, in the same cohort, early-onset schizophrenia was more prevalent in HTR2B Q*20 carriers. However, the putative role of 5-HT2B receptor in the neurobiology of schizophrenia has never been investigated. We assessed the effects of the genetic and the pharmacological ablation of 5-HT2B receptors in mice subjected to a comprehensive series of behavioral test screenings for schizophrenic-like symptoms and investigated relevant dopaminergic and glutamatergic neurochemical alterations in the cortex and the striatum. Domains related to the positive, negative, and cognitive symptom clusters of schizophrenia were affected in Htr2B−/− mice, as shown by deficits in sensorimotor gating, in selective attention, in social interactions, and in learning and memory processes. In addition, Htr2B−/− mice presented with enhanced locomotor response to the psychostimulants dizocilpine and amphetamine, and with robust alterations in sleep architecture. Moreover, ablation of 5-HT2B receptors induced a region-selective decrease of dopamine and glutamate concentrations in the dorsal striatum. Importantly, selected schizophrenic-like phenotypes and endophenotypes were rescued by chronic haloperidol treatment. We report herein that 5-HT2B receptor deficiency confers a wide spectrum of antipsychotic-sensitive schizophrenic-like behavioral and psychopharmacological phenotypes in mice and provide first evidence for a role of 5-HT2B receptors in the neurobiology of psychotic disorders