Investigating ethnic inequalities in the incidence of sexually transmitted infections: mathematical modelling study.

OBJECTIVES: To investigate ethnic differences in rates of gonorrhoea using empirical sexual behaviour data in a simple mathematical model. To explore the impact of different intervention strategies in this simulated population. METHODS: The findings from cross sectional studies of gonorrhoea rates and sexual behaviour in three ethnic groups in south east London were used to determine the parameters for a deterministic, mathematical model of gonorrhoea transmission dynamics, in a population stratified by sex, sexual activity (rate of partner change), and ethnic group (white, black African, and black Caribbean). We compared predicted and observed rates of infection and simulated the effects of targeted and population-wide intervention strategies. RESULTS: In model simulations the reported sexual behaviours and mixing patterns generated major differences in the rates of gonorrhoea experienced by each subpopulation. The fit of the model to observed data was sensitive to assumptions about the degree of mixing by level of sexual activity, the numbers of sexual partnerships reported by men and women, and the degree to which observed data underestimate female infection rates. Interventions to reduce duration of infection were most effective when targeted at black Caribbeans. CONCLUSIONS: Average measures of sexual behaviour in large populations are inadequate descriptors for the epidemiology of gonorrhoea. The consistency between the model results and empirical data shows that profound differences in gonorrhoea rates between ethnic groups can be explained by modest differences in a limited number of sexual behaviours and mixing patterns. Targeting effective services to particular ethnic groups can have a disproportionate influence on disease reduction in the whole community

Walking as a meaningful leisure occupation: the implications for occupational therapy

Introduction: In response to growing interest in leisure in occupational therapy and the importance of understanding how occupations maintain, enhance and promote health and wellbeing, a qualitative phenomenological study was conducted to explore the experiences of walking for leisure. Method: Six healthy student participants, identified as regular walkers, were interviewed using a semi-structured format. Data were analysed following interpretative phenomenological analysis methodology. Findings: Participants expressed how and why walking was meaningful to them; the four main themes were social connectedness, wellbeing, connection to nature and achievement from a challenge. Findings suggest that occupational therapists could use walking and leisure occupations in intervention, and that there is scope for an occupational therapy perspective in health promotion. Conclusion: Determining the subjective meaning of engaging in walking as a leisure occupation has implications for occupational science and health promotion in helping to explain why people do what they do

The potential impact of moxidectin on onchocerciasis elimination in Africa: an economic evaluation based on the Phase II clinical trial data

BACKGROUND: Spurred by success in several foci, onchocerciasis control policy in Africa has shifted from morbidity control to elimination of infection. Clinical trials have demonstrated that moxidectin is substantially more efficacious than ivermectin in effecting sustained reductions in skin microfilarial load and, therefore, may accelerate progress towards elimination. We compare the potential cost-effectiveness of annual moxidectin with annual and biannual ivermectin treatment. METHODS: Data from the first clinical study of moxidectin were used to parameterise the onchocerciasis transmission model EPIONCHO to investigate, for different epidemiological and programmatic scenarios in African savannah settings, the number of years and in-country costs necessary to reach the operational thresholds for cessation of treatment, comparing annual and biannual ivermectin with annual moxidectin treatment. RESULTS: Annual moxidectin and biannual ivermectin treatment would achieve similar reductions in programme duration relative to annual ivermectin treatment. Unlike biannual ivermectin treatment, annual moxidectin treatment would not incur a considerable increase in programmatic costs and, therefore, would generate sizeable in-country cost savings (assuming the drug is donated). Furthermore, the impact of moxidectin, unlike ivermectin, was not substantively influenced by the timing of treatment relative to seasonal patterns of transmission. CONCLUSIONS: Moxidectin is a promising new drug for the control and elimination of onchocerciasis. It has high programmatic value particularly when resource limitation prevents a biannual treatment strategy, or optimal timing of treatment relative to peak transmission season is not feasible. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-015-0779-4) contains supplementary material, which is available to authorized users

Aberrant phenotype in human endothelial cells of diabetic origin: Implications for saphenous vein graft failure?

Type 2 diabetes (T2DM) confers increased risk of endothelial dysfunction, coronary heart disease, and vulnerability to vein graft failure after bypass grafting, despite glycaemic control. This study explored the concept that endothelial cells (EC) cultured from T2DM and nondiabetic (ND) patients are phenotypically and functionally distinct. Cultured human saphenous vein-(SV-) EC were compared between T2DM and ND patients in parallel. Proliferation, migration, and in vitro angiogenesis assays were performed; western blotting was used to quantify phosphorylation of Akt, ERK, and eNOS. The ability of diabetic stimuli (hyperglycaemia, TNF-α, and palmitate) to modulate angiogenic potential of ND-EC was also explored. T2DM-EC displayed reduced migration (30%) and angiogenesis (40%) compared with ND-EC and a modest, nonsignificant trend to reduced proliferation. Significant inhibition of Akt and eNOS, but not ERK phosphorylation, was observed in T2DM cells. Hyperglycaemia did not modify ND-EC function, but TNF-α and palmitate significantly reduced angiogenic capacity (by 27% and 43%, resp.), effects mimicked by Akt inhibition. Aberrancies of EC function may help to explain the increased risk of SV graft failure in T2DM patients. This study highlights the importance of other potentially contributing factors in addition to hyperglycaemia that may inflict injury and long-term dysfunction to the homeostatic capacity of the endothelium

Provision of foot health services for people with rheumatoid arthritis in New South Wales: a web-based survey of local podiatrists

Background: It is unclear if podiatric foot care for people with rheumatoid arthritis (RA) in New South Wales (NSW) meets current clinical recommendations. The objective of this study was to survey podiatrists' perceptions of the nature of podiatric foot care provision for people who have RA in NSW.Methods: An anonymous, cross-sectional survey with a web-based questionnaire was conducted. The survey questionnaire was developed according to clinical experience and current foot care recommendations. State registered podiatrists practising in the state of NSW were invited to participate. The survey link was distributed initially via email to members of the Australian Podiatry Association (NSW), and distributed further through snowballing techniques using professional networks. Data was analysed to assess significant associations between adherence to clinical practice guidelines, and private/public podiatry practices.Results: 86 podiatrists participated in the survey (78% from private practice, 22% from public practice). Respondents largely did not adhere to formal guidelines to manage their patients (88%). Only one respondent offered a dedicated service for patients with RA. Respondents indicated that the primary mode of accessing podiatry was by self-referral (68%). Significant variation was observed regarding access to disease and foot specific assessments and treatment strategies. Assessment methods such as administration of patient reported outcome measures, vascular and neurological assessments were not conducted by all respondents. Similarly, routine foot care strategies such as prescription of foot orthoses, foot health advice and footwear were not employed by all respondents.Conclusions: The results identified issues in foot care provision which should be explored through further research. Foot care provision in NSW does not appear to meet the current recommended standards for the management of foot problems in people who have RA. Improvements to foot care could be undertaken in terms of providing better access to examination techniques and treatment strategies that are recommended by evidence based treatment paradigms. © 2013 Hendry et al.; licensee BioMed Central Ltd

Mineral maturity and crystallinity index are distinct characteristics of bone mineral

The purpose of this study was to test the hypothesis that mineral maturity and crystallinity index are two different characteristics of bone mineral. To this end, Fourier transform infrared microspectroscopy (FTIRM) was used. To test our hypothesis, synthetic apatites and human bone samples were used for the validation of the two parameters using FTIRM. Iliac crest samples from seven human controls and two with skeletal fluorosis were analyzed at the bone structural unit (BSU) level by FTIRM on sections 2–4 lm thick. Mineral maturity and crystallinity index were highly correlated in synthetic apatites but poorly correlated in normal human bone. In skeletal fluorosis, crystallinity index was increased and maturity decreased, supporting the fact of separate measurement of these two parameters. Moreover, results obtained in fluorosis suggested that mineral characteristics can be modified independently of bone remodeling. In conclusion, mineral maturity and crystallinity index are two different parameters measured separately by FTIRM and offering new perspectives to assess bone mineral traits in osteoporosis

Non-invasive monitoring of Streptococcus pyogenes vaccine efficacy using biophotonic imaging.

Streptococcus pyogenes infection of the nasopharynx represents a key step in the pathogenic cycle of this organism and a major focus for vaccine development, requiring robust models to facilitate the screening of potentially protective antigens. One antigen that may be an important target for vaccination is the chemokine protease, SpyCEP, which is cell surface-associated and plays a role in pathogenesis. Biophotonic imaging (BPI) can non-invasively characterize the spatial location and abundance of bioluminescent bacteria in vivo. We have developed a bioluminescent derivative of a pharyngeal S. pyogenes strain by transformation of an emm75 clinical isolate with the luxABCDE operon. Evaluation of isogenic recombinant strains in vitro and in vivo confirmed that bioluminescence conferred a growth deficit that manifests as a fitness cost during infection. Notwithstanding this, bioluminescence expression permitted non-invasive longitudinal quantitation of S. pyogenes within the murine nasopharynx albeit with a detection limit corresponding to approximately 10(5) bacterial colony forming units (CFU) in this region. Vaccination of mice with heat killed streptococci, or with SpyCEP led to a specific IgG response in the serum. BPI demonstrated that both vaccine candidates reduced S. pyogenes bioluminescence emission over the course of nasopharyngeal infection. The work suggests the potential for BPI to be used in the non-invasive longitudinal evaluation of potential S. pyogenes vaccines

An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo

Impact of Vitamin D Supplementation on Arterial Vasomotion, Stiffness and Endothelial Biomarkers in Chronic Kidney Disease Patients

Background: Cardiovascular events are frequent and vascular endothelial function is abnormal in patients with chronic kidney disease (CKD). We demonstrated endothelial dysfunction with vitamin D deficiency in CKD patients; however the impact of cholecalciferol supplementation on vascular stiffness and vasomotor function, endothelial and bone biomarkers in CKD patients with low 25-hydroxy vitamin D [25(OH)D] is unknown, which this study investigated. Methods: We assessed non-diabetic patients with CKD stage 3/4, age 17–80 years and serum 25(OH)D ,75 nmol/L. Brachial artery Flow Mediated Dilation (FMD), Pulse Wave Velocity (PWV), Augmentation Index (AI) and circulating blood biomarkers were evaluated at baseline and at 16 weeks. Oral 300,000 units cholecalciferol was administered at baseline and 8-weeks. Results: Clinical characteristics of 26 patients were: age 50614 (mean61SD) years, eGFR 41611 ml/min/1.73 m2, males 73%, dyslipidaemia 36%, smokers 23% and hypertensives 87%. At 16-week serum 25(OH)D and calcium increased (43616 to 84629 nmol/L, p,0.001 and 2.3760.09 to 2.4260.09 mmol/L; p = 0.004, respectively) and parathyroid hormone decreased (10.868.6 to 7.464.4; p = 0.001). FMD improved from 3.163.3% to 6.163.7%, p = 0.001. Endothelial biomarker concentrations decreased: E-Selectin from 566662123 to 525662058 pg/mL; p = 0.032, ICAM-1, 3.4560.01 to 3.1061.04 ng/mL; p = 0.038 and VCAM-1, 54633 to 42633 ng/mL; p = 0.006. eGFR, BP, PWV, AI, hsCRP, von Willebrand factor and Fibroblast Growth Factor-23, remained unchanged. Conclusion: This study demonstrates for the first time improvement of endothelial vasomotor and secretory functions with vitamin D in CKD patients without significant adverse effects on arterial stiffness, serum calcium or FGF-23. Trial Registration: ClinicalTrials.gov NCT0200571