Risk factors associated with ACL registry compliance: can we predict who will follow-up?

European Journal of Orthopaedic Surgery & Traumatology - The purpose of this study was to determine patient factors that influence patient compliance to fill out anterior cruciate ligament...     

Selenophene-containing inhibitors of type IIA bacterial topoisomerases

We investigated compounds related to the previously reported antistaphyloccocal agent AVE6971 in an effort to attenuate inhibition of hERG potassium channel current that has been noted for this and related antibacterial drug classes. While most modifications of the original thiophene group compromised antibacterial activity, one selenophene analogue displayed (i) improved activity against the primary target enzyme DNA gyrase, (ii) similar activities against a panel of MRSA clinical isolates, and (iii) reduced hERG channel inhibition.     

Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated

The initial antibody response to HIV-1 is targeted to envelope (Env) gp41, and is nonneutralizing and ineffective in controlling viremia. To understand the origins and characteristics of gp41-binding antibodies produced shortly after HIV-1 transmission, we isolated and studied gp41-reactive plasma cells from subjects acutely infected with HIV-1. The frequencies of somatic mutations were relatively high in these gp41-reactive antibodies. Reverted unmutated ancestors of gp41-reactive antibodies derived from subjects acutely infected with HIV-1 frequently did not react with autologous HIV-1 Env; however, these antibodies were polyreactive and frequently bound to host or bacterial antigens. In one large clonal lineage of gp41-reactive antibodies, reactivity to HIV-1 Env was acquired only after somatic mutations. Polyreactive gp41-binding antibodies were also isolated from uninfected individuals. These data suggest that the majority of gp41-binding antibodies produced after acute HIV-1 infection are cross-reactive responses generated by stimulating memory B cells that have previously been activated by non-HIV-1 antigens.     

Obesity and risk of vascular disease: importance of endothelium-dependent vasoconstriction

Obesity has become a serious global health issue affecting both adults and children. Recent devolopments in world demographics and declining health status of the world's population indicate that the prevalence of obesity will continue to increase in the next decades. As a disease, obesity has deleterious effects on metabolic homeostasis, and affects numerous organ systems including heart, kidney and the vascular system. Thus, obesity is now regarded as an independent risk factor for atherosclerosis-related diseases such as coronary artery disease, myocardial infarction and stroke. In the arterial system, endothelial cells are both the source and target of factors contributing to atherosclerosis. Endothelial vasoactive factors regulate vascular homeostasis under physiological conditions and maintain basal vascular tone. Obesity results in an imbalance between endothelium-derived vasoactive factors favouring vasoconstriction, cell growth and inflammatory activation. Abnormal regulation of these factors due to endothelial cell dysfunction is both a consequence and a cause of vascular disease processes. Finally, because of the similarities of the vascular pathomechanisms activated, obesity can be considered to cause accelerated, 'premature' vascular aging. Here, we will review some of the pathomechanisms involved in obesity-related activation of endothelium-dependent vasoconstriction, the clinical relevance of obesity-associated vascular risk, and therapeutic interventions using 'endothelial therapy' aiming at maintaining or restoring vascular endothelial health. LINKED ARTICLES: This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3.     

HLA-DPB1-COL11A2 and three additional xMHC loci are independently associated with RA in a UK cohort

The aim of this study was to investigate the complex association pattern of the extended major histocompatibility complex (xMHC) region with rheumatoid arthritis (RA) susceptibility to identify effects independent of HLA-DRB1. A total of 1804 RA cases and 1474 controls were included. High-resolution HLA-DRB1 typing was performed. Subjects were genotyped for 1546 single-nucleotide polymorphisms (SNPs) using Affymetrix GeneChip 500?K (Santa Clara, CA, USA) as part of the Wellcome Trust Case Control Consortium Study. Statistical analysis was carried out using PLINK. To avoid confounding by RA-associated HLA-DRB1 alleles, we analyzed xMHC SNPs using a data set with pairwise matching of cases and controls on DRB1 genotypes. A total of 594 case-control pairs with identical DRB1 genotypes were identified. After this adjustment, 104 SNPs remained significantly associated with RA (P<0.05), suggesting that additional RA loci independent of HLA-DRB1 can be found in the xMHC region. Of these, four loci showed the strongest associations with RA (P<0.005): ZNF391, the olfactory receptor (OR) gene cluster, C6orf26-RDBP and HLA-DPB1-COL11A2. An additional locus mapping to the BTN (butyrophilin) cluster showed independent association with RA in anti-cyclic citrullinated peptide-positive patients exclusively. We have validated the previously described independent association of the HLA-DPB1-COL11A2 locus with RA. In addition, association with three novel independent RA loci in the xMHC region (ZNF391, OR2H1 and C6orf26-RDBP) has been detected.     

An advanced nurse practitioner-led service - consequences of service redesign for managers and organizational infrastructure

barton d . & mashlan w. (2011) Journal of Nursing Management 19, 943–949 An advanced nurse practitioner-led service – consequences of service redesign for managers and organizational infrastructure Aim A service review of a secondary care advanced nurse practitioner-led service. Background An acute hospital-based elderly care rehabilitation service evolved over a 9-year period from a traditional consultant/junior doctor configuration to a consultant/advanced nurse practitioner configuration. The review evaluated the advanced nurse practitioner team’s role in the clinical setting, and the constraints experienced as a result of the traditions of the hospital organization. Evaluation The review drew its conclusions from opinion data collected from 38 professionals and non-professionals within the rehabilitation service. Key issues The organizational infrastructure and traditions that had an impact on service delivery by the advanced nurse practitioner team. There is a demand for senior management to act on developmental constraints. Conclusions The advanced nurse practitioner-led rehabilitation service was fit for purpose and an emerging model of a non-medical led care. However, important organizational constraints were identified. Implications for nursing management An advanced nurse practitioner team, working in collaboration with medical consultants, was a model for future service redesign in the acute hospital setting. Nevertheless, it presented challenges to senior health-care managers on current organizational infrastructures.     

Uncertainties in the measurement of blood glucose in paediatric intensive care: implications for clinical trials of tight glycaemic control

Purpose  

In preparation for a tight glycaemic control (TGC) clinical trial we assessed the agreement between methods used to measure blood glucose in critically ill children.     

Socioeconomic determinants of disability and depression in patients with rheumatoid arthritis

Objective

To examine the relationship between functional limitation, socioeconomic inequality, and depression in a diverse cohort of patients with rheumatoid arthritis (RA).

Methods

The study design was cross‐sectional and subjects were from the University of California, San Francisco RA Cohort. Patients were enrolled from 2 rheumatology clinics, an urban county public hospital and a university tertiary care medical center. Age, sex, race/ethnicity, disease activity, functional limitation, and medications were variables collected at clinical visits. The patient's clinic site was used as a proxy for his or her socioeconomic status. The outcome variable was depressive symptom severity measured by the Patient Health Questionnaire 9. Differences in characteristics between depressed and nondepressed patients were calculated using 2‐sided t‐tests or the Pearson's chi‐square test. For the multivariate analysis, repeated measures with generalized estimating equations were used.

Results

There were statistically significant differences between depressed and nondepressed patients related to race/ethnicity, public versus tertiary care hospital rheumatology clinic, disability, and medications. In the multivariate analysis, increased functional limitation and public clinic site remained significantly associated with increased depression scores. A significant interaction existed between clinic site and disability. Mean depression scores rose more precipitously as functional limitation increased at the public hospital rheumatology clinic.

Conclusion

There are disparities in both physical and mental health among individuals with low socioeconomic status. The psychological effects of disability vary in patients with RA such that a vulnerable population with functional limitations is at higher risk of developing depressive symptoms.