Cigarette smoking, health status, socio-economic status and access to health care in diabetes mellitus: a cross-sectional survey

BACKGROUND: In diabetes mellitus, cigarette smoking is associated with increased risk of cardiovascular mortality and microvascular complications. We evaluated cigarette smoking in people with diabetes mellitus in a socio-economically deprived area. METHODS: We carried out a cross-sectional survey of people registered with diabetes mellitus at 29 general practices in inner London. Responses were analysed for 1,899 (64%) respondents out of 2,983 eligible. RESULTS: There were 1,899 respondents of whom 968 (51%) had never smoked, 296 (16%) were current smokers and 582 (31%) were ex-smokers. Smoking was more frequent in white Europeans (men 22%, women 20%), than in African Caribbeans (men 15%, women 10%) or Africans (men 8%, women 2%). Smoking prevalence decreased with age. Smokers were more likely to be living in rented accommodation (odds ratio, OR 2.02, 95% confidence interval 1.48 to 2.74). After adjusting for confounding, current smokers had lower SF-36 scores than subjects who had never smoked (mean difference in physical functioning score -5.6, 95% confidence interval -10.0 to -1.2; general health -6.1, -9.7 to -2.5). Current smokers were less likely to have attended a hospital diabetic clinic in the last year (OR 0.59, 0.44 to 0.79), and their hypertension was less likely to be treated (OR 0.47, 0.30 to 0.74). CONCLUSIONS: Compared with non-smokers, smokers had lower socio-economic status and worse health status, but were less likely to be referred to hospital or treated for their hypertension. People with diabetes who smoke can be regarded as a vulnerable group who need more intensive support and treatment

Modelling the effects of standard prognostic factors in node-positive breast cancer

Prognostic models that predict the clinical course of a breast cancer patient are important in oncology. We propose an approach to constructing such models based on fractional polynomials in which useful transformations of the continuous factors are determined. The idea may be applied with all types of regression model, including Cox regression, the method of choice for survival-time data. We analyse a prospective study of node-positive breast cancer. Seven standard prognostic factors – age, menopausal status, tumour size, tumour grade, number of positive lymph nodes, progesterone and oestrogen receptor concentrations – were investigated in 686 patients, of whom 299 had an event for recurrence-free survival and 171 died. We determine a final model with transformations of prognostic factors and compare it with the more traditional approaches using categorized variables or assuming a straight line relationship. We conclude that analysis using fractional polynomials can extract important prognostic information which the traditional approaches may miss. © 1999 Cancer Research Campaig

Discovering unique tobacco use patterns among Alaska Native people

Background . Alaska Native people are disproportionately impacted by tobacco-related diseases in comparison to non-Native Alaskans. Design. We used Alaska's Behavioral Risk Factor Surveillance System (BRFSS) to describe tobacco use among more than 4,100 Alaska Native adults, stratified by geographic region and demographic groups. Results . Overall tobacco use was high: approximately 2 out of every 5 Alaska Native adults reported smoking cigarettes (41.2%) and 1 in 10 reported using smokeless tobacco (SLT, 12.3%). A small percentage overall (4.8%) reported using iq'mik, an SLT variant unique to Alaska Native people. When examined by geographic region, cigarette smoking was highest in remote geographic regions; SLT use was highest in the southwest region of the state. Use of iq'mik was primarily confined to a specific area of the state; further analysis showed that 1 in 3 women currently used iq'mik in this region. Conclusion . Our results suggest that different types of tobacco use are epidemic among diverse Alaska Native communities. Our results also illustrate that detailed analysis within racial/ethnic groups can be useful for public health programme planning to reduce health disparities

Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin

Pathological processes involved in the initiation of rheumatoid synovitis remain unclear. We undertook the present study to identify immune and stromal processes that are present soon after the clinical onset of rheumatoid arthritis ( RA) by assessing a panel of T cell, macrophage, and stromal cell related cytokines and chemokines in the synovial fluid of patients with early synovitis. Synovial fluid was aspirated from inflamed joints of patients with inflammatory arthritis of duration 3 months or less, whose outcomes were subsequently determined by follow up. For comparison, synovial fluid was aspirated from patients with acute crystal arthritis, established RA and osteoarthritis. Rheumatoid factor activity was blocked in the synovial fluid samples, and a panel of 23 cytokines and chemokines measured using a multiplex based system. Patients with early inflammatory arthritis who subsequently developed RA had a distinct but transient synovial fluid cytokine profile. The levels of a range of T cell, macrophage and stromal cell related cytokines ( e. g. IL-2, IL-4, IL-13, IL-17, IL-15, basic fibroblast growth factor and epidermal growth factor) were significantly elevated in these patients within 3 months after symptom onset, as compared with early arthritis patients who did not develop RA. In addition, this profile was no longer present in established RA. In contrast, patients with non-rheumatoid persistent synovitis exhibited elevated levels of interferon-gamma at initiation. Early synovitis destined to develop into RA is thus characterized by a distinct and transient synovial fluid cytokine profile. The cytokines present in the early rheumatoid lesion suggest that this response is likely to influence the microenvironment required for persistent RA

Receptor Tyrosine Kinase (RTK) Mediated Tyrosine Phosphor-Proteome from Drosophila S2 (ErbB1) Cells Reveals Novel Signaling Networks

Protein phosphorylation mediates many critical cellular responses and is essential for many biological functions during development. About one-third of cellular proteins are phosphorylated, representing the phosphor-proteome, and phosphorylation can alter a protein's function, activity, localization and stability. Tyrosine phosphorylation events mediated by aberrant activation of Receptor Tyrosine Kinase (RTK) pathways have been proven to be involved in the development of several diseases including cancer. To understand the systems biology of RTK activation, we have developed a phosphor-proteome focused on tyrosine phosphorylation events under insulin and EGF signaling pathways using the PhosphoScan® technique coupled with high-throughput mass spectrometry analysis. Comparative proteomic analyses of all these tyrosine phosphorylation events revealed that around 70% of these pY events are conserved in human orthologs and paralogs. A careful analysis of published in vivo tyrosine phosphorylation events from literature and patents revealed that around 38% of pY events from Drosophila proteins conserved on 185 human proteins are confirmed in vivo tyrosine phosphorylation events. Hence the data are validated partially based on available reports, and the credibility of the remaining 62% of novel conserved sites that are unpublished so far is very high but requires further follow-up studies. The novel pY events found in this study that are conserved on human proteins could potentially lead to the discovery of drug targets and biomarkers for the detection of various cancers and neurodegenerative diseases

A Systematic Mapping Approach of 16q12.2/FTO and BMI in More Than 20,000 African Americans Narrows in on the Underlying Functional Variation: Results from the Population Architecture using Genomics and Epidemiology (PAGE) Study

Genetic variants in intron 1 of the fat mass- and obesity-associated (FTO) gene have been consistently associated with body mass index (BMI) in Europeans. However, follow-up studies in African Americans (AA) have shown no support for some of the most consistently BMI-associated FTO index single nucleotide polymorphisms (SNPs). This is most likely explained by different race-specific linkage disequilibrium (LD) patterns and lower correlation overall in AA, which provides the opportunity to fine-map this region and narrow in on the functional variant. To comprehensively explore the 16q12.2/FTO locus and to search for second independent signals in the broader region, we fine-mapped a 646-kb region, encompassing the large FTO gene and the flanking gene RPGRIP1L by investigating a total of 3,756 variants (1,529 genotyped and 2,227 imputed variants) in 20,488 AAs across five studies. We observed associations between BMI and variants in the known FTO intron 1 locus: the SNP with the most significant p-value, rs56137030 (8.3×10-6) had not been highlighted in previous studies. While rs56137030was correlated at r2>0.5 with 103 SNPs in Europeans (including the GWAS index SNPs), this number was reduced to 28 SNPs in AA. Among rs56137030 and the 28 correlated SNPs, six were located within candidate intronic regulatory elements, including rs1421085, for which we predicted allele-specific binding affinity for the transcription factor CUX1, which has recently been implicated in the regulation of FTO. We did not find strong evidence for a second independent signal in the broader region. In summary, this large fine-mapping study in AA has substantially reduced the number of common alleles that are likely to be functional candidates of the known FTO locus. Importantly our study demonstrated that comprehensive fine-mapping in AA provides a powerful approach to narrow in on the functional candidate(s) underlying the initial GWAS findings in European populations

Protein Pattern Formation

Protein pattern formation is essential for the spatial organization of many intracellular processes like cell division, flagellum positioning, and chemotaxis. A prominent example of intracellular patterns are the oscillatory pole-to-pole oscillations of Min proteins in \textit{E. coli} whose biological function is to ensure precise cell division. Cell polarization, a prerequisite for processes such as stem cell differentiation and cell polarity in yeast, is also mediated by a diffusion-reaction process. More generally, these functional modules of cells serve as model systems for self-organization, one of the core principles of life. Under which conditions spatio-temporal patterns emerge, and how these patterns are regulated by biochemical and geometrical factors are major aspects of current research. Here we review recent theoretical and experimental advances in the field of intracellular pattern formation, focusing on general design principles and fundamental physical mechanisms.Comment: 17 pages, 14 figures, review articl

The Relative Composition of the Inflammatory Infiltrate as an Additional Tool for Synovial Tissue Classification

10.1371/journal.pone.0072494PLoS ONE88-POLN

Can racial disparities in optimal gout treatment be reduced? evidence from a randomized trial

There is a disproportionate burden of gout in African-Americans in the U.S. due to a higher disease prevalence and lower likelihood of receiving urate-lowering therapy (ULT), compared to Caucasians. There is an absence of strong data as to whether the response to ULT differs by race/ethnicity. BMC Musculoskeletal Disorders recently published a secondary analyses of the CONFIRMS trial, a large randomized controlled, double-blind trial of 2,269 gout patients. The authors reported that the likelihood of achieving the primary study efficacy end-point of achieving serum urate < 6 mg/dl was similar between African-Americans and Caucasians, for all three treatment arms (Febuxostat 40 mg and 80 mg and allopurinol 300/200 mg). More importantly, rates were similar in subgroups of patients with mild or moderate renal insufficiency. Adverse event rates were similar, as were the rates of gout flares. These findings constitute a convincing evidence to pursue aggressive ULT in gout patients, regardless of race/ethnicity. This approach will likely help to narrow the documented racial disparities in gout care