Smoking, Smoking Cessation, and Risk for Type 2 Diabetes Mellitus: A Cohort Study

Cigarette smoking is an established predictor of incident type 2 diabetes mellitus, but the effects of smoking cessation on diabetes risk are unknown

Associations between quality indicators of internal medicine residency training programs

<p>Abstract</p> <p>Background</p> <p>Several residency program characteristics have been suggested as measures of program quality, but associations between these measures are unknown. We set out to determine associations between these potential measures of program quality.</p> <p>Methods</p> <p>Survey of internal medicine residency programs that shared an online ambulatory curriculum on hospital type, faculty size, number of trainees, proportion of international medical graduate (IMG) trainees, Internal Medicine In-Training Examination (IM-ITE) scores, three-year American Board of Internal Medicine Certifying Examination (ABIM-CE) first-try pass rates, Residency Review Committee-Internal Medicine (RRC-IM) certification length, program director clinical duties, and use of pharmaceutical funding to support education. Associations assessed using Chi-square, Spearman rank correlation, univariate and multivariable linear regression.</p> <p>Results</p> <p>Fifty one of 67 programs responded (response rate 76.1%), including 29 (56.9%) community teaching and 17 (33.3%) university hospitals, with a mean of 68 trainees and 101 faculty. Forty four percent of trainees were IMGs. The average post-graduate year (PGY)-2 IM-ITE raw score was 63.1, which was 66.8 for PGY3s. Average 3-year ABIM-CE pass rate was 95.8%; average RRC-IM certification was 4.3 years. ABIM-CE results, IM-ITE results, and length of RRC-IM certification were strongly associated with each other (p < 0.05). PGY3 IM-ITE scores were higher in programs with more IMGs and in programs that accepted pharmaceutical support (p < 0.05). RRC-IM certification was shorter in programs with higher numbers of IMGs. In multivariable analysis, a higher proportion of IMGs was associated with 1.17 years shorter RRC accreditation.</p> <p>Conclusions</p> <p>Associations between quality indicators are complex, but suggest that the presence of IMGs is associated with better performance on standardized tests but decreased duration of RRC-IM certification.</p

Hemoglobin A1c and Mortality in Older Adults With and Without Diabetes: Results From the National Health and Nutrition Examination Surveys (1988-2011)

OBJECTIVE: Hemoglobin A1c (HbA1c) level has been associated with increased mortality in middle-aged populations. The optimal intensity of glucose control in older adults with diabetes remains uncertain. We sought to estimate the risk of mortality by HbA1c levels among older adults with and without diabetes. RESEARCH DESIGN AND METHODS: We analyzed data from adults aged ≥65 years (n = 7,333) from the Third National Health and Nutrition Examination Survey (NHANES III) (1998-1994) and Continuous NHANES (1999-2004) and their linked mortality data (through December 2011). Cox proportional hazards models were used to examine the relationship of HbA1c with the risk of all-cause and cause-specific (cardiovascular disease [CVD], cancer, and non-CVD/noncancer) mortality, separately for adults with diabetes and without diabetes. RESULTS: Over a median follow-up of 8.9 years, 4,729 participants died (1,262 from CVD, 850 from cancer, and 2,617 from non-CVD/noncancer causes). Compared with those with diagnosed diabetes and an HbA1c &lt;6.5%, the hazard ratio (HR) for all-cause mortality was significantly greater for adults with diabetes with an HbA1c &gt;8.0%. HRs were 1.6 (95% CI 1.02, 2.6) and 1.8 (95% CI 1.3, 2.6) for HbA1c 8.0-8.9% and ≥9.0%, respectively (P for trend &lt;0.001). Participants with undiagnosed diabetes and HbA1c &gt;6.5% had a 1.3 (95% CI 1.03, 1.8) times greater risk of all-cause mortality compared with participants without diabetes and HbA1c 5.0-5.6%. CONCLUSIONS: An HbA1c &gt;8.0% was associated with increased risk of all-cause and cause-specific mortality in older adults with diabetes. Our results support the idea that better glycemic control is important for reducing mortality; however, in light of the conflicting evidence base, there is also a need for individualized glycemic targets for older adults with diabetes depending on their demographics, duration of diabetes, and existing comorbidities

Body-Mass Index and Mortality Risk in US Blacks Compared to Whites

Objective: To compare body-mass index (BMI)-related mortality risk in US Blacks vs. Whites as the relationship appears to differ across race/ethnicity groups. Design and Methods We pooled cross-sectional surveys of nationally representative samples of 11,934 Blacks and 59,741 Whites aged 35–75 in the National Health Interview Survey from 1997–2002 with no history of cardiovascular disease or cancer. Mortality follow-up was available through 2006. BMI was calculated from self-reported height and weight. We used adjusted Cox regression analysis to adjust for potential confounders. Results: Over 9 years of follow-up, there were 4,303 deaths (1,205 among never smokers). Age-adjusted mortality rates were higher in Blacks compared to Whites at BMI < 25 kg/m2 and showed no increase at higher levels of BMI. In men, adjusted hazard ratios for all-cause death rose in a similar fashion across upper BMI quintiles in Blacks and Whites; in women, however, BMI was positively associated with mortality risk in Whites, but inversely associated in Blacks (p interaction = 0.01). Racial disparities were amplified in subsidiary analyses that introduced a 12-month lag for mortality or focused on CVD mortality. Conclusions: The relationship of elevated BMI to mortality appears weaker in US Blacks than in Whites, especially among women

Earthquake Doublet Sequences: Evidence of Static Triggering in the Strong Convergent Zones of Taiwan

Three earthquake sequences, each with two main earthquakes of almost the same magnitudes (ML from 5.9 to 7.0 with differences less than 0.1), have recently been observed in Taiwan. The two largest earthquakes in each sequence occurred with a short delay time between them, were strikingly similar in terms of magnitude, location and/or focal mechanism and are referred to as doublets. They were markedly distinct from typical single mainshock sequences. Our estimated static stress field generated by the first shock in the doublet shows that the second shock and most of their aftershocks were located within a region where static stress increased substantially. Thus, a possible explanation for earthquake doublet is that seismic energy for each shock had accumulated independently within adjacent crustal volumes, separated by an asperity, and that the second shock is triggered by the increased static stress after the first one. An important implication of doublet sequence is that works by emergency response teams after the first earthquake could be made more hazardous by the second

The Volcanic Earthquake Swarm of October 20, 2009 in the Tatun Area of Northern Taiwan

On October 20, 2009, a series of felt earthquakes with local magnitudes ranging from 2.8 - 3.2 occurred in the Tatun volcanic area off the northern tip of Taiwan. Although there was no damage caused by those earthquakes, many residents in the Taipei metropolitan area, particularly for people who live near the Yangminshan National Park, felt strong ground shaking. In order to know what the possible mechanisms were that generated those earthquakes, we carefully examined seismic data recorded by a dense seismic array in the Tatun volcanic area. During the period between October 18 and 22, 2009 we detected at least 202 micro-earthquakes. Most of the earthquakes were relocated using the double-difference method and were clustered in the shallow crust beneath the Dayoukeng area, which is the strongest fumarole in the Tatun volcanic area. Among these earthquakes, 72 focal mechanisms were determined by polarizing the first P-wave motion. Most earthquakes belonged to normal faulting. An extremely high b-value of 2.17 was obtained from those earthquakes. Based on the seismic variations in both the temporary and spatial distribution as well as an extremely high b-value, we conclude that the earthquake sequence on October 20, 2009 was a typically seismic swarm associated with possible active volcanism in the Tatun volcanic area

Diabetes and Prediabetes and Risk of Hospitalization: The Atherosclerosis Risk in Communities (ARIC) Study

To examine the magnitude and types of hospitalizations among persons with prediabetes, undiagnosed diabetes, and diagnosed diabetes

Toll-like receptor 9 agonist enhances anti-tumor immunity and inhibits tumor-associated immunosuppressive cells numbers in a mouse cervical cancer model following recombinant lipoprotein therapy

BACKGROUND: Although cytotoxic T lymphocytes (CTLs) play a major role in eradicating cancer cells during immunotherapy, the cancer-associated immunosuppressive microenvironment often limits the success of such therapies. Therefore, the simultaneous induction of cancer-specific CTLs and reversal of the immunosuppressive tumor microenvironment may be more effectively achieved through a single therapeutic vaccine. A recombinant lipoprotein with intrinsic Toll-like receptor 2 (TLR2) agonist activity containing a mutant form of E7 (E7m) and a bacterial lipid moiety (rlipo-E7m) has been demonstrated to induce robust CTL responses against small tumors. This treatment in combination with other TLR agonists is able to eliminate large tumors. METHODS: Mouse bone marrow-derived dendritic cells (DCs) were employed to determine the synergistic production of pro-inflammatory cytokines upon combination of rlipo-E7m and other TLR agonists. Antigen-specific CTL responses were investigated using immunospots or in vivo cytolytic assays after immunization in mice. Mice bearing various tumor sizes were used to evaluate the anti-tumor effects of the formulation. Specific subpopulations of immunosuppressive cells in the tumor infiltrate were quantitatively determined by flow cytometry. RESULTS: We demonstrate that a TLR9 agonist (unmethylated CpG oligodeoxynucleotide, CpG ODN) enhances CTL responses and eradicates large tumors when combined with rlipo-E7m. Moreover, combined treatment with rlipo-E7m and CpG ODN effectively increases tumor infiltration by CTLs and reduces the numbers of myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) in the tumor microenvironment. CONCLUSION: These findings suggest that the dramatic anti-tumor effects of the recombinant lipoprotein together with CpG ODN may reflect the amplification of CTL responses and the repression of the immunosuppressive environment. This promising approach could be applied for the development of additional therapeutic cancer vaccines

Borders of Cis-Regulatory DNA Sequences Preferentially Harbor the Divergent Transcription Factor Binding Motifs in the Human Genome

Changes in cis-regulatory DNA sequences and transcription factor (TF) repertoires provide major sources of phenotypic diversity that shape the evolution of gene regulation in eukaryotes. The DNA-binding specificities of TFs may be diversified or produce new variants in different eukaryotic species. However, it is currently unclear how various levels of divergence in TF DNA-binding specificities or motifs became introduced into the cis-regulatory DNA regions of the genome over evolutionary time. Here, we first estimated the evolutionary divergence levels of TF binding motifs and quantified their occurrence at DNase I-hypersensitive sites. Results from our in silico motif scan and experimentally derived chromatin immunoprecipitation (TF-ChIP) show that the divergent motifs tend to be introduced in the edges of cis-regulatory regions, which is probably accompanied by the expansion of the accessible core of promoter-associated regulatory elements during evolution. We also find that the genes neighboring the expanded cis-regulatory regions with the most divergent motifs are associated with functions like development and morphogenesis. Accordingly, we propose that the accumulation of divergent motifs in the edges of cis-regulatory regions provides a functional mechanism for the evolution of divergent regulatory circuits