Citations

The incidence and prevalence of diabetes mellitus in residents of Rochester, Minnesota, for 25 years (1945 to 1970) were determined from available medical records. The over-all incidence rate for diabetes is 133 new cases per 100,000 population per year (age-adjusted to 1970 U.S. white population). The rate increased with age for both men and women and was higher among men over 30 years of age. The average annual incidence rates per five-year period for juvenile-onset diabetes mellitus were low and variable and showed little change. Polyuria, polydipsia, glycosuria, lean habitus, loss of weight, and high levels of fasting hyperglycemia at initial diagnosis occurred more frequently in younger than in older patients. The peak incidence in 1960 through 1964 and the decrease in the following five years may be a reflection of the introduction of the AutoAnalyzer method for blood glucose in 1958. The average annual incidence rates for 1955 through 1959 and 1965 through 1969 were essentially the same. The over-all prevalence for diabetes mellitus is 1.6 per cent, with a higher rate among men than among women over 40 years of age; among school children the rate is 0.1 per cent. Survivorship in the diabetic population is lower than that in the general population. The leading cause of death was coronary heart disease, the death rate from it being higher than for the general population.

AbstractBackground: It is widely accepted that chronic inflammation plays a role in the etiology of colorectal cancer. Using a two-stage design, we examined the associations between colorectal cancer and common variation in 37 key genes in the inflammation and innate immunity pathways.Methods: In the discovery stage, 2,322 discordant sibships (2,535 cases, 3,915 sibling controls) from the Colorectal Cancer Family Registry were genotyped for more than 600 tagSNPs and 99 single-nucleotide polymorphisms (SNP) were selected for further examination based on strength of association. In the second stage, 351 SNPs tagging gene regions covered by the 99 SNPs were tested in 4,783 Multiethnic Cohort subjects (2,153 cases, 2,630 controls).Results: The association between rs9858822 in the PPARG gene and colorectal cancer was statistically significant at the end of the second stage (OR per allele = 1.36, Bonferroni-adjusted P = 0.045), based on the “effective” number of markers in stage II (n = 306). The risk allele C was common (frequency 0.3) in African Americans but rare (frequency < 0.03) in whites, Japanese Americans, Latinos, and Native Hawaiians. No statistically significant heterogeneity of effects across race/ethnicity, body mass index (BMI) levels, regular aspirin use, or pack-years of smoking was detected for this SNP. Suggestive associations were also observed for several SNPs in close vicinity to rs9858822.Conclusions: Our results provide new evidence of association between PPARG variants and colorectal cancer risk.Impact: Further replication in independent samples is warranted. Cancer Epidemiol Biomarkers Prev; 22(11); 2094–101. ©2013 AACR.

Glioma cell migration correlates with Pyk2 activity, but the intrinsic mechanism that regulates the activity of Pyk2 is not fully understood. Previous studies have supported a role for the N-terminal FERM domain in the regulation of Pyk2 activity as mutations in the FERM domain inhibit Pyk2 phosphorylation. To search for novel protein-protein interactions mediated by the Pyk2 FERM domain, we utilized a yeast two-hybrid genetic selection to identify the mammalian Ste20 homolog MAP4K4 as a binding partner for the Pyk2 FERM domain. MAP4K4 coimmunoprecipitated with Pyk2 and was a substrate for Pyk2 but did not coimmunoprecipitate with the closely related focal adhesion kinase FAK. Knockdown of MAP4K4 expression inhibited glioma cell migration and effectively blocked Pyk2 stimulation of glioma cell. Increased expression of MAP4K4 stimulated glioma cell migration; however, this stimulation was blocked by knockdown of Pyk2 expression. These data support that the interaction of MAP4K4 and Pyk2 is integrated with glioma cell migration and suggest that inhibition of this interaction may represent a potential therapeutic strategy to limit glioblastoma tumor dispersion.

The availability of population-based epidemiological data on the incident risk of stroke is very scarce in Argentina and other Latin American countries. In response to the priorities established by the World Health Organization and the United Nations, PREVISTA was envisaged as a population-based program to determine the risk of first-ever and recurrent stroke and transient ischemic attack incidence and mortality in Tandil, Buenos Aires, Argentina. The study will be conducted according to Standardized Tools for Stroke Surveillance (STEPS Stroke) methodology and will enroll all new (incident) and recurrent consecutive cases of stroke and transient ischemic attack in the City of Tandil between May 1st, 2013 and April 30, 2015. The study will include patients with ischemic stroke, non-traumatic primary intracerebral hemorrhage, subarachnoid hemorrhage, and transient ischemic attack. To ensure the inclusion of every cerebrovascular event during an observation period of two years, we will instrument an ‘intensive screening program’, consisting of a comprehensive daily tracking of every potential event of stroke or transient ischemic attack using multiple overlapping sources. Mortality would be determined during follow-up for every enrolled patient. Also, fatal community events would be screened daily through revision of death certificates at funeral homes and local offices of vital statistics. All causes of death will be adjudicated by an ad-hoc committee. The close population of Tandil is representative of a large proportion of Latin-American countries with low- and middle-income economies. The findings and conclusions of PREVISTA may provide data that could support future health policy decision-making in the region.

Background and Purpose— Meta-analyses of extant genome-wide data illustrate the need to focus on subtypes of ischemic stroke for gene discovery. The National Institute of Neurological Disorders and Stroke SiGN (Stroke Genetics Network) contributes substantially to meta-analyses that focus on specific subtypes of stroke. Methods— The National Institute of Neurological Disorders and Stroke SiGN includes ischemic stroke cases from 24 genetic research centers: 13 from the United States and 11 from Europe. Investigators harmonize ischemic stroke phenotyping using the Web-based causative classification of stroke system, with data entered by trained and certified adjudicators at participating genetic research centers. Through the Center for Inherited Diseases Research, the Network plans to genotype 10 296 carefully phenotyped stroke cases using genome-wide single nucleotide polymorphism arrays and adds to these another 4253 previously genotyped cases, for a total of 14 549 cases. To maximize power for subtype analyses, the study allocates genotyping resources almost exclusively to cases. Publicly available studies provide most of the control genotypes. Center for Inherited Diseases Research–generated genotypes and corresponding phenotypes will be shared with the scientific community through the US National Center for Biotechnology Information database of Genotypes and Phenotypes, and brain MRI studies will be centrally archived. Conclusions— The Stroke Genetics Network, with its emphasis on careful and standardized phenotyping of ischemic stroke and stroke subtypes, provides an unprecedented opportunity to uncover genetic determinants of ischemic stroke.

AbstractObjectiveThe aim of this randomized controlled trial for patients with advanced cancer receiving radiation therapy was to determine the effect of a multidisciplinary intervention on spiritual quality of life (QOL) at the end of the intervention (week 4) and at two follow‐up time points (weeks 26 and 52).MethodsOne hundred thirty‐one persons were randomized to either the intervention or control (forms only) groups. The intervention included six 90‐min in‐person sessions based on the physical, emotion, social, and spiritual domains of QOL. Three sessions included the spiritual component. Caregivers were present for four sessions, one which included a spiritual component. Ten follow‐up phone calls were made to the patients in the intervention group during the 6‐month follow‐up period. Patients completed the Functional Assessment of Cancer Therapy: General Scale, the Linear Analog Self‐Assessment which includes an assessment of spiritual QOL, and the Functional Assessment of Chronic Illness Therapy‐Spiritual Well‐Being (FACIT‐Sp) at enrollment, and weeks 4, 27, and 52.ResultsFollowing the intervention, the intervention group demonstrated improved spiritual QOL on the FACIT‐Sp, whereas the spiritual QOL of the control group decreased, resulting in significant mean changes between groups (total score: 1.7 vs. −2.9; p < 0.01; meaning/peace subscale: 1.0 vs. −3.5; p < 0.01; faith subscale: 3.1 vs. −1.7; p = 0.04).ConclusionsThe results indicate that a multidisciplinary intervention which includes a spiritual component can maintain the spiritual QOL of patients with advanced cancer during radiation therapy. Copyright © 2013 John Wiley & Sons, Ltd.

PurposeThe association of deficient DNA mismatch repair (dMMR) with prognosis in patients with colon cancer treated with adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy remains unknown.Patients and MethodsResected, stage III colon carcinomas from patients (N = 2,686) randomly assigned to FOLFOX ± cetuximab (North Central Cancer Treatment Group N0147 trial) were analyzed for mismatch repair (MMR) protein expression and mutations in BRAFV600E(exon 15) and KRAS (codons 12 and 13). Association of biomarkers with disease-free survival (DFS) was determined using Cox models. A validation cohort (Cancer and Leukemia Group B 88903 trial) was used.ResultsdMMR was detected in 314 (12%) of 2,580 tumors, of which 49.3% and 10.6% had BRAFV600Eor KRAS mutations, respectively. MMR status was not prognostic overall (adjusted hazard ratio [HR], 0.82; 95% CI, 0.64 to 1.07; P = .14), yet significant interactions were found between MMR and primary tumor site (Pinteraction= .009) and lymph node category (N1 v N2; Pinteraction= .014). Favorable DFS was observed for dMMR versus proficient MMR proximal tumors (HR, 0.71; 95% CI, 0.53 to 0.94; P = .018) but not dMMR distal tumors (HR, 1.71; 95% CI, 0.99 to 2.95; P = .056), adjusting for mutations and covariates. Any survival benefit of dMMR was lost in N2 tumors. Mutations in BRAFV600E(HR, 1.37; 95% CI, 1.08 to 1.70; P = .009) or KRAS (HR, 1.44; 95% CI, 1.21 to 1.70; P < .001) were independently associated with worse DFS. The observed MMR by tumor site interaction was validated in an independent cohort of stage III colon cancers (Pinteraction= .037).ConclusionThe prognostic impact of MMR depended on tumor site, and this interaction was validated in an independent cohort. Among dMMR cancers, proximal tumors had favorable outcome, whereas distal or N2 tumors had poor outcome. BRAF or KRAS mutations were independently associated with adverse outcome.