Colorectal cancers associated with Lynch syndrome are characterized by deficient DNA mismatch repair (MMR) function. Our aim was to evaluate the prevalence of microsatellite instability (MSI) and ...loss of MMR protein expression in Lynch syndrome-associated polyps. Sixty-two colorectal polyps--37 adenomatous polyps, 23 hyperplastic polyps, and 2 sessile serrated polyps (SSP)--from 34 subjects with germline MMR gene mutations were tested for MSI using a single pentaplex PCR for five mononucleotide repeat microsatellite markers, and also for expression of MLH1, MSH2, MSH6, and PMS2 proteins by immunohistochemistry. High-level MSI (MSI-H) was seen in 15 of 37 (41%) adenomatous polyps, one of 23 (4%) hyperplastic polyps, and one of two (50%) SSPs. Loss of MMR protein expression was seen in 18 of 36 (50%) adenomatous polyps, zero of 21 hyperplastic polyps, and zero of two SSPs. Adenomatous polyps 8 mm or larger in size were significantly more likely to show MSI-H OR, 9.98; 95% confidence interval (CI), 1.52-65.65; P = 0.02 and deficient MMR protein expression (OR, 3.17; 95% CI, 1.20-8.37; P = 0.02) compared with those less than 8 mm in size. All (six of six) adenomatous polyps 10 mm or larger in size showed both MSI-H and loss of MMR protein expression by immunohistochemistry. Our finding that the prevalence of MMR deficiency increases with the size of adenomatous polyps suggests that loss of MMR function is a late event in Lynch syndrome-associated colorectal neoplasia. Although testing large adenomatous polyps may be of value in the diagnostic evaluation of patients with suspected Lynch syndrome, the absence of an MMR-deficient phenotype in an adenoma cannot be considered as a strong evidence against Lynch syndrome, as it is with colorectal carcinomas.
•Middle Eastern/North African (MENA) women in the US have the lowest up-to-date screening rate of colorectal and cervical cancer of all races/ethnicities at 18%.•Any chronic health condition doubles ...the likelihood of having both below the belt screens compared to neither screen.•Women without insurance are more likely to only have cervical cancer compared to both colorectal and cervical cancer up-to-date screens.•54% of women 50–65 years old are up-to-date with both colorectal and cervical cancer screening.
Middle Eastern/North Africa (MENA) women are often not identified in cancer screening studies. The aim of this study was to determine the rates and predictors of cervical and colorectal cancer (CRC) screening for women 50–65 years of three race/ethnicities.
White, black and MENA women of Southeast Michigan were surveyed once in 2019 for demographics, health care barriers, chronic diseases, and cancer screening updates using in-person, telephone, and online methods. Descriptive statistics and multivariate multinomial logistic regression were used to predict up-to-date colorectal cancer and cervical cancer screening. All analyses were adjusted by local population weights for comparability and generalizability.
394 women participated with 54% up-to-date on both screenings, 21% for cervical cancer screening alone, and 12% for CRC alone. Women more likely to be up-to-date for only cervical cancer screening compared to both cancer screens are younger (aOR 0.83 (95% CI 0.76, 0.92), are of MENA descent (7.97 (2.46, 25.76) and have no insurance (9.41 (1.07, 82.92). There are no predictors for women being up-to-date for CRC screening alone compared to both screens.
Among women 50–65 years old, being up-to-date in cervical cancer screening is unrelated to being up-to-date for CRC screening. Compared to Healthy People 2020, there are significant gaps in cervical and CRC screening among women 50–65 years old of all races, but particularly among women of MENA descent who are even less likely to have CRC screening than cervical cancer screening.
Chronic inflammation is associated with the development, progression and long-term complications of type 2 diabetes. Hyperglycemia is associated with chronic low-grade inflammation, and thus has ...become the focus of many screening and treatment recommendations. We hypothesize that insulin may also be associated with inflammation and may be an additional factor to consider in screening and treatment.
This study used National Health and Nutrition Examination Survey data from 2005 to 2010 to analyze the association between fasting insulin and C-reactive protein (CRP). A two-part model was used due to the high number of values reported as 0.1 mg/L. Two models were analyzed, both with and without the addition of waist circumference to other covariates in the model.
The final sample included 4527 adults with a mean age of 43.31 years. In the first model, higher fasting insulin was associated with increased odds of CRP > 0.1 mg/L (OR = 1.02, p < .001) and with higher CRP (β = 0.03, p < .001). In the adjusted model, including waist circumference as a covariate, higher fasting insulin was not associated with CRP > 0.1 mg/L (OR = 1.00, p = .307) but the association between higher fasting insulin and higher continuous CRP remained significant (β = 0.01, p = .012).
This study found that higher fasting insulin is associated with higher CRP. These results suggest that treatment approaches that simultaneously decrease insulin levels as well as glucose levels may provide additive anti-inflammatory effects, and therefore may improve long-term outcomes for adults with type 2 diabetes.
Abstract Objectives Few studies have compared perceptions of risk, worry, severity and control across multiple diseases. This paper examines how these perceptions vary for heart disease, diabetes, ...stroke, and colon, breast, and ovarian cancers. Methods The data for this study came from the Family Healthware™ Impact Trial (FHITr), conducted in the United States from 2005 to 2007. Healthy adults ( N = 2362) from primary care practices recorded their perceptions at baseline for each disease. Analyses were conducted controlling for study site and personal risk factors. Results Perceived risk was significantly higher for cancers than for other diseases. Men worried most about getting heart disease; women worried most about getting breast cancer, followed by heart disease. Diabetes was perceived to be the least severe condition. Heart disease was perceived to be the most controllable compared to cancers, which were perceived to be the least controllable. Women had higher perceived risk and worry ratings compared to men for several diseases. Conclusions These data highlight how individuals comparatively view chronic diseases. Addressing prior disease perceptions when communicating multiple disease risks may facilitate an accurate understanding of risk for diseases, and help individuals to effectively identify and engage in relevant behaviors to reduce their risk.
The overall goal of this study was to determine whether Aquamin
, a calcium-, magnesium-, trace element-rich, red algae-derived natural product, would alter the expression of proteins involved in ...growth-regulation and differentiation in colon. Thirty healthy human subjects (at risk for colorectal cancer) were enrolled in a three-arm, 90-day interventional trial. Aquamin
was compared to calcium alone and placebo. Before and after the interventional period, colonic biopsies were obtained. Biopsies were evaluated by immunohistology for expression of Ki67 (proliferation marker) and for CK20 and p21 (differentiation markers). Tandem mass tag-mass spectrometry-based detection was used to assess levels of multiple proteins. As compared to placebo or calcium, Aquamin
reduced the level of Ki67 expression and slightly increased CK20 expression. Increased p21 expression was observed with both calcium and Aquamin
. In proteomic screen, Aquamin
treatment resulted in many more proteins being upregulated (including pro-apoptotic, cytokeratins, cell-cell adhesion molecules, and components of the basement membrane) or downregulated (proliferation and nucleic acid metabolism) than placebo. Calcium alone also altered the expression of many of the same proteins but not to the same extent as Aquamin
. We conclude that daily Aquamin
ingestion alters protein expression profile in the colon that could be beneficial to colonic health.
Background Hypertension is one of the most important cardiovascular disease risk factors and affects >100 million American adults. Hypertension-related health inequities are abundant in Black ...communities as Black individuals are more likely to use the emergency department (ED) for chronic disease–related ambulatory care, which is strongly linked to lower blood pressure (BP) control, diminished awareness of hypertension, and adverse cardiovascular events. To reduce hypertension-related health disparities, we developed MI-BP, a culturally tailored multibehavior mobile health intervention that targeted behaviors of BP self-monitoring, physical activity, sodium intake, and medication adherence in Black individuals with uncontrolled hypertension recruited from ED and community-based settings. Objective We sought to determine the effect of MI-BP on BP as well as secondary outcomes of physical activity, sodium intake, medication adherence, and BP control compared to enhanced usual care control at 1-year follow-up. Methods We conducted a 1-year, 2-group randomized controlled trial of the MI-BP intervention compared to an enhanced usual care control group where participants aged 25 to 70 years received a BP cuff and hypertension-related educational materials. Participants were recruited from EDs and other community-based settings in Detroit, Michigan, where they were screened for initial eligibility and enrolled. Baseline data collection and randomization occurred approximately 2 and 4 weeks after enrollment to ensure that participants had uncontrolled hypertension and were willing to take part. Data collection visits occurred at 13, 26, 39, and 52 weeks. Outcomes of interest included BP (primary outcome) and physical activity, sodium intake, medication adherence, and BP control (secondary outcomes). Results We obtained consent from and enrolled 869 participants in this study yet ultimately randomized 162 (18.6%) participants. At 1 year, compared to the baseline, both groups showed significant decreases in systolic BP (MI-BP group: 22.5 mm Hg decrease in average systolic BP and P<.001; control group: 24.1 mm Hg decrease and P<.001) adjusted for age and sex, with no significant differences between the groups (time-by-arm interaction: P=.99). Similar patterns where improvements were noted in both groups yet no differences were found between the groups were observed for diastolic BP, physical activity, sodium intake, medication adherence, and BP control. Large dropout rates were observed in both groups (approximately 60%). Conclusions Overall, participants randomized to both the enhanced usual care control and MI-BP conditions experienced significant improvements in BP and other outcomes; however, differences between groups were not detected, speaking to the general benefit of proactive outreach and engagement focused on cardiometabolic risk reduction in urban-dwelling, low-socioeconomic-status Black populations. High dropout rates were found and are likely to be expected when working with similar populations. Future work is needed to better understand engagement with mobile health interventions, particularly in this population. Trial Registration ClinicalTrials.gov NCT02955537; https://clinicaltrials.gov/study/NCT02955537 International Registered Report Identifier (IRRID) RR2-10.2196/12601
Predictors of Depression Stigma in Medical Students Wimsatt, Leslie A., PhD; Schwenk, Thomas L., MD; Sen, Ananda, PhD
American journal of preventive medicine,
November 2015, Volume:
49, Issue:
5
Journal Article
Peer reviewed
Introduction Suicide rates are higher among U.S. physicians than the general population. Untreated depression is a major risk factor, yet depression stigma presents a barrier to treatment. This study ...aims to identify early career indications of stigma among physicians-in-training and to inform the design of stigma-reduction programs. Methods A cross-sectional student survey administered at a large, Midwestern medical school in fall 2009 included measures of depression symptoms, attitudes toward mental health, and potential sources of depression stigma. Principal components factor analysis and linear regression were used to examine stigma factors associated with depression in medical students. Results The response rate was 65.7%, with 14.7% students reporting a previous depression diagnosis. Most students indicated that, if depressed, they would feel embarrassed if classmates knew. Many believed that revealing depression could negatively affect professional advancement. Factor analyses revealed three underlying stigma constructs: personal weakness, public devaluation, and social/professional discrimination. Students associating personal weakness with depression perceived medication as less efficacious and the academic environment as more competitive. Those endorsing public stigma viewed medication and counseling as less efficacious and associated depression with an inability to cope. Race, gender, and diagnosis of past/current depression also related to beliefs about stigma. Depression measures most strongly predicted stigma associated with personal weakness and social/professional discrimination. Conclusions Recommendations for decreasing stigma among physicians-in-training include consideration of workplace perceptions, depression etiology, treatment efficacy, and personal attributes in the design of stigma reduction programs that could facilitate help-seeking behavior among physicians throughout their career.
PURPOSE: Systemic exposures to intestinal bacteria may play a role in the etiology of the chronic, low-grade inflammation that is associated with western diets. Production of ...lipopolysaccharide-binding protein (LBP) is one biomarker of increased exposures to intestinal bacteria. This study evaluated whether changes in diet quality could affect serum LBP. METHODS: This was a randomized, controlled trial of Mediterranean and Healthy Eating diets over 6 months in 120 healthy subjects at increased risk of colon cancer. Blood samples obtained before and after intervention were analyzed for LBP, branched-chain fatty acids characteristic of intestinal bacteria, micronutrients and cytokines. Data were analyzed for changes in LBP over time and for predictors of LBP. RESULTS: Serum concentrations of branched-chain bacterial fatty acids declined significantly in both diet groups. However, there was no significant change in mean serum LBP concentrations with either diet intervention. In serum, LBP was positively associated with CRP and negatively associated with carotenoids both before and after intervention. After intervention, LBP was predicted positively by both CRP and bacterial fatty acid concentrations in serum, and negatively by serum carotenoids and the ω3/ω6 fatty acid ratio. This model accounted for 30 % of the inter-individual variation in serum LBP after intervention. CONCLUSIONS: These results indicate that dietary intervention over 6 months was insufficient to alter serum LBP. The relationships with inflammation-related markers, however, indicate that anti-inflammatory strategies other than changes in diet quality, such as weight loss or improved fitness, may have more potential for reducing systemic markers of LPS exposures in well-nourished populations.
Introduction Information is limited on patient characteristics that influence their preference among screening options and intent to be screened for colorectal cancer (CRC). A mechanistic pathway to ...intent and preference was examined through a formal mediation analysis. Methods From 2012 to 2014, a total of 570 adults aged 50–75 years were recruited from 15 primary care practices in Metro Detroit for a trial on decision aids for CRC screening. Confirmatory factor, regression, and mediation analyses were performed in 2015–2016 on baseline cross-sectional data. Main outcomes were patient intent and preference. Perceived risk and self-efficacy were secondary outcomes. Covariates included demographic information, health status, previous CRC screening experience, patient attitudes, and knowledge. Results Mean age was 57.7 years, 56.1% were women, and 55.1% white and 36.6% black. Women had 32% and 41% lower odds than men of perceiving CRC to be high/moderate risk (OR=0.68, 95% CI=0.47, 0.97, p =0.03) and having high self-efficacy (OR=0.59, 95% CI=0.42, 0.85, p =0.006), respectively. Whites had 63% and 47% lower odds than blacks of having high self-efficacy (OR=0.37, 95% CI=0.25, 0.57, p <0.001) and intent to undergo CRC screening (OR=0.53, 95% CI=0.34, 0.84, p =0.007), respectively. Younger age, higher knowledge, lower level of test worries, and medium/high versus low self-efficacy increased the odds of intent of being screened. Self-efficacy, but not perceived risk, significantly mediated the association between race, attitude, and test worries and patient screening intent. Conclusions Self-efficacy mediated the association between race, attitude, and test worries and patient intent.
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