Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.

IMpact of flash glucose Monitoring in pEople with type 2 Diabetes Inadequately controlled with non-insulin Antihyperglycaemic ThErapy (IMMEDIATE): A randomized controlled trial.

AIM: To examine the efficacy and patient satisfaction of intermittently scanned continuous glucose monitoring (isCGM) in adults using non-insulin therapies for the management of type 2 diabetes. MATERIALS AND METHODS: The IMMEDIATE study was a multisite, open label, randomized controlled trial with follow-up at 16 weeks. Adults with type 2 diabetes using at least one non-insulin therapy, with an HbA1c of 7.5% or higher (≥ 58 mmol/mol), were randomized 1:1 to receive an isCGM device plus diabetes self-management education (isCGM + DSME) or DSME alone. Enrolment occurred from 8 September 2020 to 24 December 2021. The primary outcome was percentage mean time in range (TIR), in the final 2-week period, measured via blinded CGM. RESULTS: One hundred and sixteen participants were randomized (mean age, 58 years; diabetes duration, 10 years; mean HbA1c, 8.6% [70 mmol/mol]). At 16 weeks of follow-up, the isCGM and DSME arm had a significantly greater mean TIR by 9.9% (2.4 hours) (95% CI, -17.3% to -2.5%; P < .01), significantly less time above range by 8.1% (1.9 hours) (95% CI, 0.5% to 15.7%; P = .037), and a greater reduction in mean HbA1c by 0.3% (3 mmol/mol) (95% CI, 0% to 0.7%; P = .048) versus the DSME arm. Time below range was low and not significantly different between groups and hypoglycaemic events were few in both groups. Glucose monitoring satisfaction was higher among isCGM users (adjusted difference -0.5 [95% CI, -0.7 to -0.3], P < .01). CONCLUSIONS: The IMMEDIATE study has shown that among non-insulin-treated individuals with type 2 diabetes, use of isCGM is associated with an improvement in glycaemic outcomes.

Investigating resilience and its association with stress, anthropometrics, and metabolic health in adolescents with obesity: a pilot study.

The increasing prevalence of children with obesity has contributed to a higher risk of developing cardiometabolic comorbidities. Adversity and chronic stress are negatively linked to cardiometabolic outcomes, and resilience is positively associated with improved outcomes. However, whether resilience is protective against metabolic disturbances preceding disease presentation is less understood. This study explored correlations between stress, anthropometrics, and metabolic parameters with resilience (total, individual, family, peers, school, community), and determined which resilience domains predict metabolically unhealthy obesity. Adolescents with obesity (n = 39; 12-18y) completed anthropometrics, an oral glucose tolerance test, the Adolescent Resilience Questionnaire, and Perceived Stress Scale. Lower stress (r = -0.70, p < 0.001), BMI (r = -0.42, p = 0.01), fat mass (ρ = -0.41, p = 0.01), and fat-free mass (ρ = -0.41, p = 0.01) were associated with greater resilience. Greater school resilience was associated with lower risk for having metabolically unhealthy obesity (odds ratio = 0.87, 95% Confidence Intervals, 0.78-0.98, p = 0.02). Our findings suggest that resilience is associated with lower adiposity, and that lower school resilience is an independent predictor of having metabolically unhealthy obesity. Further work exploring correlations between school resilience, perceived stress, and metabolic outcomes, would optimize programs for obesity-related chronic conditions.

Real-world glycaemic outcomes in adult persons with type 1 diabetes using a real-time continuous glucose monitor compared to an intermittently scanned glucose monitor: A retrospective observational study from the Canadian LMC diabetes registry (REAL-CGM-T1D).

Real-time continuous glucose monitoring (rtCGM) and intermittently scanned CGM (isCGM) have both been shown to improve glycaemic outcomes in people with T1D. The aim of this study was to compare real-world glycaemic outcomes at 6-12 months in a propensity score matched cohort of CGM naïve adults with T1D who initiated a rtCGM or an isCGM. Among the matched rtCGM and isCGM cohorts (n = 143/cohort), rtCGM users had a significantly greater HbA1c benefit compared to isCGM users (adjusted difference, -3 mmol/mol [95% CI, -5 to -1]; -0.3% [95% CI, -0.5 to -0.1]; p = 0.01). There was a significantly greater lowering of HbA1c for rtCGM compared to isCGM when baseline HbA1c was <69 mmol/mol (8.5%) (adjusted difference, -4 mmol/mol [95% CI, -7 mmol/mol to -2 mmol/mol]; -0.4% [95% CI, -0.6% to -0.2%]; p < 0.001), and in MDI users (adjusted difference, -3 mmol/mol [95% CI, -6 mmol/mol to -0 mmol/mol]; -0.3% [95% CI -0.5% to 0.0%], p = 0.04). The rtCGM cohort had significantly greater time in range (58.3 ± 16.1% vs. 54.5 ± 17.1%, p = 0.03), lower time below range (2.1 ± 2.7% vs. 6.1 ± 5.0%, p < 0.001) and lower glycaemic variability compared to the isCGM cohort. In this real-world analysis of adults with T1D, rtCGM users had a significantly greater reduction in HbA1c at 6-12 months compared to isCGM, and significantly greater time in range, lower time below range and lower glycaemic variability, compared to a matched cohort of isCGM users.

Post-operative assessment in patients after liver transplantation: imaging parameters associated with 1-year graft failure.

PURPOSE: To identify post-liver transplant CT findings which predict graft failure within 1 year. MATERIALS AND METHODS: We evaluated the CT scans of 202 adult liver transplants performed in our institution who underwent CT within 3 months after transplantation. We recorded CT findings of liver perfusion defect (LPD), parenchymal homogeneity, and the diameters and attenuations of the hepatic vessels. Findings were correlated to 1-year graft failure, and interobserver variability was assessed. RESULTS: Forty-one (20.3%) of the 202 liver grafts failed within 1 year. Graft failure was highly associated with LPD (n = 18/25, or 67%, versus 15/98, or 15%, p < 0.001), parenchymal hypoattenuation (n = 20/41, or 48.8% versus 17/161, or 10.6%, p < 0.001), and smaller diameter of portal veins (right portal vein [RPV], 10.7 ± 2.7 mm versus 14.7 ± 2.2 mm, and left portal vein [LPV], 9.8 ± 3.0 mm versus 12.4 ± 2.2 mm, p < 0.001, respectively). Of these findings, LPD (hazard ratio [HR], 5.43, p < 0.001) and small portal vein diameters (HR, RPV, 3.33, p < 0.001, and LPV, 3.13, p < 0.05) independently predicted graft failure. All the measurements showed fair to moderate interobserver agreement (0.233~0.597). CONCLUSION: For patients who have CT scan within the first 3 months of liver transplantation, findings of LPD and small portal vein diameters predict 1-year graft failure. KEY POINTS: •Failed grafts are highly associated with liver perfusion defect, hypoattenuation, and small portal vein. •Right portal vein < 11.5 mm and left portal vein < 10.0 mm were associated with poor graft outcome. •Liver perfusion defect and small portal vein diameter independently predicted graft failure.

Careful conversations: an educational video to support parents in communicating about weight with their children.

BACKGROUND: Parents may struggle to initiate healthy weight-related conversations with their children. Educational videos may be an effective tool for improving parents' knowledge and self-efficacy on this topic. The aim of this pilot study was to develop an educational video to assist parents in weight-related conversations with their child, and to assess changes in parents' self-efficacy on this topic. METHODS: Video development was based on a scoping review and semi-structured interviews with parents. Respondent demographics and user satisfaction were assessed at pre- and post- video, and 4-6 months later. Self-efficacy scores were compared between parent groups based on weight concerns over time. RESULTS: Fifty-seven parents participated in the video questionnaires, and 40 repeated measures 4-6 months later. Significant improvements in self-efficacy in "raising the issue of weight" and "answering questions or concerns" were found after watching the video (p ≤ 0.002) compared to baseline, and scores 4-6 months post baseline remained slightly elevated, but non-significant. Parents with concerns about their child being overweight had significantly lower perceived self-efficacy scores compared to parents with no concerns about their child's weight (p = 0.031). The video was found to be positively received and of relevance to parents across a number of different domains. CONCLUSION(S): Preliminary findings suggest an educational video about initiating weight-related conversations may be an effective tool for increasing parents' perceived self-efficacy in the short term. Further work is needed to validate findings in a randomized controlled trial, and with diverse parent populations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03664492 . Registered 10 September 2018 - Retrospectively registered.

MET Genomic Alterations in Head and Neck Squamous Cell Carcinoma (HNSCC): Rapid Response to Crizotinib in a Patient with HNSCC with a Novel MET R1004G Mutation.

Identification of effective targeted therapies for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) remains an unmet medical need. A patient with platinum-refractory recurrent oral cavity HNSCC underwent comprehensive genomic profiling (CGP) that identified an activating MET mutation (R1004). The patient was treated with the oral MET tyrosine kinase inhibitor crizotinib with rapid response to treatment.Based on this index case, we determined the frequency of MET alterations in 1,637 HNSCC samples, which had been analyzed with hybrid capture-based CGP performed in the routine course of clinical care. The specimens were sequenced to a median depth of >500× for all coding exons from 182 (version 1, n = 24), 236 (version 2, n = 326), or 315 (version 3, n = 1,287) cancer-related genes, plus select introns from 14 (version 1), 19 (version 2), or 28 (version 3) genes frequently rearranged in cancer. We identified 13 HNSCC cases (0.79%) with MET alterations (4 point mutation events and 9 focal amplification events). MET-mutant or amplified tumors represent a small but potentially actionable molecular subset of HNSCC. KEY POINTS: This case report is believed to be the first reported pan-cancer case of a patient harboring a MET mutation at R1004 demonstrating a clinical response to crizotinib, in addition to the first documented case of head and neck squamous cell carcinoma (HNSCC) with any MET alteration responding to crizotinib.The positive response to MET inhibition in this patient highlights the significance of comprehensive genomic profiling in advanced metastatic HNSCC to identify actionable targetable molecular alterations as current treatment options are limited.

Circadian genes and risk of prostate cancer in the prostate cancer prevention trial.

Circadian genes have been considered as a possible biological mechanism for the observed relationship between circadian rhythm disruptions and increased risk of hormone-related cancers. In the current study, we investigated the relationship between circadian gene variants and prostate cancer risk and whether reducing bioavailable testosterone modifies the circadian genes-prostate cancer relationship. We conducted a nested case-control study among Caucasian men in the Prostate Cancer Prevention Trial (PCPT), a randomized placebo-controlled clinical trial to assess if finasteride (an androgen bioactivation inhibitor) could prevent prostate cancer. We evaluated the associations between 240 circadian gene variations and prostate cancer risk among 1092 biopsy-confirmed prostate cancer cases and 1089 biopsy-negative controls in the study (642 cases and 667 controls from the placebo group; 450 cases and 422 controls from the finasteride group), stratified by treatment group. Among men in the finasteride group, there were suggestive associations between NPAS2 variants and total prostate cancer risk, with one SNP remaining statistically significant after Bonferroni correction (rs746924, odds ratio [OR] = 1.5, P = 9.6 × 10-5 ). However, we found little evidence of increased prostate cancer risk (overall or by low/high grade) associated with circadian gene variations in men of the placebo group, suggesting potential modification of genetic effects by treatment. We did not find strong evidence that circadian gene variants influenced prostate cancer risk in men who were not on finasteride treatment. There were suggestive associations between NPAS2 variants and prostate cancer risk among men using finasteride, which warrants further investigations.

Metabolomic profiles in breast cancer:a pilot case-control study in the breast cancer family registry.

BACKGROUND: Metabolomics is emerging as an important tool for detecting differences between diseased and non-diseased individuals. However, prospective studies are limited. METHODS: We examined the detectability, reliability, and distribution of metabolites measured in pre-diagnostic plasma samples in a pilot study of women enrolled in the Northern California site of the Breast Cancer Family Registry. The study included 45 cases diagnosed with breast cancer at least one year after the blood draw, and 45 controls. Controls were matched on age (within 5 years), family status, BRCA status, and menopausal status. Duplicate samples were included for reliability assessment. We used a liquid chromatography/gas chromatography mass spectrometer platform to measure metabolites. We calculated intraclass correlations (ICCs) among duplicate samples, and coefficients of variation (CVs) across metabolites. RESULTS: Of the 661 named metabolites detected, 338 (51%) were found in all samples, and 490 (74%) in more than 80% of samples. The median ICC between duplicates was 0.96 (25th - 75th percentile: 0.82-0.99). We observed a greater than 20% case-control difference in 24 metabolites (p < 0.05), although these associations were not significant after adjusting for multiple comparisons. CONCLUSIONS: These data show that assays are reproducible for many metabolites, there is a minimal laboratory variation for the same sample, and a large between-person variation. Despite small sample size, differences between cases and controls in some metabolites suggest that a well-powered large-scale study is likely to detect biological meaningful differences to provide a better understanding of breast cancer etiology.

CT perfusion imaging of lung cancer: benefit of motion correction for blood flow estimates.

PURPOSE: CT perfusion (CTP) imaging assessment of treatment response in advanced lung cancer can be compromised by respiratory motion. Our purpose was to determine whether an original motion correction method could improve the reproducibility of such measurements. MATERIALS AND METHODS: The institutional review board approved this prospective study. Twenty-one adult patients with non-resectable non-small-cell lung cancer provided written informed consent to undergo CTP imaging. A motion correction method that consisted of manually outlining the tumor margins and then applying a rigid manual landmark registration algorithm followed by the non-rigid diffeomorphic demons algorithm was applied. The non-motion-corrected and motion-corrected images were analyzed with dual blood supply perfusion analysis software. Two observers performed the analysis twice, and the intra- and inter-observer variability of each method was assessed with Bland-Altman statistics. RESULTS: The 95% limits of agreement of intra-observer reproducibility for observer 1 improved from -84.4%, 65.3% before motion correction to -33.8%, 30.3% after motion correction (r = 0.86 and 0.97, before and after motion correction, p < 0.0001 for both) and for observer 2 from -151%, 96% to -49 %, 36 % (r = 0.87 and 0.95, p < 0.0001 for both). The 95% limits of agreement of inter-observer reproducibility improved from -168%, 154% to -17%, 25%. CONCLUSION: The use of a motion correction method significantly improves the reproducibility of CTP estimates of tumor blood flow in lung cancer. KEY POINTS: • Tumor blood flow estimates in advanced lung cancer show significant variability. • Motion correction improves the reproducibility of CT blood flow estimates in advanced lung cancer. • Reproducibility of blood flow measurements is critical to characterize lung tumor biology and the success of treatment in lung cancer.

Generalizability of established prostate cancer risk variants in men of African ancestry.

Genome-wide association studies have identified more than 80 risk variants for prostate cancer, mainly in European or Asian populations. The generalizability of these variants in other racial/ethnic populations needs to be understood before the loci can be used widely in risk modeling. In our study, we examined 82 previously reported risk variants in 4,853 prostate cancer cases and 4,678 controls of African ancestry. We performed association testing for each variant using logistic regression adjusted for age, study and global ancestry. Of the 82 known risk variants, 68 (83%) had effects that were directionally consistent in their association with prostate cancer risk and 30 (37%) were significantly associated with risk at p < 0.05, with the most statistically significant variants being rs116041037 (p = 3.7 × 10(-26) ) and rs6983561 (p = 1.1 × 10(-16) ) at 8q24, as well as rs7210100 (p = 5.4 × 10(-8) ) at 17q21. By exploring each locus in search of better markers, the number of variants that captured risk in men of African ancestry (p < 0.05) increased from 30 (37%) to 44 (54%). An aggregate score comprised of these 44 markers was strongly associated with prostate cancer risk [per-allele odds ratio (OR) = 1.12, p = 7.3 × 10(-98) ]. In summary, the consistent directions of effects for the vast majority of variants in men of African ancestry indicate common functional alleles that are shared across populations. Further exploration of these susceptibility loci is needed to identify the underlying biologically relevant variants to improve prostate cancer risk modeling in populations of African ancestry.

Niche-based screening identifies small-molecule inhibitors of leukemia stem cells.

Efforts to develop more effective therapies for acute leukemia may benefit from high-throughput screening systems that reflect the complex physiology of the disease, including leukemia stem cells (LSCs) and supportive interactions with the bone marrow microenvironment. The therapeutic targeting of LSCs is challenging because LSCs are highly similar to normal hematopoietic stem and progenitor cells (HSPCs) and are protected by stromal cells in vivo. We screened 14,718 compounds in a leukemia-stroma co-culture system for inhibition of cobblestone formation, a cellular behavior associated with stem-cell function. Among those compounds that inhibited malignant cells but spared HSPCs was the cholesterol-lowering drug lovastatin. Lovastatin showed anti-LSC activity in vitro and in an in vivo bone marrow transplantation model. Mechanistic studies demonstrated that the effect was on target, via inhibition of HMG-CoA reductase. These results illustrate the power of merging physiologically relevant models with high-throughput screening.

Nutritional Considerations for the Overweight Young Athlete.

Nutritional considerations for the overweight young athlete have not been thoroughly discussed in the scientific literature. With the high prevalence of childhood obesity, more children participating in sports are overweight or obese. This is particularly true for select sports, such as American football, where large size provides an added advantage. While sport participation should be encouraged because of the many benefits of physical activity, appropriate nutritional practices are vital for growth, and optimizing performance and health. The overweight young athlete may face certain challenges because of variable energy costs and nutrient requirements for growth and routine training, compared with nonoverweight athletes. Special attention should be given to adopting healthy lifestyle choices to prevent adverse health effects due to increased adiposity. In this review, we aim to discuss special nutritional considerations and highlight gaps in the literature concerning nutrition for overweight young athletes compared with their nonoverweight peers.

A genome-wide association study of prostate cancer in West African men.

Age-adjusted mortality rates for prostate cancer are higher for African-American men compared with those of European ancestry. Recent data suggest that West African men also have elevated risk for prostate cancer relative to European men. Genetic susceptibility to prostate cancer could account for part of this difference. We conducted a genome-wide association study (GWAS) of prostate cancer in West African men in the Ghana Prostate Study. Association testing was performed using multivariable logistic regression adjusted for age and genetic ancestry for 474 prostate cancer cases and 458 population-based controls on the Illumina HumanOmni-5 Quad BeadChip. The most promising association was at 10p14 within an intron of a long non-coding RNA (lncRNA RP11-543F8.2) 360 kb centromeric of GATA3 (p = 1.29E-7). In sub-analyses, SNPs at 5q31.3 were associated with high Gleason score (≥7) cancers, the strongest of which was a missense SNP in PCDHA1 (rs34575154, p = 3.66E-8), and SNPs at Xq28 (rs985081, p = 8.66E-9) and 6q21 (rs2185710, p = 5.95E-8) were associated with low Gleason score (<7) cancers. We sought to validate our findings in silico in the African Ancestry Prostate Cancer GWAS Consortium, but only one SNP, at 10p14, replicated at p < 0.05. Of the 90 prostate cancer loci reported from studies of men of European, Asian or African-American ancestry, we were able to test 81 in the Ghana Prostate Study, and 10 of these replicated at p < 0.05. Further genetic studies of prostate cancer in West African men are needed to confirm our promising susceptibility loci.

High prevalence of screen detected prostate cancer in West Africans: implications for racial disparity of prostate cancer.

PURPOSE: To our knowledge the reasons for the high rates of prostate cancer in black American men are unknown. Genetic and lifestyle factors have been implicated. Better understanding of prostate cancer rates in West African men would help clarify why black American men have such high rates since the groups share genetic ancestry and yet have different lifestyles and screening practices. To estimate the prostate cancer burden in West African men we performed a population based screening study with biopsy confirmation in Ghana. MATERIALS AND METHODS: We randomly selected 1,037 healthy men 50 to 74 years old from Accra, Ghana for prostate cancer screening with prostate specific antigen testing and digital rectal examination. Men with a positive screen result (positive digital rectal examination or prostate specific antigen greater than 2.5 ng/ml) underwent transrectal ultrasound guided biopsies. RESULTS: Of the 1,037 men 154 (14.9%) had a positive digital rectal examination and 272 (26.2%) had prostate specific antigen greater than 2.5 ng/ml, including 166 with prostate specific antigen greater than 4.0 ng/ml. A total of 352 men (33.9%) had a positive screen by prostate specific antigen or digital rectal examination and 307 (87%) underwent biopsy. Of these men 73 were confirmed to have prostate cancer, yielding a 7.0% screen detected prostate cancer prevalence (65 patients), including 5.8% with prostate specific antigen greater than 4.0 ng/ml. CONCLUSIONS: In this relatively unscreened population in Africa the screen detected prostate cancer prevalence is high, suggesting a possible role of genetics in prostate cancer etiology and the disparity in prostate cancer risk between black and white American men. Further studies are needed to confirm the high prostate cancer burden in African men and the role of genetics in prostate cancer etiology.

Factors Associated With Attainment of Glycemic Targets Among Adults With Type 1 and Type 2 Diabetes in Canada: A Cross-sectional Study Using Primary and Specialty Care Electronic Medical Record Data.

OBJECTIVE: Using a new database combining primary and specialty care electronic medical record (EMR) data in Canada, we determined attainment of glycemic targets and associated predictors among adults with diabetes. METHODS: We conducted a cross-sectional observational study combining primary and specialty care EMR data in Canada. Adults with diabetes whose primary care provider contributed to the National Diabetes Repository or who were assessed at a diabetes specialty clinic (LMC Diabetes and Endocrinology) between July 3, 2015, and June 30, 2019, were included. Diabetes type was categorized as type 2 diabetes (T2D) not prescribed insulin, T2D prescribed insulin, and type 1 diabetes (T1D). Covariates were age, sex, income quintile, province, rural/urban location, estimated glomerular filtration rate, medications, and insulin pump use. Associations between predictors and the outcome (glycated hemoglobin [A1C] of ≤7.0%) were assessed by multivariable logistic regressions. RESULTS: Among 122,106 adults, consisting of 91,366 with T2D not prescribed insulin, 25,131 with T2D prescribed insulin, and 5,609 with T1D, attainment of an A1C of ≤7.0% was 60%, 25%, and 23%, respectively. Proportions with an A1C of ≤7.5% and ≤8.0% were 75% and 84% for those with T2D not prescribed insulin, 41% and 57% for those with T2D prescribed insulin, and 37% and 53% for those with T1D. Highest vs lowest income quintile was associated with greater odds of meeting the A1C target (adjusted odds ratio [95% confidence interval] for each diabetes category: 1.15 [1.10 to 1.21], 1.21 [1.10 to 1.33], and 1.29 [1.04 to 1.60], respectively). Individuals in Alberta and Manitoba had less antihyperglycemic medication use and attainment of A1C target than other provinces. CONCLUSIONS: Attainment of glycemic targets among adults with diabetes was poor and differed by income and geographic location, which must be addressed in national diabetes strategies.

Medical students' perceived comfort and competence performing physical examinations on patients with obesity: A mixed-methods needs assessment.

Physicians are unsatisfied with their training in the care of patients with obesity. Physical examination is a key component of care, and modifications to techniques are often necessary for patients with obesity. To determine learning needs, we examined medical students' perceived comfort and competency in conducting physical examinations on patients with obesity. This mixed-methods study of Canadian medical students used a questionnaire and semi-structured focus groups to assess medical students' perceived comfort and competence in examining patients with obesity. Participants included 175 Canadian medical students. A minority of medical students felt comfortable (42%) or competent (14%) examining patients with obesity. Physical exam challenges included modifying exam manoeuvres, interpreting findings and communicating sensitively around weight. Lack of early exposure to patients with obesity, minimal instruction by preceptors and a lack of curricular focus on obesity were felt to be barriers to improving these skills. Students perceived their lack of confidence as negatively impacting their ability to manage patients with obesity and more training in this area was desired to prevent disparities in care. Medical students feel that adequate training on how to perform an obesity-specific physical examination is lacking. Developing curricula and including formal teaching around these key competencies within medical education is essential.

Prospective evaluation of serum sarcosine and risk of prostate cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Metabolomic profiling has identified, sarcosine, a derivative of the amino acid glycine, as an important metabolite involved in the etiology or natural history of prostate cancer. We examined the association between serum sarcosine levels and risk of prostate cancer in 1122 cases (813 non-aggressive and 309 aggressive) and 1112 controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Sarcosine was quantified using high-throughput liquid chromatography-mass spectrometry. A significantly increased risk of prostate cancer was observed with increasing levels of sarcosine (odds ratio [OR] for the highest quartile of exposure [Q4] versus the lowest quartile [Q1] = 1.30, 95% confidence interval [CI]: 1.02, 1.65; P-trend 0.03). When stratified by disease aggressiveness, we observed a stronger association for non-aggressive cases (OR for Q4 versus Q1 = 1.44, 95% CI: 1.11, 1.88; P-trend 0.006) but no association for aggressive prostate cancer (OR for Q4 versus Q1 = 1.03, 95% CI: 0.73, 1.47; P-trend 0.89). Although not statistically significant, temporal analyses showed a stronger association between sarcosine and prostate cancer for serum collected closer to diagnosis, suggesting that sarcosine may be an early biomarker of disease. Interestingly, the association between sarcosine and prostate cancer risk was stronger among men with diabetes (OR = 2.66, 95% CI: 1.04, 6.84) compared with those without reported diabetes (OR = 1.23, 95% CI: 0.95-1.59, P-interaction = 0.01). This study found that elevated levels of serum sarcosine are associated with an increased prostate cancer risk and evidence to suggest that sarcosine may be an early biomarker for this disease.

Variants in CCK and CCKAR genes to susceptibility to biliary tract cancers and stones: a population-based study in Shanghai, China.

BACKGROUND AND AIM: Altered motility of the gallbladder is associated with an increased risk of gallstones and can result in biliary tract cancers. Cholecystokinin (CCK) is an important modulator of gallbladder motility which functions by activating CCK type-A receptor (CCKAR). The aim of this study was to determine whether genetic variants in CCK and CCKAR are associated with the risk of biliary tract cancers and stones. METHODS: We investigated the associations between nine single nucleotide polymorphisms in CCK and CCKAR in a population-based case-control study, including 439 biliary tract cancer cases (253 gallbladder, 133 extrahepatic bile duct, and 53 ampulla of Vater cancer cases), 429 biliary stone cases, and 447 population controls in Shanghai, China. RESULTS: We found that women with the CCKAR rs1800855 AA genotype had an increased risk of gallbladder cancer (odds ratio = 2.37, 95% confidence interval (CI): 1.36-4.14) compared with subjects with the TT genotype, and remained significant after Bonferroni correction (P = 0.0056). Additionally, female carriers of the CCKAR haplotype C-T-C-T (rs2071011-rs915889-rs3822222-rs1800855) had a reduced risk of gallbladder cancer (odds ratio = 0.61, 95% confidence interval: 0.43-0.86) compared with those with the G-C-C-A haplotype; the association also remained significant after Bonferroni correction. CONCLUSIONS: These findings suggest that variants in the CCKAR gene may influence the risk of gallbladder cancer in women. Additional studies are needed to confirm our findings.