Breaking up prolonged sitting time with walking does not affect appetite or gut hormone concentrations but does induce an energy deficit and suppresses postprandial glycaemia in sedentary adults

Breaking up periods of prolonged sitting can negate harmful metabolic effects but the influence on appetite and gut hormones is not understood and is investigated in this study. Thirteen sedentary (7 female) participants undertook three 5-h trials in random order: (i) uninterrupted sitting (SIT), (ii) seated with 2-min bouts of light-intensity walking every 20 min (SIT + LA), and (iii) seated with 2-min bouts of moderate-intensity walking every 20 min (SIT + MA). A standardised test drink was provided at the start of each trial and an ad libitum pasta test meal provided at the end of each trial. Subjective appetite ratings and plasma acylated ghrelin, peptide YY, insulin, and glucose were measured at regular intervals. Area under the curve (AUC) was calculated for each variable. AUC values for appetite and gut hormone concentrations were unaffected in the activity breaks conditions compared with uninterrupted sitting (linear mixed modelling: p > 0.05). Glucose AUC was lower in SIT + MA than in SIT + LA (p = 0.004) and SIT (p = 0.055). There was no difference in absolute ad libitum energy intake between conditions (p > 0.05); however, relative energy intake was lower in SIT + LA (39%; p = 0.011) and SIT + MA (120%; p < 0.001) than in SIT. In conclusion, breaking up prolonged sitting does not alter appetite and gut hormone responses to a meal over a 5-h period. Increased energy expenditure from activity breaks could promote an energy deficit that is not compensated for in a subsequent meal

Effects of follicular phase exercise on luteinizing hormone pulse characteristics in sedentary eumenorrhoeic women

OBJECTIVE Current studies reveal little regarding the Inception of exercise-induced LH changes during physical training. This study aimed to assess the susceptibility of the hypothalamic–pituitary axis to the acute physical stress of exercise in untrained, physically inactive women. The acute effects of submaximal endurance exercise upon the pulsatile LH secretion in the follicular phase were compared with those accompanying leisurely strolling for a similar time period. SUBJECTS All subjects were eumenorrhoelc, as determined by biphasic temperature patterns, detection of the urinary LH surge, and mid-luteal serum progesterone levels. Subjects were not physically active and had little history of strenuous exercise ( V o 2 max = 38·0 ± 1·8) (mean ± SEM) ml/kg/min). DESIGN All women completed a 13·5-hour pulsatility test which included three consecutive 20-minute runs on a treadmill at 50, 60 and 70% of the subjects’maximum oxygen uptake ( n = 16). Six of these same subjects completed a separate test on another occasion in which one hour of leisurely strolling was substituted for exercise. Blood was sampled every 10 minutes via an indwelling cannula for 4·5 hours before and 8 hours after one hour of exercise and or strolling. MEASUREMENTS A pulse algorithm (Pulsar) was used to quantify LH pulse characteristics. RESULTS Exercise produced no significant effects upon LH pulse frequency or mean serum LH concentration. However, exercise of moderate intensity caused a significant increase in LH pulse amplitude ( P < 0·05). Strolling produced no significant changes in LH secretion. CONCLUSION Acute exercise of moderate intensity in the follicular phase of untrained women is an insufficient stimulus to inhibit the GnRH pulse generator in the post-exercise period, yet may produce a slight stimulatory effect on the amount of LH released per pulsePeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73507/1/j.1365-2265.1994.tb02794.x.pd

Refined histopathological predictors of BRCA1 and BRCA2 mutation status: A large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the

Colonoscopic-Assisted Laparoscopic Wedge Resection for Colonic Lesions A Prospective Multicenter Cohort Study (LIMERIC-Study)

Objective: The aim of this study was to evaluate the safety and efficacy of a modified CAL-WR. Summary Background Data: The use of segmental colectomy in patients with endoscopically unresectable colonic lesions results in significant morbidity and mortality. CAL-WR is an alternative procedure that may reduce morbidity. Methods: This prospective multicenter study was performed in 13 Dutch hospitals between January 2017 and December 2019. Inclusion criteria were (1) colonic lesions inaccessible using current endoscopic resection techniques (judged by an expert panel), (2) non-lifting residual/recurrent adenomatous tissue after previous polypectomy or (3) an undetermined resection margin after endoscopic removal of a low-risk pathological T1 (pT1) colon carcinoma. Thirty-day morbidity, technical success rate and radicality were evaluated. Results: Of the 118 patients included (56% male, mean age 66 years, standard deviation +/- 8 years), 66 (56%) had complex lesions unsuitable for endoscopic removal, 34 (29%) had non-lifting residual/recurrent adenoma after previous polypectomy and 18 (15%) had uncertain resection margins after polypectomy of a pT1 colon carcinoma. CAL-WR was technically successful in 93% and R-0 resection was achieved in 91% of patients. Minor complications (Clavien-Dindo i-ii) were noted in 7 patients (6%) and an additional oncologic segmental resection was performed in 12 cases (11%). Residual tissue at the scar was observed in 5% of patients during endoscopic follow-up. Conclusions: CAL-WR is an effective, organ-preserving approach that results in minor complications and circumvents the need for major surgery. CAL-WR, therefore, deserves consideration when endoscopic excision of circumscribed lesions is impossible or incomplete.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Breast cancer risk genes: association analysis in more than 113,000 women

BACKGROUNDGenetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking.METHODSWe used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluated missense-variant associations according to domain and classification of pathogenicity.RESULTSProtein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a risk of breast cancer overall with a P value of less than 0.0001. Protein-truncating variants in 4 other genes (BARD1, RAD51C, RAD51D, and TP53) were associated with a risk of breast cancer overall with a P value of less than 0.05 and a Bayesian false-discovery probability of less than 0.05. For protein-truncating variants in 19 of the remaining 25 genes, the upper limit of the 95% confidence interval of the odds ratio for breast cancer overall was less than 2.0. For protein-truncating variants in ATM and CHEK2, odds ratios were higher for estrogen receptor (ER)-positive disease than for ER-negative disease; for protein-truncating variants in BARD1, BRCA1, BRCA2, PALB2, RAD51C, and RAD51D, odds ratios were higher for ER-negative disease than for ER-positive disease. Rare missense variants (in aggregate) in ATM, CHEK2, and TP53 were associated with a risk of breast cancer overall with a P value of less than 0.001. For BRCA1, BRCA2, and TP53, missense variants (in aggregate) that would be classified as pathogenic according to standard criteria were associated with a risk of breast cancer overall, with the risk being similar to that of protein-truncating variants.CONCLUSIONSThe results of this study define the genes that are most clinically useful for inclusion on panels for the prediction of breast cancer risk, as well as provide estimates of the risks associated with protein-truncating variants, to guide genetic counseling. (Funded by European Union Horizon 2020 programs and others.)Molecular tumour pathology - and tumour geneticsMTG1 - Moleculaire genetica en pathologie van borstkanke