Study of the circadian rhythm in healthy volunteers, obese and type 2 diabetic patients

Notre rythme circadien régule l'expression de gènes impliqués dans les métabolismes des lipides et du glucose. Notre objectif est de comparer l'expression des gènes circadiens dans la peau de patients obèses et diabétiques de type 2 (DT2), comparé aux sujets sains. Des sujets sains, obèses, et DT2 étaient recrutés. Une biopsie de la peau et une prise de sang étaient réalisées. Les gènes rapporteurs de la luciférase sous contrôle de promoteurs circadiens étaient introduits dans les fibroblasts de la peau et les profils de bioluminescence enregistrés. La durée de la période n'était pas différente entre les sujets sains et les patients DT2. La valeur de l'HbA1c était inversement corrélée à la durée de la période chez les patients DT2. Un grand nombre de gènes différentiellement exprimés en fonction du chronotype a été détecté. Il existe une interaction entre le rythme circadien et le métabolisme du glucose chez l'humain

Paraoxonase 1 (PON1) and pomegranate influence circadian gene expression and period length

The circadian timing system regulates key aspects of mammalian physiology. Here, we analyzed the effect of the endogenous antioxidant paraoxonase 1 (PON1), a high-density lipoprotein-associated lipolactonase that hydrolyses lipid peroxides and attenuates atherogenesis, on circadian gene expression in C57BL/6J and PON1KO mice fed a normal chow diet or a high-fat diet (HFD). Expression levels of core-clock transcripts Nr1d1, Per2, Cry2 and Bmal1 were altered in skeletal muscle in PON1-deficient mice in response to HFD. These findings were supported by circadian bioluminescence reporter assessments in mouse C2C12 and human primary myotubes, synchronized in vitro, where administration of PON1 or pomegranate juice modulated circadian period length

Severity of pain is associated with insufficient energy coverage in hospitalised patients: A cross-sectional study

Background & aims The severity of pain is routinely assessed in hospitalised patients but the impact of pain and pain control on energy coverage has been poorly studied. This One-day cross-sectional observational study assessed the association between severity of pain and coverage of energy needs in hospitalised patients. Methods Foods provided and consumed were assessed on one day by dedicated dieticians for unselected hospitalised patients receiving three meals per day. Severity of pain was evaluated by a visual analogue scale at the mealtimes, averaged over the study day, and categorized as no pain, slight, moderate or severe pain. The coverage of energy needs was expressed in percentage of predicted needs. Results Among the 755 included patients, 63% reported having pain. Severe pain was associated with a lower energy coverage than no pain (p = 0.001) or slight pain (p = 0.001). Insufficient energy coverage, defined as ≤70% of predicted needs, occurred in 13% of the patients. In univariate logistic regressions, predictors of insufficient energy coverage were severe pain as compared to no pain (OR 2.38; 95% CI 1.21, 4.64) and treatment with opioid drugs as compared to no pain killer (OR 1.73; 95% CI 1.07, 2.79). When including sex, age, body mass index, treatment with analgesics and severity of pain in a multivariate logistic regression, severe pain more than doubled the risk of insufficient energy coverage (OR 2.32; CI 1.15, 4.66). Conclusions Patients experiencing severe pain have a high risk of insufficient energy coverage. Optimal pain control is probably critical to prevent underfeeding in the hospital

Safety of Bioelectrical Impedance Analysis in Patients Equipped With Implantable Cardioverter Defibrillators

International audienceBACKGROUND: Current guidelines warn of potential electromagnetic interferences (EMI) when using bioelectrical impedance analysis (BIA) to measure body composition in patients equipped with implantable cardioverter-defibrillators (ICDs). We aimed to test the occurrence of EMI in a setting where this risk was experimentally maximized. MATERIALS AND METHODS: Outpatients scheduled for routine ICD controls simultaneously underwent a BIA measurement using an electrical current of 0.8 mAmp at frequencies from 5-100 kHz. ICD sensitivity levels were set to maximum levels while therapies were temporarily inactivated. The device electrograms were monitored in real time to detect sensed and/or visible EMI during BIA measurement. RESULTS: A total of 63 patients equipped with single-chamber (n = 13), dual-chamber (n = 18), or biventricular (n = 32) ICDs from 5 major manufacturers were included. No EMI were detected by the ICDs in these patients, nor were any artifacts visualized during real-time electrogram recordings. CONCLUSION: BIA can be safely performed in patients equipped with ICDs without cardiac monitoring. Current guidelines should be updated accordingl

Body composition and all-cause mortality in subjects older than 65 y.

BACKGROUND A low or high body mass index (BMI) has been associated with increased mortality risk in older subjects without taking fat mass index (FMI) and fat-free mass index (FFMI) into account. This information is essential because FMI is modulated through different healthcare strategies than is FFMI. OBJECTIVE We aimed to determine the relation between body composition and mortality in older subjects. DESIGN We included all adults ≥65 y old who were living in Switzerland and had a body-composition measurement by bioelectrical impedance analysis at the Geneva University Hospitals between 1990 and 2011. FMI and FFMI were divided into sex-specific quartiles. Quartile 1 (i.e., the reference category) corresponded to the lowest FMI or FFMI quartile. Mortality data were retrieved from the hospital database, the Geneva death register, and the Swiss National Cohort until December 2012. Comorbidities were assessed by using the Cumulative Illness Rating Scale. RESULTS Of 3181 subjects included, 766 women and 1007 men died at a mean age of 82.8 and 78.5 y, respectively. Sex-specific Cox regression models, which were used to adjust for age, BMI, smoking, ambulatory or hospitalized state, and calendar time, showed that body composition did not predict mortality in women irrespective of whether comorbidities were taken into account. In men, risk of mortality was lower with FFMI in quartiles 3 and 4 [HR: 0.78 (95% CI: 0.62, 0.98) and 0.64 (95% CI: 0.49, 0.85), respectively] but was not affected by FMI. When comorbidities were adjusted for, FFMI in quartile 4 (>19.5 kg/m(2)) still predicted a lower risk of mortality (HR: 0.72; 95% CI: 0.54, 0.96). CONCLUSIONS Low FFMI is a stronger predictor of mortality than is BMI in older men but not older women. FMI had no impact on mortality. These results suggest potential benefits of preventive interventions with the aim of maintaining muscle mass in older men. This trial was registered at clinicaltrials.gov as NCT01472679

Healthcare-associated infections are associated with insufficient dietary intake: an observational cross-sectional study

Indicators to predict healthcare-associated infections (HCAI) are scarce. Malnutrition is known to be associated with adverse outcomes in healthcare but its identification is time-consuming and rarely done in daily practice. This cross-sectional study assessed the association between dietary intake, nutritional risk, and the prevalence of HCAI, in a general hospital population

Identification of new biomarkers for human papillary thyroid carcinoma employing NanoString analysis

We previously reported an upregulation of the clock transcript BMAL1, correlating with TIMP1 expression in fresh-frozen samples from papillary thyroid carcinoma (PTC). Since frozen postoperative biopsy samples are difficult to obtain, we aimed to validate the application of high-precision NanoString analysis for formalin-fixed paraffin-embedded (FFPE) thyroid nodule samples and to screen for potential biomarkers associated with PTC. No significant differences were detected between fresh-frozen and FFPE samples. NanoString analysis of 51 transcripts in 17 PTC and 17 benign nodule samples obtained from different donors and in 24 pairs of benign and PTC nodules, obtained from the same donor (multinodular goiters), confirmed significant alterations in the levels of BMAL1, c-MET, c-KIT, TIMP1, and other transcripts. Moreover, we identified for the first time alterations in CHEK1 and BCL2 levels in PTC. A predictive score was established for each sample, based on the combined expression levels of BMAL1, CHEK1, c-MET, c-KIT and TIMP1. In combination with BRAF mutation analysis, this predictive score closely correlated with the clinicopathological characteristics of the analyzed thyroid nodules. Our study identified new thyroid transcripts with altered levels in PTC using the NanoString approach. A predictive score correlation coefficient might contribute to improve the preoperative diagnosis of thyroid nodules

Impact of body composition changes on risk of all-cause mortality in older adults

PURPOSE This study evaluates the relationship between body mass index (BMI), fat mass index (FMI) and fat-free mass index (FFMI) changes and mortality in persons ≥65 years. METHODS Adults ≥65 years with at least two body composition measurements (BCM) between 1990 and 2011 were included. We excluded persons who died within one month of the second BCM and who had two single BCM in a one-month timeframe. Mortality data was retrieved until December 2012. For each person, we calculated the regression slopes for BMI, FMI and FFMI changes. Significant positive slopes were categorized as "gain", negative slopes as "loss" and the others as "maintenance". The impact of body composition changes was evaluated by Cox regression models while adjusting for sex, age, co-morbidities and body composition at the last measurement. RESULTS We included 791 persons with 3049 BCM. After adjustment for sex, and age and co-morbidities, a loss of FFMI, but not of FMI or BMI, increased the risk of mortality (HR 2.02, 95%CI 1.28-3.19). The prediction of mortality with FFMI loss remained significant when further adjusting for FMI loss and the last available body composition (HR 1.68, 95%CI 1.04-2.70). CONCLUSIONS FFMI loss is related to increased mortality in older persons

Identification of CHEK1, SLC26A4, c-KIT, TPO and TG as new biomarkers for human follicular thyroid carcinoma

The search for preoperative biomarkers for thyroid malignancies, in particular for follicular thyroid carcinoma (FTC) diagnostics, is of utmost clinical importance. We thus aimed at screening for potential biomarker candidates for FTC. To evaluate dynamic alterations in molecular patterns as a function of thyroid malignancy progression, a comparative analysis was conducted in clinically distinct subgroups of FTC and poorly differentiated thyroid carcinoma (PDTC) nodules. NanoString analysis of FFPE samples was performed in 22 follicular adenomas, 56 FTC and 25 PDTC nodules, including oncocytic and non-oncocytic subgroups. The expression levels of CHEK1, c-KIT, SLC26A4, TG and TPO were significantly altered in all types of thyroid carcinomas. Based on collective changes of these biomarkers which correlating among each other, a predictive score has been established, allowing for discrimination between benign and FTC samples with high sensitivity and specificity. Additional transcripts related to thyroid function, cell cycle, circadian clock, and apoptosis regulation were altered in the more aggressive oncocytic subgroups only, with expression levels correlating with disease progression. Distinct molecular patterns were observed for oncocytic and non-oncocytic FTCs and PDTCs. A predictive score correlation coefficient based on collective alterations of identified here biomarkers might help to improve the preoperative diagnosis of FTC nodules