Physical activity, muscular strength, and polypharmacy among older multimorbid persons: Results from the KORA-Age study.

The purpose of this study was to examine whether physical activity (PA) and muscular strength (MS) are related to polypharmacy. Our cross-sectional analysis was based on 711 patients with multimorbidity (MMB), aged 65-94 years, who participated in the KORA-Age study. Participants underwent a face-to-face interview and extensive physical examinations including anthropometric measurements, registration of chronic diseases, determination of health-related behaviors (smoking, alcohol intake, physical activity, etc.), collection of blood samples and measurement of hand-grip strength. PPha was defined as the use of >4 drugs and MMB as having ≥2 of 13 chronic diseases. Prevalence of PPha was 44.6% (n=317), and a significant difference was found in the number of drugs used between participants with and without PPha (7.2±2.1 vs 2.5±1.2, P<.001). Patients in the lower compared to the upper tertile of physical activity had a significantly increased odds to be on PPha (OR: 1.64, 95% CI: 1.05-2.56, P=.031) after controlling for age, gender, BMI, family status, education, alcohol intake, smoking habits, number of diseases, hs-CRP, and telomere length. On the contrary, no significant association between muscular strength and PPha was found (OR: 1.04, 95% CI: 0.66-1.63, P=.873) after multivariable adjustment. Among older persons with MMB, lower levels of physical activity, but not low muscular strength, are associated with higher odds of PPha. Increasing the levels of physical activity appears to be highly recommended in order to potentially reduce the risk of PPha among multimorbid persons aged 65 and older.

(2 + 1)D-CAIPIRINHA accelerated MR spectroscopic imaging of the brain at 7T.

PURPOSE: To compare a new parallel imaging (PI) method for multislice proton magnetic resonance spectroscopic imaging (1 H-MRSI), termed (2 + 1)D-CAIPIRINHA, with two standard PI methods: 2D-GRAPPA and 2D-CAIPIRINHA at 7 Tesla (T). METHODS: (2 + 1)D-CAIPIRINHA is a combination of 2D-CAIPIRINHA and slice-CAIPIRINHA. Eight healthy volunteers were measured on a 7T MR scanner using a 32-channel head coil. The best undersampling patterns were estimated for all three PI methods. The artifact powers, g-factors, Cramér-Rao lower bounds (CRLB), and root mean square errors (RMSE) were compared quantitatively among the three PI methods. Metabolic maps and spectra were compared qualitatively. RESULTS: (2 + 1)D-CAIPIRINHA allows acceleration in three spatial dimensions in contrast to 2D-GRAPPA and 2D-CAIPIRINHA. Thus, this sequence significantly decreased the RMSE of the metabolic maps by 12.1 and 6.9%, on average, for 4 < R < 11, compared with 2D-GRAPPA and 2D-CAIPIRINHA, respectively. The artifact power was 22.6 and 8.4% lower, and the CRLB were 3.4 and 0.6% lower, respectively. CONCLUSION: (2 + 1)-CAIPIRINHA can be implemented for multislice MRSI in the brain, enabling higher accelerations than possible with two-dimensional (2D) parallel imaging methods. An eight-fold acceleration was still feasible in vivo with negligible PI artifacts with lipid decontamination, thus decreasing the measurement time from 120 to 15 min for a 64 × 64 × 4 matrix. Magn Reson Med 78:429-440, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Diffusion-weighted imaging of breast tumours at 3 Tesla and 7 Tesla: a comparison.

OBJECTIVES: To compare bilateral diffusion-weighted MR imaging (DWI) at 3 T and 7 T in the same breast tumour patients. METHODS: Twenty-eight patients were included in this IRB-approved study (mean age 56 ± 16 years). Before contrast-enhanced imaging, bilateral DWI with b = 0 and 850 s/mm(2) was performed in 2:56 min (3 T) and 3:48 min (7 T), using readout-segmented echo planar imaging (rs-EPI) with a 1.4 × 1.4 mm(2) (3 T)/0.9 × 0.9 mm(2) (7 T) in-plane resolution. Apparent diffusion coefficients (ADC), signal-to-noise (SNR) and contrast-to-noise ratios (CNR) were assessed. RESULTS: Twenty-eight lesions were detected (18 malignant, 10 benign). CNR and SNR were comparable at both field strengths (p > 0.3). Mean ADC values at 7 T were 4-22% lower than at 3 T (p ≤ 0.03). An ADC threshold of 1.275 × 10(-3) mm(2)/s resulted in a diagnostic specificity of 90% at both field strengths. The sensitivity was 94% and 100% at 3 T and 7 T, respectively. CONCLUSION: 7-T DWI of the breast can be performed with 2.4-fold higher spatial resolution than 3 T, without significant differences in SNR if compared to 3 T. KEY POINTS: • 7 T provides a 2.4-fold higher resolution in breast DWI than 3 T • 7 T DWI has a high diagnostic accuracy comparable to that at 3 T • At 7 T malignant lesions had 22 % lower ADC than at 3 T (p < 0.001).

Association between muscular strength and inflammatory markers among elderly persons with cardiac disease: results from the KORA-Age study.

Little is known about the association between muscle strength and inflammation in diseased individuals and particularly in cardiac patients. Thus, our purpose was to examine the association of muscular strength with the inflammatory status in older adults with and without cardiac disease. The cross-sectional analysis was based on 1079 adults aged 65-94 years, who participated in the KORA-Age study. Participants underwent an interview and extensive physical examinations including anthropometric measurements, registration of diseases and drug intake, determination of health-related behaviors, collection of blood samples for measurements of interleukin-6 and hs-CRP and muscle strength measurement using hand-grip dynamometry. Cardiac patients (n = 323) had higher levels of IL-6 and poorer muscle strength compared with older adults without cardiac disease. Among persons with cardiac diseases, muscle strength in the lower tertile compared to the upper tertile was significantly associated with increased odds of having elevated IL-6 levels (OR 3.53, 95 % CI 1.18-10.50, p = 0.024) after controlling for age, gender, body fat, alcohol intake, smoking status, diseases, medications and physical activity, whereas the association between muscle strength and hs-CRP remained borderline significant (OR 2.80, 95 % CI 0.85-9.24, p = 0.092). The same trends, with slightly lower odds ratios, were also observed in older adults without cardiac disease. Lower levels of muscular strength are associated with higher concentrations of IL-6 and hs-CRP in elderly individuals with and without cardiac disease suggesting a significant contribution of the muscular system in reducing low-grade inflammation that accompanies cardiac disease and aging.

Abdominal obesity is associated with arterial stiffness in middle-aged adults.

BACKGROUND AND AIMS: The relation between adiposity and arterial stiffness remains controversial. We determined whether abdominal and visceral adipose tissue may be a better predictor of arterial stiffness than general obesity in middle-aged adults. METHODS AND RESULTS: A total of 146 participants (76 men, 70 women; 50 years) were studied. The automatic vascular screening device (Omron VP-1000plus) was used to measure blood pressure simultaneously in the arms and ankles and to determine arterial stiffness by pulse wave velocity (PWV). Using multiple linear regressions, the relations between indicators of obesity and arterial stiffness were examined after adjustment for confounders. Both carotid-femoral PWV and brachial-ankle PWV were significantly associated with BMI (both P < 0.05) but not with body fat percentage. Measures of abdominal obesity, including waist circumference and visceral fat mass (via DXA), were strongly associated with PWV and remained positively associated with arterial stiffness after adjustment for age and gender. Cardiovascular fitness as assessed by maximal oxygen consumption was related to body fat percentage but not with visceral fat. More favorable cardiovascular health profile was associated with both lower visceral fat mass and PWV (both P < 0.001). CONCLUSION: Abdominal obesity and visceral fat are associated with large artery stiffness. These findings support the importance of adiposity measures as a risk factor for arterial stiffening in middle-aged adults.

Functional diversity of phytochrome family in the control of light and gibberellin-mediated germination in Arabidopsis.

In several species, seed germination is regulated by light in a way that restricts seedling emergence to the environmental conditions that are likely to be favourable for the success of the new individual, and therefore, this behaviour is recognized to have adaptive value. The phytochromes are one of the most relevant photoreceptors involved in light perception by plants. We explored the redundancy and diversity functions of the phytochrome family in the control of seed responsiveness to light and gibberellins (GA) by using a set of phytochrome mutants of Arabidopsis. Our data show that, in addition to the well-known role of phyB in the promotion of germination in response to high red to far-red ratios (R/FR), phyE and phyD stimulate germination at very low R/FR ratios, probably by promoting the action of phyA. Further, we show that phyC regulates negatively the seed responsiveness to light, unravelling unexpected functions for phyC in seed germination. Finally, we find that seed responsiveness to GA is mainly controlled by phyB, with phyC, phyD and phyE having relevant roles when acting in a phyB-deficient background. Our results indicate that phytochromes have multiple and complex roles during germination depending on the active photoreceptor background.

Coil combination of multichannel MRSI data at 7 T: MUSICAL.

The goal of this study was to evaluate a new method of combining multi-channel (1)H MRSI data by direct use of a matching imaging scan as a reference, rather than computing sensitivity maps. Seven healthy volunteers were measured on a 7-T MR scanner using a head coil with a 32-channel array coil for receive-only and a volume coil for receive/transmit. The accuracy of prediction of the phase of the (1)H MRSI data with a fast imaging pre-scan was investigated with the volume coil. The array coil (1)H MRSI data were combined using matching imaging data as coil combination weights. The signal-to-noise ratio (SNR), spectral quality, metabolic map quality and Cramér-Rao lower bounds were then compared with the data obtained by two standard methods, i.e. using sensitivity maps and the first free induction decay (FID) data point. Additional noise decorrelation was performed to further optimize the SNR gain. The new combination method improved significantly the SNR (+29%), overall spectral quality and visual appearance of metabolic maps, and lowered the Cramér-Rao lower bounds (-34%), compared with the combination method based on the first FID data point. The results were similar to those obtained by the combination method using sensitivity maps, but the new method increased the SNR slightly (+1.7%), decreased the algorithm complexity, required no reference coil and pre-phased all spectra correctly prior to spectral processing. Noise decorrelation further increased the SNR by 13%. The proposed method is a fast, robust and simple way to improve the coil combination in (1)H MRSI of the human brain at 7 T, and could be extended to other (1)H MRSI techniques.

Resistance training, visceral obesity and inflammatory response: a review of the evidence.

Intra-abdominal obesity is an important risk factor for low-grade inflammation, which is associated with increased risk for diabetes mellitus and cardiovascular disease. For the most part, recommendations to treat or prevent overweight and obesity via physical activity have focused on aerobic endurance training as it is clear that aerobic training is associated with much greater energy expenditure during the exercise session than resistance training. However, due to the metabolic consequences of reduced muscle mass, it is understood that normal ageing and/or decreased physical activity may lead to a higher prevalence of metabolic disorders. Whether resistance training alters visceral fat and the levels of several pro-inflammatory cytokines produced in adipose tissue has not been addressed in earlier reviews. Because evidence suggests that resistance training may promote a negative energy balance and may change body fat distribution, it is possible that an increase in muscle mass after resistance training may be a key mediator leading to a better metabolic control. Considering the benefits of resistance training on visceral fat and inflammatory response, an important question is: how much resistance training is needed to confer such benefits? Therefore, the purpose of this review was to address the importance of resistance training on abdominal obesity, visceral fat and inflammatory response.

Effects of monounsaturated fatty acids on cardiovascular risk factors: a systematic review and meta-analysis.

The appropriate pattern of macronutrient distribution for dietary protocols aimed at treating or preventing obesity and its associated cardiovascular diseases is still a controversial topic of discussion. Recommendations considering a specific percentage or range for monounsaturated fatty acids (MUFA) are rare. It was the aim of this study to analyze long-term, randomized, controlled dietary intervention trials and to investigate the effects of MUFA on the biomarkers of obesity and cardiovascular risk factors. Dietary regimens with a high amount of MUFA (>12%) were compared to those with ≤12%. The biomarkers taken into account were weight, waist circumference, fat mass, total cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerols, systolic and diastolic blood pressure, as well as C-reactive protein. A total of 12 studies met the inclusion criteria. Data analysis was performed using the Review Manager 5.0.25 software. Significant differences between high- and low-MUFA protocols could be observed with respect to fat mass [-1.94 kg (confidence interval -3.72, -0.17), p = 0.03], systolic blood pressure [-2.26 mm Hg (confidence interval -4.28, -0.25), p = 0.03] and diastolic blood pressure [-1.15 mm Hg (confidence interval -1.96, -0.34), p = 0.005] favoring the dietary protocols with >12% MUFA. Therefore, MUFA might represent a useful tool in the design of dietary regimens for obesity and cardiovascular disease.

Effects of monounsaturated fatty acids on glycaemic control in patients with abnormal glucose metabolism: a systematic review and meta-analysis.

BACKGROUND/AIMS: In 2008, the American Diabetes Association recommended low-carbohydrate or low-fat diets for weight management in patients with established type 2 diabetes (T2D), while the amount of monounsaturated fatty acids (MUFA) was not specified. This systematic review focused on the effects of diets high in MUFA versus diets low in MUFA on important risk factors of T2D (i.e. plasma glucose, insulin, homeostasis model assessment of insulin resistance and glycosylated haemoglobin, HbA1c). METHODS: Nine randomized controlled intervention trials with a total of 1,547 participants and a running time of at least 6 months, comparing diets high versus low in MUFA among adults with abnormal glucose metabolism (T2D, impaired glucose tolerance and insulin resistant), being overweight or obese, have been included in the meta-analysis. We performed a random effects meta-analysis to determine the weighted mean differences with 95% confidence intervals using the software package Review Manager 5.0.25 of the Cochrane Collaboration. RESULTS: Significant differences in HbA1c were found (weighted mean difference -0.21%, 95% CI -0.40 to -0.02; p = 0.03), favouring the high MUFA groups. In contrast, fasting plasma glucose, fasting plasma insulin as well as the homeostasis model assessment of insulin resistance were not affected by the amounts of MUFA in the dietary protocols. CONCLUSIONS: In summary, this systematic review found that high MUFA diets appear to be effective in reducing HbA1c, and therefore, should be recommended in the dietary regimes of T2D.

Fat loss depends on energy deficit only, independently of the method for weight loss.

BACKGROUND: This study was designed to compare the effects of 2 different but isocaloric fat reduction programs with the same amount of energy deficit - diet alone or diet combined with aerobic training - on body composition, lipid profile and cardiorespiratory fitness in non- or moderately obese women. METHODS: Twenty non- or moderately obese (BMI 24.32 +/- 3.11) females (27.3 +/- 6.6 years) were tested at the beginning and after an 8-week period of a mild hypocaloric diet for the following parameters: (1) body mass and body fat; (2) total cholesterol, HDL-C, LDL-C and triglycerides; (3) lactate (millimol/liter) during submaximal exertion (100 W); (4) heart rate during submaximal exertion (100 W), and (5) maximum exercise performance (watt). Subjects were randomly divided into either a diet alone (D, -2,095 +/- 659 kJ/day) or a diet (-1,420 +/- 1,084 kJ/day) plus exercise (DE, three 60-min sessions per week at 60% of VO(2)max or -5,866 kJ/week) group. RESULTS: Body mass and body fat decreased significantly in D (-1.95 +/- 1.13 kg or -1.47 +/- 0.87%; p < 0.05) and DE (-2.23 +/- 1.28 kg or -1.59 +/- 0.87%; p < 0.05), but there was no significant difference observed between the groups. Statistical analysis revealed no significant changes of total cholesterol, HDL-C, LDL-C, triglycerides and heart rate during submaximal exertion (100 W). Lactic acid accumulation during submaximal exertion (100 W) decreased significantly (-0.8 +/- 1.4 mmol/l, p < 0.05) in DE and increased significantly (+0.4 +/- 0.5 mmol/l, p < 0.05) in D. Maximum exercise performance improved significantly (+12.2 +/- 8.8 W, p < 0.05) in DE and did not change significantly in D. CONCLUSIONS: This study showed that independently of the method for weight loss, the negative energy balance alone is responsible for weight reduction.

Strength and endurance training lead to different post exercise glucose profiles in diabetic participants using a continuous subcutaneous glucose monitoring system.

BACKGROUND: Although both strength training (ST) and endurance training (ET) seem to be beneficial in type 2 diabetes mellitus (T2D), little is known about post-exercise glucose profiles. The objective of the study was to report changes in blood glucose (BG) values after a 4-month ET and ST programme now that a device for continuous glucose monitoring has become available. MATERIALS AND METHODS: Fifteen participants, comprising four men age 56.5 +/- 0.9 years and 11 women age 57.4 +/- 0.9 years with T2D, were monitored with the MiniMed (Northridge, CA, USA) continuous glucose monitoring system (CGMS) for 48 h before and after 4 months of ET or ST. The ST consisted of three sets at the beginning, increasing to six sets per week at the end of the training period, including all major muscle groups and ET performed with an intensity of maximal oxygen uptake of 60% and a volume beginning at 15 min and advancing to a maximum of 30 min three times a week. RESULTS: A total of 17,549 single BG measurements pretraining (619.7 +/- 39.8) and post-training (550.3 +/- 30.1) were recorded, correlating to an average of 585 +/- 25.3 potential measurements per participant at the beginning and at the end of the study. The change in BG-value between the beginning (132 mg dL(-1)) and the end (118 mg dL(-1)) for all participants was significant (P = 0.028). The improvement in BG-value for the ST programme was significant (P = 0.02) but for the ET no significant change was measured (P = 0.48). Glycaemic control improved in the ST group and the mean BG was reduced by 15.6% (Cl 3-25%). CONCLUSION: In conclusion, the CGMS may be a useful tool in monitoring improvements in glycaemic control after different exercise programmes. Additionally, the CGMS may help to identify asymptomatic hypoglycaemia or hyperglycaemia after training programmes.

Continuous glucose monitoring in diabetic long distance runners.

Marathon running is growing in popularity, and many diabetic patients are participating in various marathon races all over the world each year. This study aimed to investigate the prevalence and extent of glycemic excursions (hypo- and hyperglycemic) during a marathon run in patients with well-controlled diabetes mellitus using a continuous glucose monitoring system (CGMS). Five subjects with type 1 and one patient with type 2 diabetes mellitus were monitored with the Medtronic MiniMed CGMS during the 2002 Vienna City Marathon (n = 3) or the "Fernwärme run" (n = 3) long distance runs of 42.19/15.8 km. All six patients finished their course. The CGSM system was well tolerated in all patients over an average duration of 34 +/- 4.0 hours and it did not limit the patients' activities. The mean running time for the Vienna city marathon was 257 +/- 8 min (247 to 274 min) and for the Fernwärme run 134 +/- 118 min (113 to 150 min). A total of 1470 blood glucose measurements (mean 245 readings per subject) were performed. During and after the marathons frequent hypo- and hyperglycemic episodes with and without clinical symptoms were measured. Our data confirm that the CGMS may help to identify asymptomatic hypoglycemia or hyperglycemia during and after a long distance run. The system may also be helpful to improve our understanding about the individual changes of glucose during and after a marathon and may protect hypoglycemic or hyperglycemic periods in future races.

Molecular diseases and diseased molecules: ontological and epistemological dimensions.

In 1949, Linus Pauling and collaborators published in Science a paper provocatively titled: 'Sickle cell anemia, a molecular disease'. What was actually meant by 'molecular disease'? We interpret the concept of molecular disease in the frame of the traditional positions about the nature of diseases, the ontological and the physiological positions. We conclude that the physiological does not give an adequate account of what molecular diseases are. The ontological position, when correctly reinterpreted, leads to an understanding of molecular diseases where the macromolecule is seen as a symptom or as a part of a mechanism leading to the symptoms of the disease. We then show that the concept of molecular disease leads to a particular view of therapy, emphasizing eugenics as a way of eliminating disease. On the individual level, this concept leads to an increased power of diagnosis, and especially predictive diagnosis, but has little therapeutic consequence. Lastly, we examine how this concept of disease unifies two contemporary classifications of diseases, one based on the location of the diseases, the other on the cause of the diseases.

Eye-blink rates and depression. Is the antidepressant effect of sleep deprivation mediated by the dopamine system?

A series of studies demonstrated a possible correlation between eye-blink rate and central dopamine activity. The hypothesis has been put forward that the antidepressant effect of sleep deprivation (SD) is mediated by an enhanced dopamine release resulting in an amphetaminelike action of SD. Therefore, the blink rates of 12 drug-naive patients with major depression and 12 healthy controls were compared before and after SD and before and after 2.5 mg bromocriptine as a dopaminergic challenge. The main result of the study was that the depressed patients had a significantly higher increase of blinking after SD both with and without a dopaminergic challenge. Basal eye-blink rate was not different in nonretarded major depression patients compared to controls. Sleep deprivation increased blink rate in depression patients but not in controls, and the increase was proportional to improvements in depressive state after sleep deprivation. Bromocriptine did not increase blink rate 1 hour after application. This result is consistent with the hypothesis that antidepressant SD acts through dopamine release, although it is not conclusive, because other neurotransmitters like acetylcholine may be involved in the regulation of blinking.

Use of MagniSep chromium dioxide particles in an immunoassay system.

The use of chromium dioxide particles as a solid support for very sensitive and rapid immunoassays, is the result of the combination of large surface area (40 m2) and high protein uptake capacity (40 mg/g) allowing rapid capture kinetics and high binding capacity. Magnetic and physical properties of these particles give a rapid separation, a complete resuspension and a rapid high-efficiency washing, highly desirable characteristics for efficient automation of immunoassays. Good precision and accuracy, exemplified by excellent recovery, parallelism and correlation were demonstrated. Test results prove that the technology is highly flexible and applicable to a variety of assay formats.