Transient caloric restriction and cancer risk (The Netherlands)

Over the past century, many animal experiments have shown that caloric restriction can reduce the risk of cancer, a finding that proved to be highly reproducible. Many papers have been published on its potential for human health, but until know little evidence is available on its actual effects in humans. In Utrecht, The Netherlands, we have been investigating the effects of the 1944–1945 Dutch famine on breast cancer risk factors and breast cancer risk, and paradoxically the relatively short-term famine seemed to be related to increased breast cancer risk in later life. One of the differences between the famine situation and the large body of evidence from animal experiments is the duration of caloric restriction. Almost all animal experiments investigated sustained caloric restriction and information on the effects of short-term transient caloric restriction is very scarce. A search in the literature identified some animal experiments on short-term transient caloric restriction and these seemed to be at least supportive to the famine findings. Because caloric restriction in humans for preventive health measures would be mostly short-term, it is important to extend animal research on short-term caloric restriction

Volumetric breast density affects performance of digital screening mammography

PURPOSE: To determine to what extent automatically measured volumetric mammographic density influences screening performance when using digital mammography (DM). METHODS: We collected a consecutive series of 111,898 DM examinations (2003-2011) from one screening unit of the Dutch biennial screening program (age 50-75 years). Volumetric mammographic density was automatically assessed using Volpara. We determined screening performance measures for four density categories comparable to the American College of Radiology (ACR) breast density categories. RESULTS: Of all the examinations, 21.6% were categorized as density category 1 ('almost entirely fatty') and 41.5, 28.9, and 8.0% as category 2-4 ('extremely dense'), respectively. We identified 667 screen-detected and 234 interval cancers. Interval cancer rates were 0.7, 1.9, 2.9, and 4.4‰ and false positive rates were 11.2, 15.1, 18.2, and 23.8‰ for categories 1-4, respectively (both p-trend < 0.001). The screening sensitivity, calculated as the proportion of screen-detected among the total of screen-detected and interval tumors, was lower in higher density categories: 85.7, 77.6, 69.5, and 61.0% for categories 1-4, respectively (p-trend < 0.001). CONCLUSIONS: Volumetric mammographic density, automatically measured on digital mammograms, impacts screening performance measures along the same patterns as established with ACR breast density categories. Since measuring breast density fully automatically has much higher reproducibility than visual assessment, this automatic method could help with implementing density-based supplemental screening

Single-conformation spectroscopy of hydrogen bonding networks: Solvation, synthetic foldamers, and neurodegenerative diseases

The hydrogen bond is one of the most important interactions in natural processes ranging from protein folding to chemical reactions. Two complementary methodologies are applied to understanding this important interaction: top-down and bottom-up. Top-down methods use large molecules, such as proteins, revealing secondary structure information. Bottom-up experiments are performed on small molecules, utilizing high-resolution spectroscopy to reveal underlying quantum mechanical effects. The complexity gap is formed between these two experimental regimes; between large and small molecules; between bulk and individual solvent molecules; between classical mechanics calculations and quantum chemical calculations. This dissertation will focus on the application of gas phase, single-conformation ultraviolet (UV) and infrared (IR) spectroscopies to the study of molecules and clusters in the size and solvation complexity gap, with the goal of bridging the gulf between the two experimental approaches. Single-conformation spectroscopy is perfectly suited to study solvation. Solvent molecules, in many instances water, can be frozen onto the solute in a stepwise manner. Here, we solvate a prototypical flexible bichromophore—1,2-diphenoxyethane (DPOE)—by stepwise addition of water molecules. Single-conformation spectroscopy reveals both the structural perturbations associated with water molecule addition and their effect on DPOE’s pair of closely spaced excited electronic states. These experimental studies provide excellent insight into solvent effects on vibronic and excitonic coupling, and can be used to further develop the models used to describe such processes. Similarly, single-conformation spectroscopy can reveal the effects of conformational flexibility on the innate conformational preferences and hydrogen bonding motifs in peptides. Results obtained from a study of a cyclically constrained γ peptide, γACHC, reveal that increased conformational flexibility can be controlled by synthetic chemists in order to direct folding into pre-programmed secondary structures and that these structures are stabilized with intramolecular rather than intermolecular hydrogen bonds. This theme of conformational flexibility is continued in studies of glutamine containing peptides. Glutamine—with its flexible, hydrogen bond forming sidechain—is intimately involved with neurodegenerative diseases such as Huntington’s disease. Single-conformation studies help reveal the delicate interplay between three different types of hydrogen bonds within the molecule: backbone-backbone, sidechain-backbone, and sidechain-sidechain hydrogen bonds. The importance of these competing hydrogen bonds on the conformational preferences will be discussed both locally and within the larger context of disease pathogenesis

Associations between lifestyle factors and an unhealthy diet.

: Unhealthy dietary patterns have been associated with other unhealthy lifestyle factors such as smoking and physical inactivity. Whether these associations are similar in high- and low-educated individuals is currently unknown

Effect of diet with or without exercise on abdominal fat in postmenopausal women:A randomised trial

Background: We assessed the effect of equivalent weight loss with or without exercise on (intra-) abdominal fat in postmenopausal women in the SHAPE-2 study. Methods: The SHAPE-2 study is a three-armed randomised controlled trial conducted in 2012-2013 in the Netherlands. Postmenopausal overweight women were randomized to a diet (n = 97), exercise plus diet (n = 98) or control group (n = 48). Both intervention groups aimed for equivalent weight loss (6-7%) following a calorie-restricted diet (diet group) or a partly supervised intensive exercise programme (4 h per week) combined with a small caloric restriction (exercise plus diet group). Outcomes after 16 weeks are amount and distribution of abdominal fat, measured by magnetic resonance imaging (MRI) with the use of the three-point IDEAL Dixon method. Results: The diet and exercise plus diet group lost 6.1 and 6.9% body weight, respectively. Compared to controls, subcutaneous and intra-abdominal fat reduced significantly with both diet (- 12.5% and - 12.0%) and exercise plus diet (- 16.0% and - 14.6%). Direct comparison between both interventions revealed that the reduction in subcutaneous fat was statistically significantly larger in the group that combined exercise with diet: an additional 10.6 cm 2 (95%CI -18.7; - 2.4) was lost compared to the diet-only group. Intra-abdominal fat loss was not significantly larger in the exercise plus diet group (- 3.8 cm 2 , 95%CI -9.0; 1.3). Conclusions: We conclude that weight loss of 6-7% with diet or with exercise plus diet reduced both subcutaneous and intra-abdominal fat. Only subcutaneous fat statistically significantly reduced to a larger extent when exercise is combined with a small caloric restriction. Trial register: NCT01511276 (clinicaltrials.gov), prospectively registered

Природный и антропогенный факторы формирования и развития культурного ландшафта Форосского парка

Цель данной статьи: на примере небольшой территории Южного берега Крыма – парка в пгт. Форос и прилегающей к нему местности – показать роль и место культурного ландшафта в формировании человеком исторического геокультурного пространства

Effects of an 18-week exercise programme started early during breast cancer treatment: a randomised controlled trial

Background: Exercise started shortly after breast cancer diagnosis might prevent or diminish fatigue complaints. The Physical Activity during Cancer Treatment (PACT) study was designed to primarily examine the effects of an 18-week exercise intervention, offered in the daily clinical practice setting and starting within 6 weeks after diagnosis, on preventing an increase in fatigue. Methods: This multi-centre controlled trial randomly assigned 204 breast cancer patients to usual care (n = 102) or supervised aerobic and resistance exercise (n = 102). By design, all patients received chemotherapy between baseline and 18 weeks. Fatigue (i.e., primary outcome at 18 weeks), quality of life, anxiety, depression, and physical fitness were measured at 18 and 36 weeks. Results: Intention-to-treat mixed linear model analyses showed that physical fatigue increased significantly less during cancer treatment in the intervention group compared to control (mean between-group differences at 18 weeks: -1.3; 95 % CI -2.5 to -0.1; effect size -0.30). Results for general fatigue were comparable but did not reach statistical significance (-1.0, 95% CI -2.1; 0.1; effect size -0.23). At 18 weeks, submaximal cardiorespiratory fitness and several muscle strength tests (leg extension and flexion) were significantly higher in the intervention group compared to control, whereas peak oxygen uptake did not differ between groups. At 36 weeks these differences were no longer statistically significant. Quality of life outcomes favoured the exercise group but were not significantly different between groups. Conclusions: A supervised 18-week exercise programme offered early in routine care during adjuvant breast cancer treatment showed positive effects on physical fatigue, submaximal cardiorespiratory fitness, and muscle strength. Exercise early during treatment of breast cancer can be recommended. At 36 weeks, these effects were no longer statistically significant. This might have been caused by the control participants' high physical activity levels during follow-up

Validation of previously identified serum biomarkers for breast cancer with SELDI-TOF MS: a case control study

<p>Abstract</p> <p>Background</p> <p>Serum protein profiling seems promising for early detection of breast cancer. However, the approach is also criticized, partly because of difficulties in validating discriminatory proteins. This study's aim is to validate three proteins previously reported to be discriminative between breast cancer cases and healthy controls. These proteins had been identified as a fragment of inter-alpha trypsin inhibitor H4 (4.3 kDa), C-terminal-truncated form of C3a des arginine anaphylatoxin (8.1 kDa) and C3a des arginine anaphylatoxin (8.9 kDa).</p> <p>Methods</p> <p>Serum protein profiles of 48 breast cancer patients and 48 healthy controls were analyzed with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Differences in protein intensity between breast cancer cases and controls were measured with the Mann-Whitney U test and adjusted for confounding in a multivariate logistic regression model.</p> <p>Results</p> <p>Four peaks, with mass-to-charge ratio (<it>m/z</it>) 4276, 4292, 8129 and 8941, were found that were assumed to represent the previously reported proteins. <it>M/</it>z 4276 and 4292 were statistically significantly decreased in breast cancer cases compared to healthy controls (p < 0.001). M/<it>z </it>8941 was decreased in breast cancer cases (p < 0.001) and <it>m/z </it>8129 was not related with breast cancer (p = 0.87). Adjustment for sample preparation day, sample storage duration and age did not substantially alter results.</p> <p>Conclusion</p> <p><it>M/z </it>4276 and 4292 both represented the previously reported 4.3 kDa protein and were both decreased in breast cancer patients, which is in accordance with the results of most previous studies. <it>M/z </it>8129 was in contrast with previous studies not related with breast cancer. Remarkably, <it>m/z </it>8941 was decreased in breast cancer cases whereas in previous studies it was increased. Differences in patient populations and pre-analytical sample handling could have contributed to discrepancies. Further research is needed before we can conclude on the relevance of these proteins as breast cancer biomarkers.</p