Exercise, sleep quality, and mediators of sleep in breast and prostate cancer patients receiving radiation therapy

Cancer patients often report impaired sleep quality. Impaired sleep quality may be due to increased levels of sleep-mediating cytokines resulting from cancer treatment. Exercise may have a positive influence on sleep-mediating cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and soluble tumor necrosis factor-alpha receptor (sTNF-R), which may improve sleep quality. This two-arm pilot study compared the influence of a home-based exercise intervention with standard care/control on sleep quality and mediators of sleep. Breast and prostate cancer patients (n = 38) beginning radiation therapy were randomized to a 4-week exercise program or no exercise arm. Global sleep quality, subjective sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction were assessed with the Pittsburgh Sleep Quality Index. IL-6, TNF-α, and sTNF-R were measured before and after intervention. There was a greater improvement in sleep quality in the exercise group from pre- to postintervention, although the difference was not significant. Additionally, there were associations between IL-6 and sleep efficiency and duration, suggesting that regulation of sleep-mediating cytokines by exercise may mediate improvements in sleep-quality components.     

Predictors of heart rhythm disturbances in hypertensive obese patients with obstructive sleep apnea

Objective To assess the incidence and predictors of heart rhythm and conduction disturbances in hypertensive obese patients with and without obstructive sleep apnea (OSA). Methods This is an open, cohort, prospective study. Out of 493 screened patients, we selected 279 hypertensive, obese individuals without severe concomitant diseases: 75 patients without sleep-disordered breathing (non-SDB group), and 204 patients with OSA (OSA group). At baseline, all patients underwent examination, including ECG, Holter ECG monitoring, and sleep study. During follow-up (on 3, 5, 7 and 10^th years; phone calls once per 6 months), information about new events, changes in therapy and life style was collected, diagnostic procedures were performed. As the endpoints, we registered significant heart rhythm and conduction disorders as following: atrial fibrillation (AF), ventricular tachycardia, atrioventricular block (AV) 2–3 degree, sinoatrial block, significant sinus pauses (> 2000 ms), and the required pacemaker implantation. Results The median follow-up was 108 (67.5–120) months. The frequency of heart rhythm disorders was higher in OSA patients (29 cases, χ² = 5.5; P = 0.019) compared to the non-SDB patients (three cases; OR: 3.92, 95% CI: 1.16–13.29). AF was registered in 15 patients (n = 12 in OSA group; P = 0.77). Heart conduction disturbance developed in 16 patients, without an association with the rate of coronary artery disease onset. Regression analysis showed that only hypertension duration was an independent predictor of AF (OR: 1.10, 95% CI: 1.04–1.16; P = 0.001). In case of heart conduction disturbances, apnea duration was the strongest predictor (Р = 0.002). Conclusions Hypertensive obese patients with OSA demonstrate 4-fold higher incidence of heart rhythm and conduction disturbances than subjects without SDB. Hypertension duration is an independent predictor for AF development, while sleep apnea/hypopnea duration is the main factor for heart conduction disorders onset in hypertensive obese patients with OSA.     

Tracing of noradrenergic projections using manganese-enhanced MRI

We examined the applicability of manganese-enhanced MRI (MEMRI) to the in vivo tracing of diffuse neuromodulatory projections by means of simultaneous iontophoretic injections of an extremely low, non-toxic concentration of MnCl₂ (10 mM) and fluorescent dextran in the locus coeruleus (LC) in the rat. We validated the use of the iontophoretic injection by reproducing previously reported results from pressure injections of MnCl₂ in primary somatosensory cortex. Twenty four hours after injection in LC, Mn^2 + labeling was detected in major cortical and subcortical targets of LC projections including predominantly ipsilateral primary motor and somatosensory cortices, hippocampus and amygdala. Although the injections were in most cases centered in the core of LC, the pattern of Mn^2 + labeling greatly varied across rats. In addition, despite a certain degree of overlap of the labeling obtained with both MEMRI and classical tracing, MEMRI tracing consistently failed to reliably label not only several minor but also major targets of LC, notably the thalamus. The lack of Mn^2 + labeling in thalamus possibly reflected a weaker functional connectivity within coeruleothalamic projections that could not be predicted by anatomical tracing. Inversely, a number of brain regions, particularly contralateral motor cortex, that were not or only sparsely labeled with fluorescent dextran were strongly labeled by Mn^2 +. This discrepancy could be partly due to both the activity-dependent and transsynaptic nature of Mn^2 + transport. The overall labeling produced using MEMRI with iontophoretic injections in LC indicates that the Mn^2 + imaging of highly diffuse projections is in principle feasible. However, the labeling pattern of each individual case needs to be carefully interpreted particularly before submitting data for group analysis or in the case of longitudinal examination of discrete changes in functional connectivity under various physiological or behavioral conditions.     

Besteht ein Zusammenhang zwischen der Refluxerkrankung und dem obstruktiven Schlafapnoesyndrom?

Reflux of gastric contents can be associated with many ENT disorders. Some authors describe an association with obstructive sleep apnea, but it is not clear whether the reflux causes the apnea or vice versa. Furthermore, authors did not distinguish between gastroesophageal reflux and extraesophageal reflux, which is essential to understand a connection with obstructive sleep apnea. Therefore, we performed polysomnography and two-channel pH testing simultaneously in patients with obstructive sleep apnea syndrome (OSAS) and compared the findings with data of healthy volunteers. After exclusion of a changed sleep architecture due to the pH testing system, the results show that patients with OSAS do not suffer more often from reflux than healthy volunteers. This is true for gastroesophageal as well as for extraesophageal reflux. Furthermore, an increasing number of reflux events during the night is not correlated with the number of apnea events. Thus, in summary our data cannot support the postulation that there is a connection between obstructive sleep apnea syndrome and reflux disease.     

Physical activity and risk of endometrial cancer in the Norwegian Women and Cancer (NOWAC) study

Few studies have investigated the association between endometrial cancer and physical activity (PA) using repeated measures of PA and different subtypes of endometrial cancer. We aimed to investigate the association between endometrial cancer and PA level at two points in time in women with different body mass index (BMI) profiles, and to calculate the population attributable fraction (PAF) of endometrial cancer for low PA levels. We included 82,759 women with complete information on PA at baseline in the Norwegian Women and Cancer Study; 52,370 had follow‐up information on PA. 687 endometrial cancer cases were identified. Multivariate cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). The PAF indicated the proportion of endometrial cancer that could be avoided in the population if these women had a higher PA level. There was a statistically significant association between low PA levels at baseline and follow‐up and endometrial cancer risk, with a dose‐response trend (lowest PA level: HR = 1.60, 95% CI 1.16–2.20; highest PA level: HR = 0.73, 95% CI 0.45–1.16 compared to the median). Analyses that included follow‐up measurements yielded similar results. 21.9% (95% CI 7.1–34.3) of endometrial cancers could be avoided if women with low PA levels (≤ 4 in a 1–10 degree self reported PA scale) increased their PA levels to 5‐10. We found an inverse dose‐response association between PA and endometrial cancer, independent of BMI. In this nationally representative cohort, 21.9% of endometrial cancers could potentially be avoided if PA levels increased to higher PA levels.     

Evidence for an important role of alcohol- and aldehyde-metabolizing genes in cancers of the upper aerodigestive tract.

BACKGROUND: Incidence and mortality rates of upper aerodigestive tract cancers in Central Europe are among the highest in the world and have increased substantially in recent years. This increase is likely to be due to patterns of alcohol and tobacco consumption. Genetic susceptibility to upper aerodigestive tract cancer in relation to such exposures is an important aspect that should be investigated among populations in this region. METHODS: A multicenter case-control study comprising 811 upper aerodigestive tract cancer cases and 1,083 controls was conducted in: Bucharest (Romania), Lodz (Poland), Moscow (Russia), Banska Bystrika (Slovakia), and Olomouc and Prague (Czech Republic). We analyzed six SNPs in three genes related to ethanol metabolism: alcohol dehydrogenase 1B and 1C (ADH1B, ADH1C) and aldehyde dehydrogenase 2 (ALDH2). RESULTS: The ADH1B histidine allele at codon 48 was associated with a decreased risk of upper aerodigestive tract cancer; odds ratios (OR) were 0.36 [95% confidence interval (95% CI), 0.17-0.77] for medium/heavy drinkers and 0.57 (95% CI, 0.36-0.91) for never/light drinkers. Moderately increased risks were observed for the ADH1C (350)Val allele (OR, 1.19; 95% CI, 0.98-1.55) and ADH1C (272)Gln allele (OR, 1.24; 95% CI, 0.98-1.55). Medium/heavy drinkers who were heterozygous or homozygous at ALDH2 nucleotide position 248 were at a significantly increased risk of upper aerodigestive tract cancer (OR, 1.76; 95% CI, 1.13-2.75; OR, 5.79; 95% CI, 1.49-22.5, respectively), with a significant dose response for carrying variant alleles (P = 0.0007). Similar results were observed for the ALDH2 +82A>G and ALDH2 -261C>T polymorphisms. When results were analyzed by subsite, strong main effects were observed for squamous cell carcinoma of the esophagus for all six variants. Among the 30% of the population who were carriers of at least one ALDH2 variant, the attributable fraction among carriers (AF(c)) was 24.2% (5.7-38.3%) for all upper aerodigestive tract cancers, increasing to 58.7% (41.2-71.0%) for esophageal cancer. Among carriers who drank alcohol at least thrice to four times a week, the AF(c) for having at least one ALDH2 variant was 49% (21.3-66.8%) for all upper aerodigestive tract cancers, increasing to 68.9% (42.9-83.1%) for esophageal cancer. CONCLUSIONS: Polymorphisms in the ADH1B and ALDH2 genes are associated with upper aerodigestive tract cancer in Central European populations and interact substantially with alcohol consumption.     

Yeast ts secretory mutation rgs1 is suppressed by the SEC4 gene of Saccharomyces cerevisiae

Yeast rgs1 cells accumulate secretory vesicles in the cytoplasm and stop the secretion of proteins at the restrictive temperature. The ts mutation rgs1 may be suppressed by several different genes; the S. cerevisiae SEC4 gene, encoding the small G-protein involved in the late secretory stage, is one of them. Synthetic lethality of the double rgs1 sec4 mutant is demonstrated.