Differences in survival by histologic type of pancreatic cancer.

OBJECTIVE: Although pancreatic cancer has an extremely high case fatality rate, little is known about differences in mortality by histologic types. We examined median survival and risk of mortality for endocrine pancreatic tumors and two types of exocrine tumors, adenocarcinomas, and mucinous tumors. METHOD: This analysis included 35,276 pancreatic cancer cases reported to the nine population-based cancer registries participating in the Surveillance, Epidemiology, and End Results program from 1973 to 2000. Survival among cases with pancreatic adenocarcinomas, mucinous tumors, and endocrine tumors were compared using Kaplan-Meier plots. Comparative risks of mortality were evaluated using multivariate adjusted Cox regression models. RESULTS: Endocrine pancreatic cancer cases had a median survival of 27 months compared with a median survival of 4 months for adenocarcinoma and mucinous tumor cases. Compared with adenocarcinoma cases, endocrine tumor cases had a 0.28-fold lower risk of mortality [95% confidence interval (95% CI), 0.26-0.30], and mucinous tumor cases had a 0.88-fold lower risk (95% CI, 0.84-0.91). These results were similar for men and women. Within histologic types, advanced tumor stage, older diagnosis age, surgery, and Black race were associated with increased risks of mortality, whereas female sex and more recent year of diagnosis were associated with decreased risks. CONCLUSION: This study confirms the clinical observation that patients with endocrine pancreatic cancer survive longer than patients with exocrine tumors. A better understanding of these differences could contribute to identifying the underlying causes of pancreatic cancer and to improving survival rates across all histologic types.     

Mutant huntingtin impairs immune cell migration in Huntington disease

In Huntington disease (HD), immune cells are activated before symptoms arise; however, it is unclear how the expression of mutant huntingtin (htt) compromises the normal functions of immune cells. Here we report that primary microglia from early postnatal HD mice were profoundly impaired in their migration to chemotactic stimuli, and expression of a mutant htt fragment in microglial cell lines was sufficient to reproduce these deficits. Microglia expressing mutant htt had a retarded response to a laser-induced brain injury in vivo. Leukocyte recruitment was defective upon induction of peritonitis in HD mice at early disease stages and was normalized upon genetic deletion of mutant htt in immune cells. Migration was also strongly impaired in peripheral immune cells from pre-manifest human HD patients. Defective actin remodeling in immune cells expressing mutant htt likely contributed to their migration deficit. Our results suggest that these functional changes may contribute to immune dysfunction and neurodegeneration in HD, and may have implications for other polyglutamine expansion diseases in which mutant proteins are ubiquitously expressed.     

Efficiency of neuromuscular electrical stimulation: A comparison of elicited force and subject tolerance using three electrical waveforms

Objective: Efficacy of neuromuscular electrical stimulation (NMES) is limited by the discomfort of electrically elicited contractions. Most studies of tolerance to NMES have examined stimulation to maximal tolerance. NMES efficiency is the amount of elicited force at a specific level of tolerance. This study is the first to describe and examine such. Design: A repeated measures design was used. Electrically elicited force (EEF) was measured using three waveforms: burst-modulated alternating current (BMAC), pulsed current (PC), and burst-modulated pulsed current (BMPC). EEF at a tolerance rating of 5/10 on a visual analog scale (VAS) was recorded. The dependent variables were EEF up to 5/10 VAS, current amplitude at 5/10, and percent maximal isometric force at 5/10. Results: EEF and percent maximal voluntary isometric force were significantly greater with BMPC versus BMAC (p = 0.001 and 0.004). No differences were noted between PC and BMAC or BMPC and PC. Amplitude was significantly greater with BMAC compared to BMPC and PC (p = 0.003 and 0.015). No difference in amplitude was noted between PC and BMPC. Conclusion: For the same level of discomfort, BMPC yielded one-third greater muscle force than BMAC and at a lesser current amplitude. These data evidence a greater efficiency for BMPC than BMAC.     

Increasing dietary EPA and DHA influence estimated fatty acid desaturase activity in systemic organs which is reflected in the red blood cell in mice

Delta-5 (D5D) and delta-6 (D6D) desaturase are key enzymes in fatty acid (FA) metabolism. Dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may alter tissue FA composition via D5D and D6D. The purpose was to determine the relationship between dietary EPA?+?DHA, estimated desaturase activities of various tissues and the reflection of desaturase activity in the red blood cell (RBC). Mice were fed diets with increasing percent of energy from EPA?+?DHA. Phospholipid FA composition of heart, muscle, spleen, lung, adipose tissues and RBC were analysed. D5D and D6D enzyme activity estimates (EAE) were calculated as the ratio of 20:4/20:3 and 20:3/18:2, respectively. D5D EAE decreased in all tissues, except muscle, with increasing dietary EPA?+?DHA. RBC D5D EAE positively correlated with D5D EAE in all tissues. RBC D6D EAE positively correlated with muscle and inversely correlated with adipose D6D EAE. Our findings suggest differential influence of dietary EPA?+?DHA upon tissue desaturase activities.     

Antidepressant Use is Associated with Increased Energy Intake and Similar Levels of Physical Activity

Antidepressants have been associated with weight gain, but the causes are unclear. The aims of this study were to assess the association of antidepressant use with energy intake, macronutrient diet composition, and physical activity. We used data on medication use, energy intake, diet composition, and physical activity for 3073 eligible adults from the 2005–2006 National Health and Nutrition Examination Survey (NHANES). Potential confounding variables, including depression symptoms, were included in the models assessing energy intake, physical activity, and sedentary behavior. Antidepressant users reported consuming an additional (mean ± S.E.) 215 ± 73 kcal/day compared to non-users (p = 0.01). There were no differences in percent calories from sugar, fat, or alcohol between the two groups. Antidepressant users had similar frequencies of walking or biking, engaging in muscle-strengthening activities, and engaging in moderate or vigorous physical activity. Antidepressant users were more likely to use a computer for ≥2 h/day (OR 1.77; 95% CI: 1.09–2.90), but TV watching was similar between the two groups. These results suggest increased energy intake and sedentary behavior may contribute to weight gain associated with antidepressant use. Focusing on limiting food intake and sedentary behaviors may be important in mitigating the weight gain associated with antidepressant use.