Citations

Background: There is an assumption that baseball athletes who reside in warm-weather climates experience larger magnitude adaptations in throwing shoulder motion and strength compared with their peers who reside in cold-weather climates. Hypotheses: (1) The warm-weather climate (WWC) group would exhibit more pronounced shoulder motion and strength adaptations than the cold-weather climate (CWC) group, and (2) the WWC group would participate in pitching activities for a greater proportion of the year than the CWC group, with the time spent pitching predicting throwing shoulder motion and strength in both groups. Study Design: Cross-sectional study; Level of evidence, 3. Methods: One hundred uninjured high school pitchers (50 each WWC, CWC) were recruited. Rotational shoulder motion and isometric strength were measured and participants reported the number of months per year they pitched. To identify differences between groups, t tests were performed; linear regression was used to determine the influence of pitching volume on shoulder motion and strength. Results: The WWC group pitched more months per year than athletes from the CWC group, with the number of months spent pitching negatively related to internal rotation motion and external rotation strength. The WWC group exhibited greater shoulder range of motion in all planes compared with the CWC group, as well as significantly lower external rotation strength and external/internal rotation strength ratios. There was no difference in internal rotation strength between groups, nor a difference in the magnitude of side-to-side differences for strength or motion measures. Conclusion: Athletes who reside in cold- and warm-weather climates exhibit differences in throwing shoulder motion and strength, related in part to the number of months spent participating in pitching activities. The amount of time spent participating in pitching activities and the magnitude of range of motion and strength adaptations in athletes who reside in warm-weather climates may make these athletes more susceptible to throwing-related injuries.

Abstract Early B cell factor (EBF) is a transcription factor essential for specification and commitment to the B cell fate. In this study, we show downregulation of a developmentally regulated cluster of hoxa genes, notably hoxa9, coincides with induction of EBF at the Pro-B cell stage of B cell differentiation. Analysis of the hematopoietic progenitor compartment in Hoxa9−/− mice revealed significantly reduced frequencies and expression levels of Flt3, a cytokine receptor important for lymphoid priming and the generation of B cell precursors (BCPs). We show that Hoxa9 directly regulates the flt3 gene. Chromatin immunoprecipitation analysis revealed binding of Hoxa9 to the flt3 promoter in a lymphoid progenitor cell line. Knockdown of Hoxa9 significantly reduced Flt3 transcription and expression. Conversely, forced expression of Hoxa9 increased Flt3 transcription and expression in a Pro-B cell line that expressed low levels of Flt3. Hoxa9 inversely correlated with ebf1 in ex vivo-isolated bone marrow progenitors and BCPs, suggesting that EBF might function to silence a Hoxa9 transcriptional program. Restoration of EBF function in an EBF−/− cell line induced B lineage gene expression but did not directly suppress hoxa9 transcription, revealing alternate mechanisms of Hoxa9 regulation in BCPs. These data provide new insight into Hoxa9 function and regulation during lymphoid and B cell development. Furthermore, they suggest that failure to upregulate Flt3 provides a molecular basis for the lymphoid/early B cell deficiencies in Hoxa9−/− mice.

Abnormal expression of genes for energy regulation in Parkinson’s disease patients identifies a master regulator as a possible therapeutic target for early intervention.

Abstract The Eighth Annual Frontiers in Cancer Prevention Research meeting was held in Houston, Texas, in November 2009. This report highlights significant presentations that advance the fields of chemoprevention, clinical trial recruitment and retention, cancer screening including optical imaging, energy balance, and nutritional epidemiology, and health communications and decision making. In findings from the randomized Reduction by Dutasteride of Prostate Cancer Events trial, dutasteride reduced the risk of biopsy-detectable prostate cancer in high-risk men by 23% compared with placebo. Important clues about the dosing and window of susceptibility for supplementation with choline, vitamin D, and folate were revealed from epigenetic research that has implications for future nutritional epidemiology research. Noninvasive optical imaging techniques using endoscopic ultrasound and autofluorescence for the early detection of cancers in the lung, pancreas, and oral cavity are being studied. The report also addresses the challenges of promoting cancer prevention. Understanding how individuals process risk information and make sustained behavior changes and the effect of socioeconomic status on health disparities were identified as critical areas of research. This multidisciplinary research meeting of basic, clinical, and behavioral scientists and epidemiologists continues to play a major role in identifying the research priority areas of cancer prevention, elucidating new mechanisms of carcinogenesis for targeted chemoprevention therapies and delivering a comprehensive strategy for engaging individuals in the unifying goal to reduce cancer incidence. Cancer Prev Res; 3(8); 1044–8. ©2010 AACR.

Background— Circadian rhythms with regard to time of symptom onset for patients with acute myocardial infarction have been observed, although their relationship to outcomes has been debated. We evaluated these rhythms in patients with ST-elevation myocardial infarction as a function of the 24-hour circadian cycle. Methods and Results— The relationship between onset of symptoms during the 24-hour circadian cycle and prehospital delays from symptom onset to hospital arrival, timeliness of reperfusion, and in-hospital death was assessed in 2143 patients with ST-elevation myocardial infarction presenting from 2004–2008 at 1 of 3 tertiary-care healthcare ST-elevation myocardial infarction systems. There was a significant association between time of onset and the circadian cycle, with the greatest percentage (39%) of patients experiencing onset between 8 am and 3 pm ( P <0.001). Time of onset was associated with prehospital delay and timeliness of reperfusion. Patients with onset from 12 am to 5:59 am had median prehospital delays of 121 minutes versus 70 minutes from 12 pm to 5:59 pm ( P <0.001). Patients with onset time from 12 am to 5:59 am had median door-to-balloon times of 75 minutes versus 60 minutes from 6 am to 11:59 am ( P <0.001). Using multivariable modeling to control for baseline patient characteristics, prehospital delay, and timeliness of reperfusion, there was no significant association between time of symptom onset with in-hospital death. Conclusions— Patients with ST-elevation myocardial infarction exhibit significant circadian patterns in symptom onset, prehospital delay, and timeliness of reperfusion. Patients who develop symptoms from 12 am to 5:59 am present with longer prehospital delays and have longer door-to-balloon times. After multivariable adjustment, there was no significant association between circadian patterns of time of onset and in-hospital death.

Purpose Prior reports have indicated that patients with colon cancer who demonstrate high-level microsatellite instability (MSI-H) or defective DNA mismatch repair (dMMR) have improved survival and receive no benefit from fluorouracil (FU) -based adjuvant therapy compared with patients who have microsatellite-stable or proficient mismatch repair (pMMR) tumors. We examined MMR status as a predictor of adjuvant therapy benefit in patients with stages II and III colon cancer. Methods MSI assay or immunohistochemistry for MMR proteins were performed on 457 patients who were previously randomly assigned to FU-based therapy (either FU + levamisole or FU + leucovorin; n = 229) versus no postsurgical treatment (n = 228). Data were subsequently pooled with data from a previous analysis. The primary end point was disease-free survival (DFS). Results Overall, 70 (15%) of 457 patients exhibited dMMR. Adjuvant therapy significantly improved DFS (hazard ratio [HR], 0.67; 95% CI, 0.48 to 0.93; P = .02) in patients with pMMR tumors. Patients with dMMR tumors receiving FU had no improvement in DFS (HR, 1.10; 95% CI, 0.42 to 2.91; P = .85) compared with those randomly assigned to surgery alone. In the pooled data set of 1,027 patients (n = 165 with dMMR), these findings were maintained; in patients with stage II disease and with dMMR tumors, treatment was associated with reduced overall survival (HR, 2.95; 95% CI, 1.02 to 8.54; P = .04). Conclusion Patient stratification by MMR status may provide a more tailored approach to colon cancer adjuvant therapy. These data support MMR status assessment for patients being considered for FU therapy alone and consideration of MMR status in treatment decision making.