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Radiotherapy-induced gut toxicity is among the most prevalent dose-limiting toxicities following radiotherapy. Prevention of radiation enteropathy requires protection of the small intestine. However, despite the prevalence and burden of this pathology, there are currently no effective treatments for radiotherapy-induced gut toxicity, and this pathology remains unclear. The present study aimed to investigate the changes induced in the rat small intestine after external irradiation of the tongue, and to explore the potential radio-protective effects of melatonin gel. Male Wistar rats were subjected to irradiation of their tongues with an X-Ray YXLON Y.Tu 320-D03 irradiator, receiving a dose of 7.5 Gy/day for 5 days. For 21 days post-irradiation, rats were treated with 45 mg/day melatonin gel or vehicle, by local application into their mouths. Our results showed that mitochondrial oxidative stress, bioenergetic impairment, and subsequent NLRP3 inflammasome activation were involved in the development of radiotherapy-induced gut toxicity. Oral treatment with melatonin gel had a protective effect in the small intestine, which was associated with mitochondrial protection and, consequently, with a reduced inflammatory response, blunting the NF-κB/NLRP3 inflammasome signaling activation. Thus, rats treated with melatonin gel showed reduced intestinal apoptosis, relieving mucosal dysfunction and facilitating intestinal mucosa recovery. Our findings suggest that oral treatment with melatonin gel may be a potential preventive therapy for radiotherapy-induced gut toxicity in cancer patients.

Breast cancer is the leading cause of cancer death among Hispanic women. Certain dietary factors have been associated with the risk of breast cancer recurrence, but data in Hispanic survivors is scarce., Objective: to examine dietary patterns and diet quality in two groups of Hispanic breast cancer survivors., Methods: 23 Mexican-American (MA) and 22 Puerto Rican (PR) female breast cancer survivors completed a culturally adapted validated food frequency questionnaire. Intake was standardized per 1000 kcal and compared to US Dietary Guidelines and the DASH-style diet adherence score was calculated., Results: Overweight/obese was 70 % in MA and 91 % in PR. PR consumed diets rich in fruit/100 % fruit juices and beans, while MA diets were high in vegetables, beans, and total grains. Both groups consumed high amounts of starchy vegetables, refined grains, animal protein and calories from solid fats and added sugars but low intakes of whole grains, dairy products and nuts and seeds. DASH scores were relatively low., Conclusion: MA and PR female breast cancer survivors have different dietary patterns but both groups had relatively low diet quality. These groups could benefit from culturally tailored interventions to improve diet quality, which could potentially reduce cancer recurrence. ClinicalTrials.gov Identifier NCT01504789.

The endoplasmic reticulum (ER) has the ability to signal organelle dysfunction via a complex signaling network known as the unfolded protein response (UPR). In this work, hamster fibroblast cells exhibiting moderate levels of ER stress were compared to those exhibiting severe ER stress. Inhibition of N-linked glycosylation was accomplished via a temperature-sensitive mutation in the Dad1 subunit of the oligosaccharyltransferase (OST) complex or by direct inhibition with tunicamycin (Tm). Temperature shift (TS) treatment generated weak activation of ER stress signaling when compared to doses of Tm that are typically used in ER stress studies (500-1000 nM). A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment. In parental BHK21 cells, moderate (20-40 nM) and high doses (200-1000 nM) of Tm were compared to identify physiological and signaling-based differences in stress response. Inhibition of ER Ca 2+ release via ITPR activity with 2-aminoethoxydiphenyl borate (2-APB) or Xestospongin C (XeC) was sufficient to protect against apoptosis induced by moderate but not higher doses of Tm. Analysis of kinase activation over a range of Tm exposures revealed the p38 stress-activated protein kinase (SAPK) to display increasing activation with Tm dosage. Interestingly, Tm induced the extracellular regulated kinases (Erk1/2) only at moderate doses of Tm. Inhibition of ER transmembrane stress sensors (IRE1, PERK) or cytosolic signaling mediators (p38, Jnk1, Erk1/2) was used to evaluate pathways involved in apoptosis activation during ER stress. Inhibition of either PERK or p38 was sufficient to reduce cell death and apoptosis induced by moderate, but not high, doses of Tm. During ER stress, cells exhibited a rapid decline in anti-apoptotic Mcl-1 and survivin proteins. Inhibition of PERK was sufficient to block this affect. This work reveals moderate doses of ER stress to generate patterns of stress signaling that are distinct from higher doses and that apoptosis activation at moderate levels of stress are dependent upon PERK and p38 signaling. Studies exploring ER stress signaling should recognize that this signaling acts as a rheostat rather than a simple switch, behaving distinctively in a dose-dependent manner.

Objective: Breast cancer survivors do not engage in appropriate levels of physical activity, despite the known benefits of such activity. This study aims to describe physical-activity levels and the barriers to it in a group of Puerto Rican breast cancer survivors, as well as detailing their preferences for an intervention., Methods: Participants who finished their chemotherapy and/or radiotherapy for breast cancer at least 4 months prior to the study were included. Demographic, anthropometric, and clinical data were obtained. The Godin Leisure-Time Exercise Questionnaire (GLTEQ) and questionnaires on exercise self-efficacy, barriers to self-efficacy, modeling, and social support were filled out by study participants. Data on access to exercise equipment and preferences regarding a physical-activity intervention were collected. Descriptive statistics and correlation analyses were performed., Results: Fifty breast cancer survivors were recruited. Almost all the participants reported that they did not engage in any kind of strenuous physical activity (94%), with more than three fourths (76%) reporting that they did not even participate in any kind of moderate physical activity. The GLTEQ score was associated with barriers to selfefficacy, while the association with exercise self-efficacy approached significance (p = 0.055). Nearly half of the patients (44%) had access to exercise equipment. Preferred methods for the delivery of physical-activity interventions were participating in group settings (72%) and receiving material in the postal mail (44%)., Conclusion: The study described herein reports on the low levels of physical activity being practiced by a group of Puerto Rican breast cancer survivors, despite the fact that many of them had access to exercise equipment and facilities. Further studies aimed at understanding breast cancer survivors' barriers to physical activity and at developing culturally competent interventions to increase the levels of such activity are warranted.

Background and Aim: Breast milk has been shown to be associated with greater success with regard to weaning children with intestinal failure off parenteral nutrition (PN). There are only a few studies investigating the role of breast milk in decreasing PN-associated liver disease (PNALD). The aim of our study was to determine whether breast milk is better than formula milk in preventing PNALD in infants receiving PN for >4 weeks., Methods: We conducted a retrospective analysis of newborns requiring prolonged parenteral nutrition. We divided the sample into 3 different groups (exclusive breast-feeding, exclusive formula-feeding, and mixed feeding. We compared baseline characteristics, feeding profiles and liver function tests, and liver enzymes among the 3 groups., Results: Among infants receiving PN for >4 weeks, we found that infants who were fed only breast milk were significantly less likely to develop PNALD (34.6%) compared with those who were fed only formula milk (72.7%; P = 0.008). The mean maximum conjugated bilirubin (P = 0.03) and the mean maximum aspartate aminotransferase were significantly lower in the breast-fed group (P = 0.04) compared with the formula-fed group. Among the mixed-feeding group, infants who received a higher percentage of breast milk showed a significant negative correlation with the mean maximum conjugated bilirubin. (Pearson correlation -0.517, P = 0.027). The mean number of days receiving PN and the average daily lipid intake in the 2 groups was not significantly different., Conclusions: As a modality for early enteral nutrition, breast milk is protective against the development of PNALD in infants receiving PN for >4 weeks.

This study evaluated an integrated treatment for comorbid problem gambling, anger, and substance use. Problem gamblers with comorbid anger problems (N=42), half of whom also had substance use disorders, were randomized to either a 14-week integrated treatment targeting anger and addictions (i.e., both gambling and substance use) or a specialized treatment-as-usual (TAU) for gambling and substance use. Participants were assessed at baseline (Tl), 14 weeks (T2), and 12 weeks follow-up (T3). Relative to the TAU, participants in the integrated anger and addictions treatment reported significantly less gambling at T2 and T3 and less trait anger and substance use at T3. Findings suggest that it is important to screen gambling clients for the presence of comorbid anger and substance use problems and that, when present, these problems need to be addressed concurrently in gambling treatment in order to optimize treatment outcomes.