Exercise, physical activity and breast cancer: the role of tumor-associated macrophages.

Regular exercise and physical activity provide many health benefits and are encouraged by medical professionals for the primary prevention of and adjuvant treatment of breast cancer Current consensus in the discipline of exercise oncology is that both regular physical activity and exercise training exert some protective effect against breast cancer risk, and may reduce morbidity in some advanced cases. While there is growing interest in the role of exercise and physical activity in breast cancer prevention, it is currently unclear how exercise may modulate tumor behavior. The tumor microenvironment is populated by stromal cells such as fibroblasts and adipocytes, as well as macrophages. Termed tumor-associated macrophages (TAMs), these immune cells are highly plastic and respond to different signals from the cancer microenvironment, causing them to either display tumor-promoting or tumor-suppressing phenotypes. Because of such plasticity, there has been considerable interest by immunologists to develop immunotherapies based on skewing the behavior of TAMs to become cancer-suppressive. Previous studies have indirectly shown the ability of exercise training to induce an anti-tumor effect of macrophages, although the studies did not address this in the tumor microenvironment. Nevertheless, this opens up the possibility that regular exercise training may exert a protective innate immune effect against breast cancer, potentially by inducing a cancer-suppressing phenotype of TAMs. This review will describe potential mechanisms through which exercise may modulate the behavior of TAMs.

An older male with an unusual presentation of disseminated coccidioidomycosis.

Coccidioidomycosis is a fungal disease endemic to the southwestern United States and other areas in the Western Hemisphere. Infection is usually acquired through inhalation. While infection is most often asymptomatic, early respiratory illness and infrequently extrapulmonary dissemination may occur. Immunocompromised individuals, particularly those with impaired cell-mediated immunity, are at greatest risk for dissemination. We present an atypical case of disseminated coccidioidomycosis in an immunocompetent male manifesting as peritoneal disease diagnosed during elective inguinal herniorrhaphy.

Mice expressing an XRCC1 truncated protein are at increased risk for insulin resistance.

Insulin resistance is a metabolic disorder that is highly prevalent in older populations. Mice expressing a truncated X-ray repair cross-complementing protein 1 (XRCC1tp) have normal repair of single-stranded breaks (SSBs) but are sensitive to alkylating agents. XRCC1tp mice thus provide a model to study perturbations in physiological function, such as metabolism, in the presence of normal DNA repair but attenuated XRCC1 activity. XRCC1tp male mice at six months of age fed a diet high in fat (lard) and sugar (sucrose) (HFSD) for three months showed a significant delay in glucose clearance, indicative of insulin resistance. These mice also had a decrease in respiratory exchange ratio, suggesting a change in the way fats and carbohydrates are used as a fuel source. Mechanisms for these observations are of interest, since there is a suggestion that XRCC1 is involved in glucoregulatory pathways, and XRCC1tp mice would provide an excellent model to pursue these studies in an age-related manner.

Long-term outcomes of deep brain stimulation in severe Parkinson's disease utilizing UPDRS III and modified Hoehn and Yahr as a severity scale.

OBJECTIVES: Deep brain stimulation (DBS) is the surgical treatment of choice for moderate to severe Parkinson's Disease (PD). However, few studies have assessed its efficacy in severe PD as defined by the modified Hoehn and Yahr scale (HY). This study evaluates long-term and medication outcomes of DBS in severe PD. PATIENTS AND METHODS: We retrospectively collected the data of 15 patients from 2008 to 2014 with severe PD treated with DBS. Retrospective assessment with the modified Hoehn and Yahr scale and motor subset of the Unified Parkinson's Disease Rating Scale (UPDRS III) were used to objectively track severity and motor function improvement, respectively. Levodopa equivalence daily doses (LEDD), number of anti-PD medications and number of daily medication doses were used to measure improvements in medication burden. Data was evaluated using univariate analyses, one sample paired t-test, two sample paired t-test, and Wilcoxon signed-rank test. RESULTS: The mean post-operative follow-up was 44.63 months, average age at diagnosis and the average age at time of DBS was 51.3 years and 61.5 years, respectively, and the time from diagnosis to treatment was 13.2 years. Significant decreases were seen in UPDRS III scores (pre-op = 44.533; post-op = 26.13; p = 0.0094), LEDD (pre-op = 1679.34 mg; post-op = 837.48 mg; p = 0.0049), and number of daily doses (pre-op = 21.266; post-op 12.2; p = 0.0046). No significant decrease was seen in the number of anti-PD medications (pre-op = 3.8; post-op = 3.2; p = 0.16). CONCLUSION: Following DBS, severe PD patients demonstrated significant improvements in motor function and medication burden during long-term follow-up. We believe our results prove that DBS is efficacious in the management of severe PD, and that further research should follow to expand DBS criteria to include severe disease.