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Paul Y Takahashi,1 Gregory D Jenkins,2 Benjamin P Welkie,2 Shannon K McDonnell,2 Jared M Evans,2 James R Cerhan,2 Janet E Olson,2 Stephen N Thibodeau,3 Mine S Cicek,3 Euijung Ryu2 1Division of Primary Care Internal Medicine, 2Department of Health Sciences Research, 3Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA Purpose: In aging adults, mitochondrial dysfunction may be an important contributor. We evaluated the association between mitochondrial DNA (mtDNA) copy number, which is a biomarker for mitochondrial function, and self-rated health status.Patients and methods: We conducted a cross-sectional study of patients enrolled within the Mayo Clinic Biobank. We utilized the questionnaire and sequence data from 944 patients. We examined the association between mtDNA copy number and self-rated health status with 3 collapsed categories for the latter variable (excellent/very good, good, and fair/poor). For analysis, we used proportional odds models after log-transforming mtDNA copy number, and we adjusted for age and sex. Results: We found the median age at enrollment was 61 years (25th–75th percentile: 51–71), and 64% reported excellent or very good health, 31% reported good health, and 6% reported fair/poor health. Overall, the median mtDNA copy number was 88.9 (25th–75th percentile: 77.6–101.1). Higher mtDNA copy number was found for subjects reporting better self-rated health status after adjusting for age, sex, and comorbidity burden (OR =2.3 [95% CI: 1.2–4.5] for having better self-rated health for a one-unit increase in log-transformed mtDNA copy number). Conclusion: We found that a higher mtDNA copy number is associated with better self-rated health status after adjustment for age, sex, and comorbidity burden. The current study implies that mtDNA copy number may serve as a biomarker for self-reported health. Further studies, potentially including cohort studies, may be required. Keywords: mitochondrial DNA copy number, self-rated health, personalized medicine

Human dicrocoeliosis is reported sporadically in various parts of the world. We report a case in a 21-year-old male, who had right upper abdominal pain, weight loss, and chronic relapsing watery diarrhea three to four times daily for four weeks. The patient had abdominal tenderness to palpation in the right upper quadrant. Alkaline phosphatase, alanine aminotransferase, and serum immunoglobulin E levels were slightly elevated; all other biochemical and hematological findings were in their normal ranges. The duodenal biopsy samples were normal and an abdominal ultrasonography showed no biliary or hepatic abnormality. Stool microscopy revealed numerous eggs of Dicrocoelium dendriticum. As pseudoparasitosis can result from eating raw, infected animal liver, the patient was given a liver-free diet for three days, to rule out that possibility. Subsequent stool examinations showed eggs in each of the samples indicating that the infection was genuine. The patient was treated with triclabendazole 10 mg/kg in a single dose. Four weeks later, no parasite eggs were detected in the microscopic examination of the stool samples. The patient got better gradually and the symptoms disappeared. Physicians should keep in mind parasitic diseases such as the rarely encountered dicrocoeliosis.

Abstract Background Carboxypeptidase 4 (CPA4) is a zinc-dependent metallocarboxypeptidase on chromosome 7q32 in a region linked to prostate cancer aggressiveness. CPA4 is involved in the histone hyperacetylation pathway and may modulate the function of peptides that affect the growth and regulation of prostate epithelial cells. We examined the association between genetic variation in CPA4 and intermediate-to-high risk prostate cancer. Methods We studied 1012 men (506 cases and 506 controls) from Cleveland, Ohio. All cases had Gleason ≥ 7, clinical stage ≥ T2c, or PSA ≥ 10 ng/mL at diagnosis. Six CPA4 single-nucleotide polymorphisms were genotyped, and evaluated for their relation to prostate cancer. We also evaluated whether CPA4 variants influence risk of disease among men diagnosed at an earlier age (< 66 years). Results The nonsynonymous coding SNP (rs2171492, Cys303Gly) in CPA4 was associated with an increased risk of aggressive prostate cancer among younger patients (< 66 years). Specifically, men carrying the TT genotype had an approximately two-fold increased risk for being diagnosed with intermediate-to-high risk disease (Odds Ratio = 1.83, p = 0.04). In the overall population (all ages) none of the CPA4 SNPs demonstrated a statistically significant association with prostate cancer. Conclusion Coding variation in CPA4 may confer increased risk of intermediate-to-high risk prostate cancer among younger patients. Further work is needed to identify the functional aspects of this variation and understand its biological effects on prostate cancer. Such work may translate into more precise screening of higher risk individuals as well as guiding clinicians and patients toward earlier and more definitive treatment modalities in patients genetically identified as higher risk.

Abstract Background Osteopontin (OPN), a secreted phosphoglycoprotein, has been strongly associated with tumor progression and aggressive cancers. MDA-MB-435 cells secrete very high levels of OPN. However metastasis-suppressed MDA-MB-435 cells, which were transfected with breast cancer metastasis suppressor 1 (BRMS1), expressed significantly less OPN. BRMS1 is a member of mSin3-HDAC transcription co-repressor complex and has been shown to suppress the metastasis of breast cancer and melanoma cells in animal models. Hence we hypothesized that BRMS1 regulates OPN expression. Results The search for a BRMS1-regulated site on the OPN promoter, using luciferase reporter assays of the promoter deletions, identified a novel NF-κB site (OPN/NF-κB). Electrophoretic mobility shift assays and chromatin immunoprecipitations (ChIP) confirmed this site to be an NF-κB-binding site. We also show a role of HDAC3 in suppression of OPN via OPN/NF-κB. Conclusion Our results show that BRMS1 regulates OPN transcription by abrogating NF-κB activation. Thus, we identify OPN, a tumor-metastasis activator, as a crucial downstream target of BRMS1. Suppression of OPN may be one of the possible underlying mechanisms of BRMS1-dependent suppression of tumor metastasis.