Effects of a community-based healthy heart program on increasing healthy women's physical activity: a randomized controlled trial guided by Community-based Participatory Research (CBPR)

Background  

Cardiovascular disease remains the leading killer of women in most developed areas of the world. Rates of physical inactivity and poor nutrition, which are two of the most important modifiable risk factors for cardiovascular disease in women, are substantial. This study sought to examine the effectiveness of a community-based lifestyle-modification program on increasing women's physical activity in a randomized trial guided by community-based participatory research (CBPR) methods.     

An orthotopic metastatic prostate cancer model in SCID mice via grafting of a transplantable human prostate tumor line

Metastasis is the major cause of prostate cancer deaths and there is a need for clinically relevant in vivo models allowing elucidation of molecular and cellular mechanisms underlying metastatic behavior. Here we describe the development of a new in vivo model system for metastatic prostate cancer. Pieces of prostate cancer tissue from a patient were grafted in testosterone-supplemented male NOD-SCID mice at the subrenal capsule graft site permitting high tumor take rates. After five serial transplantations, the tumor tissues were grafted into mouse prostates. Resulting tumors and suspected metastatic lesions were subjected to histopathological and immunohistochemical analysis. Samples of metastatic tissue were regrafted in mouse anterior prostates and their growth and spread examined, leading to isolation from lymph nodes of a metastatic subline, PCa1-met. Orthotopic grafting of PCa1-met tissue in 47 hosts led in all cases to metastases to multiple organs (lymph nodes, lung, liver, kidney, spleen and, notably, bone). Histopathological analysis showed strong similarity between orthotopic grafts and their metastases. The latter were of human origin as indicated by immunostaining using antibodies against human mitochondria, androgen receptor, prostate-specific antigen and Ki-67. Spectral karyotyping showed few chromosomal alterations in the PCa1-met subline. This study indicates that transplantable subrenal capsule xenografts of human prostate cancer tissue in NOD-SCID mice can, as distinct from primary cancer tissue, be successfully grown in the orthotopic site. Orthotopic xenografts of the transplantable tumor lines and metastatic sublines can be used for studying various aspects of metastatic prostate cancer, including metastasis to bone.     

Epitope-specific humoral immunity to Plasmodium vivax Duffy binding protein

Erythrocyte invasion by Plasmodium vivax is completely dependent on binding to the Duffy blood group antigen by the parasite Duffy binding protein (DBP). The receptor-binding domain of this protein lies within a cysteine-rich region referred to as region II (DBPII). To examine whether antibody responses to DBP correlate with age-acquired immunity to P. vivax, antibodies to recombinant DBP (rDBP) were measured in 551 individuals residing in a village endemic for P. vivax in Papua New Guinea, and linear epitopes mapped in the critical binding region of DBPII. Antibody levels to rDBP(II) increased with age. Four dominant linear epitopes were identified, and the number of linear epitopes recognized by semi-immune individuals increased with age, suggesting greater recognition with repeated infection. Some individuals had antibodies to rDBP(II) but not to the linear epitopes, indicating the presence of conformational epitopes. This occurred in younger individuals or subjects acutely infected for the first time with P. vivax, indicating that repeated infection is required for recognition of linear epitopes. All four dominant B-cell epitopes contained polymorphic residues, three of which showed variant-specific serologic responses in over 10% of subjects examined. In conclusion, these results demonstrate age-dependent and variant-specific antibody responses to DBPII and implicate this molecule in partial acquired immunity to P. vivax in populations in endemic areas.     

Intrathoracic gastric fistula after bariatric surgery: a systematic review and pooled analysis

Even in the hands of highly experienced bariatric surgeons, perioperative complications are inevitable. Of these, leaks and fistulas are amongst the scariest complications. Intrathoracic gastric fistulas (ITGF) can be associated with serious morbidity, mostly when cases are misdiagnosed or detected with delay. This is a systematic review of the literature to investigate the clinical and surgical outcomes of morbidly obese adult patients with a confirmed diagnosis of ITGF following bariatric surgery. A pooled analysis of 25 articles, encompassing 76 patients with post-bariatric ITGF, showed that the clinical outcome depends on the initial presentation, timing of the diagnosis in relation to symptom onset, and prompt and effective treatment. Any septic or unstable patient must undergo urgent surgical intervention, while stable patients might tolerate a step-up approach and watchful waiting for nonsurgical treatment. Among those who undergo surgery, treatment failure and the mortality rate are substantially high. Contingent upon a prompt management strategy, patients with postbariatric ITGF can generally have a favorable outcome in the long term.     

Combined effects of caffeine and malnutrition on the newborn rat's myocardium.

We hypothesized that the pathological effects on the neonatal rat heart could be aggravated by Cu deficiency due to the combined effects of caffeine exposure and malnutrition. Upon birth, pups were mixed and randomly picked; 8 pups were assigned to each dam and then divided into 4 groups. Group 1 dams received a normal diet containing 20% protein. Group 2 dams were fed 20% protein diet supplemented with caffeine (4 mg/100 g BW). Group 3 dams received 6% protein diet as a malnourished group, and group 4 dams received 6% protein diet supplemented with caffeine (4 mg/100 g BW). On postnatal day 10, dams and pups were killed. Group 2 tended to have a decrease in the Cu levels of dams' plasma and milk and in pups' plasma and heart tissue compared to those of group 1. This pattern was not observed consistently between groups 3 and 4. Transmission electron microscopy of group 2 pups' hearts revealed a degree of disruption in the mitochondria compared to normal mitochondria seen in group 1. There was no consistent change in the mitochondria of group 4 compared to group 3. The caffeine level observed in all categories of group 4 (dams' plasma and milk, pups' plasma and heart tissue) was lower than those in group 2. Although malnutrition affected body weight and heart weight, combined effects of caffeine and malnutrition on Cu content in the neonatal heart was relatively minor compared to the well nourished group. This well nourished group showed that the effects of caffeine on Cu were more consistent, resulting the changes of mitochondria.     

Copy number variations in DCC/18q and ERBB2/17q are associated with disease‐free survival in microsatellite stable colon cancer

We conducted a prospective study to assess the prognostic impact of selected copy number variations (CNVs) in Stage II–III microsatellite stable (MSS) colon cancer. A total of 401 patients were included from 01/2004 to 01/2009. The CNVs in 8 selected target genes, DCC/18q, EGFR/7p, TP53/17p, BLK/8p, MYC/8q, APC/5q, ERBB2/17q and STK6/20q, were detected using a quantitative multiplex polymerase chain reaction of short fluorescent fragment (QMPSF) method. The primary end‐point was the impact of the CNVs on the 4‐year disease‐free survival (DFS). The recurrence rate at 4 years was 20.9%, corresponding to 14% Stage II patients versus 31% Stage III patients (p < 0.0001). The 4‐year DFS was significantly decreased in patients with a loss at DCC/18q (p = 0.012) and a gain at ERBB2/17q (p = 0.041). The multivariate analysis demonstrated that Stage III, a loss at DCC/18q and a gain at ERBB2/17q were independent factors associated with DFS. A combination of DCC/18q and ERBB2/17q was also associated with relapse, with the hazard ratio increasing from 1 to 2.4 (95% confidence interval (CI), 1.5–4.1) and 3.1 (95% CI, 1.2–8.4) in the presence of 0, 1 or 2 alterations, respectively (p = 0.0013). CNVs in DCC/18q and ERBB2/17q are significantly associated with DFS in Stage II–III MSS colon cancer.