Pathogenic Intestinal Bacteria Enhance Prostate Cancer Development via Systemic Activation of Immune Cells in Mice

A role for microbes has been suspected in prostate cancer but difficult to confirm in human patients. We show here that a gastrointestinal (GI) tract bacterial infection is sufficient to enhance prostate intraepithelial neoplasia (PIN) and microinvasive carcinoma in a mouse model. We found that animals with a genetic predilection for dysregulation of wnt signaling, Apc[superscript Min/+] mutant mice, were significantly susceptible to prostate cancer in an inflammation-dependent manner following infection with Helicobacter hepaticus. Further, early neoplasia observed in infected Apc[superscript Min/+] mice was transmissible to uninfected mice by intraperitoneal injection of mesenteric lymph node (MLN) cells alone from H. hepaticus-infected mutant mice. Transmissibility of neoplasia was preventable by prior neutralization of inflammation using anti-TNF-α antibody in infected MLN donor mice. Taken together, these data confirm that systemic inflammation triggered by GI tract bacteria plays a pivotal role in tumorigenesis of the prostate gland.RO1CA108854National Institute of Environmental Health Sciences (Massachusetts Institute of Technology. Center for Environmental Health Sciences Pilot Project Award P30-ES002109

Clinical and scientific progress related to the interface between cardiology and psychology: lessons learned from 35 years of experience at the Thoraxcenter of the Erasmus Medical Center in Rotterdam

In November 1975, as the first in the Netherlands, a full-time psychologist was employed at the Department of Cardiology of the Thoraxcenter of the Erasmus Medical Center. This innovative decision was consistent with a view to treat the patient as a whole rather than the heart as a single body part in need of repair, combined with the understanding that the heart and mind interact to affect health. The present selective review addresses the broad range of contributions of 35 years of psychology to clinical cardiology and cardiovascular research with a focus on research, teaching, psychological screening and patient care. The review ends with lessons to be learned and challenges for the future with respect to improving the care and management of patients with heart disease in order to enhance secondary prevention and the role of behavioural and psychological factors in this endeavour

Microbial Reprogramming Inhibits Western Diet-Associated Obesity

A recent epidemiological study showed that eating ‘fast food’ items such as potato chips increased likelihood of obesity, whereas eating yogurt prevented age-associated weight gain in humans. It was demonstrated previously in animal models of obesity that the immune system plays a critical role in this process. Here we examined human subjects and mouse models consuming Westernized ‘fast food’ diet, and found CD4[superscript +] T helper (Th)17-biased immunity and changes in microbial communities and abdominal fat with obesity after eating the Western chow. In striking contrast, eating probiotic yogurt together with Western chow inhibited age-associated weight gain. We went on to test whether a bacteria found in yogurt may serve to lessen fat pathology by using purified Lactobacillus reuteri ATCC 6475 in drinking water. Surprisingly, we discovered that oral L. reuteri therapy alone was sufficient to change the pro-inflammatory immune cell profile and prevent abdominal fat pathology and age-associated weight gain in mice regardless of their baseline diet. These beneficial microbe effects were transferable into naïve recipient animals by purified CD4[superscript +] T cells alone. Specifically, bacterial effects depended upon active immune tolerance by induction of Foxp3[superscript +] regulatory T cells (Treg) and interleukin (Il)-10, without significantly changing the gut microbial ecology or reducing ad libitum caloric intake. Our finding that microbial targeting restored CD4[superscript +] T cell balance and yielded significantly leaner animals regardless of their dietary ‘fast food’ indiscretions suggests population-based approaches for weight management and enhancing public health in industrialized societies.National Institutes of Health (U.S.) (Grant P30-ES002109)National Institutes of Health (U.S.) (Grant RO1CA108854)National Institutes of Health (U.S.) (Grant P01 AI045757)National Institutes of Health (U.S.) (Grant U19 AI046130)National Institutes of Health (U.S.) (Grant U19 AI070352)National Institutes of Health (U.S.) (Grant P01 AI039671)National Institute of Neurological Disorders and Stroke (U.S.) (Jacob Javits Merit Award NS2427)The Penates FoundationNancy Taylor Foundation for Chronic Diseases, Inc

Recurrent Modification of a Conserved Cis-Regulatory Element Underlies Fruit Fly Pigmentation Diversity

The development of morphological traits occurs through the collective action of networks of genes connected at the level of gene expression. As any node in a network may be a target of evolutionary change, the recurrent targeting of the same node would indicate that the path of evolution is biased for the relevant trait and network. Although examples of parallel evolution have implicated recurrent modification of the same gene and cis-regulatory element (CRE), little is known about the mutational and molecular paths of parallel CRE evolution. In Drosophila melanogaster fruit flies, the Bric-à-brac (Bab) transcription factors control the development of a suite of sexually dimorphic traits on the posterior abdomen. Female-specific Bab expression is regulated by the dimorphic element, a CRE that possesses direct inputs from body plan (ABD-B) and sex-determination (DSX) transcription factors. Here, we find that the recurrent evolutionary modification of this CRE underlies both intraspecific and interspecific variation in female pigmentation in the melanogaster species group. By reconstructing the sequence and regulatory activity of the ancestral Drosophila melanogaster dimorphic element, we demonstrate that a handful of mutations were sufficient to create independent CRE alleles with differing activities. Moreover, intraspecific and interspecific dimorphic element evolution proceeded with little to no alterations to the known body plan and sex-determination regulatory linkages. Collectively, our findings represent an example where the paths of evolution appear biased to a specific CRE, and drastic changes in function were accompanied by deep conservation of key regulatory linkages. © 2013 Rogers et al

Parvovirus B19 infection in Tunisian patients with sickle-cell anemia and acute erythroblastopenia

<p>Abstract</p> <p>Background</p> <p>Human parvovirus B19 is the etiologic agent of erythema infectiosum in children. It is also associated with other clinical manifestations in different target groups. Patients with chronic hemolytic anemia are at high risk of developing acute erythroblastopenia following infection by the virus. They usually become highly viremic and pose an increased risk of virus transmission. Close monitoring of such high risk groups is required for epidemiologic surveillance and disease prevention activities. Here we report a molecular epidemiological study on B19 virus infection in Tunisian patients with chronic hemolytic anemia.</p> <p>Methods</p> <p>This study was conducted on 92 young chronic hemolytic anemia patients who attended the same ward at the National Bone Marrow Transplantation Center of Tunis and 46 controls from a different hospital. Screening for IgM and IgG anti-B19 antibodies was performed using commercially available enzyme immunoassays and B19 DNA was detected by nested PCR in the overlapping <it>VP1/VP2 </it>region. DNA was sequenced using dideoxy-terminator cycle sequencing technology.</p> <p>Results</p> <p>Anti-parvovirus B19 IgG antibodies were detected in 26 of 46 sickle-cell anemia patients, 18 of 46 β-thalassemia and 7 of 46 controls. Anti-parvovirus B19 IgM antibodies were detected only in 4 of the sickle-cell anemia patients: two siblings and two unrelated who presented with acute erythroblastopenia at the time of blood collection for this study and had no history of past transfusion. B19 DNA was detected only in sera of these four patients and the corresponding 288 bp nested DNA amplicons were sequenced. The sequences obtained were all identical and phylogenetic analysis showed that they belonged to a new B19 virus strain of Genotype1.</p> <p>Conclusion</p> <p>A new parvovirus B19 strain of genotype1 was detected in four Tunisian patients with sickle-cell anemia. Virus transmission appeared to be nosocomial and resulted in acute erythroblastopenia in the four patients. The possibility of independent transmission of this B19 variant to the patients is unlikely in light of the present epidemiological data. However this possibility cannot be ruled out because of the low genetic variability of the virus.</p

Effects of isoflavones (soy phyto-estrogens) on serum lipids: a meta-analysis of randomized controlled trials

OBJECTIVES: To determine the effects of isoflavones (soy phyto-estrogens) on serum total cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL) and triglyceride (TG). METHODS: We searched electronic databases and included randomized trials with isoflavones interventions in the forms of tablets, isolated soy protein or soy diets. Review Manager 4.2 was used to calculate the pooled risk differences with fixed effects model. RESULTS: Seventeen studies (21 comparisons) with 853 subjects were included in this meta-analysis. Isoflavones tablets had insignificant effects on serum TC, 0.01 mmol/L (95% CI: -0.17 to 0.18, heterogeneity p = 1.0); LDL, 0.00 mmol/L (95% CI: -0.14 to 0.15, heterogeneity p = 0.9); HDL, 0.01 mmol/L (95% CI: -0.05 to 0.06, heterogeneity p = 1.0); and triglyceride, 0.03 mmol/L (95% CI: -0.06 to 0.12, heterogeneity p = 0.9). Isoflavones interventions in the forms of isolated soy protein (ISP), soy diets or soy protein capsule were heterogeneous to combine. CONCLUSIONS: Isoflavones tablets, isolated or mixtures with up to 150 mg per day, seemed to have no overall statistical and clinical benefits on serum lipids. Isoflavones interventions in the forms of soy proteins may need further investigations to resolve whether synergistic effects are necessary with other soy components

Elevated Plasma Von Willebrand Factor and Propeptide Levels in Malawian Children with Malaria

In children with malaria plasma VWF and propeptide levels are markedly elevated in both cerebral and mild paediatric malaria, with levels matching disease severity, and these normalize upon recovery. High levels of both markers also occur in retinopathy-negative 'cerebral malaria' cases, many of whom are thought to be suffering from diseases other than malaria, indicating that further studies of these markers will be required to determine their sensitivity and specificity

Protein supplementation in strength and conditioning adepts: knowledge, dietary behaviour and practice in Palermo, Italy

Background: It is known that supplement use is a widespread and accepted practice by athletes and people who attend commercial gyms. Little is known about protein supplement amongst people undertaking strength training in commercial gyms in Italy when compared to the US. Objective: The purpose of this study was to examine the use of protein supplementation, alone or in association with other supplements, and dietary behavior amongst regular fitness center attendees in Palermo, Italy. Design: Resistance training information have been collected from 800 regular fitness center attendees for the initial analysis. A specific questionnaire was generated for the experimentation. Data were collected using a face-to-face interview method. Supplement users were then compared to the non users and analyzed using a one-way ANOVA, Kruskall-Wallis, chi-square test or exact test of Fisher when appropriate. Results: 30.1% of the respondents use dietary supplements during their training as a believe it is the "way to gain muscles and strength". Whey protein shakes (50.0%) mixed with creatine and amino-acids (48.3%) were the most frequent choices amongst the users. A majority of the subjects (34.0%) appeared to rely on their gym instructors' advice for their intake; a lower proportion (13.0%) consulted physicians, while none of them consulted nutritionists. A high consumption of milk has been noticed in both users (67,7%) and non-users (52,8%); supplement non-users consumed significantly more snacks and bakery products than users per week (P < 0.001), while users consumed significantly more protein-rich foods (P < 0.01) with a particular preference for meat (48.0%). Conclusions: A considerable number of regular strength training adepts consume protein supplements mixed with other products (mainly creatine and amino-acids). Limited numbers consult "dietary specialists" and rely mainly on their instructors. We emphasize on the importance of the dissemination of scientifically based information about supplementation in this environment and the promotion of updated educational programs for the instructors

A Review of the Rationale for Additional Therapeutic Interventions to Attain Lower LDL-C When Statin Therapy Is Not Enough

Statins alone are not always adequate therapy to achieve low-density lipoprotein (LDL) goals in many patients. Many options are available either alone or in combination with statins that makes it possible to reach recommended goals in a safe and tolerable fashion for most patients. Ezetimibe and bile acid sequestrants reduce cholesterol transport to the liver and can be used in combination. Niacin is very effective at lowering LDL, beyond its ability to raise high-density lipoprotein and shift LDL particle size to a less atherogenic type. When statins cannot be tolerated at all, red yeast rice can be used if proper formulations of the product are obtained. Nutrients can also be added to the diet, including plant stanols and sterols, soy protein, almonds, and fiber, either individually or all together as a portfolio diet. A clear understanding of how each of these strategies works is essential for effective results