Chagas disease in rural areas of Chaco Province, Argentina: epidemiologic survey in humans, reservoirs, and vectors

We studied the seroprevalence of antibodies against Trypanosoma cruzi in the human population along with domiciliary infestation by triatomine bugs in an area endemic for Chagas disease in the Chaco Province of Argentina. In addition, we carried out parasitologic surveys in patients, dogs, wild mammals, and vectors. The mean seroprevalence in humans was 27.81% (109 of 392) and 24.14% (63 of 261) in 1-15-year-old children. The minimum domiciliary infestation rate was 13.33%, with certain areas reaching 53.85%. The prevalence was 15.09% (16 of 106) in dogs and 35.71% (10 of 28) in opossums. Infection with T. cruzi was detected in 30.10% (59 of 196) of the Triatoma infestans tested. Compared with nationwide studies, our data suggest that 1) there are zones requiring immediate sanitary action, and 2) nationwide estimates are based on very heterogeneous epidemiologic situations. This heterogeneity emphasizes the importance of in-depth studies of restricted areas to provide additional information for a better understanding of the present status of Chagas disease in Argentina.     

Evidence that the retroviral DNA integration process triggers an ATR-dependent DNA damage response

Caffeine is an efficient inhibitor of cellular DNA repair, likely through its effects on ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related) kinases. Here, we show that caffeine treatment causes a dose-dependent reduction in the total amount of HIV-1 and avian sarcoma virus retroviral vector DNA that is joined to host DNA in the population of infected cells and also in the number of transduced cells. These changes were observed at caffeine concentrations that had little or no effect on overall cell growth, synthesis, and nuclear import of the viral DNA, or the activities of the viral integrase in vitro. Substantial reductions in the amount of host-viral-joined DNA in the infected population, and in the number of transductants, were also observed in the presence of a dominant-negative form of the ATR protein, ATRkd. After infection, a significant fraction of these cells undergoes cell death. In contrast, retroviral transduction is not impeded in ATM-deficient cells, and addition of caffeine leads to the same reduction that was observed in ATM-proficient cells. These results suggest that activity of the ATR kinase, but not the ATM kinase, is required for successful completion of the viral DNA integration process and/or survival of transduced cells. Components of the cellular DNA damage repair response may represent potential targets for antiretroviral drug development.     

First heart sound and opening snap in patients with mitral valve disease. Phonocardiographic and pathomorphologic study

Patients with exercise angina >2 months (n:13) showed significantly lower SigmaST elevation during 120 s balloon coronary occlusion than those with =<2 months (n:7), or those with angina at rest <=2 days (n:8) but similar to patients with angina at rest >2 days (n:7). These results underscore the importance of the kind and duration of angina in limiting the extent of ischemia during coronary occlusion.     

Pyridoxal isonicotinoyl hydrazone (PIH) and its analogs as protectants against anthracycline-induced cardiotoxicity

The risk of cardiotoxicity is the main drawback of anthracycline antibiotics. However, these drugs remain among the most effective and frequently used anti cancer drugs. In this study we aimed to assess the cardioprotective effects of aroylhydrazone iron (FE) chelators: pyridoxal isonicotinoyl hydrazone (PIH) and its two analogs: salicyladehyde isonicotinoyl hydrazone (SIH) and pyridoxal o-chlorbenzoyl hydrazone (o-108). In rabbits, chronic treatment with daunorubicin (DAU) (3 mg/kg weekly for 10 weeks) induced mortality (33%) as well as left ventricular (LV) dysfunction. Co-administrations of PIH (25 mg/kg, i.p.), SIH hydrochloride [1 mg/kg, iv] as well as o-108 (10 mg/kg, i.p.), fully prevented premature deaths and most of the DAU-induced functional impairments were significantly suppressed. However, when 2- to 2.5-fold higher doses of the chelators were used, they led to rather paradoxical and mostly negative results regarding both cardioprotection and overall mortality.     

Heterogeneity of Randomized Controlled Trials of Fecal Microbiota Transplantation in Recurrent Clostridioides difficile Infection

Digestive Diseases and Sciences - Clinical trials have demonstrated the efficacy of FMT for reduction in CDI recurrences (rCDI), but this treatment and its reporting in the literature has...     

Is visfatin an adipokine or myokine? Evidence for greater visfatin expression in skeletal muscle than visceral fat in chickens

Visfatin, an adipokine hormone produced primarily by visceral adipose tissue in mammals, has been implicated in the immune system, cellular aging, and glucose metabolism. Increased visceral adiposity and hyperglycemia have been correlated with elevated plasma visfatin levels in humans. The present study investigated visfatin cDNA and protein expression as well as plasma visfatin levels in chickens that are selected for rapid growth and are naturally hyperglycemic relative to mammals. By RT-PCR, we detected visfatin cDNA in multiple tissues in the chicken. The deduced amino acid sequence of full-length chicken visfatin was 92-93% homologous to mammalian visfatin. Using real-time quantitative PCR and Western blotting, chicken skeletal muscle was found to contain 5- and 3-fold greater quantities of visfatin mRNA and protein than abdominal fat pad, respectively. Visfatin mRNA and protein quantities were not significantly different among sc and visceral adipose tissue depots. Skeletal muscle visfatin mRNA and protein quantities as well as plasma visfatin levels determined by enzyme immunoassay were significantly higher in 8-wk-old compared with 4-wk-old chickens, possibly due to rapid skeletal muscle growth and visceral fat accretion occurring in broiler chickens during this period. However, fasting and refeeding did not affect plasma visfatin levels in the chicken. Collectively, our results provide novel evidence that skeletal muscle, not the visceral adipose tissue, is the primary source of visfatin in chickens, thereby raising the possibility that visfatin may be acting as a myokine affecting skeletal muscle growth and metabolism.     

Antiprothrombin antibody testing: detection and clinical utility

Anticardiolipin antibody (aCL), anti-beta2 glycoprotein I antibodies, and lupus anticoagulant (LA) are the only laboratory tests considered within the revised criteria for the classification of the antiphospholipid syndrome (APS). Recently, antibodies against phosphatidylserine-prothrombin complex (aPS/PT) have been detected, and these antibodies, rather than antibodies against prothrombin alone, are closely associated with APS and LA. The sensitivity and specificity of aPS/PT for the diagnosis of APS were assessed in a population of patients with a variety of autoimmune disorders. aCL and aPS/PT have similar diagnostic value for APS, therefore aPS/PT should be further explored, not only for research purposes but also as a candidate for one of the laboratory criteria for the classification of the APS.