Reconstructing the origins of high-alpine niches and cushion life form in the genus Androsace S.L. (Primulaceae).

Relatively, few species have been able to colonize extremely cold alpine environments. We investigate the role played by the cushion life form in the evolution of climatic niches in the plant genus Androsace s.l., which spreads across the mountain ranges of the Northern Hemisphere. Using robust methods that account for phylogenetic uncertainty, intraspecific variability of climatic requirements and different life-history evolution scenarios, we show that climatic niches of Androsace s.l. exhibit low phylogenetic signal and that they evolved relatively recently and punctually. Models of niche evolution fitted onto phylogenies show that the cushion life form has been a key innovation providing the opportunity to occupy extremely cold environments, thus contributing to rapid climatic niche diversification in the genus Androsace s.l. We then propose a plausible scenario for the adaptation of plants to alpine habitats.

Borrelia-like spirochetes recovered from ticks and small mammals collected in the Atlantic Forest Reserve, Cotia county, State of São Paulo, Brazil

Forty-four marsupials, 77 rodents and 161 ticks were captured in an Atlantic Forest Reserve in Cotia county, State of São Paulo, where human cases of Lyme disease (LD) simile were reported. Twenty-one borrelia-like spirochete isolates were recovered from the mammals' blood and rodent livers or spleens, and triturated ticks inoculated into BSK II medium. Our results suggest that the reservoirs and ticks collected may harbor borrelia-like spirochetes, some of which have an antigenic similarity with the unknown causative agent of LD simile in Brazil, and/or with North American Borrelia burgdorferi s.s.

Prevalence of human papillomavirus types in women with pre-neoplastic and neoplastic cervical lesions in the Federal District of Brazil

As a contribution to the public health authorities in planning prophylactic and therapeutic vaccine strategies, we describe the prevalence of human papillomavirus (HPV) types in women presenting abnormal cytological results in Pap smear screening tests in the Federal District, Central Brazil. We studied 129 cervical scraping samples from women whose cytological tests showed either pre-neoplastic or neoplastic lesions. Amplification of HPV DNA was performed by polymerase chain reaction using consensus primers MY09 and MY11 followed by identification of isolates by restriction fragment length polymorphism. We detected HPV DNA in 62% of the samples, including HPV-16 in 43.8%, HPV-58 in 12.5%, HPV-31 in 10%, HPV-53 in 6.3%, each of HPV-18 and HPV-33 in 3.8% of the isolates. Other types (HPV-35, -52, -66, -CP8304, -6, -11, and -CP8061) were less frequent (= or < 2.5% each). The prevalence of HPV-58 was relatively higher in this population than in data in South America, but similar to results obtained in other studies in Latin America, Europe, and Eastern Asia. Case-control studies need to be carried out to establish the association between the prevalence of HPV types specially the less frequent high-risk types and cervical cancer.

Cutting edge: an essential role for Notch-1 in the development of both thymus-independent and -dependent T cells in the gut.

Whereas most T cells arise in the thymus, a distinct lineage of extrathymically derived T cells is present in the gut mucosa. The developmental origin of extrathymic T cells is poorly understood. We show here that Notch-1, a transmembrane receptor involved in T cell fate specification of bipotential T/B precursors in the thymus, is absolutely required for the development of extrathymic (as well as thymus-derived) mature T cells in the intestinal epithelium. In the absence of Notch-1, CD117(+) T cell precursors are relatively more abundant in the gut than the thymus, whereas immature B cells accumulate in the thymus but not the gut. Collectively, these data demonstrate that Notch-1 is essential for both thymic and extrathymic T cell fate specification and further suggest that bipotential T/B precursors that do not receive a Notch-1 signal adopt a B cell fate in the thymus but become developmentally arrested in the gut.

Disagreement between ultrasound and magnetic resonance imaging in the identification of schistosomal periportal fibrosis

Abdominal ultrasound (US) has been widely used in the evaluation of patients with schistosomiasis mansoni. It represents an important indirect method of diagnosis and classification of the disease, and it has also been used as a tool in the evaluation of therapeutic response and regression of fibrosis. We describe the case of a man in whom US showed solid evidence of schistosomal periportal fibrosis and magnetic resonance imaging revealed that periportal signal alteration corresponded to adipose tissue which entered the liver togheter with the portal vein.

Effect of sphingosine and phorbol-12-myristate-13-acetate on the growth and dimethylsulfoxide-induced differentiation in the insect trypanosomatid Herpetomonas samuelpessoai

We investigated the effect of two modulators of protein kinase C, sphingosine and phorbol-12-myristate-13-acetate (PMA), on the growth and dimethylsulfoxide (DMSO)-induced differentiation in Herpetomonas samuelpessoai. Sphingosine did not stimulate the transformation of undifferentiated-promastigotes in differentiated-paramastigotes. PMA alone or in association with DMSO increased the number of paramastigotes in comparison to control cells. DMSO inhibited the parasite growth (35%) and several unusual morphological features resembling aberrant cell division were observed. Sphingosine did not significantly reduce the growth in contrast to PMA. Collectively, our results demonstrated that the reduction of the proliferation translates in an increase of the differentiation rate in the insect trypanosomatid H. samuelpessoai.

Access to diagnosis and treatment of Chagas disease/infection in endemic and non-endemic countries in the XXI century

In this article, Médicos Sin Fronteras (MSF) Spain faces the challenge of selecting, piecing together, and conveying in the clearest possible way, the main lessons learnt over the course of the last seven years in the world of medical care for Chagas disease. More than two thousand children under the age of 14 have been treated; the majority of whom come from rural Latin American areas with difficult access. It is based on these lessons learnt, through mistakes and successes, that MSF advocates that medical care for patients with Chagas disease be a reality, in a manner which is inclusive (not exclusive), integrated (with medical, psychological, social, and educational components), and in which the patient is actively followed. This must be a multi-disease approach with permanent quality controls in place based on primary health care (PHC). Rapid diagnostic tests and new medications should be available, as well as therapeutic plans and patient management (including side effects) with standardised flows for medical care for patients within PHC in relation to secondary and tertiary level, inclusive of epidemiological surveillance systems.

The role of bile acid retention and a common polymorphism in the ABCB11 gene as host factors affecting antiviral treatment response in chronic hepatitis C.

Summary.  The outcome of hepatitis C virus (HCV) infection and the likelihood of a sustained virological response (SVR) to antiviral therapy depends on both viral and host characteristics. In vitro studies demonstrated that bile acids (BA) interfere with antiviral interferon effects. We investigate the influence of plasma BA concentrations and an ABCB11 polymorphism associated with lower transporter expression on viral load and SVR. Four hundred and fifty-one Caucasian HCV-patients treated with PEG-interferon and ribavirin were included in the study. ABCB11 1331T>C was genotyped, and plasma BA levels were determined. The 1331C allele was slightly overrepresented in HCV-patients compared to controls. In HCV-patients, a significant difference between patients achieving SVR vs non-SVR was observed for HCV-2/3 (5 vs 9 μm; P = 0.0001), while median BA levels in HCV-1 were marginally elevated. Normal BA levels <8 μm were significantly associated with SVR (58.3%vs 36.3%; OR 2.48; P = 0.0001). This difference was significant for HCV-2/3 (90.7%vs 67.6%; P = 0.002) but marginal in HCV-1 (38.7%vs 27.8%; P = 0.058). SVR rates were equivalent between ABCB11 genotypes for HCV-1, but increased for HCV-2/3 (TT 100%vs CC 78%; OR 2.01; P = 0.043). IL28B genotype had no influence on these associations. No correlation between BA levels and HCV RNA was detected for any HCV genotype. The higher allelic frequency of ABCB11 1331C in HCV-patients compared to controls may indirectly link increased BA to HCV chronicity. Our data support a role for BA as host factor affecting therapy response in HCV-2/3 patients, whereas a weaker association was found for HCV-1.

Blood lipid and lipoprotein concentrations and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition

Objective To examine the association between serum concentrations of total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol, triglycerides, apolipoprotein A-I (apoA), apolipoprotein B and the incidence of colorectal cancer (CRC). Design Nested case–control study. Setting The study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort of more than 520 000 participants from 10 western European countries. Participants 1238 cases of incident CRC, which developed after enrolment into the cohort, were matched with 1238 controls for age, sex, centre, follow-up time, time of blood collection and fasting status. Main outcome measures Serum concentrations were quantitatively determined by colorimetric and turbidimetric methods. Dietary and lifestyle data were obtained from questionnaires. Conditional logistic regression models were used to estimate incidence rate ratios (RRs) and 95% CIs which were adjusted for height, weight, smoking habits, physical activity, education, consumption of fruit, vegetables, meat, fish, alcohol, fibre and energy. Results After adjustments, the concentrations of HDL and apoA were inversely associated with the risk of colon cancer (RR for 1 SD increase of 16.6 mg/dl in HDL and 32.0 mg/dl in apoA of 0.78 (95% CI 0.68 to 0.89) and 0.82 (95% CI 0.72 to 0.94), respectively). No association was observed with the risk of rectal cancer. Additional adjustment for biomarkers of systemic inflammation, insulin resistance and oxidative stress or exclusion of the first 2 years of follow-up did not influence the association between HDL and risk of colon cancer. Conclusions These findings show that high concentrations of serum HDL are associated with a decreased risk of colon cancer. The mechanism behind this association needs further elucidation.

Immunological imbalance between IFN-³ and IL-10 levels in the sera of patients with the cardiac form of Chagas disease

The immune response is crucial for protection against disease; however, immunological imbalances can lead to heart and digestive tract lesions in chagasic patients. Several studies have evaluated the cellular and humoral immune responses in chagasic patients in an attempt to correlate immunological findings with clinical forms of Chagas disease. Moreover, immunoglobulins and cytokines are important for parasitic control and are involved in lesion genesis. Here, cytokine and IgG isotype production were studied, using total epimastigote antigen on sera of chagasic patients with indeterminate (IND, n = 27) and cardiac (CARD, n = 16) forms of the disease. Samples from normal, uninfected individuals (NI, n = 30) were use as controls. The results showed that sera from both IND and CARD patients contained higher levels of Trypanosoma cruzi-specific IgG1 (IgG1) antibodies than sera from NI. No difference in IgG2 production levels was observed between NI, IND and CARD patients, nor was a difference in IL-10 and IFN-³ production detected in the sera of IND, CARD and NI patients. However, IND patients displayed a positive correlation between IL-10 and IFN-³ levels in serum, while CARD patients showed no such correlation, indicating an uncontrolled inflammatory response in CARD patients. These findings support the hypothesis that a lack of efficient regulation between IFN-³ and IL-10 productions in CARD patients may lead to cardiac immunopathology.

The interaction between Histoplasma capsulatum cell wall carbohydrates and host components: relevance in the immunomodulatory role of histoplasmosis

Histoplasma capsulatum is an intracellular fungal pathogen that causes respiratory and systemic disease by proliferating within phagocytic cells. The binding of H. capsulatum to phagocytes may be mediated by the pathogen's cell wall carbohydrates, glucans, which consist of glucose homo and hetero-polymers and whose glycosydic linkage types differ between the yeast and mycelial phases. The ±-1,3-glucan is considered relevant for H. capsulatum virulence, whereas the ²-1,3-glucan is antigenic and participates in the modulation of the host immune response. H. capsulatum cell wall components with lectin-like activity seem to interact with the host cell surface, while host membrane lectin-like receptors can recognize a particular fungal carbohydrate ligand. This review emphasizes the relevance of the main H. capsulatum and host carbohydrate-driven interactions that allow for binding and internalization of the fungal cell into phagocytes and its subsequent avoidance of intracellular elimination.

Comparison of multislice computerized tomography angiography and digital subtraction angiography in the postoperative evaluation of patients with clipped aneurysms.

OBJECT: In this study the accuracy of multislice computerized tomography (MSCT) angiography in the postoperative examination of clip-occluded intracranial aneurysms was compared with that of intraarterial digital subtraction (DS) angiography METHODS: Forty-nine consecutive patients with 60 clipped aneurysms (41 of which had ruptured) were studied with the aid of postoperative MSCT and DS angiography. Both types of radiological studies were reviewed independently by two observers to assess the quality of the images, the artifacts left by the clips, the completeness of aneurysm occlusion, the patency of the parent vessel, and the duration and cost of the examination. The quality of MSCT angiography was good in 42 patients (86%). Poor-quality MSCT angiograms (14%) were a result of the late acquisition of images in three patients and the presence of clip or motion artifacts in four. Occlusion of the aneurysm on good-quality MSCT angiograms was confirmed in all but two patients in whom a small (2-mm) remnant was confirmed on DS angiograms. In one patient, occlusion of a parent vessel was seen on DS angiograms but missed on MSCT angiograms. The sensitivity and specificity for detecting neck remnants on MSCT angiography were both 100%, and the sensitivity and specificity for evaluating vessel patency were 80 and 100%, respectively (95% confidence interval 29.2-100%). Interobserver agreements were 0.765 and 0.86, respectively. The mean duration of the examination was 13 minutes for MSCT angiography and 75 minutes for DS angiography (p < 0.05). Multislice CT angiography was highly cost effective (p < 0.01). CONCLUSIONS: Current-generation MSCT angiography is an accurate noninvasive tool used for assessment of clipped aneurysms in the anterior circulation. Its high sensitivity and low cost warrant its use for postoperative routine control examinations following clip placement on an aneurysm. Digital subtraction angiography must be performed if the interpretation of MSCT angiograms is doubtful or if the aneurysm is located in the posterior circulation.

Cellular and genetic mechanisms involved in the generation of protective and pathogenic immune responses in human Chagas disease

Perhaps one of the most intriguing aspects of human Chagas disease is the complex network of events that underlie the generation of protective versus pathogenic immune responses during the chronic phase of the disease. While most individuals do not develop patent disease, a large percentage may develop severe forms that eventually lead to death. Although many efforts have been devoted to deciphering these mechanisms, there is still much to be learned before we can fully understand the pathogenesis of Chagas disease. It is clear that the host's immune response is decisive in this process. While characteristics of the parasite influence the immune response, it is becoming evident that the host genetic background plays a fundamental role in the establishment of pathogenic versus protective responses. The involvement of three complex organisms, host, parasite and vector, is certainly one of the key aspects that calls for multidisciplinary approaches towards the understanding of Chagas disease. We believe that now, one hundred years after the discovery of Chagas disease, it is imperative to continue with highly interactive research in order to elucidate the immune response associated with disease evolution, which will be essential in designing prophylactic or therapeutic interventions.

Study of sand fly fauna in an endemic area of American cutaneous leishmaniasis and canine visceral leishmaniasis in the municipality of Espírito Santo do Pinhal, São Paulo, Brazil

Canine American visceral leishmaniasis and American cutaneous leishmaniasis (ACL) cases have been recorded in Espírito Santo do Pinhal. The aim of this study was to gather knowledge of the sand fly community and its population ecology within the municipality. Captures were made weekly over a period of 15 months in the urban, periurban and rural areas of the municipality, using automatic light traps. A total of 5,562 sand flies were collected, comprising 17 species. The most abundant species were Nyssomyia whitmani and Pintomyia pessoai in the rural area, Lutzomyia longipalpis and Ny. whitmani in the periurban area and Lu. longipalpis in the urban area. The highest species richness and greatest index species diversity were found in the rural area. The similarity index showed that urban and periurban areas were most alike. Lu. longipalpis was found in great numbers during both dry and humid periods. The presence of dogs infected with Leishmania infantum chagasi in the urban area indicates a high risk for the establishment of the disease in the region. A high abundance of Ny. whitmani and Pi. pessoai in the rural and periurban areas indicates the possibility of new cases of ACL occurring in and spreading to the periurban area of Espírito Santo do Pinhal.