Cross-resistance of Leishmania infantum isolates to nitric oxide from patients refractory to antimony treatment, and greater tolerance to antileishmanial responses by macrophages.

Visceral leishmaniasis is a life-threatening disease characterized by intense parasitism of the spleen, liver, and bone marrow. Antimonials have served as front-line antileishmanial therapeutics for decades, but the increasing failure rates under antimonial treatment have challenged the continued use of these drugs. Pentavalent antimonials are known to reinforce the killing mechanisms of macrophages, although the associated mechanism remains unclear.

Fatal attack on black-tufted-ear marmosets (Callithrix penicillata) by a Boa constrictor: a simultaneous assault on two juvenile monkeys.

Here we report the first witnessed attack on a marmoset by a constrictor snake. The incident occurred mid-morning in a gallery forest within an altered landscape of the Cerrado region of central Brazil and refers to a fatal attack by a Boa constrictor on two juvenile black-tufted-ear marmosets (Callithrix penicillata) simultaneously. The snake captured both individuals at a height of ~ 4 m while a group of eight marmosets traveled through the subcanopy.

Single-Molecule Live-Cell Visualization of Pre-mRNA Splicing.

Microscopy protocols that allow live-cell imaging of molecules and subcellular components tagged with fluorescent conjugates are indispensable in modern biological research. A breakthrough was recently introduced by the development of genetically encoded fluorescent tags that combined with fluorescence-based microscopic approaches of increasingly higher spatial and temporal resolution made it possible to detect single protein and nucleic acid molecules inside living cells. Here, we describe an approach to visualize single nascent pre-mRNA molecules and to measure in real time the dynamics of intron synthesis and excision.

SHUEE on the evaluation of upper limb in cerebral palsy.

Objective: To demonstrate the use of the tool for evaluation of spastic upper limb SHUEE (Shriners Hospital Upper Extremity Evaluation) in the evaluation of upper limb in cerebral palsy (CP) and its ability to detect changes after surgical treatment of identified deformities.

Methods: 19 patients with spastic hemiplegic CP had their upper limb evaluated by SHUEE. Five patients underwent surgical treatment of deformities detected and performed the test at one year postoperatively.

Newly recognized Mendelian disorders with rheumatic manifestations.

Purpose Of Review: We review newly discovered monogenic immune-dysregulatory disorders that were reported in Pubmed over the last year.

Recent Findings: Fourteen novel monogenic immune-dysregulatory disorders that present with innate and acquired/adaptive immune dysregulation and inflammatory clinical phenotypes were identified. These include autosomal-dominant gain-of function mutations in viral innate immune sensors or their adaptors, TMEM173/STING IFIH1/MDA5 and DDX58/RIG-I that cause complex clinical syndromes distinct from IL-1-mediated diseases and present with a chronic type I interferon (IFN Type I) signature in peripheral blood.

In vitro infection by Leishmania infantum in the peripheral blood mononuclear cell-derived macrophages from crab-eating foxes (Cerdocyon thous).

Wild canids are natural reservoirs of visceral leishmaniais (VL). In Brazil, only the crab-eating fox (Cerdocyon thous) is a natural reservoir of this zoonotic disease, but there is still a lack of understanding regarding the sylvatic transmission of the Leishmania infantum infection. This is the first study on the isolation, cultivation and infection with L.

Media internalization and conformity to traditional masculine norms in relation to body image concerns among men.

Previous studies have separately examined conformity to masculine norms and internalization of body ideals in the media in relation to the drive for muscularity (DM). This study was designed to examine these factors together in relation to DM, and further examine how they may differ in relation to drive for thinness (DT) and drive for leanness (DL). Participants were 284 Australian males between ages 18 and 42.

Single-Molecule Imaging of RNA Splicing in Live Cells.

Expression of genetic information in eukaryotes involves a series of interconnected processes that ultimately determine the quality and amount of proteins in the cell. Many individual steps in gene expression are kinetically coupled, but tools are lacking to determine how temporal relationships between chemical reactions contribute to the output of the final gene product. Here, we describe a strategy that permits direct measurements of intron dynamics in single pre-mRNA molecules in live cells.

Curvature sensing MARCKS-ED peptides bind to membranes in a stereo-independent manner.

Membrane curvature and lipid composition plays a critical role in interchanging of matter and energy in cells. Peptide curvature sensors are known to activate signaling pathways and promote molecular transport across cell membranes. Recently, the 25-mer MARCKS-ED peptide, which is derived from the effector domain of the myristoylated alanine-rich C kinase substrate protein, has been reported to selectively recognize highly curved membrane surfaces.

Molecular mechanisms in genetically defined autoinflammatory diseases: disorders of amplified danger signaling.

Patients with autoinflammatory diseases present with noninfectious fever flares and systemic and/or disease-specific organ inflammation. Their excessive proinflammatory cytokine and chemokine responses can be life threatening and lead to organ damage over time. Studying such patients has revealed genetic defects that have helped unravel key innate immune pathways, including excessive IL-1 signaling, constitutive NF-κB activation, and, more recently, chronic type I IFN signaling.

Health related quality of life measure in systemic pediatric rheumatic diseases and its translation to different languages: an international collaboration.

Background: Rheumatic diseases in children are associated with significant morbidity and poor health-related quality of life (HRQOL). There is no health-related quality of life (HRQOL) scale available specifically for children with less common rheumatic diseases. These diseases share several features with systemic lupus erythematosus (SLE) such as their chronic episodic nature, multi-systemic involvement, and the need for immunosuppressive medications.

Pyridoxamine is a substrate of the energy-coupling factor transporter HmpT.

Energy-coupling factor (ECF) transporters belong to a novel family of proteins that forms a subset within the ATP-binding cassette (ABC) transporter family. These proteins are responsible for the uptake of micronutrients in bacteria. ECF transporters are composed of four proteins: the A- and A'-components, the T-component and the S-component.

Clinical severity of visceral leishmaniasis is associated with changes in immunoglobulin g fc N-glycosylation.

Unlabelled: Visceral leishmaniasis (VL) has a high fatality rate if not treated; nevertheless, the majority of human infections with the causative agent, Leishmania infantum chagasi, are asymptomatic. Although VL patients often present with increased levels of serum immunoglobulins, the contribution of antibodies to resistance or progression to disease remains unknown. Effector and regulatory functions of antibodies rely on their interactions with type I and II Fc receptors, and these interactions are tuned by the patterns of antibody Fc N-glycosylation.

[Cardiopulmonary exercise testing and dyspnea in patients with chronic respiratory diseases].

Cardiopulmonary exercise testing (CPET) is the most comprehensive investigation for understanding the mechanisms responsible for dyspnea in patients with chronic respiratory disease. The two observations presented here illustrate how CPET can contribute to the management of patients with interstitial lung diseases. A 60-year-old woman had been followed for 20 years for non-progressive pulmonary sarcoidosis, untreated for many years.

Improved compliance with venous thromboembolism pharmacologic prophylaxis for patients with gynecologic malignancies hospitalized for nonsurgical indications did not reduce venous thromboembolism incidence.

Objective: National guidelines recommend prophylactic anticoagulation for all hospitalized patients with cancer to prevent hospital-acquired venous thromboembolism (VTE). However, adherence to these evidence-based recommended practice patterns remains low. We performed a quality improvement (QI) project to increase VTE pharmacologic prophylaxis rates among patients with gynecologic malignancies hospitalized for nonsurgical indications and evaluated the resulting effect on rates of development of VTE.

Targeting latent TGFβ release in muscular dystrophy.

Latent transforming growth factor-β (TGFβ) binding proteins (LTBPs) bind to inactive TGFβ in the extracellular matrix. In mice, muscular dystrophy symptoms are intensified by a genetic polymorphism that changes the hinge region of LTBP, leading to increased proteolytic susceptibility and TGFβ release. We have found that the hinge region of human LTBP4 was also readily proteolysed and that proteolysis could be blocked by an antibody to the hinge region.

Interleukin 17A acts synergistically with interferon γ to promote protection against Leishmania infantum infection.

Interleukin 17 (IL-17) is an inflammatory cytokine that plays a protective role against intracellular parasites. The role of IL-17 during Leishmania infection remains controversial and poorly defined. We evaluated whether IL-17 participates in the host immune response to Leishmania infantum.

Leprosy in children under fifteen years in Brazil, 2011.

The aim of this study is to describe the occurrence of Hansen's disease in children under 15 years of age and to analyse the burden of disease in the same population in Brazil in 2011. This is a descriptive epidemiological study on the positive cases of Hansen's disease in minors below 15 years of age notified in Brazil. Data was collected from the Information System on Disease Notification for Hansen's disease cases, and the Brazilian Institute of Geographic Statistics for population data.

p-Akt and its relationship with clinicopathological features and survival in oral squamous cell carcinoma: an immunohistochemical study.

Background: The aim of this study was to evaluate, through immunohistochemical reaction in samples of oral squamous cell carcinoma, the correlation between the expression status of protein kinase B (p-Akt) and patient survival as well as histological grade and some clinicopathological features.

Methods: Samples were collected from 46 patients with oral squamous cell carcinoma. The immunohistochemical expression of p-Akt was analysed, as were clinicopathological features including the use of tobacco, tumour stage, size and infiltration of metastatic lymph nodes.

An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome.

Inflammasomes are innate immune sensors that respond to pathogen- and damage-associated signals with caspase-1 activation, interleukin (IL)-1β and IL-18 secretion, and macrophage pyroptosis. The discovery that dominant gain-of-function mutations in NLRP3 cause the cryopyrin-associated periodic syndromes (CAPS) and trigger spontaneous inflammasome activation and IL-1β oversecretion led to successful treatment with IL-1-blocking agents. Herein we report a de novo missense mutation (c.

Biophysical investigations with MARCKS-ED: dissecting the molecular mechanism of its curvature sensing behaviors.

Curved membranes are a common and important attribute in cells. Protein and peptide curvature sensors are known to activate signaling pathways, initiate vesicle budding, trigger membrane fusion, and facilitate molecular transport across cell membranes. Nonetheless, there is little understanding how these proteins and peptides achieve preferential binding of different membrane curvatures.

Differentiation of Salmonella strains from the SARA, SARB and SARC reference collections by using three genes PCR-RFLP and the 2100 Agilent Bioanalyzer.

Rapid molecular typing methods are important tools in surveillance and outbreak investigations of human Salmonella infections. Here we described the development of a three-genes PCR-RFLP typing method for the differentiation of Salmonella species, subspecies and serovars using the Agilent 2100 Bioanalyzer. The fliC, gnd, and mutS genes were PCR-amplified in 160 Salmonella strains representing the two Salmonella species, six subspecies, and 41 different serovars of S.

New microbiological assay for determination of caspofungin in the presence of its degradation products and its measurement uncertainty.

Caspofungin is an echinocandin antifungal used in the treatment of invasive fungal infections. Several methods have been reported for the quantitative analysis of echinocandins; however, there is no microbiological assay for determination of caspofungin potency in the presence of its degradation products. This study aimed to develop and validate a microbiological method for quantitative analysis of caspofungin in lyophilized powder, evaluate the stability, and determinate the degradation kinetics of the drug when the finished product is submitted to heat stress.

Pathways to economic opportunity: an overview of innovative career pathway collaborations for Latinos into frontline health care occupations.

Extraordinary Latino population growth has created demand for bilingual and culturally competent frontline health care providers to address the "culture gap" in health care delivery meeting the linguistic and cultural needs of Latino communities (Cohen, Gabriel, & Terrell, 2002). This article reviews career pathway programs that serve as workforce development models for Latinos seeking opportunity within frontline health care occupations, a sector with high-projected employment growth in the coming decade. The programs examined reflect innovative approaches that target Latino participants for entrance into some of these occupations including registered nurses (RNs), licensed practical nurses (LPNs), human service assistants, and bachelor's level social worker positions that offer low-wage Latinos the possibility of entering a profession where they may earn a livable wage.