Azole resistance in Candida albicans from animals: Highlights on efflux pump activity and gene overexpression

This study investigated potential mechanisms of azole resistance among Candida albicans from animals, including efflux pump activity, ergosterol content and gene expression. For this purpose, 30 azole‐resistant C. albicans strains from animals were tested for their antifungal susceptibility, according to document M27‐A3, efflux pump activity by rhodamine 6G test, ergosterol content and expression of the genes CDR1, CDR2, MDR1, ERG11 by RT‐qPCR. These strains were resistant to at least one azole derivative. Resistance to fluconazole and itraconazole was detected in 23 and 26 strains respectively. Rhodamine 6G tests showed increased activity of efflux pumps in the resistant strains, showing a possible resistance mechanism. There was no difference in ergosterol content between resistant and susceptible strains, even after fluconazole exposure. From 30 strains, 22 (73.3%) resistant animal strains overexpressed one or more genes. From this group, 40.9% (9/22) overexpressed CDR1, 18.2% (4/22) overexpressed CDR2, 59.1% (13/22) overexpressed MDR1 and 54.5% (12/22) overexpressed ERG11. Concerning gene expression, a positive correlation was observed only between CDR1 and CDR2. Thus, azole resistance in C. albicans strains from animals is a multifactorial process that involves increased efflux pump activity and the overexpression of different genes.     

Episodic memory in progressive supranuclear palsy: a neuropsychological and neuroimaging study

Neurological Sciences - Episodic memory impairment may occur in progressive supranuclear palsy (PSP). However, it remains uncertain whether this is due to executive dysfunction or to the...     

The inflammatory response triggered by Influenza virus: a two edged sword

Influenza A virus (IAV) is a relevant respiratory tract pathogen leading to a great number of deaths and hospitalizations worldwide. Secondary bacterial infections are a very common cause of IAV associated morbidity and mortality. The robust inflammatory response that follows infection is important for the control of virus proliferation but is also associated with lung damage, morbidity and death. The role of the different components of immune response underlying protection or disease during IAV infection is not completely elucidated. Overall, in the context of IAV infection, inflammation is a ‘double edge sword’ necessary to control infection but causing disease. Therefore, a growing number of studies suggest that immunomodulatory strategies may improve disease outcome without affecting the ability of the host to deal with infection. This review summarizes recent aspects of the inflammatory responses triggered by IAV that are preferentially involved in causing severe pulmonary disease and the anti-inflammatory strategies that have been suggested to treat influenza induced immunopathology.     

Amplification and diffusion of manual preference from lateralized practice in children

The effect of lateralized practice on manual preference was investigated in right-handed children. Probing tasks required reaching and grasping a pencil at distinct eccentricities in the right and left hemifields (simple), and its transportation and insertion into a small hole (complex). During practice, the children experienced manipulative tasks different from that used for probing, using the left hand only. Results showed that before practice the children used almost exclusively the right hand in the right hemifield and at the midline position. Following lateralized practice frequency of use of the left hand increased in most lateral positions. A more evident effect of lateralized practice on shift of manual preference was detected in the complex task. Implications for lateralization of behavior in a developmental timescale are discussed on the basis of the proposition of amplification and diffusion of manual preference from lateralized practice.     

Pathways in the association between sugar sweetened beverages and child asthma traits in the 2nd year of life: Findings from the BRISA cohort

Studies on the exposure of children to sugar-sweetened beverages (SSBs) at an early age may contribute to better understand the common causes and the temporal order of the relationships between obesity and asthma in early childhood. The objective of this study was to estimate the association between SSB and child asthma traits in the 2nd year of life, modeling direct and indirect pathways mediated by the highest BMI-z of the child and allergic inflammation. Data from the BRISA cohort, São Luís-MA, Brazil (n = 1140), were obtained from the baseline and from the follow-up performed at the 2nd year of life. The main explanatory variable was the calories from added sugars in SSBs as a percentage of the total daily energy intake. The outcome child asthma traits was a latent variable deduced from four indicators: medical diagnosis of asthma, wheezing, emergency visit due to intense wheezing, and medical diagnosis of rhinitis. A high percentage of daily calories from sugars added to SSBs was directly associated with higher values of child asthma traits (standardized coefficient (SC = 0.073; P = .030)). High levels of eosinophils were also directly associated with child asthma traits (SC = 0.118; P = .049). No mediation pathways were observed via greater BMI-z or eosinophil counts. Therefore, early exposure of children to SSB may contribute to increased risk of childhood asthma, preceding the link between sugar consumption and overweight/obesity, not yet evident in children in the first 2 years of life.     

Radiotherapy for early glottic cancer and salvage surgery after recurrence

Early glottic cancer can be effectively treated with radiation or surgery, but recurrence is a possibility when using any of the treatment modalities.AimTo assess the outcome of radiotherapy as initial treatment in the control of squamous cell carcinoma of vocal cord (T1) and the effectiveness of salvage surgery (endoscopic or open) after treatment failure.Materials and MethodsA retrospective study was based on the analysis of medical records from 43 patients with T1 squamous cell carcinoma of the glottis, radiotherapy as initial treatment and follow-up period of five years.ResultsThe rate of recurrence after radiotherapy was 30.2% of the cases, mean diagnosis interval was 29.5 months. As an option for salvage treatment, patients underwent open partial laryngectomy or endoscopic surgery with control rates of 77.7% and 25% respectively.ConclusionOur cases showed high rates of recurrence after radiotherapy and open partial laryngectomy was more effective for the salvage surgery.     

Characterization of a novel protein of Leptospira interrogans exhibiting plasminogen,vitronectin and complement binding properties

Leptospirosis is a severe zoonosis caused by pathogenic species of the genus Leptospira. This work focuses on a hypothetical protein of unknown function, encoded by the gene LIC13259, and predicted to be a surface protein, widely distributed among pathogenic leptospiral strain. The gene was amplified from L. interrogans serovar Copenhageni, strain Fiocruz L1-130, cloned and the protein expressed using Escherichia coli as a host system. Immunofluorescence assay showed that the protein is surface-exposed. The recombinant protein LIC13259 (rLIC13259) has the ability to interact with the extracellular matrix (ECM) laminin, in a dose-dependent manner but saturation was not reach. The rLIC13259 protein is a plasminogen (PLG)-binding protein, generating plasmin, in the presence of urokinase PLG-activator uPA. The recombinant protein is able to mediate the binding to human purified terminal complement route vitronectin, C7, C8 and C9, and to recruit and interact with these components from normal human serum (NHS). These interactions are dose-dependent on NHS increased concentration. The binding of rLIC13259 to C8 and vitronectin was slight and pronounced inhibited in the presence of increasing heparin concentration, respectively, suggesting that the interaction with vitronectin occurs via heparin domain. Most interesting, the interaction of rLIC13259 with C9 protein was capable of preventing C9 polymerization, suggesting that the membrane attack complex (MAC) formation was inhibited. Thus, we tentatively assign the coding sequence (CDS) LIC13259, previously annotated as unknown function, as a novel protein that may play an important role in the host’s invasion and immune evasion processes, contributing to the establishment of the leptospiral infection.