Phase Ib study of poly-epitope peptide vaccination to thymidylate synthase (TSPP) and GOLFIG chemo-immunotherapy for treatment of metastatic colorectal cancer patients.

Thymidylate synthase (TS) is a tumor-associated enzyme critical for DNA replication and main 5'-fluorouracil (5'-FU) target. TSPP/VAC1 is a multi-arm trial phase-Ib trial program aimed to investigate the toxicity and biomodulatory activity of a poly-epitope-peptide vaccine to TS (TSPP) in cancer patients (pts). Here, we present the results of the TSPP/VAC1/arm C trial aimed to evaluate TSPP in combination with chemo-immunotherapy in pretreated metastatic colo-rectal cancer (mCRC) pts.

Pregnancy and lactation differentially modify the transcriptional regulation of steroidogenic enzymes through DNA methylation mechanisms in the hippocampus of aged rats.

In the present study, we examined the mRNA expression and DNA methylation state of steroidogenic enzymes in the hippocampus of young adult (90-days-old) and middle-aged (450-days-old) nulliparous rats, and middle-aged multiparous rats subjected to three pregnancies with and without lactation. Aging decreased the mRNA levels of steroidogenic-related genes, while pregnancy and lactation significantly reduced the effect of aging, maintaining high expression levels of cytochrome P450 side-chain cleavage (P450scc), steroid 5α-reductase-1 (5αR-1), cytochrome P450arom (P450arom) and aldosterone synthase (P450(11β)-2). In addition, pregnancy and lactation diminished the methylation state of the 5αR-1 promoter and increased the transcription of brain-derived neurotrophic factor, synaptophysin and spinophilin.

First insight into the molecular epidemiology of Mycobacterium tuberculosis in Santa Catarina, southern Brazil.

Molecular epidemiology of Mycobacterium tuberculosis is useful for understanding disease transmission dynamics, and to establish strategic measures for TB control and prevention. The aim of this study was to analyze clinical, epidemiological and molecular characteristics of MTBC clinical isolates from Santa Catarina state, southern Brazil. During one-year period, 406 clinical isolates of MTBC were collected from Central Laboratory of Public Health and typed by spoligotyping.

Association of human papillomavirus and Chlamydia trachomatis with intraepithelial alterations in cervix samples.

The influence of different infectious agents and their association with human papillomavirus (HPV) in cervical carcinogenesis have not been completely elucidated. This study describes the association between cytological changes in cervical epithelium and the detection of the most relevant aetiological agents of sexually transmitted diseases. Samples collected from 169 patients were evaluated by conventional cytology followed by molecular analysis to detect HPV DNA, Chlamydia trachomatis, herpes simplex virus 1 and 2,Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis, andTreponema pallidum, besides genotyping for most common high-risk HPV.

Single Nucleotide Polymorphisms in IL17A and IL6 Are Associated with Decreased Risk for Pulmonary Tuberculosis in Southern Brazilian Population.

In Mycobacterium tuberculosis (MTB) infection, the complex interaction of host immune system and the mycobacteria is associated with levels of cytokines production that play a major role in determining the outcome of the disease. Several single-nucleotide polymorphisms (SNPs) in cytokine genes have been associated with tuberculosis (TB) outcome. The aim of this study was to evaluate the association between previously reported SNPs IL2-330 T>G (rs2069762); IL4-590 C>T (rs2243250); IL6-174 G>C (rs1800795); IL10-592 A>C (rs1800872); IL10-1082 G>A (rs1800896); IL17A -692 C>T (rs8193036); IL17A -197 G>A (rs2275913); TNF -238 G>A (rs361525); TNF -308 G>A (rs1800629) and IFNG +874 T>A (rs2430561) and pulmonary TB (PTB) susceptibility.

Two Novel Psychomotor Tasks in Idiopathic Normal Pressure Hydrocephalus.

Objective: Idiopathic normal pressure hydrocephalus (INPH) is a neurological disorder presenting with gait, cognitive, and bladder symptoms in the context of ventricular enlargement. Although gait is the primary indicator for treatment candidacy and outcome, additional monitoring tools are needed. Line Tracing Test (LTT) and Serial Dotting Test (SDT), two psychomotor tasks, have been introduced as potential outcome measures but have not been widely studied.

Revisiting adult neurogenesis and the role of erythropoietin for neuronal and oligodendroglial differentiation in the hippocampus.

Recombinant human erythropoietin (EPO) improves cognitive performance in neuropsychiatric diseases ranging from schizophrenia and multiple sclerosis to major depression and bipolar disease. This consistent EPO effect on cognition is independent of its role in hematopoiesis. The cellular mechanisms of action in brain, however, have remained unclear.

Feasibility and effectiveness of a combined individual and psychoeducational group intervention in psychiatric residential facilities: A controlled, non-randomized study.

This controlled, non-randomized study explored the feasibility of introducing a Combined Individual and Group Intervention (CIGI) for users with mental disorders in residential facilities, and tested whether users who received the CIGI had better functioning than users who received the Treatment-As-Usual (TAU), at two-year follow up. In the CIGI, a structured cognitivebehavioral approach called VADO (in English, Skills Assessment and Definition of Goals) was used to set specific goals with each user, while Falloon's psychoeducational treatment was applied with the users as a group. Thirty-one professionals attended a training course in CIGI, open to users' voluntary participation, and applied it for two years with all users living in 8 residential facilities of the Mental Health Department of Modena, Italy.

The SNP rs9677 of VPAC1 gene is associated with glycolipid control and heart function in female patients with type 2 diabetes: A follow-up study.

Background And Aims: In a previous study, the single-nucleotide polymorphism (SNP) rs9677, mapped in the 3'-UTR of vasoactive intestinal peptide receptor 1 (VPAC1) gene, was found to be associated with type 2 diabetes (T2D) in Caucasian women. Moreover, the CC genotype correlated with a worse glycolipid profile. The objectives of this study were to confirm this correlation and assess the prevalence of coronary artery disease (CAD) in the previously investigated diabetic women after a follow-up of 4.

Disordered eating behavior and mental health correlates among treatment seeking obese women.

Background And Objectives: Previous research has suggest that obesity is associated with increased risk for psychopathological disorders, however, little is known about which obese patients are most vulnerable to psychopathological disorders. We therefore investigated 126 treatment-seeking obese women to describe eating disorder pathology and mental health correlates, and to identify disordered eating behaviors that may place obese at increased risk for psychopathological disorders.

Materials And Methods: The Structured Clinical Interview for DSM-IV (SCID) was used to identify Eating Disorders (ED).

Multidrug-Resistant Mycobacterium tuberculosis of the Latin American Mediterranean Lineage, Wrongly Identified as Mycobacterium pinnipedii (Spoligotype International Type 863 [SIT863]), Causing Active Tuberculosis in South Brazil.

We recently detected the spoligotype patterns of strains of Mycobacterium pinnipedii, a species of the Mycobacterium tuberculosis complex, in sputum samples from nine cases with pulmonary tuberculosis residing in Porto Alegre, South Brazil. Because this species is rarely encountered in humans, we further characterized these nine isolates by additional genotyping techniques, including 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing, verification of the loci TbD1, RD9, pks15/1, RD(Rio), and fbpC, the insertion of IS6110 at a site specific to the M. tuberculosis Latin American Mediterranean (LAM) lineage, and whole-genome sequencing.

A Modular, DNA-Based Beacon for Single-Step Fluorescence Detection of Antibodies and Other Proteins.

A versatile platform for the one-step fluorescence detection of both monovalent and multivalent proteins has been developed. This system is based on a conformation-switching stem-loop DNA scaffold that presents a small-molecule, polypeptide, or nucleic-acid recognition element on each of its two stem strands. The steric strain associated with the binding of one (multivalent) or two (monovalent) target molecules to these elements opens the stem, enhancing the emission of an attached fluorophore/quencher pair.

Hepatitis B Virus Genotype D Isolates Circulating in Chapecó, Southern Brazil, Originate from Italy.

Hepatitis B virus genotype A1 (HBV/A1), of African origin, is the most prevalent genotype in Brazil, while HBV/F predominates in the other South American countries. However, HBV/D is the most common in the three states of southern Brazil, where 'islands' of elevated prevalence, as Chapecó and other cities, have been described. In this study, 202 HBV chronic carriers attending in 2013 the viral hepatitis ambulatory of Chapecó, were investigated.

Acute intermittent porphyria in Argentina: an update.

Porphyrias are a group of metabolic diseases that arise from deficiencies in the heme biosynthetic pathway. A partial deficiency in hydroxymethylbilane synthase (HMBS) produces a hepatic disorder named Acute Intermittent Porphyria (AIP); the acute porphyria is more frequent in Argentina. In this paper we review the results obtained for 101 Argentinean AIP families and 6 AIP families from foreign neighbour countries studied at molecular level at Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP).

Impact of INICC Multidimensional Hand Hygiene Approach in ICUs in Four Cities in Argentina.

We evaluated the impact of the International Nosocomial Infection Control Consortium multidimensional approach to hand hygiene in 11 intensive care units in 4 cities in Argentina and analyzed predictors of poor hand hygiene compliance. We had a baseline period and a follow-up period. We observed 21 100 hand hygiene opportunities.

Phase I trial of thymidylate synthase poly-epitope peptide (TSPP) vaccine in advanced cancer patients.

Thymidylate synthase (TS) poly-epitope peptide (TSPP) is a 27-mer peptide vaccine containing the amino acidic sequences of three epitopes with HLA-A2.1-binding motifs of TS, an enzyme overexpressed in cancer cells, which plays a crucial role in DNA repair and replication. Based on the results of preclinical studies, we designed a phase Ib trial (TSPP/VAC1) to investigate, in a dose escalation setting, the safety and the biological activity of TSPP vaccination alone (arm A) or in combination with GM-CSF and IL-2 (arm B) in cancer patients.

A real-time PCR signature to discriminate between tuberculosis and other pulmonary diseases.

The goal of this study was to identify a host gene signature that can distinguish tuberculosis (TB) from other pulmonary diseases (OPD). We conducted real-time PCR on whole blood samples from patients in Brazil. TB and OPD patients (asthma and non-TB pneumonia) differentially expressed granzyme A (GZMA), guanylate binding protein 5 (GBP5) and Fc gamma receptor 1A (CD64).

Environmental enrichment attenuates the age-related decline in the mRNA expression of steroidogenic enzymes and reduces the methylation state of the steroid 5α-reductase type 1 gene in the rat hippocampus.

We analyzed the effects of aging and environmental enrichment on the mRNA expression and DNA methylation state of steroidogenic enzymes in the hippocampus. The effects of aging were evaluated by comparing young adult (90-day-old) and middle-aged (450-day-old) female Wistar rats. To elucidate the effects of environmental enrichment, a subgroup of middle-aged rats exposed to sensory and social stimulation for 105 days was compared to rats housed under standard laboratory conditions.

Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil.

Drug resistant tuberculosis continues to increase and new approaches for its treatment are necessary. The identification of M. tuberculosis clinical isolates presenting efflux as part of their resistant phenotype has a major impact in tuberculosis treatment.

Joint analysis of BICEP2/keck array and Planck Data.

We report the results of a joint analysis of data from BICEP2/Keck Array and Planck. BICEP2 and Keck Array have observed the same approximately 400  deg^{2} patch of sky centered on RA 0 h, Dec. -57.

Picosecond pulse amplification up to a peak power of 42 W by a quantum-dot tapered optical amplifier and a mode-locked laser emitting at 1.26 µm.

We experimentally study the generation and amplification of stable picosecond-short optical pulses by a master oscillator power-amplifier configuration consisting of a monolithic quantum-dot-based gain-guided tapered laser and amplifier emitting at 1.26 µm without pulse compression, external cavity, gain- or Q-switched operation. We report a peak power of 42 W and a figure-of-merit for second-order nonlinear imaging of 38.

Regulatory T-Cell Therapy in Transplantation and Severe Autoimmunity.

Current approaches to prevent or treat transplant rejection, graft-versus-host disease and severe autoimmunity rely on non-specific immunosuppressive drugs. Ongoing efforts aimed at harnessing regulatory T (Treg) cells hold promise for revolutionizing the current therapeutic options, reducing if not abandoning immune suppression in favor of immune tolerance. This paradigm shift carries the potential of dramatically enhancing efficacy, persistency, and specificity while reducing side effects.

Physicochemical properties of honey from Marche, Central Italy: classification of unifloral and multifloral honeys by multivariate analysis.

The purpose of this study was the physicochemical characterization and classification of Italian honey from Marche Region with a chemometric approach. A total of 135 honeys of different botanical origins [acacia (Robinia pseudoacacia L.), chestnut (Castanea sativa), coriander (Coriandrum sativum L.