HLA-DR in Cytotoxic T lymphocytes predicts breast cancer patients' response to neoadjuvant chemotherapy

Prediction of breast cancer response to Neoadjuvant Chemotherapy (NACT) is an urgent need to promptly direct non-responder patients to alternative therapies. Infiltrating T lymphocytes, namely cytotoxic T lymphocytes (CTLs) have been appointed as predictors of response. However, cancer cells have the ability to dampen CTLs' activity and thus, the prognostic value of the CTLs, per se, is debatable. Here, we disclose that more than the occurrence of CTLs, it is their activation state, revealed by HLA-DR expression, that can accurately predict response to NACT. Flow cytometry analysis of breast cancer biopsies showed that the frequency of CTLs and other lymphocytes were similar regardless disease stage and between NACT responders and non-responders. However, only breast cancer patients without axillary lymph node metastasis and NACT responders have HLA-DRhi CTLs. Interestingly, HLA-DR levels in tumor CTLs is correlated with HLA-DR levels in systemic CTLs. These HLA-DR+ CTLs produce IFN-γ and Granzyme B, enlightening their effector and probable anti-tumor activity profile. Moreover, the level of HLA-DR in CTLs is negatively correlated with the level of HLA-DR in T regulatory lymphocytes and with immunosuppressive and pro-tumor molecules in the tumor microenvironment. Hence, HLA-DR levels in CTLs is a highly sensitive and specific potential predictive factor of NACT-response, which can be assessed in blood to guide therapeutic decisions.Fundacao para a Ciencia e Tecnologia: PD/BD/114023/2015; PTDC/BBB-BMD/4497/2014. Liga Portuguesa Contra o Cancroinfo:eu-repo/semantics/publishedVersio

Correlates of measured prehypertension and hypertension in Latina women living along the US-Mexico border, 2007-2009.

IntroductionAlthough Latinos have lower hypertension rates than non-Latino whites and African Americans, they have a higher prevalence of undiagnosed and uncontrolled hypertension. Research on predictors of hypertension has mostly focused on intrapersonal factors with no studies assessing the combined influence of intrapersonal, interpersonal, and environmental factors. The purpose of this study was to assess a broad range of correlates including intrapersonal, interpersonal, and environmental factors on measured blood pressure category (nonhypertensive, prehypertensive, and hypertensive) in a sample of Latina women residing in San Diego, California.MethodsThis cross-sectional study used baseline data from the San Diego Prevention Research Center's Familias Sanas y Activas program, a promotora-led physical activity intervention. The sample was 331 Latinas who self-selected into this program. Backward conditional logistic regression analysis was conducted to determine the strongest correlates of measured blood pressure category.ResultsLogistic regression analysis suggested that the strongest correlates of prehypertension were soda consumption (odds ratio [OR] = 1.34, [1.00-1.80], P ≤ .05) and age (OR = 1.03, [1.00-1.05], P ≤ .05). The strongest correlates of hypertension were soda consumption (OR = 1.92, [1.20-3.07], P ≤ .01), age (OR = 1.09, [1.05-1.13], P ≤ .001), and measured body mass index (OR = 1.13, [1.05-1.22], P ≤ .001). All analyses controlled for age and education. No interpersonal or environmental correlates were significantly associated with blood pressure category.ConclusionFuture research should aim to further understand the role of soda consumption on risk for hypertension in this population. Furthermore, interventions aimed at preventing hypertension may want to focus on intrapersonal level factors

Descriptions of unknown sexes, new geographical records, and host associations for two South American species of Megachile (Hymenoptera: Megachilidae)

The cosmopolitan genus Megachile include many species described on the basis of only one sex. Sexual dimorphism is very pronounced in these taxa and therefore sexes are often difficult to associate, thus making species identification nearly impossible. The females of M. (Chrysosarus) concava and M. (Pseudocentron) variplantis are described and illustrated. Additional geographical and host records are provided as well as comments on their diagnostic features and identification based on existing keys.Fil: Durante, Silvana P.. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Entomología; ArgentinaFil: Torretta, Juan Pablo. Universidad de Buenos Aires. Facultad de Agronomia. Cátedra de Botanica General; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Colombo, María Guadalupe. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Entomología; Argentin

How many diseases is triple negative breast cancer; the protagonism of the immune microenvironment

Triple negative breast cancer (TNBC) is a type of breast cancer (BC) that does not express the oestrogen and the progesterone receptors and the human epidermal growth factor receptor type 2 (HER2). Since there are no positive markers to reliably classify TNBC, these tumours are not yet treated with targeted therapies. Perhaps for this reason they are the most aggressive form of breast carcinomas. However, the clinical observation that these patients do not carry a uniformly dismal prognosis, coupled with data coming from pathology and epidemiology, suggests that this negative definition is not capturing a single clinical entity, but several. We critically evaluate this evidence in this paper, reviewing clinical and epidemiological data and new studies that aim to subclassify TNBC. Moreover, evidence on the role of tumour infiltrating lymphocytes (TILs) on TNBC progression, response to chemotherapy and patient outcome have been published. The heterogeneity, observed even at TILs level, highlights the idea that TNBC is much more than a single disease with a unique treatment. The exploration of the immune environment present at the tumour site could indeed help in answering the question 'How many diseases is TNBC' and will help to define prognosis and eventually develop new therapies, by stimulating the immune effector cells or by inhibiting immunological repressor molecules. In this review, we focus on the prospect of the patient's diverse immune signatures within the tumour as potential biomarkers and how they could be modulated to fight the disease.publishersversionpublishe

Analysis of polymeric phenolics in red wines using different techniques combined with gel permeation chromatography fractionation

A multiple-step analytical method was developed to improve the analysis of polymeric phenolics in red wines. With a common initial step based on the fractionation of wine phenolics by gel permeation chromatography (GPC), different analytical techniques were used: high-performance liquid chromatography-diode array detection (HPLC-DAD), HPLC-mass spectrometry (MS), capillary zone electrophoresis (CZE) and spectrophotometry. This method proved to be valid for analyzing different families of phenolic compounds, such as monomeric phenolics and their derivatives, polymeric pigments and proanthocyanidins. The analytical characteristics of fractionation by GPC were studied and the method was fully validated, yielding satisfactory statistical results. GPC fractionation substantially improved the analysis of polymeric pigments by CZE, in terms of response, repeatability and reproducibility. It also represented an improvement in the traditional vanillin assay used for proanthocyanidin (PA) quantification. Astringent proanthocyanidins were also analyzed using a simple combined method that allowed these compounds, for which only general indexes were available, to be quantified. © 2005 Elsevier B.V. All rights reserved

Risk Factors for Soil-Transmitted Helminth Infections during the First 3 Years of Life in the Tropics; Findings from a Birth Cohort.

Background: Soil-transmitted helminths (STH) infect more than 2 billion humans worldwide, causing significant morbidity in children. There are few data on the epidemiology and risk factors for infection in pre-school children. To investigate risk factors for infection in early childhood, we analysed data prospectively collected in the ECUAVIDA birth cohort in Ecuador. Methods and Findings: Children were recruited at birth and followed up to 3 years of age with periodic collection of stool samples that were examined microscopically for STH parasites. Data on social, demographic, and environmental risk factors were collected from the mother at time of enrolment. Associations between exposures and detection of STH infections were analysed by multivariable logistic regression. Data were analysed from 1,697 children for whom a stool sample was obtained at 3 years. 42.3% had at least one STH infection in the first 3 years of life and the most common infections were caused by A. lumbricoides (33.2% of children) and T. trichiura (21.2%). Hookworm infection was detected in 0.9% of children. Risk of STH infection was associated with factors indicative of poverty in our study population such as Afro-Ecuadorian ethnicity and low maternal educational level. Maternal STH infections during pregnancy were strong risk factors for any childhood STH infection, infections with either A. lumbricoides or T. trichiura, and early age of first STH infection. Children of mothers with moderate to high infections intensities with A. lumbricoides were most at risk. Conclusions: Our data show high rates of infection with STH parasites during the first 3 years of life in an Ecuadorian birth cohort, an observation that was strongly associated with maternal STH infections during pregnancy. The targeted treatment of women of childbearing age, in particular before pregnancy, with anthelmintic drugs could offer a novel approach to the prevention of STH infections in pre-school children

Cadastro de pessoas

Esta nota técnica apresenta os problemas e propõe soluções técnicas para a implantação do processo de atualização dos dados cadastrais. A atualização dos dados cadastrais dos usuários da rede UNA-SUS é um processo desejável para a evolução da segurança, qualidade e a validade da informação administrada pela Secretaria Executiva do Sistema UNA-SUS (SE-UNA-SUS)

Increasing Pediatric Hearing Aid Use: Considerations for Clinical Practice

Purpose: Hearing aid use can be variable for young children, and inconsistent wear time can undermine spoken language development. This study explored the effectiveness of hearing aid data logging (DL) awareness and coaching sessions on increasing hours of hearing aid use. We also collected qualitative data on challenges participants experienced managing hearing aid use. Method: We used a single-subject design that included three conditions, during a 6-week period, in the same order for each participant. Condition A was baseline, Condition B was DL monitoring alone, and Condition C was remote coaching calls plus DL monitoring. Results: Hours of hearing aid use increased for each child from baseline to the end of the study, ranging from 1.19 to 4.4 hr. Mothers reported that the coaching calls were beneficial and helped them identify and problem-solve issues. Conclusions: Parents were able to increase hours of hearing aid use with DL awareness and coaching support. Tele-audiology offers an opportunity to provide parents with more frequent support that can be individualized based on their situation, challenges, and family needs

By-Catch Species in the Greenland Halibut Spanish (NAFO Divisions 3LM and 3NO): 1991-1994

The specific composition of by-catch was studied: 17 species, their presence calculated by depth strata, month and Division, and variations in monthly yield by division in the Spanish Greenland halibut fishery, developed in the NAFO regulated area for the period 1991-1994. Two groups of species were identified depending on the importance of their presence in catches: the more and less frequent species. The more frequent species were considered those with a value of above 5 kg/h annual yield, i.e. Skate, Roundnose grenadier and Roughhead grenadier, American plaice, Witch flounder and Redfish. Analyzing the data on a monthly basis, however, reveals the presence of higher values of yield than other species. Some species show a stational pattern, such as Grenadiers, Skate and American plaice, particularly in Division 3N. An other hand, other species have increased yields in recent years. In this fishery, the characteristic species of the demersal fisheries (Skate, American plaice) showed a wider bathymetric distribution than that considered typical in each case. The transfer of effort southwards (Divs.3NO) in recent years, mainly in the case of small vessels, has meant variation in the composition and relative abundance of by-catch in this fleet