A case-control study of breast cancer and hormonal contraception in Costa Rica

By 1981, 11% of married women in Costa Rica ages 20-49 years had used depot-medroxyprogesterone acetate (DMPA) and 58% had used oral contraceptives (OCs). Since 1977, the Costa Rican Ministry of Health has maintained a nationwide cancer registry. These circumstances provided an opportunity for a population-based, case-control study of DMPA, OCs, and breast cancer in Costa Rica. Cases were 171 women ages 25-58 years with breast cancer diagnosed between 1982 and 1984; controls were 826 women randomly chosen during a nationwide household survey. Cases and controls were interviewed with the use of a standard questionnaire covering their reproductive and contraceptive histories. Logistic regression methods were used to adjust for confounding factors. While few cases or controls had ever used DMPA, DMPA users had an elevated relative risk (RR) estimate of breast cancer of 2.6 (95% confidence limits=1.4-4.7) compared with never users. However, no dose-response relationship was found; even the group of women who had used DMPA for less than 1 year had an elevated RR estimate (RR =2.3; 95% confidence limits=1.0-5.1). In contrast, OC users had no elevation in RR compared with never users (RR=1.2; 95% confidence limits= 0.8-1.8). The results of the DMPA analysis are inconclusive. Before decisions are made on whether to continue providing this effective contraceptive method, other ongoing studies will need to confirm of refute these findings.Universidad de Costa Rica, Instituto de investigaciones en SaludUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

EVALUACIÓN DE CINCO MÉTODOS PARA EL PRONÓSTICO Y EL ANÁLISIS DE TENDENCIA DE LA PRODUCCIÓN AGRÍCOLA DE PANAMÁ: : UNA HERRAMIENTA PARA LAS INSTITUCIONES Y EMPRESAS DEL SECTOR

As an orientation for agricultural science managers and practitioners to improve budget planning and projected financial statements, five forecasting methods and the trend of linear regression, over a time series, for 30 agricultural crops in Panama were analyzed. The five forecasting methods applied were Simple Moving Average (SMA), Weighted Moving Average (WMA), Exponential Smoothing (SE), Simple Linear Regression (SLR) and Polynomial Regression (PR) and the only trend method used was SLR. The data was run in Excel software. The results of the basic statistics (see table 1) showed that, of 30 items analyzed in 2019, in 16 cases production was below the average of the historical series. Table 2 shows that, of the 30 items predicted, 6 cases corresponded to the SMA, 14 cases to the WMA, 9 cases to the SE and in one case to the PR method.  In the trend analysis, for after 2019, of the 30 cases analyzed, 19 items showed a tendency to decrease, 9 showed an increase and two to were predicted to maintain constant production.  It is concluded that the forecasts to produce agricultural crops may vary from one method to another, depending also on addition to the data and time, a high coefficient of determination of the regression model, a result in positive real numbers and the lowest percentage error of absolute deviation.Como una orientación para que los administradores y profesionales de las ciencias agrícolas mejoren la planificación de presupuestos y estados financieros proyectados, se analizaron cinco métodos de pronósticos y la tendencia de la regresión lineal, en una serie de tiempo, para 30 cultivos agrícolas en Panamá. Los cinco métodos de pronósticos aplicados fueron el Promedio Móvil Simple (PMS), el Promedio Móvil Ponderado (PMP), la Suavización Exponencial (SE), la Regresión lineal simple (RLS) y la Regresión Polinómica (RP) y el único método de tendencia utilizado fue el RLS. Los datos se corrieron en el software Excel. Los resultados de las estadísticas básicas (ver tabla1) mostraron que, de 30 rubros analizados en el 2019, en 16 casos la producción estuvo por debajo del promedio de la serie histórica. En la tabla 2 se observa que, de los 30 rubros pronosticados, 6 casos correspondieron al PMS, 14 casos al PMP, 9 casos a la SE y en un caso al método de la RP.  En el análisis de tendencia, para después del año 2019, de los 30 casos analizados, 19 rubros mostraron tendencia al decrecimiento, 9 mostraron al incremento y dos a mantener la producción constante.  Se concluye que los pronósticos para la producción de cultivos agrícolas pueden variar de un método a otro, dependiendo además de la data y del tiempo, de un alto coeficiente de determinación del modelo de regresión, de un resultado en números reales positivos y del menor error porcentual de desviación absoluta

Neurofilament light chain level is a weak risk factor for the development of MS

Altres ajuts: T Jens Kuhle was supported by an ECTRIMS Research Fellowship Programme and by the Forschungsfonds of the University of Basel, Switzerland.To determine the prognostic value of selected biomarkers in clinically isolated syndromes (CIS) for conversion to multiple sclerosis (MS) and disability accrual. Data were acquired from 2 CIS cohorts. The screening phase evaluated patients developing clinically definite MS (CIS-CDMS) and patients who remained as CIS during a 2-year minimum follow-up (CIS-CIS). We determined levels of neurofascin, semaphorin 3A, fetuin A, glial fibrillary acidic protein, and neurofilament light (NfL) and heavy chains in CSF (estimated mean [95% confidence interval; CI]). We evaluated associations between biomarker levels, conversion, disability, and magnetic resonance parameters. In the replication phase, we determined NfL levels (n = 155) using a 900 ng/L cutoff. Primary endpoints in uni- and multivariate analyses were CDMS and 2010 McDonald MS. The only biomarker showing significant differences in the screening was NfL (CIS-CDMS 1,553.1 [1,208.7-1,897.5] ng/L and CIS-CIS 499.0 [168.8-829.2] ng/L, p < 0.0001). The strongest associations were with brain parenchymal fraction change (r = −0.892) and percentage brain volume change (r = −0.842) at 5 years. NfL did not correlate with disability. In the replication phase, more NfL-positive patients, according to the cutoff, evolved to MS. Every 100-ng/L increase in NfL predicted CDMS (hazard ratio [HR] = 1.009, 95% CI 1.005-1.014) and McDonald MS (HR = 1.009, 95% CI 1.005-1.013), remaining significant for CDMS in the multivariate analysis (adjusted HR = 1.005, 95% CI 1.000-1.011). This risk was lower than the presence of oligoclonal bands or T2 lesions. NfL is a weak independent risk factor for MS. Its role as an axonal damage biomarker may be more relevant as suggested by its association with medium-term brain volume changes

Deep gray matter volume loss drives disability worsening in multiple sclerosis.

OBJECTIVE: Gray matter (GM) atrophy occurs in all multiple sclerosis (MS) phenotypes. We investigated whether there is a spatiotemporal pattern of GM atrophy that is associated with faster disability accumulation in MS. METHODS: We analyzed 3,604 brain high-resolution T1-weighted magnetic resonance imaging scans from 1,417 participants: 1,214 MS patients (253 clinically isolated syndrome [CIS], 708 relapsing-remitting [RRMS], 128 secondary-progressive [SPMS], and 125 primary-progressive [PPMS]), over an average follow-up of 2.41 years (standard deviation [SD] = 1.97), and 203 healthy controls (HCs; average follow-up = 1.83 year; SD = 1.77), attending seven European centers. Disability was assessed with the Expanded Disability Status Scale (EDSS). We obtained volumes of the deep GM (DGM), temporal, frontal, parietal, occipital and cerebellar GM, brainstem, and cerebral white matter. Hierarchical mixed models assessed annual percentage rate of regional tissue loss and identified regional volumes associated with time-to-EDSS progression. RESULTS: SPMS showed the lowest baseline volumes of cortical GM and DGM. Of all baseline regional volumes, only that of the DGM predicted time-to-EDSS progression (hazard ratio = 0.73; 95% confidence interval, 0.65, 0.82; p < 0.001): for every standard deviation decrease in baseline DGM volume, the risk of presenting a shorter time to EDSS worsening during follow-up increased by 27%. Of all longitudinal measures, DGM showed the fastest annual rate of atrophy, which was faster in SPMS (-1.45%), PPMS (-1.66%), and RRMS (-1.34%) than CIS (-0.88%) and HCs (-0.94%; p < 0.01). The rate of temporal GM atrophy in SPMS (-1.21%) was significantly faster than RRMS (-0.76%), CIS (-0.75%), and HCs (-0.51%). Similarly, the rate of parietal GM atrophy in SPMS (-1.24-%) was faster than CIS (-0.63%) and HCs (-0.23%; all p values <0.05). Only the atrophy rate in DGM in patients was significantly associated with disability accumulation (beta = 0.04; p < 0.001). INTERPRETATION: This large, multicenter and longitudinal study shows that DGM volume loss drives disability accumulation in MS, and that temporal cortical GM shows accelerated atrophy in SPMS than RRMS. The difference in regional GM atrophy development between phenotypes needs to be taken into account when evaluating treatment effect of therapeutic interventions. Ann Neurol 2018;83:210-222

A histologic scoring system for prognosis of patients with Alcoholic hepatitis

BACKGROUND & AIMS: There is no histologic classification system to determine prognoses of patients with alcoholic hepatitis (AH). We identified histologic features associated with disease severity and created a histologic scoring system to predict short-term (90-day) mortality. METHODS: We analyzed data from 121 patients admitted to the Liver Unit (Hospital Clinic, Barcelona, Spain) from January 2000 to January 2008 with features of AH and developed a histologic scoring system to determine the risk of death using logistic regression. The system was tested and updated in a test set of 96 patients from 5 academic centers in the United States and Europe, and a semiquantitative scoring system called the Alcoholic Hepatitis Histologic Score (AHHS) was developed. The system was validated in an independent set of 109 patients. Interobserver agreement was evaluated by weighted κ statistical analysis. RESULTS: The degree of fibrosis, degree of neutrophil infiltration, type of bilirubinostasis, and presence of megamitochondria were independently associated with 90-day mortality. We used these 4 parameters to develop the AHHS to identify patients with a low (0-3 points), moderate (4-5 points), or high (6-9 points) risk of death within 90 days (3%, 19%, and 51%, respectively; P < .0001). The AHHS estimated 90-day mortality in the training and test sets with an area under the receiver operating characteristic value of 0.77 (95% confidence interval, 0.71-0.83). Interrater agreement values were 0.65 for fibrosis, 0.86 for bilirubinostasis, 0.60 for neutrophil infiltration, and 0.46 for megamitochondria. Interestingly, the type of bilirubinostasis predicted the development of bacterial infections. CONCLUSIONS: We identified histologic features associated with the severity of AH and developed a patient classification system that might be used in clinical decision making

Activating Transcription Factor 4 Modulates TGFβ-Induced Aggressiveness in Triple-Negative Breast Cancer via SMAD2/3/4 and mTORC2 Signaling

Purpose: On the basis of the identified stress-independent cellular functions of activating transcription factor 4 (ATF4), we reported enhanced ATF4 levels in MCF10A cells treated with TGFβ1. ATF4 is overexpressed in patients with triple-negative breast cancer (TNBC), but its impact on patient survival and the underlying mechanisms remain unknown. We aimed to determine ATF4 effects on patients with breast cancer survival and TNBC aggressiveness, and the relationships between TGFβ and ATF4. Defining the signaling pathways may help us identify a cell signaling-tailored gene signature.Experimental Design: Patient survival data were determined by Kaplan-Meier analysis. Relationship between TGFβ and ATF4, their effects on aggressiveness (tumor proliferation, metastasis, and stemness), and the underlying pathways were analyzed in three TNBC cell lines and in vivo using patient-derived xenografts (PDX).Results: ATF4 overexpression correlated with TNBC patient survival decrease and a SMAD-dependent crosstalk between ATF4 and TGFβ was identified. ATF4 expression inhibition reduced migration, invasiveness, mammosphere-forming efficiency, proliferation, epithelial-mesenchymal transition, and antiapoptotic and stemness marker levels. In PDX models, ATF4 silencing decreased metastases, tumor growth, and relapse after chemotherapy. ATF4 was shown to be active downstream of SMAD2/3/4 and mTORC2, regulating TGFβ/SMAD and mTOR/RAC1-RHOA pathways independently of stress. We defined an eight-gene signature with prognostic potential, altered in 45% of 2,509 patients with breast cancer.Conclusions: ATF4 may represent a valuable prognostic biomarker and therapeutic target in patients with TNBC, and we identified a cell signaling pathway-based gene signature that may contribute to the development of combinatorial targeted therapies for breast cancer

International conference on the healthy effect of virgin olive oil

Ageing represents a great concern in developed countries because the number of people involved and the pathologies related with it, like atherosclerosis, morbus Parkinson, Alzheime's disease, vascular dementia, cognitive decline, diabetes and cancer. Epidemiological studies suggest that a Mediterranean diet (which is rich in virgin olive oil) decreases the risk of cardiovascular disease. The Mediterranean diet, rich in virgin olive oil, improves the major risk factors for cardiovascular disease, such as the lipoprotein profile, blood pressure, glucose metabolism and antithrombotic profile. Endothelial function, inflammation and oxidative stress are also positively modulated. Some of these effects are attributed to minor components of virgin olive oil. Therefore, the definition of the Mediterranean diet should include virgin olive oil. Different observational studies conducted in humans have shown that the intake of monounsaturated fat may be protective against age-related cognitive decline and Alzheimer's disease. Microconstituents from virgin olive oil are bioavailable in humans and have shown antioxidant properties and capacity to improve endothelial function. Furthermore they are also able to modify the haemostasis, showing antithrombotic properties. In countries where the populations fulfilled a typical Mediterranean diet, such as Spain, Greece and Italy, where virgin olive oil is the principal source of fat, cancer incidence rates are lower than in northern European countries. The protective effect of virgin olive oil can be most important in the first decades of life, which suggests that the dietetic benefit of virgin olive oil intake should be initiated before puberty, and maintained through life. The more recent studies consistently support that the Mediterranean diet, based in virgin olive oil, is compatible with a healthier ageing and increased longevity. However, despite the significant advances of the recent years, the final proof about the specific mechanisms and contributing role of the different components of virgin olive oil to its beneficial effects requires further investigations. © 2005 Blackwell Publishing Ltd

Dendritic Cells Exposed to MVA-Based HIV-1 Vaccine Induce Highly Functional HIV-1-Specific CD8+ T Cell Responses in HIV-1-Infected Individuals

Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC) and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B) in human monocyte-derived dendritic cells (MDDC) and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α). MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8+ T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8+ T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4+ T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA) and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B

Doñana. Acta vertebrata. vol 12(1)

Contribución a la biometría y biología de la Bermejuela Rutilus arcasii (Steindch., 1866) del embalse de PinillaSistemática de iguanidae, sensu lato y de anolinae en Cuba (Repitilia, sauria)Nueva subespecie de Anolis isolepis (Lacertilia: Iguanidae) para CubaAlimentación del ratonero común (Buteo buteo,L. 1758) en el norte de España.Censo y datos sobre la biología del Halcón de Eleonor (Falco eleonorae Gené, 1839) en las Islas Canarias. Agosto-septiembre 1983Selección de hábitat en un grupo de aves forestales del norte de la Península Ibérica:Importancia de la estructura de la vegetación y competencia interespecíficaThe intersexual differentiation in the foraging behaviour of Oenanthe hispanica L. during the breeding seasonEtograma de Gazella dorcasAlgunos datos sobre el crecimiento y las dimorfometrías sexuales del esqueleto postcraneal de Mus spretus Lataste, 1883 (Rodentia: muridaeDistribución y taxonomía de Molossops temminckii (Chiroptera, Molossidae) en Venezuela.Estudio de una población rural de ratones (Mus musculus L.) II. Análisis comparativo de once estimadores del tamaño poblacional.Distribución de Hyla arborea L. (AMPHIBIA, ANURA, HYLIDAE) en el macizo ibérico septentrionaPresencia y nidificación de gavilán (Accipiter nisus granti Sharpe 1890) en la isla de el Hierro.Autumn food of the ptarmigan (Lagopus mutus Montin, 17776 in the spanish central pyreneesPollo atípico en nido de Hirundo rustica.Primera cita del chorlito social (Vanellus gragarius) en las marismas del GuadalquivirPeer reviewe