Phenotypic heterogeneity of antigen-specific CD4 T cells under different conditions of antigen persistence and antigen load.

The factors responsible for the phenotypic heterogeneity of memory CD4 T cells are unclear. In the present study, we have identified a third population of memory CD4 T cells characterized as CD45RA(+)CCR7(-) that, based on its replication history and the homeostatic proliferative capacity, was at an advanced stage of differentiation. Three different phenotypic patterns of memory CD4 T cell responses were delineated under different conditions of antigen (Ag) persistence and load using CD45RA and CCR7 as markers of memory T cells. Mono-phenotypic CD45RA(-)CCR7(+) or CD45RA(-)CCR7(-) CD4 T cell responses were associated with conditions of Ag clearance (tetanus toxoid-specific CD4 T cell response) or Ag persistence and high load (chronic HIV-1 and primary CMV infections), respectively. Multi-phenotypic CD45RA(-)CCR7(+), CD45RA(-)CCR7(-) and CD45RA(+)CCR7(-) CD4 T cell responses were associated with protracted Ag exposure and low load (chronic CMV, EBV and HSV infections and HIV-1 infection in long-term nonprogressors). The mono-phenotypic CD45RA(-)CCR7(+) response was typical of central memory (T(CM)) IL-2-secreting CD4 T cells, the mono-phenotypic CD45RA(-)CCR7(-) response of effector memory (T(EM)) IFN-gamma-secreting CD4 T cells and the multi-phenotypic response of both IL-2- and IFN-gamma-secreting cells. The present results indicate that the heterogeneity of different Ag-specific CD4 T cell responses is regulated by Ag exposure and Ag load.

P-selectin glycoprotein ligand-1 decameric repeats regulate selectin-dependent rolling under flow conditions.

P-selectin glycoprotein ligand-1 (PSGL-1) interacts with selectins to support leukocyte rolling along vascular wall. L- and P-selectin bind to N-terminal tyrosine sulfate residues and to core-2 O-glycans attached to Thr-57, whereas tyrosine sulfation is not required for E-selectin binding. PSGL-1 extracellular domain contains decameric repeats, which extend L- and P-selectin binding sites far above the plasma membrane. We hypothesized that decamers may play a role in regulating PSGL-1 interactions with selectins. Chinese hamster ovary cells expressing wild-type PSGL-1 or PSGL-1 molecules exhibiting deletion or substitution of decamers with the tandem repeats of platelet glycoprotein Ibalpha were compared in their ability to roll on selectins and to bind soluble L- or P-selectin. Deletion of decamers abrogated soluble L-selectin binding and cell rolling on L-selectin, whereas their substitution partially reversed these diminutions. P-selectin-dependent interactions with PSGL-1 were less affected by decamer deletion. Videomicroscopy analysis showed that decamers are required to stabilize L-selectin-dependent rolling. Importantly, adhesion assays performed on recombinant decamers demonstrated that they directly bind to E-selectin and promote slow rolling. Our results indicate that the role of decamers is to extend PSGL-1 N terminus far above the cell surface to support and stabilize leukocyte rolling on L- or P-selectin. In addition, they function as a cell adhesion receptor, which supports approximately 80% of E-selectin-dependent rolling.

Women working at university restaurants: life and work conditions and gender-based violence

This is an exploratory and descriptive study with a quantitative approach that aimed to understand the social production and reproduction processes of women working at university restaurants and the occurrence and the magnitude of gender-based violence committed against them by their intimate partners. The data were collected through semi-structured interviews. The analysis categories used were social production and reproduction, gender and gender-based violence. The interviewees held a subordinate social position during the productive and reproductive periods of their lives. Approximately 70% reported having experienced gender-based violence from an intimate partner (66% psychological violence, 36.3% physical violence and 28.6% sexual violence). Most of the health problems resulting from violence were related to mental health. The results indicate that the situation requires immediate interventions, mostly guided by the instrumentalization of these women and the support by the state and the university as appropriate to address violence.

Trait decoupling promotes evolutionary diversification of the trophic and acoustic system of damselfishes.

Trait decoupling, wherein evolutionary release of constraints permits specialization of formerly integrated structures, represents a major conceptual framework for interpreting patterns of organismal diversity. However, few empirical tests of this hypothesis exist. A central prediction, that the tempo of morphological evolution and ecological diversification should increase following decoupling events, remains inadequately tested. In damselfishes (Pomacentridae), a ceratomandibular ligament links the hyoid bar and lower jaws, coupling two main morphofunctional units directly involved in both feeding and sound production. Here, we test the decoupling hypothesis by examining the evolutionary consequences of the loss of the ceratomandibular ligament in multiple damselfish lineages. As predicted, we find that rates of morphological evolution of trophic structures increased following the loss of the ligament. However, this increase in evolutionary rate is not associated with an increase in trophic breadth, but rather with morphofunctional specialization for the capture of zooplanktonic prey. Lineages lacking the ceratomandibular ligament also shows different acoustic signals (i.e. higher variation of pulse periods) from others, resulting in an increase of the acoustic diversity across the family. Our results support the idea that trait decoupling can increase morphological and behavioural diversity through increased specialization rather than the generation of novel ecotypes.

Rapport sur le projet d'un code pénal, fait à l'assemblée générale de l'État de la Louisiane , par M. Édouard Livingston, suivi des Observations sur les conditions nécessaires à la perfection d'un code pénal, par M. Mill, avec une introduction et des notes, par M. A.-H. Taillandier,...

Comprend : Observations sur les conditions nécessaires à la perfection d'un code pénal...

Cytogenetic response to imatinib in chronic myeloid leukaemia patients: concentration dependency and associated influences under field-conditions

Introduction: Imatinib, a first-line drug for chronic myeloid leukaemia (CML), has been increasingly proposed for therapeutic drug monitoring (TDM), as trough concentrations >=1000 ng/ml (Cmin) have been associated with improved molecular and complete cytogenetic response (CCyR). The pharmacological monitoring project of EUTOS (European Treatment and Outcome Study) was launched to validate retrospectively the correlation between Cmin and response in a large population of patients followed by central TDM in Bordeaux.¦Methods: 1898 CML patients with first TDM 0-9 years after imatinib initiation, providing cytogenetic data along with demographic and comedication (37%) information, were included. Individual Cmin, estimated by non-linear regression (NONMEM), was adjusted to initial standard dose (400 mg/day) and stratified at 1000 ng/ml. Kaplan-Meier estimates of overall cumulative CCyR rates (stratified by sex, age, comedication and Cmin) were compared using asymptotic logrank k-sample test for interval-censored data. Differences in Cmin were assessed by Wilcoxon test.¦Results: There were no significant differences in overall cumulative CCyR rates between Cmin strata, sex and comedication with P-glycoprotein inhibitors/inducers or CYP3A4 inhibitors (p >0.05). Lower rates were observed in 113 young patients <30 years (p = 0.037; 1-year rates: 43% vs 60% in older patients), as well as in 29 patients with CYP3A4 inducers (p = 0.001, 1-year rates: 40% vs 66% without). Higher rates were observed in 108 patients on organic-cation-transporter-1 (hOCT-1) inhibitors (p = 0.034, 1-year rates: 83% vs 56% without). Considering 1-year CCyR rates, a trend towards better response for Cmin above 1000 ng/ml was observed: 64% (95%CI: 60-69%) vs 59% (95%CI: 56-61%). Median Cmin (400 mg/day) was significantly reduced in male patients (732 vs 899ng/ml, p <0.001), young patients <30 years (734 vs 802 ng/ml, p = 0.037) and under CYP3A4 inducers (758 vs 859 ng/ml, p = 0.022). Under hOCT-1 inhibitors, Cmin was increased (939 vs 827 ng/ml, p = 0.038).¦Conclusion: Based on observational TDM data, the impact of imatinib Cmin >1000 ng/ml on CCyR was not salient. Young CML patients (<30 years) and patients taking CYP3A4 inducers probably need close monitoring and possibly higher imatinib doses, due to lower Cmin along with lower CCyR rates. Patients taking hOCT-1 inhibitors seem in contrast to have improved CCyR response rates. The precise role for imatinib TDM remains to be established prospectively.

Social determinants of hospitalizations for ambulatory care sensitive conditions in Guarulhos, São Paulo

The study goals present an overview of Hospitalizations for Ambulatory Care Sensitive Conditions (ACSC) in Guarulhos, SP, from 2008 to 2012. This is an ecological study based on secondary data obtained from the Brazilian Hospital Information System, and supported by the Praxical Theory of Intervention of Collective Health Nursing. Applied descriptive statistics for analysis. It was observed that Guarulhos shows an upward trend in hospitalizations by ACSC (20% increase), the most frequent causes of heart failure (11.8%), cerebrovascular disease (10.6%) and angina (9.7%), most frequently in the age group ≥ 65years old, for both sexes. The results are similar to other Brazilian studies, but their analysis should extrapolate the biological limits and the supply of healthcare resources, focusing on the social determinants of the health-disease process.




Overview of hospitalizations by ambulatory care sensitive conditions in the municipality of Cotia, Brazil

Objective To describe the profile of Hospitalizations by Amulatory Care Sensitive Conditions (HACSC), in the Municipality of Cotia, from 2008 to 2012. Method ecological, exploratory, longitudinal study with a quantitative approach. Data on HACSC, by age group and sex, were obtained from the Department of the Unified Health System. For data analysis descriptive statistics were used. Results During the period, there were 46,676 admissions, excluding deliveries, 7,753 (16.61%) by HACSC. The main causes were cerebrovascular diseases, 16.96%, heart failure, 15.50%, hypertension, 10.80% and infection of the kidney and urinary tract, 10.51%. Regarding gender, HACSC occurred predominantly in males. There was a greater number of HACSC at extreme age ranges, especially in the elderly. Conclusion Chronic diseases predominate among the leading causes of HACSC and there was no significant difference between sex.





An analisys of suply and Demand Conditions for Cape Verde´s Banana Industry

Michigan State University

Hospital admissions due to ambulatory care sensitive conditions among children by age group and health region

OBJECTIVE to describe hospital admissions for ambulatory care sensitive conditions in children under five years of age in the State of Paraná, Brazil by condition type, age group and health region. METHOD a temporal ecological study was conducted using data from the Unified Health System Hospital Information System for the period 2000 to 2011. Conditions were grouped in accordance with the list of ambulatory care sensitive conditions in Brazil. RESULTS there was an increase in the rate of admissions for ambulatory care sensitive conditions in all age groups in 50% of the health regions, with a marked increase in children under the age of one. Pneumonia, gastroenteritis and asthma were the main causes of admissions. There was an increase in the proportion of overall admissions accounted for by pneumonia and gastroenteritis. CONCLUSION the increase in admissions reveals the need for actions to improve access to primary healthcare and provide effective treatment of the main ambulatory care sensitive conditions in order to prevent hospital admissions among children.

Health risk behaviors in adolescents with chronic conditions

OBJECTIVE: The objective of this study was to compare the frequency of risk behaviors and to measure the extent of co-occurrence of these behaviors in chronically ill and healthy adolescents. METHODS: Data were drawn from the 2002 Swiss Multicenter Adolescent Survey on Health database, a nationally representative survey of 7548 adolescents in postmandatory school aged 16 to 20 years. There were 760 subjects who reported a chronic illness and/or a disability. The comparison group consisted of 6493 subjects who answered negatively to both questions. We defined 8 risk behaviors: daily smoking, alcohol misuse, current cannabis use, current use of any other illegal drug, early sexual debut, eating disorder, violent acts, and antisocial acts. We analyzed each behavior and the sum of behaviors, controlling for age, gender, academic track, parents' education level, depression, and health status. Results are given as adjusted odds ratios using the comparison group as the reference category. RESULTS: Youth with a chronic condition were more likely to smoke daily, to be current cannabis users, and to have performed violent or antisocial acts. Youth with a chronic condition were also more likely to report 3 or >or=4 risk behaviors. CONCLUSIONS: These results indicate that having a chronic condition carries additional risks for engaging in health risk behaviors and emphasize the importance of health risk screening and preventive counseling for young people in general and among those suffering from chronic conditions in particular.

Determining underlying macroeconomic fundamentals during emerging market crises: Are conditions as bad as they seem?

Emerging market crises are characterized by large swings in both macroeconomic fundamentalsand asset prices. The economic significance of observed movements in macroeconomicvariables is obscured by the brief and extreme nature of crises. In this paper we propose to study the macroeconomic consequences of crises by studying the behavior of effective fundamentals, constructed by studying the relative movements of stock prices during crises. We find that these effective fundamentals provide a different picture than that implied by observed fundamentals. First, asset prices often reflect expectations of improvement in fundamentals after the initial devaluations; specifically, effective depreciations are positive but not as large as the observed ones. Second, crises vary in their effect on credit market conditions, with investors expecting tightening of credit in some cases (Mexico 1994, Philippines 1997), but loosening of credit in others (Sweden 1992, Korea 1997, Brazil 1999).

Relative and absolute reliability of the clinical version of the Narrow Path Walking Test (NPWT) under single and dual task conditions.

Decline in gait stability has been associated with increased fall risk in older adults. Reliable and clinically feasible methods of gait instability assessment are needed. This study evaluated the relative and absolute reliability and concurrent validity of the testing procedure of the clinical version of the Narrow Path Walking Test (NPWT) under single task (ST) and dual task (DT) conditions. Thirty independent community-dwelling older adults (65-87 years) were tested twice. Participants were instructed to walk within the 6-m narrow path without stepping out. Trial time, number of steps, trial velocity, number of step errors, and number of cognitive task errors were determined. Intraclass correlation coefficients (ICCs) were calculated as indices of agreement, and a graphic approach called "mountain plot" was applied to help interpret the direction and magnitude of disagreements between testing procedures. Smallest detectable change and smallest real difference (SRD) were computed to determine clinically relevant improvement at group and individual levels, respectively. Concurrent validity was assessed using Performance Oriented Mobility Assessment Tool (POMA) and the Short Physical Performance Battery (SPPB). Test-retest agreement (ICC1,2) varied from 0.77 to 0.92 in ST and from 0.78 to 0.92 in DT conditions, with no apparent systematic differences between testing procedures demonstrated by the mountain plot graphs. Smallest detectable change and smallest real change were small for motor task performance and larger for cognitive errors. Significant correlations were observed for trial velocity and trial time with POMA and SPPB. The present results indicate that the NPWT testing procedure is highly reliable and reproducible.