Viral suppression rates in salvage treatment with raltegravir improved with the administration of genotypic partially active or inactive nucleoside/tide reverse transcriptase inhibitors.

BACKGROUND: Nucleoside reverse transcriptase inhibitors (NRTIs) are often administered in salvage therapy even if genotypic resistance tests (GRTs) indicate high-level resistance, but little is known about the benefit of these additional NRTIs. METHODS: The effect of <2 compared with 2 NRTIs on viral suppression (HIV-1 RNA < 50 copies/mL) at week 24 was studied in salvage patients receiving raltegravir. Intent-to-treat and per-protocol analyses were performed; last observation carried forward imputation was used to deal with missing information. Logistic regressions were weighted to create a pseudopopulation in which the probability of receiving <2 and 2 NRTIs was unrelated to baseline factors predicting treatment response. RESULTS: One-hundred thirty patients were included, of whom 58.5% (n = 76) received <2 NRTIs. NRTIs were often replaced by other drug classes. Patients with 2 NRTIs received less additional drug classes compared with patients with <2 NRTIs [median (IQR): 1 (1-2) compared with 2 (1-2), P Wilcoxon < 0.001]. The activity of non-NRTI treatment components was lower in the 2 NRTIs group compared with the <2 NRTIs group [median (IQR) genotypic sensitivity score: 2 (1.5-2.5) compared with 2.5 (2-3), P Wilcoxon < 0.001]. The administration of <2 NRTIs was associated with a worse viral suppression rate at week 24. The odds ratios were 0.34 (95% confidence interval: 0.13 to 0.89, P = 0.027) and 0.19 (95% confidence interval: 0.05 to 0.79, P = 0.023) when performing the last observation carried forward and the per-protocol approach, respectively. CONCLUSIONS: Our findings showed that partially active or inactive NRTIs contribute to treatment response, and thus the use of 2 NRTIs in salvage regimens that include raltegravir seems warranted.

Impact croisé du sexe et du niveau scolaire sur les intérêts professionnels d'écoliers suisses

Cette article traite de la manière dont le développement des aspirations professionnelles contribuent à la formation d'inégalités entre hommes et femmes sur le marché du travail au travers d'une étude empirique portant sur l'influence du sexe et de la filière scolaire sur les intérêts professionnels d'écoliers suisses. Les résultats indiquent que le croisement de ces deux variables affecte particulièrement les jeunes filles dans une filière à exigences élémentaires en restreignant doublement les options envisageables. Les moyens d'action pour les conseiller-e-s en orientation afin d'accompagner spécifiquement cette population est discutée. This article investigates how the development of career aspirations contributes to the formation of inequalities between women and men in the labor market. More precisely the influence of gender and school level on the professional interests of Swiss schoolchildren was investigated. The results indicate that these two variables reinforce each other and interact and that girls in the lower school stream are especially affected by having, for two distinct reasons, less professional options available. Several practical implications and suggestions in order to improve interventions for career counselors working with this specific population are discussed.

Candidat à l'échec scolaire incompris et ignoré : l'enfant de migrants = Misunderstood and ignored candidate to the school failure: The child of migrants

Immigration, intégration, précarité, échec scolaire, ignorance du français, délinquance sont des thèmes qui animent régulièrement les débats publics, médiatiques et politiques. Bien que les migrations ont toujours fait partie de l'histoire humaine, elles sont souvent décrites comme un trouble aux identités nationales, elles-mêmes mises à mal par la mondialisation. Cependant, les mécanismes sous-tendant les difficultés rencontrées par certains enfants de migrants demeurent bien moins débattus et considérés que leurs conséquences bruyantes et visibles. Après une réflexion sur l'impact de la migration elle-même sur le sujet et un bref aperçu de l'ethnopsychiatrie, nous allons décrire les difficultés que peut rencontrer l'enfant de migrants, leurs origines et leurs conséquences. Nous nous intéresserons ensuite à la manière dont notre société, nos institutions en tiennent compte ou pas. Nous terminerons notre propos par la mise en relief des besoins thérapeutiques et éducatifs spéciaux de ces enfants et la manière dont ceux-ci sont comblés (ou non). Immigration, social integration, precariousness, language barrier, delinquency are constantly stimulating public, political and media debate. Migrations always were part of the human history but they are often described like a disorder of the national identities, themselves put at evil by globalization. However, the origin of the difficulties that certain children of migrants encounter is often overlooked. Only their disturbing implications are frequently studied. After a brief comment on the impact of the migration and the ethnopsychiatry, we will outline the difficulties sometimes faced by the children of migrants, their origins and consequences. Then we will describe how the society and the institutions take them in account (or not). We finally will delineate the specific needs of those children and how they are meeting (or not).

High-resolution mass spectrometry applied to the study of metabolome modifications in various chicken tissues after amoxicillin administration

The performance of high resolution accurate mass spectrometry (HRMS) operating in full scan MS mode was investigated for the quantitative determination of amoxicillin (AMX) as well as qualitative analysis of metabolomic profiles in tissues of medicated chickens. The metabolomic approach was exploited to compile analytical information on changes in the metabolome of muscle, kidney and liver from chickens subjected to a pharmacological program with AMX. Data consisting of m/z features taken throughout the entire chromatogram were extracted and filtered to be treated by Principal Component Analysis. As a result, it was found that medicated and non-treated animals were clearly clustered in distinct groups. Besides, the multivariate analysis revealed some relevant mass features contributing to this separation. In this context, recognizing those potential markers of each chicken class was a priority research for both metabolite identification and, obviously, evaluation of food quality and health effects associated to food consumption.

The release of antidiuretic hormone is appropriate in response to hypovolemia and/or sodium administration in children with severe head injury: a trial of lactated Ringer's solution versus hypertonic saline.

We conducted an open, randomized, and prospective study to determine the effect of hypertonic saline on the secretion of antidiuretic hormone (ADH) and aldosterone in children with severe head injury (Glasgow coma scale <8). Thirty-one consecutive patients at a level III pediatric intensive care unit at a children's hospital received either lactated Ringer's solution (Ringer's group, n = 16) or hypertonic saline (Hypertonic Saline group, n = 15) over a 3-day period. Serum ADH levels were significantly larger in the Hypertonic Saline group as compared with the Ringer's group (P = 0.001; analysis of variance) and were correlated to sodium intake (Ringer's group: r = 0.39, R(2) = 0.15, P = 0.02; Hypertonic Saline group: r = 0.42, R(2) = 0.18, P = 0.02) and volume of fluids given IV (Ringer's group: r = 0.38, R(2) = 0.15, P = 0.02; Hypertonic Saline group: r = 0.32, R(2) = 0.1, P = not significant). Correlation of ADH to plasma osmolality was significant if plasma osmolality was >280 mOsm/kg (r = 0.5, R(2) = 0.25, P = 0.06), indicating an osmotic threshold for ADH release. Serum aldosterone levels were larger on the first day than during Days 2 and 3 in both groups and inversely correlated to serum sodium levels only in the Ringer's group (r = -0.55, R(2) = 0.3, P < 0.001). This group received a significantly larger fluid volume on Day 1 (P = 0.05, Mann-Whitney U-test) than did patients in the Hypertonic Saline group, indicating hypovolemia during the first day. Head-injured children have appropriate levels of ADH. They may be hypovolemic during the first day of treatment, especially if they receive lactated Ringer's solution. IMPLICATIONS: In head-injured patients, we recommend fluid restriction to avoid inappropriate secretion of antidiuretic hormone. In a prospective, randomized, and controlled study in 31 children, we were able to show that the antidiuretic hormone levels are appropriate in response to hypovolemia, sodium load, or both.

Severe and prolonged hypophosphatemia after intravenous iron administration in a malnourished patient.

Malnutrition may result in a phosphate-deficient state owing to a chronically insufficient phosphate intake. Concomitant iron deficiency is common and often supplemented by the intravenous route. It is not widely recognized that some parenteral iron formulations can induce hypophosphatemia. Herein we report a case of a severe and symptomatic hypophosphatemia (0.18 mM, normal range 0.8-1.4 mM) associated with an inappropriately reduced tubular reabsorption of phosphate (33%, norm >95%) in a malnourished patient with anorexia/bulimia who received 2 × 500 mg iron carboxymaltose (FCM) intravenously. Despite intravenous and oral phosphate supplements, it required 2 months to achieve a normal serum phosphate level. Our case demonstrates that in a chronically malnourished and phosphate-deficient state intravenous FCM could potentially be dangerous. If this form of iron application cannot be avoided, phosphate supplementation before and after iron infusion as well as close monitoring of phosphate levels are needed.

DuP 532, an angiotensin II receptor antagonist: first administration and comparison with losartan.

We investigated the tolerability and angiotensin II antagonist activity of oral DuP 532 in healthy male subjects. DuP 532 (1 to 200 mg) was well tolerated, with no effect on blood pressure or heart rate. Compared with losartan (100 mg), DuP 532 (200 mg) was a weak antagonist of pressor responses to intravenous angiotensin II. Maximum inhibition of diastolic pressor response was 86% (95% confidence interval [CI], 84%, 88%) approximately 4.6 hours after losartan and 48% (95% CI, 38%, 56%) 8.7 hours after DuP 532. Twenty-four hours after dosing, inhibition by losartan and DuP 532 was similar (40% to 45%). DUP 532 is extensively bound in human plasma, with an in vitro free fraction of 0.06. Although DuP 532 and EXP3174 (losartan's active metabolite) have similar AT1-receptor potency, and plasma concentrations of DuP 532 were much greater than losartan/EXP3174, the level of antagonism was much less for DuP 532. These results indicate that multiple factors determine the in vivo potency of angiotensin II antagonists, including affinity for and distribution to the receptor as modulated by plasma binding.

Report on a review of selected general and application controls over the University of Northern Iowa Facility Administration and Maintenance Information System for the period April 29, 2014 through June 5, 2014

Report on a review of selected general and application controls over the University of Northern Iowa Facility Administration and Maintenance Information System for the period April 29, 2014 through June 5, 2014

In vivo administration of a lentiviral vaccine targets DCs and induces efficient CD8(+) T cell responses.

The present study evaluates the potential of third-generation lentivirus vectors with respect to their use as in vivo-administered T cell vaccines. We demonstrate that lentivector injection into the footpad of mice transduces DCs that appear in the draining lymph node and in the spleen. In addition, a lentivector vaccine bearing a T cell antigen induced very strong systemic antigen-specific cytotoxic T lymphocyte (CTL) responses in mice. Comparative vaccination performed in two different antigen models demonstrated that in vivo administration of lentivector was superior to transfer of transduced DCs or peptide/adjuvant vaccination in terms of both amplitude and longevity of the CTL response. Our data suggest that a decisive factor for efficient T cell priming by lentivector might be the targeting of DCs in situ and their subsequent migration to secondary lymphoid organs. The combination of performance, ease of application, and absence of pre-existing immunity in humans make lentivector-based vaccines an attractive candidate for cancer immunotherapy.

Administration of growth hormone to underweight patients with chronic obstructive pulmonary disease. A prospective, randomized, controlled study.

Patients with chronic obstructive pulmonary disease (COPD) often develop weight loss, which is associated with increased mortality. Recombinant human growth hormone (rhGH) treatment has been proposed to improve nitrogen balance and to increase muscle strength in these patients. The aim of this study was to assess the effects of rhGH administration on the nutritional status, resting metabolism, muscle strength, exercise tolerance, dyspnea, and subjective well-being of underweight patients with stable COPD. Sixteen patients attending a pulmonary rehabilitation program (age: 66 +/- 9 yr; weight: 77 +/- 7% of ideal body weight; FEV1: 39 +/- 13% of predicted) were randomly treated daily with either 0.15 IU/kg rhGH or placebo during 3 wk in a double-blind fashion. Measurements were made at the beginning (DO) and at the end (D21) of treatment and 2 mo later (D81). Body weight was similar in the two groups during the study, but lean body mass was significantly higher in the rhGH group at D21 (p < 0.01) and D81 (p < 0.05). The increase in lean body mass was 2.3 +/- 1.6 kg in the rhGH group and 1.1 +/- 0.9 kg in the control group at D21 and 1.9 +/- 1.6 kg in the rhGH group and 0.7 +/- 2.1 kg in the control group at D81. At D21, the resting energy expenditure was increased in the rhGH group (107.8% of DO, p < 0.001 compared with the control group). At D21 and D81, the changes in maximal respiratory pressures, handgrip strength, maximal exercise capacity, and subjective well-being were similar in the two groups. At D21, the 6-min walking distance decreased in the rhGH group (-13 +/- 31%) and increased in the control group (+10 +/- 14%; p < 0.01). We conclude that the daily administration of 0.15 IU/kg rhGH during 3 wk increases lean body mass but does not improve muscle strength or exercise tolerance in underweight patients with COPD.

A propos de la ségrégation professionnelle : étude sociologique du travail féminin auprès de l'administration cantonale vaudoise

La ségrégation professionnelle horizontale et verticale selon le sexe est l'un des traits dominants du marché du travail: les femmes et les hommes exercent rarement le même type d'activité ou la même fonction. L'objectif de la recherche réalisée dans le cadre de mon mémoire de licence est de cerner les mécanismes sociaux qui contribuent au maintien de la division hiérarchique du travail entre les sexes. L'enquête a été menée au sein d'une administration cantonale et combine une étude de la politique de gestion du personnel et de trajectoires d'activité professionnelle d'employé·e·s et de cadres des deux sexes (« employé d'administration » est une fonction féminisée, celle d'« adjoint » est majoritairement occupée par des hommes). Elle met en évidence l'influence des rapports sociaux de sexe dans la production des différences de sexe. L'étude du système de classification des fonctions, de promotion et de formation continue met au jour la manière dont les stéréotypes de sexe et les représentations de rôles de sexe structurent la politique de gestion du personnel. Il ressort que les « employées » interviewées ont un niveau de formation supérieur à celui de leurs homologues masculins. Par ailleurs, la mobilité professionnelle est régie par des logiques différentes : les femmes rapportent avoir demandé une promotion alors que les hommes disent avoir été promus par les supérieurs. L'analyse des trajectoires d'activité montre que les « employé·e·s » n'accomplissent pas le même type de tâches, les femmes sont cantonnées à un travail de secrétariat alors que les hommes assument des tâches diversifiées, ce qui se répercute ensuite sur le type de cours de formation continue suivis. Mais surtout la mobilité spatiale et l'autonomie féminines sont moindres. « Employée» n'est donc pas le féminin d'«employé». La fonction d'« adjoint » comprend l'exercice de responsabilités diverses, notamment la direction et l'encadrement de personnel administratif. Pourtant, les « adjointes » sont exclues des fonctions de direction - où se prennent les décisions - et quasi exclues des fonctions d'encadrement hiérarchique importantes. Par ailleurs, les dossiers en mains masculines concernent davantage des questions économiques, financières ou techniques, ceux des femmes des dimensions juridique et sociale. Enfin, les « adjointes » connaissent un avancement de carrière plus lent que leurs collègues de sexe masculin.

Drug concentration response relationships in normal volunteers after oral administration of losartan, an angiotensin II receptor antagonist.

The aim of this study was to investigate the relationships between plasma concentrations of losartan, an orally active angiotensin II inhibitor, its active metabolite EXP3174, and angiotensin II blockade. Six healthy subjects received single oral doses of 40, 80, or 120 mg losartan and placebo at 1-week intervals in a crossover study. Angiotensin II blockade was assessed by the blood pressure response to exogenous angiotensin II before and after losartan administration. EXP3174 reached higher plasma concentrations and was eliminated more slowly than its parent compound; its levels paralleled the profile of angiotensin II blockade closer than losartan. Inhibition of the pressure response was dose dependent. The Hill-shaped relationship between response and EXP3174 concentration (or time-integrated variables) approached a plateau with 80 mg. The dose-dependent increase in plasma renin and angiotensin II exhibited a considerable individual scatter. We conclude that losartan produces a dose-dependent, effective angiotensin II blockade that is largely determined by the active metabolite EXP3174.