R57K polymorphism in the human immunodeficiency virus type 1 protease as predictor of early virological failure in a cohort of antiretroviral-naive patients treated mostly with a nelfinavir-containing regimen

In 243 antiretroviral-naive human immunodeficiency-infected patients starting a first-line-protease inhibitor (mainly nelfinavir)-containing therapy, the presence of the polymorphism R57K in the protease at the inception of therapy was independently associated with a higher rate of virological failure.     

Management of lymphoblastic lymphomas during pregnancy

Lymphoblastic lymphoma (non-Hodgkin lymphoma) is a highly uncommon but serious condition during pregnancy. With multidisciplinary management (obstetrics, pediatrics, hematology and anesthesia), outcome is generally good for both mother and child. Chemotherapy must be initiated rapidly, during pregnancy. Consequences depend on the stage of the disease, its progressive nature and the of pregnancy. During the first trimester, medical termination should be proposed in order to initiate chemotherapy cannot be started until the second trimester using alkaloids. Chemotherapy has little effect on the fetus during the second trimester. During the trimester, extraction should be discussed as soon as the fetal maturity is sufficient.     

Conformational rearrangements and signaling cascades involved in ligand-biased mitogen-activated protein kinase signaling through the beta1-adrenergic receptor

In recent years, several studies have demonstrated that different ligands can have distinct efficacy profiles toward various signaling pathways through a unique receptor. For example, beta1-adrenergic compounds that are inverse agonists toward the adenylyl cyclase (AC) can display agonist activity for the mitogen-activated protein kinase (MAPK) pathway. Such a phenomenon, often termed functional selectivity, has now been clearly established for many G protein-coupled receptors when considering distinct signaling output. However, the possibility that ligands could selectively engage distinct effectors to activate a single signaling output by promoting specific receptor conformations has not been extensively examined. Here, we took advantage of the fact that isoproterenol, bucindolol and propranolol (full, partial, and inverse agonists for the AC pathway, respectively) all activate MAPK through the beta1-adrenergic receptor (beta1AR) to probe such conformational-biased signaling. Although the three compounds stimulated MAPK in a src-dependent manner, isoproterenol acted through both Galpha(i)betagamma- and G protein-independent pathways, whereas bucindolol and propranolol promoted MAPK activation through the G protein-independent pathway only. The existence of such distinct signaling cascades linking beta1AR to MAPK activation was correlated with ligand-specific conformational rearrangements of receptor/G protein complexes measured by bioluminescence resonance energy transfer. Taken together, our data indicate that discrete local conformational changes can selectively promote the recruitment of distinct proximal signaling partners that can engage distinct signaling outputs and/or converge on the same signaling output.     

The immunization practices of nursing staff in local community health centers

BACKGROUND: Nurses have an important role in keeping the youth of Quebec vaccinated. Little, however, is known about nurses' immunization practices. The purpose of this research is to identify the immunization practices of nursing staff in local community health centres who vaccinate children aged 0 to 5 years and to outline personal outcomes and barriers to performing these practices. METHODS: A Delphi consultation project was conducted with immunization experts in Quebec. The consultation included 4 phases during which participants expressed their opinions on concepts through a series of questionnaires. The research team created a consolidated common response at each stage in order to produce a final consensus. RESULTS: Eighteen specialists participated in at least 1 of the consultation phases. The consultation allowed for the identification of 35 ideal immunization practices which were grouped into 11 higher-order categories. Eleven expected outcomes were also identified as well as 51 barriers to ideal immunization practices which in turn were grouped into 7 higher-order categories. CONCLUSION: According to experts, immunization practices are varied and include technical acts as well as relational, organizational, and continuing education activities. These practices are expected to generate outcomes for professionals and their clientele. However, a number of barriers to achieving ideal vaccination practices are also observed. The picture of immunization practices by nurses in local community health centres and their perception of outcomes and barriers will be studied during the next stages of the project. This process will lead to developing intervention strategies with vaccinators.     

Experience of Autistic Children and Their Families During the Pandemic: From Distress to Coping Strategies

Journal of Autism and Developmental Disorders - To understand the perspectives and needs of autistic children and their families in the context of an emergency, 109 parents and 56 autistic children...     

Lack of alteration of endogenous nitric oxide pathway during prolonged nitric oxide inhalation in intensive care unit patients

OBJECTIVE: To compare hemodynamic and gasometric variables and the plasma concentrations of nitric oxide metabolites (cyclic guanosine monophosphate and nitrate and nitrite), endothelin-1, and renin-angiotensin metabolites before and after the start of nitric oxide inhalation, after prolonged nitric oxide inhalation, and before and after nitric oxide withdrawal. DESIGN: Prospective study. SETTING: Surgical intensive care unit, university hospital. SUBJECTS: Patients with acute lung injury and right ventricular failure. INTERVENTIONS: Nitric oxide inhalation (10-12 ppm) during a median of 2.9 days (12 hrs to 6.5 days). MEASUREMENTS AND MAIN RESULTS: The pulmonary vasodilator effects of inhaled nitric oxide improved arterial oxygenation in patients with acute lung injury (p < .05) and reduced right atrial pressure in patients with right ventricular dysfunction (p < .01). These beneficial effects lasted the whole period of prolonged inhaled nitric oxide therapy up to 6.5 days. However, when inhaled nitric oxide was withdrawn, pulmonary vasodilator effects rapidly disappeared, and Pao2/Fio2 ratio markedly deteriorated in all studied patients to return to pre-inhaled nitric oxide levels. Changes in plasma cyclic guanosine monophosphate and nitrate and nitrite paralleled those of pulmonary vasodilatory effects. An immediate increase in plasma cyclic guanosine monophosphate with a slightly delayed increase in plasma nitrate and nitrite was observed at inhaled nitric oxide start with no attenuation during the prolonged inhaled nitric oxide therapy. A marked decrease toward pre-inhaled nitric oxide levels was seen within hours of inhaled nitric oxide withdrawal. In addition, no alteration of plasma endothelin-1 or renin-angiotensin mediators was observed during or after inhaled nitric oxide therapy. CONCLUSIONS: Our study showed a lack of attenuation in the beneficial effects of inhaled nitric oxide and a lack of alteration of endogenous nitric oxide, endothelin-1, and renin-angiotensin pathways during prolonged nitric oxide inhalation.     

Implementation and evaluation of a therapeutic patient education programme during a clinical trial in Yaoundé, Cameroon – Trial ANRS-12286/MOBIDIP

Objectives

High adherence is needed to maintain antiretroviral therapy efficacy. Few attempts at therapeutic patient education (TPE) have been made in sub-Saharan Africa. We describe patients’ achievements before intervention and identified needs, TPE programme implementation and evaluation, and patients’ satisfaction.

Reflections on treatment of IBD in children and adolescents

Abstract

Major pharmaceutical advancements in the field of inflammatory bowel diseases benefit to children and adolescents affected with this progressive chronic condition. Scientific organisations such as ESPGHAN and ECCO actively publish guidelines related to the many aspects of care from these patients. Clinical studies and long-term prospective registries in the appropriate age groups are crucial to support an evidence based strategy.     

A model to characterize psychopathological features in adults with Prader‐Willi syndrome

High prevalence of behavioral and psychiatric disorders in adults with Prader‐Willi Syndrome (PWS) has been reported in last few years. However, data are confusing and often contradictory. In this article, we propose a model to achieve a better understanding of the psychopathological features in adults with PWS. The study is based on clinical observations of 150 adult inpatients, males and females. Non‐parametric statistics were performed to analyse the association of psychopathological profiles with genotype, gender and age. We propose a model of psychiatric disorders in adults with PWS based on cognitive, emotional and behavioural issues. This model defines four psychopathological profiles: Basic, Impulsive, Compulsive, and Psychotic. The Basic profile is defined by traits and symptoms that are present in varying degrees in all persons with PWS. In our cohort, this Basic profile corresponds to 55% of the patients. The rest show, in addition to these characteristics, salient features of impulsivity (Impulsive profile, 19%), compulsivity (Compulsive profile, 7%), or psychosis (Psychotic profile, 19%). The analysis of factors associated with different profiles reveals an effect of genotype on Basic and Psychotic profiles (Deletion: 70% Basic, 9% Psychotic; Non‐deletion: 23% Basic, 43% Psychotic) and a positive correlation between male sex and impulsivity, unmediated by sex hormone treatment. This is a clinical study, based on observation proposing an original model to understand the psychiatric and behavioural disorders in adults with PWS. Further studies are needed in order to test the validity of this model.