Students’ evolving beliefs about nursing: From entry to graduation in a four-year baccalaureate programme

Students become socialised into nursing during an educational programme through interaction with faculty members, classes and seminars, and by the experience of practicing nursing. In this paper, some results from a qualitative study that examined the socialisation of nursing students from one four-year baccalaureate programme are described. The changes in the students’ attitudes and values are presented. Fred Davis theory of doctrinal conversion is used to examine progress in the process of socialisation. There is evidence that students moved from a lay to a professional image of nursing over the course of their four-year programme. While they tended to remain idealistic, elements of realism were evident in the final year as they looked toward their role as a registered nurse and recognised the constraints inherent in the hospital system.     

Efficacy of Anti-inflammatory Agents to Improve Symptoms in Patients With Schizophrenia: An Update

Background: The inflammatory hypothesis of schizophrenia is not new, but recently it has regained interest because more data suggest a role of the immune system in the pathogenesis of schizophrenia. If increased inflammation of the brain contributes to the symptoms of schizophrenia, reduction of the inflammatory status could improve the clinical picture. Lately, several trials have been conducted investigating the potential of anti-inflammatory agents to improve symptoms of schizophrenia. This study provides an update regarding the efficacy of anti-inflammatory agents on schizophrenic symptoms in clinical studies performed so far. Methods: An electronic search was performed using PubMed, Embase, the National Institutes of Health web site http://www.clinicaltrials.gov, Cochrane Schizophrenia Group entries in PsiTri, and the Cochrane Database of Systematic Reviews. Only randomized, double-blind, placebo-controlled studies that investigated clinical outcome were included. Results: Our search yielded 26 double-blind randomized controlled trials that provided information on the efficacy on symptom severity of the following components: aspirin, celecoxib, davunetide, fatty acids such as eicosapentaenoic acids and docosahexaenoic acids, estrogens, minocycline, and N-acetylcysteine (NAC). Of these components, aspirin (mean weighted effect size [ES]: 0.3, n = 270, 95% CI: 0.06–0.537, I² = 0), estrogens (ES: 0.51, n = 262, 95% CI: 0.043–0.972, I² = 69%), and NAC (ES: 0.45, n = 140, 95% CI: 0.112–0.779) showed significant effects. Celecoxib, minocycline, davunetide, and fatty acids showed no significant effect. Conclusion: The results of aspirin addition to antipsychotic treatment seem promising, as does the addition of NAC and estrogens. These 3 agents are all very broadly active substances, and it has to be investigated if the beneficial effects on symptom severity are indeed mediated by their anti-inflammatory aspects.Key words: add-on antipsychotic therapy, aspirin, N-acetylcysteine, estrogens     

From the Cover: Molecular determinants of Hv1 proton channel inhibition by guanidine derivatives

The voltage-gated proton channel Hv1 plays important roles in proton extrusion, pH homeostasis, and production of reactive oxygen species in a variety of cell types. Excessive Hv1 activity increases proliferation and invasiveness in cancer cells and worsens brain damage in ischemic stroke. The channel is composed of two subunits, each containing a proton-permeable voltage-sensing domain (VSD) and lacking the pore domain typical of other voltage-gated ion channels. We have previously shown that the compound 2-guanidinobenzimidazole (2GBI) inhibits Hv1 proton conduction by binding to the VSD from its intracellular side. Here, we examine the binding affinities of a series of 2GBI derivatives on human Hv1 channels mutated at positions located in the core of the VSD and apply mutant cycle analysis to determine how the inhibitor interacts with the channel. We identify four Hv1 residues involved in the binding: aspartate 112, phenylalanine 150, serine 181, and arginine 211. 2GBI appears to be oriented in the binding site with its benzo ring pointing to F150, its imidazole ring inserted between residue D112 and residues S181 and R211, and the guanidine group positioned in the proximity of R211. We also identify a modified version of 2GBI that is able to reach the binding site on Hv1 from the extracellular side of the membrane. Understanding how compounds like 2GBI interact with the Hv1 channel is an important step to the development of pharmacological treatments for diseases caused by Hv1 hyperactivity.The Hv1 voltage-gated proton channel (also known as HVCN1 or voltage-sensor–only protein) regulates the production of superoxide and other reactive oxygen species by NADPH oxidase (NOX) enzymes in a variety of cell types, including microglial cells (1) and leukocytes (2). NOX activity causes membrane depolarization and intracellular accumulation of protons. Hv1 allows sustained NOX activity by repolarizing the membrane and extruding excess protons from the cell (3–5).Hv1 has been shown to enhance brain damage in a mouse model of ischemic stroke through its NOX-modulating activity (1). The channel was also found overexpressed in many B-cell malignancies (6) and breast and colorectal cancer tissues (7, 8). High Hv1 activity was shown to increase invasiveness of breast cancer cells and be associated with shorter overall and recurrence-free survival in breast cancer patients (7). These findings highlight that excessive activity of the Hv1 channel can have serious pathological consequences in ischemic stroke and cancer and that small-molecule inhibitors targeting Hv1 could lead to the development of new neuroprotective or anticancer drugs.The Hv1 protein is made of four membrane-spanning segments (S1–S4) (9, 10), and it is related to the voltage-sensing domains (VSDs) of other voltage-gated ion channels (11) and voltage-sensitive phosphatases (VSPs) (12). The inner end of the S4 segment is connected to a coiled-coil domain responsible for protein dimerization (13, 14). As a result, the channel is made of two VSD subunits, each containing a gated proton pore (15–17).The block of voltage-gated sodium, potassium, and calcium channels by small molecules has been studied for decades. Its mechanism has been elucidated for many drugs, and in the majority of cases, the inhibitors were found to bind to different regions of the pore domain (18, 19). With the exception of peptide toxins (20, 21), not much is known about compounds interacting with VSDs (22), and only recently have there been successful attempts to produce small-molecule drugs that specifically target these domains in voltage-gated ion channels (23, 24).We have recently shown that some guanidine derivatives have the ability to inhibit Hv1 activity and that one of these compounds, 2-guanidinobenzimidazole (2GBI), binds the channel''s VSD only in the open conformation (25). We have also found that the binding site is within the proton permeation pathway and faces the cytoplasm.Here, we explore the chemical space available to guanidine derivatives for Hv1 binding. We then use a mutation cycle analysis approach to identify the residues in the channel that contribute to the binding environment of 2GBI and establish the overall orientation of the blocker within the VSD in the open conformation. Our results suggest that residues D112, F150, S181, and R211 are located close to each other deep within the membrane and in the proximity of the intracellular vestibule of the VSD, where they can interact with the blocker. We discuss our binding model in the context of a recent crystal structure of the channel (26).     

Point prevalence of pressure ulcers in three second‐level hospitals in Mexico

Pressure ulcers (PU) are the source of multiple complications and even death. To our knowledge, there is no available data about PU prevalence in Mexico. The objective of this study was to determine the point prevalence of PU in three second‐level hospitals in Mexico. Every adult hospitalised patient was included in each hospital. Age, gender, hospitalisation ward, Braden score, and the number, location and stage of the ulcers encountered were recorded, as well as any pressure relief measures. In total, 294 patients were examined (127 were male); of these, 63 were considered to be at risk. The average age was 48·6 years. The overall prevalence of the PU was 17%. The service with the highest prevalence was the ICU. The most frequent stage was II (32%) and they were most commonly found in the sacrum (74%). The average Braden score of the patients with ulcers was 10, and 21·4% of the patients obtained moderate‐ to high‐risk Braden scores. Of them, 60·3% had ulcers and only 46% had any preventive measures. The prevalence of PU in three hospitals in Mexico is 17%. The most common stage is II and the most commonly affected site is the sacrum. Only 46% of patients with PU had at least one pressure release measure.     

Searching health information via the web: Hong Kong chinese older adults' experience

OBJECTIVE AND SAMPLE: This paper reports on the learning experience of 88 Chinese older adults who attended a health Web-navigating workshop. DESIGN: Through a 3-hr training workshop, participants were guided to browse through seven health Web sites that provide authoritative health information by the Hong Kong government, academic institutions, or professional bodies. METHODS: Upon completion of the workshop, an evaluation was made of the participants' confidence in navigating health Web sites by themselves at home and in utilizing the health information sources. RESULTS: The findings indicated that participants' confidence in seeking health information via the Internet was not associated with their age, educational level, or experience of using computers before the workshop but was significantly associated with their satisfaction with the workshop (p<.05). Significant change of source of health information was noted at follow-up, suggesting that the workshop was successful. CONCLUSIONS: Implications of the results for running health Web-navigating programs among Chinese older adults are discussed.     

Risk Factors for Severe Acute Graft-versus-Host Disease in Donor Graft Composition

Acute graft-versus-host disease (aGVHD) is 1 of the main major complications of post–hematopoietic stem cell transplantation (HSCT). Identifying patients at risk of severe aGVHD may lead to earlier intervention and treatment, resulting in increased survival and a better quality of life. We aimed to identify biomarkers in donor grafts and patient plasma around the time of transplantation that might be predictive of aGVHD development. We build on our previously published methods by using multiplex assays and multicolor flow cytometry. We identified 5 easily assessable cellular markers in donor grafts that combined could potentially be used to calculate risk for severe aGVHD development. Most noteworthy are the T cell subsets expressing IL-7 receptor-α (CD127) and PD-1. Additionally, we identified a potential role for elevated tumor necrosis factor-α levels in both graft and patient before HSCT in development of aGVHD.     

Phenotype in girls and women with Turner syndrome: Association between dysmorphic features,karyotype and cardio-aortic malformations

Introduction

Turner syndrome (TS) is a genetic disorder characterized by the (partial) absence or a structural aberration of the second sex chromosome and is associated with a variety of phenotypes with specific physical features and cardio-aortic malformations. The objective of this study was to gain a better insight into the differences in dysmorphic features between girls and women with TS and to explore the association between these features, karyotype and cardio-aortic malformations.

Exploring neurologists’ perspectives on the return of next generation sequencing results to their patients: a needed step in the development of guidelines

Background

The use of Next Generation Sequencing such as Whole Genome Sequencing (WGS) is a promising step towards a better understanding and treatment of neurological diseases. WGS can result into unexpected information (incidental findings, IFs), and information with uncertain clinical significance. In the context of a Genome Canada project on ‘Personalized Medicine in the Treatment of Epilepsy’, we intended to address these challenges surveying neurologists’ opinions about the type of results that should be returned, and their professional responsibility toward recontacting patients regarding new discovered mutations.

Methods

Potential participants were contacted through professional organizations or direct invitations.

Results

A total of 204 neurologists were recruited. Fifty nine percent indicated that to be conveyed, WGS results should have a demonstrated clinical utility for diagnosis, prognosis or treatment. Yet, 41% deemed appropriate to return results without clinical utility, when they could impact patients’ reproductive decisions, or on patients’ request. Current use of targeted genetic testing and age of patients influenced respondents’ answers. Respondents stated that analysis of genomics data resulting from WGS should be limited to the genes likely to be relevant for the patient’s specific medical condition (69%), so as to limit IFs. Respondents felt responsible to recontact patients and inform them about newly discovered mutations related to the medical condition that triggered the test (75%) for as long as they are following up on the patient (55%). Finally, 53.5% of the respondents felt responsible to recontact and inform patients of clinically significant, newly discovered IFs.

Conclusion

Our results show the importance of formulating professional guidelines sensitive to the various – and sometimes opposite – viewpoints that may prevail within a same community of practice, as well as flexible so as to be attuned to the characteristics of the neurological conditions that triggered a WGS.