188 research outputs found
Treatment for IgG and IgA paraproteinaemic neuropathy
Paraproteinaemic neuropathy refers to those neuropathies associatedwith amonoclonal gammopathy or paraprotein. Themost common of these present with a chronic, predominantly sensory, symmetrical neuropathy, similar to chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but with relatively more sensory involvement, both clinically and neurophysiologically. The optimal treatment for neuropathies associated with IgG and IgA monoclonal gammopathy of uncertain significance is not known. This is an update of a review first published in 2007.
Objectives
To assess the effects of any treatment for IgG or IgA paraproteinaemic peripheral neuropathy.
Search methods
On 18 January 2014 we searched the Cochrane NeuromuscularDisease Group Trials Specialized Register, CENTRAL, MEDLINE and EMBASE. We also checked bibliographies for controlled trials of treatments for IgG or IgA paraproteinaemic peripheral neuropathy. We checked clinical trials registries for ongoing studies in November 2014.
Selection criteria
We considered for inclusion randomised controlled trials (RCTs) and quasi-RCTs using any treatment for IgG or IgA paraproteinaemic peripheral neuropathy. We excluded people with IgM paraproteins. We excluded people where the monoclonal gammopathy was considered secondary to an underlying disorder. We included participants of any age with a diagnosis of monoclonal gammopathy of uncertain significance with a paraprotein of the IgG or IgA class and a neuropathy. Included participants were not required to fulfil specific electrophysiological diagnostic criteria.
Data collection and analysis
We used standard Cochrane methodology to select studies, extract data and analyse results. One trial author provided additional data and clarification.
Main results
We identified one RCT, with 18 participants, that fulfilled the predetermined inclusion criteria. The trial compared plasma exchange to sham plasma exchange in participants with IgG or IgA paraproteinaemic neuropathy over a three-week follow-up period. We identified four other studies but these were not RCTs or quasi-RCTs. The included RCT did not report our predefined primary outcome measure, change in disability six months after randomisation. The trial revealed a modest benefit of plasma exchange in the weakness component of the Neuropathy Disability Score (NDS, now the Neuropathy Impairment Score); the mean improvement with plasma exchange was 17 points (95% confidence interval (CI) 5.2 to 28.8 points) versus 1 point (95% CI -7.7 to 9.7 points) in the sham exchange group at three weeks' follow-up (mean difference (MD) 16.00; 95% CI 1.37 to 30.63, low quality evidence). There was no statistically significant difference in the overall NDS (MD 18.00; 95% CI -2.03 to 38.03, low quality evidence), vibration thresholds or neurophysiological indices. Adverse events were not reported. The trial was at low risk of bias overall, although limitations of trial size and duration reduce the quality of the evidence in support of its conclusions.
Authors' conclusions
The evidence fromRCTs for the treatment of IgGor IgA paraproteinaemic neuropathy is currently inadequate. More RCTs of treatments are required. These should have adequate follow-up periods and contain larger numbers of participants, perhaps through multicentre collaboration, considering the relative infrequency of this condition. Observational or open trial data provide limited support for the use of treatments such as plasma exchange, cyclophosphamide combined with prednisolone, intravenous immunoglobulin, and corticosteroids. These interventions show potential therapeutic promise but the potential benefits must be weighed against adverse effects. Their optimal use and the long-term benefits need to be considered and validated with well-designed RCTs
Fostering Sustainable Citizenship: A University-Wide Sustainability Competencies Framework for T-Shaped Professionals through Inter- and Transdisciplinary Education
Context
Hasselt University wants to shape its students into critical citizens with a sustainable mindset who are prepared to take on complex societal challenges. An emphasis on inter- and transdisciplinary education is crucial for preparing students to navigate the interconnected nature of these societal challenges. We envision our students to be T-shaped professionals, who possess in-depth disciplinary expertise on the one hand and transversal competencies on the other hand. T-shaped professionals are able to look across different perspectives and disciplines to find new solutions (Bierema, 2019).
Approach and methodology
In order to prepare our students for the wicked problems of society and to become T-shaped professionals, we developed an university-wide competencies framework focussed on sustainability. The goal is that every student acquires these sustainability competencies, so this sustainability competencies framework must be implemented in all curricula at our university by 2029. This sustainability competencies framework is inspired by literature such as Ploum et al. (2018) and Wiek et al. (2015), as well as the GreenComp Framework (Bianchi et al., 2022). The framework consists of 4 interrelated competencies, namely:
Inclusive collaboration
Systems thinking
Ethical and sustainable reflection
Sustainable action
This framework has been established by a reciprocal exchange of perspectives and expectations with the study programmes, as well as the input of an expertise panel.
Inter- and transdisciplinary education is essential if we want our students to acquire these sustainability competencies. We aim to broaden students' perspectives so that they can take on their societal role and reflect on the impact of their role and actions.
Imlementation
To achieve this, we know that the role of teachers is crucial. Therefore, we aim to professionalize our teachers on the themes of sustainability and inter- and transdisciplinary education. During the poster presentation, we will give an overview of our implementation process as well as the various initiatives we undertake for teachers. For the sustainability competencies framework, we provide an online toolbox with content related to education for sustainable development and specific tools for the implementation of the competencies framework in curricula and courses. Moreover, thematic professionalisation sessions are offered. For the theme of inter- and transdisciplinary education, we developed a framework with a clarification of multi-, inter- and transdisciplinary education as well as a roadmap for teachers in order to implement this into their educational practice.
Follow-up
The integration of the sustainability competencies framework is monitored yearly by meetings with every program, followed by feedforward. These meetings can also be used to discuss the implementation of multi-, inter- and transdisciplinary education in each programs, as well as specific needs programs and teachers may have concerning this theme.
In addition, we are in search of a way of monitoring the student side, more specifically:
How can we assess if the students have acquired these competencies?
Which criteria are relevant for this assessment?
Which tools can we use for this assessment?
How can we involve the workings field and the broader society in the assessment of our students?
These questions will guide the discussion during our poster presentation
Methylprednisolon bij traumatische dwarslaesie: voorlopig nog geen baten voor de patiënt
Ever since the publication in 1990 in The New England Journal of Medicine of a multicentre, randomised, double-blind, placebo-controlled trial on the efficacy of methylprednisolone (MP) in the treatment of acute, traumatic spinal cord injury, the advice is to administer MP as soon as possible to every patient presenting a traumatic spinal cord injury. This recommendation has been followed throughout the world, especially by traumatologists, and seems to be above criticism. However, the results of most cited studies, which have had a major influence on the treatment of patients with an acute, traumatic spinal cord lesion, show that the improvements in the neurological condition due to MP cannot be translated into a specific improvement in the functional status. Until it has been proven beyond reasonable doubt that MP can play a significant role in the treatment of these patients, we advise that MP should not be administered to a patient with acute, traumatic spinal cord injury, awaiting the results of more quantitative research. Such research is being performed by the Cochrane Brain and Spinal Cord Injury Grou
Surgery in adults with tethered cord syndrome: outcome study with independent clinical review
The authors conducted a study to evaluate the risks and short-term benefits of surgical treatment for tethered cord syndrome (TCS) in patients older than 18 years of age. The authors studied a series of 57 consecutive adult patients with TCS of varying origins. Patients were examined by the same neurologist in a standardized fashion before and after surgery, and most were followed for at least 2 years postoperatively. Patient age ranged from 19 to 75 years. The mean age at onset of symptoms and diagnosis was 30 years and 37 years, respectively. Muscle strength improved (15 cases) or showed no change postoperatively (38 cases) in a large majority of patients (93%). In four patients a minor decrease in muscle strength was demonstrated, and there was significant deterioration in two (3.5%). In the two latter patients, a rapid decline in motor function was present preoperatively. Subjective assessment of pain, gait, sensory function, and bladder/bowel function at 4 weeks, 6 months, and 2 years postsurgery revealed improvement in a substantial percentage of patients. No major surgery-related complications occurred. This is the largest series to date in which adult patients with TCS comprise the report. Untethering procedures in these patients were safe and effective, at least in the short term. Patients with rapid loss of motor function, lipomyelomeningocele, or split cord malformation seem to be at a higher risk of postsurgery deterioration. A follow-up period of many more years will be necessary to determine whether aggressive surgery is beneficial in the long ter
Emergence and global spread of epidemic healthcare-associated clostridium difficile
Epidemic C. difficile (027/BI/NAP1) has rapidly emerged in the past decade as the leading cause of antibiotic-associated diarrhea worldwide. However, the key events in evolutionary history leading to its emergence and the subsequent patterns of global spread remain unknown. Here, we define the global population structure of C. difficile 027/BI/NAP1 using whole-genome sequencing and phylogenetic analysis. We show that two distinct epidemic lineages, FQR1 and FQR2, not one as previously thought, emerged in North America within a relatively short period after acquiring the same fluoroquinolone resistance–conferring mutation and a highly related conjugative transposon. The two epidemic lineages showed distinct patterns of global spread, and the FQR2 lineage spread more widely, leading to healthcare-associated outbreaks in the UK, continental Europe and Australia. Our analysis identifies key genetic changes linked to the rapid transcontinental dissemination of epidemic C. difficile 027/BI/NAP1 and highlights the routes by which it spreads through the global healthcare system
The analysis of para-cresol production and tolerance in Clostridium difficile 027 and 012 strains.
BACKGROUND: Clostridium difficile is the major cause of antibiotic associated diarrhoea and in recent years its increased prevalence has been linked to the emergence of hypervirulent clones such as the PCR-ribotype 027. Characteristically, C. difficile infection (CDI) occurs after treatment with broad-spectrum antibiotics, which disrupt the normal gut microflora and allow C. difficile to flourish. One of the relatively unique features of C. difficile is its ability to ferment tyrosine to para-cresol via the intermediate para-hydroxyphenylacetate (p-HPA). P-cresol is a phenolic compound with bacteriostatic properties which C. difficile can tolerate and may provide the organism with a competitive advantage over other gut microflora, enabling it to proliferate and cause CDI. It has been proposed that the hpdBCA operon, rarely found in other gut microflora, encodes the enzymes responsible for the conversion of p-HPA to p-cresol. RESULTS: We show that the PCR-ribotype 027 strain R20291 quantitatively produced more p-cresol in-vitro and was significantly more tolerant to p-cresol than the sequenced strain 630 (PCR-ribotype 012). Tyrosine conversion to p-HPA was only observed under certain conditions. We constructed gene inactivation mutants in the hpdBCA operon in strains R20291 and 630Δerm which curtails their ability to produce p-cresol, confirming the role of these genes in p-cresol production. The mutants were equally able to tolerate p-cresol compared to the respective parent strains, suggesting that tolerance to p-cresol is not linked to its production. CONCLUSIONS: C. difficile converts tyrosine to p-cresol, utilising the hpdBCA operon in C. difficile strains 630 and R20291. The hypervirulent strain R20291 exhibits increased production of and tolerance to p-cresol, which may be a contributory factor to the virulence of this strain and other hypervirulent PCR-ribotype 027 strains
Efeito dos antioxidantes ascorbato e n-acetil-cisteína associados à terapia antirretroviral em pacientes HIV positivos
Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências de Saúde. Programa de Pós-Graduação em FarmáciaA infecção pelo vírus da imunodeficiência humana (HIV) resulta em alterações efetivas e complexas no sistema imunológico, caracterizada por uma depleção de linfócitos CD4+, as quais acompanham o aumento progressivo dos níveis plasmáticos da carga viral. Entre os mecanismos envolvidos nesta progressão, está a produção de espécies reativas de oxigênio (EROs), proveniente do estresse oxidativo gerado pela própria ativação crônica do sistema imune. A ação de EROs, assim como por constituintes virais, favorece a replicação viral via ativação de NF-kB e a depleção de linfócitos por apoptose, com conseqüente comprometimento do sistema imune. O objetivo desse estudo, duplo cego, controlado por placebo, foi investigar e comparar o possível efeito dos compostos antioxidantes ascorbato (CewinÒ, 2g/dia) e N-Acetil-Cisteína (NAC)(FluimucilÒ,600mg/dia), quando associados ao efeito inibidor da replicação viral dos antirretrovirais, através de parâmetros virológicos e celulares em pacientes soropositivos para o HIV-1. Foram avaliados: a carga viral do HIV-1, linfócitos CD4+, CD8+, relação CD4/CD8, percentual de células vivas, em apoptose e mortas, globulinas, IgA, IgG, IgM e b-2 microglobulina. Participaram do estudo 38 pacientes; destes, 13 foram suplementados com ascorbato 2g/dia, 10 suplementados com NAC, 800 mg/dia, e 15 fizeram uso de placebo. As análises foram realizadas antes do início do tratamento e após 60, 120 e 180 dias. Os resultados obtidos demonstraram significativa diminuição da carga viral em todos os grupos, em decorrência da terapia antirretroviral, acompanhada de um aumento significativo no número de linfócitos CD4+ e relação CD4/CD8, bem como diminuição significativa dos níveis de globulinas, IgA, IgG, IgM. Os resultados demonstraram ainda, um efeito significativo da suplementação com ascorbato sobre o percentual de linfócitos vivos, em apoptose, e sobre os níveis de b-2 Microglobulina. Neste estudo, conclui-se que a suplementação com ascorbato, 2g/dia, via oral, associada à terapia antirretroviral, propiciou um aumento na viabilidade dos linfócitos circulantes em pacientes HIV+, o que sugere um efeito benéfico na reconstituição do sistema imune nos pacientes que fazem uso do ascorbato. A NAC, entretanto, não apresentou nenhum resultado significante
Growth Of Enterotoxin Producing Bacillus Cereus In Meat Substrate At 10°c And 30°c
The behaviour of enterotoxin-producing Bacillus cereus in meat was investigated by inoculating spore suspensions of five cultures into meat substrate (pH 5.8) and incubating at 10°C and 30°C. The bacterial populations were evaluated after different times by plate counts in nutrient agar. All the cultures presented growth at 30°C with the generation time varying from 28.8 to 36.0 minutes. Three cultures also presented growth at 10°C with generation times between 10.16 and 28.38 h. Considering the results, it was concluded that meat kept at abusive temperatures would be subject to development of this microorganism.43414011405Agata, N., Otha, M., Arakawa, Y., Mori, M., The bceT gene of Bacillus cereus encodes an enterotoxic protein (1995) Microbiol. Read, 141 (4), pp. 983-988Asano, S.I., Nukumizu, Y., Bando, H., Iizuca, T., Yamamoto, T., Cloning of novel enterotoxin genes from Bacillus cereus and Bacillus thuringiensis (1997) Appl. Environ. 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Detection of new SHV-12, SHV-5 and SHV-2a variants of extended spectrum beta-lactamase in Klebsiella pneumoniae in Egypt.
BACKGROUND: Klebsiella pneumoniae outbreaks possessing extended-spectrum β-lactamase- (ESBL) mediated resistance to third-generation cephalosporins have increased significantly in hospital and community settings worldwide. The study objective was to characterize prevalent genetic determinants of TEM, SHV and CTX-M types ESBL activity in K. pneumoniae isolates from Egypt. METHODS: Sixty five ESBL-producing K. pneumoniae strains, isolated from nosocomial and community-acquired infections from 10 Egyptian University hospitals (2000-2003), were confirmed with double disc-synergy method and E-test. blaTEM, blaSHV and blaCTX-m genes were identified by PCR and DNA sequencing. Pulsed-field gel electrophoresis (PFGE) was conducted for genotyping. RESULTS: All isolates displayed ceftazidime and cefotaxime resistance. blaTEM and blaSHV genes were detected in 98% of the isolates' genomes, while 11% carried blaCTX-m. DNA sequencing revealed plasmid-borne SHV-12,-5,-2a (17%), CTX-m-15 (11%), and TEM-1 (10%) prevalence. Among SHV-12 (n=8), one isolate displayed 100% blaSHV-12 amino acid identity, while others had various point mutations: T17G (Leu to Arg, position 6 of the enzyme: n=2); A8T and A10G (Tyr and Ile to Phe and Val, positions 3 and 4, respectively: n=4), and; A703G (Lys to Glu 235: n=1). SHV-5 and SHV-2a variants were identified in three isolates: T17G (n=1); A703G and G705A (Ser and Lys to Gly and Glu: n=1); multiple mutations at A8T, A10G, T17G, A703G and G705A (n=1). Remarkably, 57% of community-acquired isolates carried CTX-m-15. PFGE demonstrated four distinct genetic clusters, grouping strains of different genetic backgrounds. CONCLUSIONS: This is the first study demonstrating the occurrence of SHV-12, SHV-5 and SHV-2a variants in Egypt, indicating the spread of class A ESBL in K. pneumoniae through different mechanisms
Methylprednisolon bij traumatische dwarslaesie: Voorlopig nog geen baten voor de patient
Ever since the publication in 1990 in The New England Journal of Medicine of a multicentre, randomised, double-blind, placebo-controlled trial on the efficacy of methylprednisolone (MP) in the treatment of acute, traumatic spinal cord injury, the advice is to administer MP as soon as possible to every patient presenting a traumatic spinal cord injury. This recommendation has been followed throughout the world, especially by traumatologists, and seems to be above criticism. However, the results of most cited studies, which have had a major influence on the treatment of patients with an acute, traumatic spinal cord lesion, show that the improvements in the neurological condition due to MP cannot be translated into a specific improvement in the functional status. Until it has been proven beyond reasonable doubt that MP can play a significant role in the treatment of these patients, we advise that MP should not be administered to a patient with acute, traumatic spinal cord injury, awaiting the results of more quantitative research. Such research is being performed by the Cochrane Brain and Spinal Cord Injury Group
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