Treatment of the CRND8 mouse model for cerebral amyloid angiopathy, exhibited increased levels of neuron specific enolase in brain tissue following long-term treatment with a modified C5a receptor agonist, accompanied by improved cognitive function.

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder characterized by amyloid plaques, neurofibrillary tangles, and cerebral amyloid angiopathy (CAA). CAA is a condition manifesting as amyloid deposits in the cerebral vasculature, eventually leading to microhemorrhage. Here, we have treated the CRND8 mouse model with the C5a agonist (EP67) in order to observe the effects on cerebral amyloidosis, CAA, and hyperphosphorylated tau. EP67 attaches to the C5a receptor on phagocytes and stimulates the engulfment and digestion of fibrillar and prefibrillar amyloid while exhibiting minimal inflammation. Older CRND8 mice and their respective controls were treated with EP67 for a prolonged period of time. Following treatment, the CRND8 mice displayed improved spatial memory, while both amyloid deposition and tau hyperphosphorylation were found to be diminished.

Nurses attitudes and knowledge regarding patient rights: a systematic review / Atitudes e conhecimentos dos enfermeiros em relação aos direitos do paciente: uma revisão sistemática / Actitudes y conocimientos de las enfermeras sobre los derechos de los pacientes: una revisión sistemática

ABSTRACT Objective: To synthesize current evidence on nurses' attitudes and/or knowledge on the entire spectrum of patient rights. Method: A systematic search of the literature was performed in Web of Science, PubMed, Scopus and CINAHL. Studies were selected according to pre-defined inclusion/exclusion criteria. The Cochrane and PRISMA guidelines, including templates for systematic reviews, were applied. For rigor assessment, the Critical Appraisal Skills Program Qualitative Research Checklist, and the Center for Evidence-Based Management tool were employed. Results: Thirteen studies were included, that exhibited important methodological limitations, such as convenience sampling, mediocre response rates and inadequate instrument validity. Findings indicated: a) low level of awareness regarding patient rights among nurses, b) knowledge discrepancies on specific aspects of patient rights, c) low priority ascribed to a patient's right to access information, and d) insufficient evidence on formal educational sources of knowledge on the topic of patient rights. Conclusion: Narrow geographical localization, heterogeneity and methodological limitations render generalizability of the conclusions difficult. Further research based on robust methodology is proposed.

RESUMO Objetivo: Sintetizar as evidências atuais sobre as atitudes e/ou conhecimentos dos enfermeiros sobre todo o espectro dos direitos do paciente. Método: Uma busca sistemática da literatura foi realizada na Web of Science, PubMed, Scopus e CINAHL. Os estudos foram selecionados de acordo com critérios de inclusão/exclusão pré-definidos. As diretrizes Cochrane e PRISMA, incluindo modelos para revisões sistemáticas, foram aplicadas. Para uma avaliação rigorosa, foram utilizados o Critical Appraisal Skills Program Qualitative Research Checklist e a ferramenta do Center for Evidence-Based Management. Resultados: Foram incluídos 13 estudos que exibiram limitações metodológicas importantes, como amostragem por conveniência, taxas de resposta medíocres e validade inadequada do instrumento. Os resultados indicaram: a) baixo nível de consciência sobre os direitos do paciente entre os enfermeiros, b) discrepâncias de conhecimento sobre aspectos específicos dos direitos do paciente, c) baixa prioridade atribuída ao direito do paciente de acessar informações, e d) evidências insuficientes sobre fontes de conhecimento educacionais formais sobre o tema dos direitos do paciente. Conclusão: A localização geográfica estreita, a heterogeneidade e as limitações metodológicas dificultam a generalização das conclusões. Outras pesquisas baseadas em metodologia robusta são propostas.

RESUMEN Objetivo: Sintetizar la evidencia actual sobre las actitudes y/o conocimientos de las enfermeras sobre todo el espectro de los derechos del paciente. Método: Se realizó una búsqueda sistemática de la literatura en Web of Science, PubMed, Scopus y CINAHL. Los estudios se seleccionaron de acuerdo con criterios de inclusión/exclusión predefinidos. Se aplicaron las guías Cochrane y PRISMA, incluidas las plantillas para revisiones sistemáticas. Para una evaluación más rigurosa, se emplearon el Critical Appraisal Skills Program Qualitative Research Checklist y la herramienta del Center for Evidence-Based Management. Resultados: Se incluyeron trece estudios, que exhibieron importantes limitaciones metodológicas, como muestreo por conveniencia, tasas de respuesta mediocres y validez inadecuada del instrumento. Los hallazgos indicaron: a) bajo nivel de conciencia sobre los derechos del paciente entre las enfermeras, b) discrepancias de conocimiento sobre aspectos específicos de los derechos del paciente, c) baja prioridad atribuida al derecho del paciente a acceder a la información, y d) evidencia insuficiente sobre fuentes formales de conocimiento educativo sobre el tema de los derechos del paciente. Conclusión: La estrecha localización geográfica, la heterogeneidad y las limitaciones metodológicas dificultan la generalización de las conclusiones. Se propone más investigación basada en una metodología robusta.

The frequency of central nervous system complications in the Cypriot cohort of ATTRV30M neuropathy transplanted patients.

BACKGROUND: Hereditary transthyretin amyloidosis (ATTR) is a hereditary, sensorimotor and autonomic neuropathy caused by deposits of mutated transthyretin (TTR). The commonest TTR mutation is V30M (ATTRV30M) with patients usually living for about 10 years after disease onset. Liver transplantation (LT) until recently was considered the standard treatment. OBJECTIVE AND METHODS: This study aims to assess the frequency of CNS complications in post-LT patients from the Cypriot cohort. Epidemiological data were collected for all genetically confirmed ATTRV30M neuropathy patients diagnosed at CING since 1992, and CNS-associated symptoms were assessed and evaluated by two neurology specialists. RESULTS: Out of the 48 transplanted patients, 10 (20.8%) presented with a CNS complication. All patients had ocular involvement, mainly glaucoma (7/10). Eight presented with transient focal neurological episodes (TFNEs), with expressive dysphasia being reported by four of them. The mean time of TFNE-emergence was 16.6 years after the LT. Three died from cerebral hemorrhage. CONCLUSIONS: CNS complications in post-LT ATTRV30M patients are not rare and usually manifest themselves at a time that surpasses the mean time the patients would have survived without a LT. CNS involvement is associated with increased mortality, due to cerebral hemorrhage.

A novel case of inclusion body myositis and myasthenia gravis.

The co-existence of myasthenia gravis and other inflammatory myopathies has been reported in the literature before, but no clinical cases involving inclusion body myositis have been reported. We report a case of a 67-year-old patient who presented with dysphagia, exhibiting the typical electrophysiological features of postsynaptic neuromuscular junction defect with positive muscle acetylcholine receptor antibodies, consistent with the diagnosis of myasthenia gravis. Nevertheless, response to acetylcholinesterase inhibitors and immunomodulatory treatment was unexpectedly poor. As the disease progressed, the patient developed asymmetric muscle weakness, initially affecting mainly the quadriceps and the finger flexors. Muscle MRI imaging supported the presence of an inflammatory myopathy and muscle biopsy confirmed the diagnosis of inclusion body myositis. Thus, our patient represents the first reported overlap case of myasthenia gravis and inclusion body myositis.

Epidemiology of ATTRV30M neuropathy in Cyprus and the modifier effect of complement C1q on the age of disease onset.

BACKGROUND: ATTRV30M amyloidosis is a lethal autosomal dominant sensorimotor and autonomic neuropathy caused by amyloid deposition composed of aggregated misfolded TTR monomers with the V30M mutation. The age of onset in patients with ATTRV30M varies in different foci and the mechanism behind it is still unknown. METHODS: The tertiary neurology center following all ATTRV30M patients in Cyprus was used to collect demographic data to estimate; prevalence, incidence, penetrance, anticipation, time from disease onset to diagnosis and transplantation. Ocular, cardiac and leptomeningeal involvement in transplanted patients was explored. Correlation of C1q tagging SNPs with age of disease onset was carried out. RESULTS: Prevalence and incidence for ATTRV30M neuropathy in Cyprus are 5.4/100,000 and 0.3/100,000 respectively. Mean age of onset is 40.6 years and anticipation is 8.3 years. Penetrance reaches 51% and 75% by the ages of 50 and 80 years respectively. In liver transplanted patients rates of ocular, cardiac and leptomeningeal involvement were estimated to be 60%, 20% and 16%, respectively. C1q polymorphisms correlated with age of disease onset. CONCLUSIONS: ATTRV30M neuropathy has a rising prevalence in Cyprus due to improved survival of patients. Late onset complications are becoming a major problem. Complement C1q appears to be a modifier in this disease.

Pharmacological Stimulation of Phagocytosis Enhances Amyloid Plaque Clearance; Evidence from a Transgenic Mouse Model of ATTR Neuropathy.

Hereditary ATTR V30M amyloidosis is a lethal autosomal dominant sensorimotor and autonomic neuropathy caused by deposition of aberrant transthyretin (TTR). Immunohistochemical examination of sural nerve biopsies in patients with amyloidotic neuropathy show co-aggregation of TTR with several proteins; including apolipoprotein E, serum amyloid P and components of the complement cascade. Complement activation and macrophages are increasingly recognized to play a crucial role in amyloidogenesis at the tissue bed level. In the current study we test the effect of two C5a receptor agonists and a C5a receptor antagonist (PMX53) on disease phenotype in ATTR V30M mice. Our results indicate that amyloid deposition was significantly reduced following treatment with the C5a receptor agonists, while treatment with the antagonist resulted in a significant increase of amyloid load. Administration of the C5a receptor agonists triggered increased recruitment of phagocytic cells resulting in clearance of amyloid deposits.

C1q ablation exacerbates amyloid deposition: A study in a transgenic mouse model of ATTRV30M amyloid neuropathy.

ATTRV30M amyloid neuropathy is a lethal autosomal dominant sensorimotor and autonomic neuropathy, caused by deposition of amyloid fibrils composed of aberrant transthyretin (TTR). Ages of onset and penetrance exhibit great variability and genetic factors have been implicated. Complement activation co-localizes with amyloid deposits in amyloidotic neuropathy and is possibly involved in the kinetics of amyloidogenesis. A candidate gene approach has recently identified C1q polymorphisms to correlate with disease onset in a Cypriot cohort of patients with ATTRV30M amyloid neuropathy. In the current study we use a double transgenic mouse model of ATTRV30M amyloid neuropathy in which C1q is ablated to elucidate further a possible modifier role for C1q. Amyloid deposition is found to be increased by 60% in the absence of C1q. Significant up regulation is also recorded in apoptotic and cellular stress markers reflecting extracellular toxicity of pre-fibrillar and fibrillar TTR. Our data further indicate that in the absence of C1q there is marked reduction of macrophages in association with amyloid deposits and thus less effective phagocytosis of TTR.

21 Mb deletion in chromosome band 13q22.2q32.1 associated with mild/moderate psychomotor retardation, growth hormone insufficiency, short neck, micrognathia, hypotonia, dysplastic ears and other dysmorphic features.

We report on a 9-month old boy carrying a 21 Mb de novo 13q interstitial deletion. The imbalance was detected by chromosomal analysis and investigated by Fluorescence In Situ Hybridization (FISH) and Comparative Genomic Hybridization (array-CGH) using two different platforms: a BAC microarray with 516 kb resolution (Cytochip) and a 15 kb resolution oligonucleotide microarray (Agilent 244K). The deletion has been estimated to span 21.46 Mb on chromosomal bands 13q22.2-13q32.1. The patient has mild/moderate psychomotor retardation, growth hormone insufficiency, hypertelorism, short neck, micrognathia, hypotonia, dysplastic ears and other dysmorphic features. Further investigation revealed that the abnormality is de novo and causative of the patient's phenotype. The described patient is unique among similar rare cases with different deletion breakpoints. It is the first case of 13q22.2q32.1 deletion where the breakpoints are clearly defined, indicating the importance of detailed clinical description and high-resolution genomic analysis for characterization of rare genetic syndromes.

Sox1 maintains the undifferentiated state of cortical neural progenitor cells via the suppression of Prox1-mediated cell cycle exit and neurogenesis.

Neural stem/progenitor cells maintain their identity via continuous self-renewal and suppression of differentiation. Gain-of-function experiments in the chick revealed an involvement for Sox1-3 transcription factors in the maintenance of the undifferentiated neural progenitor (NP) identity. However, the mechanism(s) employed by each factor has not been resolved. Here, we derived cortical neural/stem progenitor cells from wild-type and Sox1-null mouse embryos and found that Sox1 plays a key role in the suppression of neurogenic cell divisions. Loss of Sox1 leads to progressive depletion of self-renewing cells, elongation of the cell cycle of proliferating cells, and significant increase in the number of cells exiting the cell cycle. In proliferating NP cells, Sox1 acts via a prospero-related homeobox 1 (Prox1)-mediated pathway to block cell cycle exit that leads to neuronal differentiation in vivo and in vitro. Thus, our results demonstrate that Sox1 regulates the size of the cortical NP pool via suppression of Prox1-mediated neurogenic cell divisions.

Generation of an ABCG2(GFPn-puro) transgenic line--a tool to study ABCG2 expression in mice.

The ATP-binding cassette (ABC) transporter 2 (ABCG2) is expressed by stem cells in many organs and in stem cells of solid tumors. These cells are isolated based on the side population (SP) phenotype, a Hoechst 3342 dye efflux property believed to be conferred by ABCG2. Because of the limitations of this approach we generated transgenic mice that express Nuclear GFP (GFPn) coupled to the Puromycin-resistance gene, under the control of ABCG2 promoter/enhancer sequences. We show that ABCG2 is expressed in neural progenitors of the developing forebrain and spinal cord and in embryonic and adult endothelial cells of the brain. Using the neurosphere assay, we isolated tripotent ABCG2-expressing neural stem cells from embryonic mouse brain. This transgenic line is a powerful tool for studying the expression of ABCG2 in many tissues and for performing functional studies in different experimental settings.