Clinical and Pathological Findings in Women with Fabry Disease

Introduction. Fabry disease is a rare metabolic disorder caused by the genetic deficiency of the lysosomal hydrolase alpha-galactosidase A, located on chromosome X. Females with the defective gene are more than carriers and can develop a wide range of symptoms. Nevertheless, disease symptoms generally occur later and are less severe in women than in men. The enzyme deficiency manifests as a glycosphingolipidosis with progressive accumulation of glycosphingolipids and deposit of inclusion bodies in lysosomes giving a myelinlike appearance. Patients and Methods. Records of renal biopsies performed on adults from 1st January 2008 to 31st August 2011, were retrospectively examined at the Renal Pathology Laboratory. We retrieved biopsies diagnosed with Fabry disease and reviewed clinical and laboratory data and pathology findings. Results. Four female patients with a mean age of 49.3±4.5 (44-55) years were identified. The mean proteinuria was 0.75±0.3 g/24h (0.4-1.2) and estimated glomerular filtration rate (CKD EPI equation) was 71±15.7 ml/min/1.73m2 (48-83). Three patients experienced extra-renal organ involvement (cerebrovascular, cardiac, dermatologic, ophthalmologic and thyroid) with distinct severity degrees. Leukocyte α-GAL A activity was below normal range in the four cases but plasma and urinary enzymatic activity was normal. Light microscopy showed predominant vacuolisation of the podocyte cytoplasm and darkly staining granular inclusions on paraffin and plastic-embedded semi-thin sections. Electron microscopy showed in three patients the characteristic myelin-like inclusions in the podocyte cytoplasm and also focal podocyte foot process effacement. In one case the inclusions were also present in parietal glomerular cells, endothelial cells of peritubular capillary and arterioles. Conclusion. Clinical signs and symptoms are varied and can be severe among heterozygous females with Fabry disease. Intracellular accumulation of glycosphingolipids is a characteristic histologic finding of Fabry nephropathy. Since this disease is a potentially treatable condition, its early identification is imperative. We should consider it in the differential diagnosis of any patient presenting with proteinuria and/or chronic kidney disease, especially if there is a family history of kidney disease

Interplay between topological insulators and superconductors

Topological insulators are insulating in the bulk but possess metallic surface states protected by time-reversal symmetry. Here, we report on a detailed electronic transport study in high-quality Bi 2Se 3 topological insulator thin films contacted by superconducting (In, Al, and W) electrodes. The resistance of the film shows an abrupt and significant upturn when the electrodes become superconducting. In turn, the Bi 2Se 3 film greatly weakens the superconductivity of the electrodes, significantly reducing both their transition temperatures and their critical fields. A possible interpretation of these results is that the superconducting electrodes are accessing the surface states and the experimental results are consequences of the interplay between the Cooper pairs of the electrodes and the spin-polarized current of the surface states in Bi 2Se 3. © 2012 American Physical Society.published_or_final_versio

Burden of rare variants in ALS genes influences survival in familial and sporadic ALS

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Gene mapping of familial amyotrophic lateral sclerosis

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disorder characterized by gradual death of motor neurons in cerebral cortex, brain stem, and spinal cord. The pathogenetic mechanism remains unclear for the vast majority of cases. About 10% of ALS cases are familial (FALS). Cu/Zn superoxide dismutase (SOD1) gene accounts for about 10% of autosomal dominant FALS and the gene(s) responsible for the rest of ALS/ FALS remain(s) to be found. METHOD: We recruited a large Chinese kindred without SOD1 mutation for linkage analysis. Peripheral blood samples were collected and DNA were extracted from peripheral lymphocyte. We screened the family with ~ 400 polymorphic microsatellite markers. The genotyping data were subjected to model-based and model-free linkage analysis. RESULT: Using MLINK of LINKAGE (Ver 5.2) package, we found a maximum LOD score of 4.357, ?[m=f]=0.0 at a microsatellite marker located at distal long arm of chromosome 8. Multipoint analysis by GENEHUNTER (Ver 1.2) revealed a maximum multipoint LOD score of 3.909 and NPL score 9.209. Haplotype analyses revealed a critical region which spanned 10.18-cM on chromosome 8. CONCLUSION: We identified a 10.18-cM critical FALS region on chromosome 8. Further analyses using positional cloning and candidate gene approach are indicated to delineate the underlying genetic defect for FALS in this family.published_or_final_versio

Competências não técnicas do enfermeiro instrumentista

Relatório de Estágio apresentado para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Enfermagem PerioperatóriaO presente relatório de estágio enquadra-se no 1º Curso de Mestrado em Enfermagem Perioperatória, da Escola Superior de Saúde do Instituto Politécnico de Setúbal. Foi redigido segundo a metodologia de projeto, focando-se na integração de conhecimentos e competências adquiridas durante o curso, no domínio da enfermagem perioperatória. Tem como objetivos estabelecidos: (1) reflexão crítica acerca das atividades realizadas em contexto de estágio; (2) desenvolvimento de um projeto acerca das competências não técnicas do enfermeiro instrumentista; (3) reflexão crítica acerca do desenvolvimento de competências de mestre em enfermagem perioperatória. De forma a responder aos objetivos propostos organizou-se a estrutura deste relatório por três capítulos distintos: Capítulo I – onde consta o enquadramento concetual, considerando a teoria do autocuidado de Dorothea Elizabeth Orem; e enquadramento teórico, acerca do conceito de competência em enfermagem perioperatória. Capítulo II – corresponde ao enquadramento metodológico, onde é fundamentado o método seguido para a construção do projeto, exposto o tipo de estudo conduzido, o trabalho de campo desenvolvido, bem como os processos de colheita e tratamento de dados, considerando sempre as questões éticas do processo de investigação. Capítulo III – é realizada a reflexão sobre o estágio realizado, assim como a aquisição do perfil de competências de mestre em enfermagem perioperatória. A realização deste relatório de estágio permitiu a aquisição de conhecimentos no domínio da enfermagem perioperatória. Com os contributos da investigação elaborada, foi possível a compreensão e aplicação destes saberes para a resolução de problemas, em ambiente clinico multidisciplinar, consciente das implicações científicas, éticas, deontológicas e jurídicas.This internship report is part of the 1st Master in Perioperative Nursing, taken in Escola Superior de Saúde do Instituto Politécnico de Setúbal. It has been drafted according to project methodology, focusing on the integration of knowledge and skills acquired during the course in the field of perioperative nursing. Its stated objetives are: (1) critical analysis of the activities undertaken in the stage context; (2) project development for scrub nurses non-technical skills; (3) critical assessment on the development master competencies in perioperative nursing. In order to meet the proposed objetives, this report is organized by three chapters: Chapter I – with the conceptual framework, considering the self-care theory of Dorothea Elizabeth Orem; and theoretical framework of competence in perioperative nursing. Chapter II - corresponds to the methodological framework, which is based the method followed for the construction of the project, stated the type of study conducted, the field work and the procedures for collection and processing of data, always considering ethical issues in research process. Chapter III - is held to assess the internship stage, as well as the acquisition of master skills profile in perioperative nursing. The completion of this internship report allowed the acquisition of knowledge in the field of perioperative nursing. With the contributions of elaborate investigation, it was possible the understanding and application of this knowledge to solve problems in a multidisciplinary clinical environment, aware of the scientific, ethical, ethical and legal implications

A large Chinese kindred with familial ALS without SOD1 mutation

This journal suppl. contain abstracts of the 8th Medical Research Conference, Medical Science Group, Queen Mary Hospital, Hong Kongpublished_or_final_versio

Application of solid phase microextraction in the determination of paralytic shellfish poisoning toxins

A SPME-HPLC-post-column fluorescent derivatization method for the direct determination of saxitoxin (STX), the most potent paralytic shellfish poisoning (PSP) toxin, in water has been developed. Commercially available SPME devices with 50 μm Carbowax templated resin (CW/TPR) coating was found to be able to pre-concentrate STX from aqueous media. A special pre-conditioning treatment of soaking the SPME coating in 0.1 M NaOH solution significantly improved the extraction efficiency. The optimal pH for the SPME process is 8.1 and the equilibration time is 40 min. The partition coefficient, K, of the distribution of STX between the SPME coating and the aqueous media was measured to be 2.99 ± 0.04 × 103. Extracted toxin on the SPME stationary phase was difficult to be desorbed by the HPLC mobile phase under dynamic desorption mode. A static ion-pairing desorption technique using a desorption solvent mixture of 20 mM sodium 1-heptanesulfonate in 30% aqueous acetonitrile acidified with 50 mM sulfuric acid was developed to overcome this problem. The method detection limit and repeatability achieved by this SPME-HPLC method were 0.11 ng ml-1 and 3.7%, respectively, with a sample volume of just 5 ml of water. This analytical method is adequate for the monitoring of the PSP toxin in fresh/drinking waters. However, serious interference was observed when this technique was applied to saline water samples. This is probably due to competition of sodium ions with the cationic STX for absorption into the SPME stationary phase. © The Royal Society of Chemistry 2005.link_to_subscribed_fulltex

Effects of estrogen on parkin, UCH-L1, and uncoupling protein (UCP) 2, -4, and -5 on MPP+-induced apoptosis in human neuroblastoma

This journal suppl. entitled: Supplement: 8th International Congress of Parkinson's Disease and Movement DisordersPoster Session 1 - Basic ScienceOBJECTIVE: To explore the role of Parkin, UCH-L1 and uncoupling proteins (UCP2, 4 and 5) in estrogenic neuroprotection in MPP-induced cell death. BACKGROUND: Parkin and UCH-L1 are crucial enzymes in the ubiquitin-proteasome proteolytic system, and may be neuroprotective, and their activities are lost in juvenile-onset autosomal parkinsonism. Uncoupling Un-coupling proteins (UCPs) are mitochondrial transporter proteins involved in metabolic and thermoregulation. UCP2, 4 and 5 are abundantly expressed in the brain but their functions are unclear. UCP2 has neuroprotective properties, but whether UCP4 and 5 have similar properties is unknown. We explored whether neuroprotective effects of estrogen involve modulation of Parkin, UCH-L1, and UCPs to alleviate MPP-induced toxicity. METHODS: We used the MPP+ concentration that caused apoptosis as measured by caspase 3 activity (from total cell protein) and significant cell death as indicated by LDH release (from charcoal-stripped culture medium). Differentiated SK-N-SH cells were incubated for 24 hr in 17β- estradiol (E2; 1 µM) before MPP exposure for another 0, 24, 48 and 72 hr. Total RNA was digested with DNase I before spectrophotometric quantification. Corresponding mRNA levels of Parkin, UCH-L1, UCP2, 4 and 5 were measured using real-time RT-PCR. Ribosomal-18S RNA was used to normalize RNA amount. RESULTS: MPP (0.5 mM) exposure caused significant LDH release after 48 and 72 hr by 65% and 68%, respectively (P < 0.05), and increased caspase 3 activity by 15% after 24 hr and 36% after 48 hr (P < 0.01), and back to control level after 72 hr. E2 (1 µM) prevented apoptosis, and reduced MPP+-induced caspase 3 activity by 11% at 48 hr, although no significant differences were found at 24 or 72 hr. MPP+ increased UCP2 (0% at 24 hr, 16% at 48 hr, 38% at 72 hr) and UCP5 (33% at 24 hr, 55% at 48 hr, 65% at 72 hr), but not Parkin, UCH-L1, and UCP4. E2 pretreatment did not affect Parkin, UCH-L1, and UCP2, -4, -5 gene expression in MPP+-treated cells. CONCLUSION: Estrogen can protect against MPP-induced toxicity but it did not appear to involve modulation of Parkin, UCH-L1, UCP2, -4, and -5. However, the increase in UCP2 and -5 in MPP+ toxicity may indicate their possible roles in neuroprotection