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General Fusion is building the Fusion Demonstration Plant to demonstrate a magnetized target fusion scheme in which a deuterium plasma is heated from 200 eV to 10 keV by piston-driven compression of a liquid-lithium liner. The multilayer coaxial time-of-flight neutron emission spectrometer is designed to measure the ion temperature near peak compression at which time the neutron yield will approach 1018 neutrons/s. The neutron energy distribution is expected to be Gaussian since the machine uses no neutral beam or radio-frequency heating. In this case, analysis shows that as few as 500 coincidence events should be sufficient to accurately measure the ion temperature. This enables a fast time resolution of 10 µs, which is required to track the rapid change in temperature approaching peak compression. We overcome the challenges of neutron pile-up and event ambiguity with a compact design having two layers of segmented scintillators. The error in the ion temperature measurement is computed as a function of the neutron spectrometer's geometric parameters and used to optimize the design for the case of reaching 10 keV at peak compression.
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INTRODUCTION: Non-unions remain a clinical problem and are characterised by the failure to heal after a defined period of time. Current preclinical non-union models apply a wide variety of techniques to diminish intrinsic healing potential deviating from the clinical situation. The aim of this study was to develop and characterise a non-union model in rats using internal plate fixation without the need for additional healing insults, whereby bone healing can be longitudinally assessed using microCT. It was hypothesized that healing/non-unions can be accurately predicted at early time points by microCT. MATERIALS AND METHODS: Female, skeletally mature Fischer F344 rats received a 2 mm or 1 mm femoral osteotomy, stabilized with either a 2 mm thick plate or a 1.25 mm thick plate. Healing was monitored by microCT over 14 weeks and histological analysis at euthanasia. The mechanical environment was characterised using finite element (FE) modelling and biomechanical testing. RESULTS: The majority of animals receiving the 2 mm thick plate displayed poor healing responses in both the 2 mm and 1 mm defect size groups. Bone and cartilage formation were markedly improved using the 1.25 mm thick plate. MicroCT could accurately predict bone forming capacity at early time points (3-4 weeks). CONCLUSIONS: The 2 mm thick plating system confers poor healing responses in female Fischer F344 rats, comparable to atrophic non-unions. By reducing plate thickness to increase interfragmentary strain within the defect site healing is improved, leading to borderline healing situations or increased abundance of cartilage tissue present in the defect site with ultimate failure to bridge the defect (hypertrophic non-union). Furthermore, microCT can reliably identify delayed/non-healing animals within 4 weeks, thereby allowing their selective targeting for the testing of novel, clinically relevant treatment strategies in different clinical situations aimed at restoring impaired bone healing.
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Placas Ósseas , Consolidação da Fratura , Animais , Feminino , Fixação Interna de Fraturas/métodos , Consolidação da Fratura/fisiologia , Ratos , Ratos Endogâmicos F344 , Microtomografia por Raio-XRESUMO
Diatoms are single cell eukaryotic microalgae; their surface possesses a porous nanostructured silica cell wall or frustule. Diatomaceous earth (DE) or diatomite is a natural siliceous sediment of diatoms. Since silica has been proved to have adjuvant capabilities, we propose that diatoms and DE may provide an inexpensive and abundant source of adjuvant readily available to use in livestock vaccines.In a first experiment, the safety of diatoms used as an adjuvant for in-ovo vaccination was investigated. In a second experiment, we assessed the humoral immune response after one in-ovo vaccination with inactivated Newcastle Disease Virus (NDV) and DE as adjuvant followed by 2 subcutaneous boosters on d 21 and 29 of age. In both experiments, results were compared to Freund's incomplete adjuvant and aluminum hydroxide.No detrimental effects on hatchability and chick quality were detected after in-ovo inoculation of diatoms and DE in experiments 1 and 2 respectively. In experiment 2 no humoral responses were detected after the in-ovo vaccination until 29 d of age. Seven d after the second subcutaneous booster an antibody response against NDV was detected in chickens that had received vaccines adjuvanted with Freund's incomplete adjuvant, aluminum hydroxide, and DE. These responses became significantly higher 10 d after the second booster. Finally, 15 d after the second booster, the humoral responses induced by the vaccine with Freund's incomplete adjuvant were statistically higher, followed by comparable responses induced by vaccines containing DE or aluminum hydroxide that were significantly higher than DE+PBS, PBS+INDV and PBS alone. From an applied perspective, we can propose that DE can serve as a potential adjuvant for vaccines against poultry diseases.
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Galinhas , Terra de Diatomáceas/farmacologia , Diatomáceas/química , Doença de Newcastle/imunologia , Vírus da Doença de Newcastle/imunologia , Doenças das Aves Domésticas/imunologia , Vacinas Virais/imunologia , Adjuvantes Imunológicos/farmacologia , Animais , Embrião de Galinha/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Imunização Secundária/veterinária , Injeções Subcutâneas , Vacinas de Produtos Inativados/imunologiaRESUMO
OBJECTIVES: Minocycline is a tetracycline antibiotic increasingly recognized in psychiatry for its pleiotropic anti-inflammatory and neuroprotective potential. While underlying mechanisms are still incompletely understood, several lines of evidence suggest a relevant functional overlap with retinoic acid (RA), a highly potent small molecule exhibiting a great variety of anti-inflammatory and neuroprotective properties in the adult central nervous system (CNS). RA homeostasis in the adult CNS is tightly controlled through local RA synthesis and cytochrome P450 (CYP450)-mediated inactivation of RA. Here, we hypothesized that minocycline may directly affect RA homeostasis in the CNS via altering local RA degradation. METHODS: We used in vitro RA metabolism assays with metabolically competent synaptosomal preparations from murine brain and human SH-SY5Y neuronal cells as well as viable human SH-SY5Y neuroblastoma cell cultures. RESULTS: We revealed that minocycline potently blocks RA degradation as measured by reversed-phase high-performance liquid chromatography and in a viable RA reporter cell line, even at low micromolar levels of minocycline. CONCLUSIONS: Our findings provide evidence for enhanced RA signalling to be involved in minocycline's pleiotropic mode of action in the CNS. This novel mode of action of minocycline may help in developing more specific and effective strategies in the treatment of neuroinflammatory or neurodegenerative disorders.
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Encéfalo/efeitos dos fármacos , Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Minociclina/farmacologia , Neurônios/efeitos dos fármacos , Tretinoína/metabolismo , Animais , Encéfalo/metabolismo , Linhagem Celular Tumoral , Humanos , Masculino , Neuroblastoma/metabolismo , Ratos , Ratos Wistar , Análise de RegressãoRESUMO
Diatoms are a renewable (biologically reproducible) source of three-dimensional (3-D) nanostructured silica that could be attractive for a variety of photonic devices, owing to the wide range of quasi-periodic patterns of nano-to-microscale pores available on the silica microshells (frustules) of various diatom species. We have investigated the optical behavior of the silica frustule of a centric marine diatom, Coscinodiscus wailesii, using a coherent broadband (400-1700 nm) supercontinuum laser focused to a fine (20 µm diameter) spot. The C. wailesii frustule valve, which possessed a quasi-periodic hexagonal pore array, exhibited position-dependent optical diffraction. Changes in such diffraction behavior across the frustule were consistent with observed variations in the quasi-periodic pore pattern.
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Diatomáceas , Luz , Nanoestruturas , Dióxido de Silício/análise , AnimaisRESUMO
Duplications of 7q11.23, deleted in Williams-Beuren Syndrome, have been implicated in autism spectrum disorders (ASDs). A 1.5 Mb duplication was identified in one girl with severe expressive language deficits and anxiety among 1,142 ASD individuals screened for this duplication. Family-based association studies of Tag-SNPs in three genes (STX1A , CYLN2 and GTF2i) in two multiplex autism family cohorts revealed strong association of two GTF2i SNPs and their haplotype in Cohort 1 and the combined families. The risk alleles and haplotype were associated with severe problems in social interaction and excessive repetitive behaviors. Our findings suggest the GTF2i gene is important in the etiology of autism in individuals with this duplication and in non-duplication cases with severe social interaction problems and repetitive behaviors.
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Alelos , Transtornos Globais do Desenvolvimento Infantil/genética , Deleção Cromossômica , Duplicação Cromossômica/genética , Cromossomos Humanos Par 7/genética , Estudos de Associação Genética , Polimorfismo de Nucleotídeo Único/genética , Fatores de Transcrição TFII/genética , Síndrome de Williams/genética , Regiões 5' não Traduzidas/genética , Transtornos de Ansiedade/genética , Criança , Éxons/genética , Feminino , Triagem de Portadores Genéticos , Marcadores Genéticos/genética , Testes Genéticos , Humanos , Relações Interpessoais , Transtornos do Desenvolvimento da Linguagem/genética , Análise de Sequência com Séries de Oligonucleotídeos , Comportamento EstereotipadoRESUMO
This prospective study was performed in order to establish whether improvement of endothelial function after weight reduction can be explained by a decrease of elevated asymmetric dimethyl arginine (ADMA), an inhibitor of endogenous NO-synthase (eNOS). Therefore, 21 obese subjects (BMI: 41.1±6.4 kg/m(2)) were studied at baseline and after 12 weeks of weight reduction with a very low calorie diet. Biochemical and clinical parameters of endothelial function were assessed before and after weight loss. Biochemical parameters were determined by measurement of ADMA and soluble intercellular adhesion molecule (sICAM). Clinical parameters were assessed by pulse wave analysis (PWA). Weight intervention resulted in a 21.4±6.8 kg reduction of body weight from 119.7±12.8 kg at study start to 98.3±11.6 kg at study end (p<0.001). Accordingly, biochemical markers improved under weight reduction (ADMA from 0.47±0.07 mmol/l to 0.42±0.08 mmol/l; p=0.002; ICAM from 276±42 ng/ml to 236±29 ng/ml; p<0.001). Further, clinical parameters of functional endothelial function improved with an increase of deltaRI after salbutamol inhalation from -1% before to -9% after weight reduction (p=0.02). Interestingly, improvement of endothelial function correlated with improved HOMA index only (r=-0.60, p=0.04) but not with reduced ADMA levels, improved hypertension or reduced body weight. In conclusion, weight reduction with a very low calorie diet improves endothelial function measured by pulse wave velocity. The missing correlation with ADMA suggests possible further mechanisms underlying this observed effect, for example, improvement of insulin resistance.
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Arginina/análogos & derivados , Células Endoteliais/fisiologia , Obesidade/metabolismo , Redução de Peso , Adolescente , Adulto , Idoso , Arginina/metabolismo , Índice de Massa Corporal , Restrição Calórica/estatística & dados numéricos , Moléculas de Adesão Celular/metabolismo , Células Endoteliais/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/dietoterapia , Obesidade/fisiopatologia , Adulto JovemRESUMO
A 29-year old man is admitted in our hospital for a dry cough which appeared a few weeks earlier and is now associated with a breath depending thoracic pain. As an engineer, he is realizing a thesis about the sound waves produced by coughing and is therefore frequently exposed to patients with various pulmonary infections. The chest X-ray, presents predominant pulmonary infiltrates on the periphery of the upper fields of the lungs. Blood analysis revealed a hypereosinophilia of 4.650/microl. The various bacteriological, parasitic and viral investigation tests are negative. The bronchioalveolar washing reveals more than 50% eosinophils. Exclusive pulmonary impairment and lack of autoantibody moved us to the diagnosis of chronic eosinophilic pneumonia (or Carrington syndrome). Corticosteroids were started at the dosis of 0,5 mg/kg of methyl-prednisolone. Clinical and biological features improved amazingly within 48 hours. This case report illustrates the overlap between the chronic eosinophilic pneumonia and the Churg-Strauss desease who can be considered as variants of the hypereosinophilic syndrome (HES). Therefore, the use of anti-interleukin-5 antibodies, already used in the SHE and Churg-Strauss syndrome, might be useful in this case.
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Pneumonia/diagnóstico por imagem , Pneumonia/etiologia , Som , Corticosteroides/uso terapêutico , Adulto , Algoritmos , Síndrome de Churg-Strauss/complicações , Síndrome de Churg-Strauss/diagnóstico por imagem , Síndrome de Churg-Strauss/tratamento farmacológico , Tosse/complicações , Tosse/diagnóstico por imagem , Tosse/tratamento farmacológico , Diagnóstico Diferencial , Humanos , Síndrome Hipereosinofílica/complicações , Síndrome Hipereosinofílica/diagnóstico por imagem , Síndrome Hipereosinofílica/tratamento farmacológico , Masculino , Pneumonia/tratamento farmacológico , Eosinofilia Pulmonar/complicações , Eosinofilia Pulmonar/diagnóstico por imagem , Eosinofilia Pulmonar/tratamento farmacológico , Radiografia Torácica , Som/efeitos adversosRESUMO
BACKGROUND AND PURPOSE: SKF96365 (SKF), originally identified as a blocker of receptor-mediated calcium entry, is widely used diagnostically, as a blocker of transient receptor potential canonical type (TRPC) channels. While SKF has been used as a tool to define the functional roles of TRPC channels in various cell and tissue types, there are notable overlapping physiological and pathophysiological associations between TRPC channels and low-voltage-activated (LVA) T-type calcium channels. The activity of SKF against T-type Ca channels has not been previously explored, and here we systematically investigated the effects of SKF on recombinant and native voltage-gated Ca channel-mediated currents. EXPERIMENTAL APPROACH: Effects of SKF on recombinant Ca channels were studied under whole-cell patch clamp conditions after expression in HEK293 cells. The effect of SKF on cerebellar Purkinje cells (PCs) expressing native T-type Ca channels was also assessed. KEY RESULTS: SKF blocked recombinant Ca channels, representative of each of the three main molecular genetic classes (Ca(V)1, Ca(V)2 and Ca(V)3) at concentrations typically utilized to assay TRPC function (10 microM). Particularly, human Ca(V)3.1 T-type Ca channels were more potently inhibited by SKF (IC(50) approximately 560 nM) in our experiments than previously reported for similarly expressed TRPC channels. SKF also inhibited native Ca(V)3.1 T-type currents in a rat cerebellar PC slice preparation. CONCLUSIONS AND IMPLICATIONS: SKF was a potent blocker of LVA T-type Ca channels. We suggest caution in the interpretation of results using SKF alone as a diagnostic agent for TRPC activity in native tissues.
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Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo T/efeitos dos fármacos , Imidazóis/farmacologia , Animais , Bloqueadores dos Canais de Cálcio/administração & dosagem , Canais de Cálcio Tipo T/metabolismo , Linhagem Celular , Humanos , Imidazóis/administração & dosagem , Concentração Inibidora 50 , Rim/citologia , Masculino , Técnicas de Patch-Clamp , Células de Purkinje/efeitos dos fármacos , Células de Purkinje/metabolismo , Ratos , Ratos Wistar , Canais de Potencial de Receptor Transitório/antagonistas & inibidoresRESUMO
Myosin VIIA mutations have been associated with non-syndromic hearing loss (DFNB2; DFNA11) and Usher syndrome type 1B (USH1B). We report clinical and genetic analyses of a consanguineous Iranian family segregating autosomal recessive non-syndromic hearing loss (ARNSHL). The hearing impairment was mapped to the DFNB2 locus using Affymetrix 50K GeneChips; direct sequencing of the MYO7A gene was completed. The Iranian family (L-1419) was shown to segregate a novel homozygous missense mutation (c.1184G>A) that results in a p.R395H amino acid substitution in the motor domain of the myosin VIIA protein. As one affected family member had significantly less severe hearing loss, we used a candidate approach to search for a genetic modifier. This novel MYO7A mutation is the first reported to cause DFNB2 in the Iranian population and this DFNB2 family is the first to be associated with a potential modifier. The absence of vestibular and retinal defects, and less severe low frequency hearing loss, is consistent with the phenotype of a recently reported Pakistani DFNB2 family. Thus, we conclude this family has non-syndromic hearing loss (DFNB2) rather than USH1B, providing further evidence that these two diseases represent discrete disorders.
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Perda Auditiva/genética , Mutação de Sentido Incorreto , Miosinas/genética , Adulto , Sequência de Aminoácidos , Sequência de Bases , Mapeamento Cromossômico , Consanguinidade , Família , Feminino , Perda Auditiva Neurossensorial/genética , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Miosina VIIaRESUMO
BACKGROUND: The government's proposals to openly report clinical outcomes poses challenges to the National Bowel Cancer Audit now funded by the UK department of health. AIM: To identify the benefits and risks of open reporting and to propose ways the risks might be minimized. METHODS: A review of the literature on clinical audit and the consequences of open reporting. RESULTS: There are significant potential benefits of a national audit of bowel cancer including protecting patients from sub-standard care, providing clinicians with externally validated evidence of their performance, outcome data for clinical governance and evidence that increases in government expenditure are achieving improvements in survival from bowel cancer. These benefits will only be achieved if the audit captures most of the cases of bowel cancer in the UK, the data collected is complete and accurate, the results are risk adjusted and these are presented to the public in a way that is fair, clear and understandable. Involvement of clinicians who have confidence in the results of the audit and who actively compare their own results against a national standard is essential. It is suggested that a staged move to open reporting should minimise the risk of falsely identifying an outlying unit. CONCLUSION: The fundamental aim of the National Bowel Cancer Audit is the pursuit of excellence by identification and adoption of best practice. This could achieve a continuous improvement in the care of all patients with bowel cancer in the UK. The ACPGBI suggests a safer way of transition to open reporting to avoid at least some of its pitfalls.
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Auditoria Clínica/métodos , Neoplasias Intestinais/terapia , Avaliação de Resultados em Cuidados de Saúde/métodos , Garantia da Qualidade dos Cuidados de Saúde/métodos , Humanos , Avaliação de Resultados em Cuidados de Saúde/legislação & jurisprudência , Melhoria de Qualidade , Medição de Risco , Reino UnidoRESUMO
An outstanding example of biological pattern formation at the single cell level is the diversity of biomineral structures in the silica cell walls of the unicellular eukaryotic algae known as diatoms. We present a survey of cell wall silica structures of 16 diatom species, which included all major cell wall components (valves, girdle bands and setae), imaged across the nano-, meso- and microscales using atomic force microscopy. Because of atomic force microscopy's superior ability to image surface topology, this approach enabled visualization of the organization of possible underlying organic molecules involved in mineral structure formation. Diatom nanoscale silica structure varied greatly comparing the same feature in different species and different features within a single species, and frequently on different faces of the same object. These data indicate that there is not a strict relation between nanoscale silica morphology and the type of structure that contains it. On the mesoscale, there was a preponderance of linear structures regardless of the object imaged, suggesting that assembly or organization of linear organic molecules or subcellular assemblies that confine a linear space play an essential and conserved role in structure formation on that scale. Microscale structure imparted an overall influence over nano- and mesoscale structure, indicating that shaping of the silica deposition vesicle plays a key role in structure formation. These results provide insights into the design and assembly principles involved in diatom silica structure formation, facilitating an understanding of the native system and potentially aiding in development of biomimetic approaches.
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Parede Celular/ultraestrutura , Diatomáceas/ultraestrutura , Microscopia de Força Atômica/métodos , Dióxido de SilícioRESUMO
BACKGROUND: Autism spectrum disorders (ASDs) are common, heritable neurobiologic conditions of unknown aetiology confounded by significant clinical and genetic heterogeneity. METHODS: This study evaluated a broad categorisation of phenotypic traits (or phenome) for 100 subjects with Autism Diagnostic Interview-Revised/Autism Diagnostic Observation Schedule-Generic (ADI-R/ADOS-G) confirmed idiopathic ASD undergoing 1 Mb bacterial artificial chromosome (BAC) array comparative genomic hybridisation (CGH). RESULTS AND CONCLUSIONS: Array CGH uncovered nine different pathogenic copy number variants (pCNVs) in 9/100 ASD subjects having complex phenotypes (ASD+/- intellectual disability (ID; IQ<70)) and/or physical anomalies), normal karyotype, fragile X analysis, and comprehensive evaluation by a clinical geneticist. Unique pCNVs in our cohort included del(5)(p15.2p15.31) (2.4 Mb), del(3)(p24.3) (0.1 Mb) and dup(18)(p11.3)(0.9 Mb). Five pCNVs were recurrent in our cohort or were previously described in subjects with ASD+/-ID: (dup(7)(q11.23)(1.5 Mb); del(2)(p15p16.1) (6.1 Mb and 7.9 Mb); del(14)(q11.2) (0.7 Mb) and dup(15)(q11q13) (10 Mb), including del(X)(p11.22) (470 Kb) in two autistic brothers. Male: female distribution in subjects with pCNVs was reduced to 1.25:1 from 3.2:1 in the original cohort. The authors stratified the study population according to a broad spectrum of clinical features and correlated specific phenotypes with respect to CNV load and pathogenicity. The findings indicate increased prevalence of pCNVs in subjects with microcephaly (<2nd centile; n = 2 of 4 ASD subjects with microcephaly; p = 0.04), and ID (n = 9 of 64 subjects with ASD and ID; p = 0.02). Interestingly, in the absence of ID co-morbidity with an ASD, no pCNVs were found. The relationship between parental ages at delivery and CNV load and pathogenicity was also explored.
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Transtornos Globais do Desenvolvimento Infantil/genética , Variação Genética , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Dosagem de Genes , Genótipo , Humanos , Masculino , FenótipoRESUMO
We describe two brothers with autistic disorder, intellectual disability (ID) and cleft lip/palate with a microdeletion of Xp11.22 detected through screening individuals with autism spectrum disorders (ASDs) for microdeletions and duplications using 1-Mb resolution array comparative genomic hybridization. The deletion was confirmed by fluorescence in situ hybridization/real-time quantitative polymerase chain reaction (RT-qPCR) and shown to be inherited from their unaffected mother who had skewed (100%) X inactivation of the aberrant chromosome. RT-qPCR characterization of the del(X)(p11.22) region ( approximately 53,887,000-54,359,000 bp) revealed complete deletion of the plant homeodomain finger protein 8 (PHF8) gene as well as deletions of the FAM120C and WNK lysine-deficient protein kinase 3 (WNK3) genes, for which a definitive phenotype has not been previously characterized. Xp11.2 is a gene-rich region within the critical linkage interval for several neurodevelopmental disorders. Rare interstitial microdeletions of Xp11.22 have been recognized with ID, craniofacial dysmorphism and/or cleft lip/palate and truncating mutations of the PHF8 gene within this region. Despite evidence implicating genes within Xp11.22 with language and cognitive development that could contribute to an ASD phenotype, their involvement with autism has not been systematically evaluated. Population screening of 481 (319 males/81 females) and 282 X chromosomes (90 males/96 females) in respective ASD and control cohorts did not identify additional subjects carrying this deletion. Our findings show that in addition to point mutations, a complete deletion of the PHF8 gene is associated with the X-linked mental retardation Siderius-Hamel syndrome (OMIM 300263) and further suggest that the larger size of the Xp11.22 deletion including genes FAM120C and WNK3 may be involved in the pathogenesis of autism.
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Transtorno Autístico/genética , Deleção Cromossômica , Cromossomos Humanos X/genética , Proteínas de Membrana/genética , Proteínas Serina-Treonina Quinases/genética , Fatores de Transcrição/genética , Transtorno Autístico/etiologia , Estudos de Casos e Controles , Fenda Labial/genética , Fissura Palatina/genética , Saúde da Família , Feminino , Deleção de Genes , Histona Desmetilases , Humanos , Masculino , Programas de Rastreamento , Proteínas de Membrana/deficiência , Transtornos Mentais/genética , Deficiência Intelectual Ligada ao Cromossomo X/genética , Linhagem , Proteínas Serina-Treonina Quinases/deficiência , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Irmãos , Fatores de Transcrição/deficiência , Inativação do Cromossomo XRESUMO
BACKGROUND: Minimising the soft tissue trauma and early rehabilitation are among the major aims using the MIS technique in joint replacement. AIM: The aim of this prospective randomised study is to compare the results after TKA using an MIS approach versus a standard approach. METHOD: We compared 30 TKA using a mini-midvastus approach (MIS group) with 30 conventionelly performed TKA using a midvastus approach (control group). In all cases the same implants (NexGen LPS) were used. The Knee Society score (KSS), an activity score, the visual analogue scale, myoglobin and creatinine kinase as well as the blood loss were measured up to 12 weeks postoperatively. Implant positioning was evaluated using the Knee Society Roentgenographic evaluation and scoring system. RESULTS: Advantages of the MIS group were measured in KSS and activity score up to 12 weeks postoperatively. The increase of myoglobin and creatinine kinase was lower in the MIS group up to 24 hours or 72 hours, respectively. No differences were found comparing the implant positioning and blood loss. CONCLUSION: The MIS technique in TKA with minimisation of the soft tissue trauma leads to better clinical and functional results in the early postoperative time and does not modify the implant positioning.
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Artroplastia do Joelho/métodos , Procedimentos Cirúrgicos Minimamente Invasivos , Complicações Pós-Operatórias/reabilitação , Idoso , Perda Sanguínea Cirúrgica/prevenção & controle , Creatina Quinase/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mioglobina/sangue , Medição da Dor , Complicações Pós-Operatórias/sangue , Estudos Prospectivos , Amplitude de Movimento Articular/fisiologiaRESUMO
Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with a strong genetic aetiology. In approximately 1% of cases, duplication of the 15q11-13 region has been reported. We report the clinical, array-comparative genomic hybridization (CGH) and cytogenetic evaluation of two individuals from a multiplex family demonstrating autism due to a maternally inherited gain of 15q11-13. Our findings indicate that unlike most 15q11-13 gains, which are caused by interstitial duplication of this region or supernumerary marker chromosomes deriving from proximal 15q, the 15q gain in this family is the result of abnormal segregation of a cryptic familial translocation with breakpoints at 14q11.2 and 15q13.3. The affected members of this family were found to have a normal karyotype at >550 band resolution. This translocation was identified using the 1-Mb resolution whole genome array (Spectral Genomics). The affected individuals have a gain of seven clones from proximal 15q, a loss of two clones from proximal 14q and a gain of two clones from 6q. Fluorescent in situ hybridization (FISH) analysis with clones from chromosomes 14 and 15, combined with DAPI reverse banding, showed an abnormal karyotype with one normal chromosome 15 and the der(15) t(14;15)(q11.2.;q13.3), resulting in the gain of proximal 15q and the loss of proximal 14q in affected individuals. The duplication of two clones from 6q in the affected subjects was also found in unaffected members of the family. Our findings suggest that the gain of 15q in autism may in some cases be due to cryptic translocations with breakpoints in the pericentromic regions of chromosome 15 and a different acrocentric chromosome. Variation in the size of pericentromic regions of any acrocentric chromosome may justify karyotype and FISH studies of autistic probands and their parents using probes from the 15q proximal region to determine recurrence risk for autism in some families.
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Transtorno Autístico/genética , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 15/genética , Duplicação Gênica , Translocação Genética/genética , Adolescente , Adulto , Criança , Bandeamento Cromossômico , Saúde da Família , Feminino , Genoma Humano , Genômica , Humanos , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Masculino , Hibridização de Ácido Nucleico , LinhagemRESUMO
The small basic histone-like protein H-NS is known for bacteria to attenuate virulence of several animal pathogens. An hns homologue from E. amylovora was identified by complementing an E. coli hns-mutant strain with a cosmid library from E. amylovora. A 1.6 kb EcoRI-fragment complemented the mucoid phenotype and repressed the ss-glucosidase activity of E. coli PD32. The open reading frame encoding an H-NS-like protein of 134 amino acid was later shown to be located on plasmid pEA29 (McGhee and Jones 2000). A chromosomal hns gene was amplified with PCR consensus primers and localized near galU of E. amylovora. E. amylovora mutants were created by insertion of a resistance cassette, and the intact gene was inserted into a high copy number plasmid for constitutive expression. Purified chromosomal H-NS protein preferentially bound to a DNA fragment from the lsc region and bending was predicted for an adjacent fragment with the rlsB-promoter. Levan production was significantly increased by hns mutations. Synthesis of the capsular exopolysaccharide amylovoran and of levan were reduced, when hns from the E. amylovora plasmid was overexpressed. A mutation in chromosomal hns of E. amylovora increased amylovoran synthesis, and both mutations retarded symptom formation on immature pears.