Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy: parallels with Stiff-Person Syndrome and other movement disorders

Background Cerebral palsy (CP) is an heterogeneous group of neurological disorders of movement and/or posture, with an estimated incidence of 1 in 1000 live births. Non-progressive forms of symmetrical, spastic CP have been identified, which show a Mendelian autosomal recessive pattern of inheritance. We recently described the mapping of a recessive spastic CP locus to a 5 cM chromosomal region located at 2q24-31.1, in rare consanguineous families. Methods Here we present data that refine this locus to a 0.5 cM region, flanked by the microsatellite markers D2S2345 and D2S326. The minimal region contains the candidate gene GAD1, which encodes a glutamate decarboxylase isoform (GAD67), involved in conversion of the amino acid and excitatory neurotransmitter glutamate to the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Results A novel amino acid mis-sense mutation in GAD67 was detected, which segregated with CP in affected individuals. Conclusions This result is interesting because auto-antibodies to GAD67 and the more widely studied GAD65 homologue encoded by the GAD2 gene, are described in patients with Stiff-Person Syndrome (SPS), epilepsy, cerebellar ataxia and Batten disease. Further investigation seems merited of the possibility that variation in the GAD1 sequence, potentially affecting glutamate/GABA ratios, may underlie this form of spastic CP, given the presence of anti-GAD antibodies in SPS and the recognised excitotoxicity of glutamate in various contexts

Effect of nanosilica-based activators on the performance of an alkali-activated fly ash

This paper assesses the effect of the use of an alternative activator based on nanosilica/MOH (M = K+ or Na+) blended solutions on the performance of alkali-activated fly ash binders. Binders produced with commercial silicate activators display a greater degree of reaction, associated with increased contents of geopolymer gel; however, mortars produced with the alternative nanosilica-based activators exhibited lower water demand and reduced permeability, independent of the alkali cation used. Na-based activators promote higher compressive strength compared with K-based activators, along with a refined pore structure, although K-activated samples exhibit reduced water demand. Zeolite type products are the major crystalline phases formed within these binders. A wider range of zeolites is formed when using commercial silicate solutions compared with the alternative activators. These results suggest that there are variations in the availability of Si in the system, and consequently in the alkalinity, depending on the silicate source in the activator, which is important in determining the nanostructure of the geopolymer gel.This study was sponsored by the Ministerio de Ciencia e Innovacion of Spain (Project GEORES MAT2010-19934 and research scholarship BES-2008-002440), European regional development fund (FEDER), and the Universitat Politecnica de Valencia (Spain). The participation of SAB and JLP was funded by the Australian Research Council (ARC), including partial funding through the Particulate Fluids Processing Centre, a Special Research Centre of the ARC. A special acknowledgement is also due to the Centre of Electron Microscopy of the Universitat Politecnica de Valencia and Pedro Garces from the Universidad de Alicante for support in some experiments.Rodriguez Martinez, ED.; Bernal, SA.; Provis, JL.; Paya Bernabeu, JJ.; Monzó Balbuena, JM.; Borrachero Rosado, MV. (2013). Effect of nanosilica-based activators on the performance of an alkali-activated fly ash. Cement and Concrete Composites. 35(1):1-11. doi:10.1016/j.cemconcomp.2012.08.025S11135

Dental amalgam and mercury in dentistry

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Mercury in dentistry has re-emerged as a contentious issue in public health, predominantly because so many people are inadvertently exposed to mercury in order to obtain the benefits of dental amalgam fillings, and the risks remain difficult to interpret. This commentary aims to examine the issues involved in public policy assessment of the continued use of dental amalgam in dentistry.AJ Spence

Estudo comparativo da análise de ciclo de vida de concretos geopoliméricos e de concretos à base de cimento Portland composto (CP II)

A Análise de Ciclo de Vida (ACV) é um método que inclui a compilação e avaliação das entradas, saídas e dos impactos de um produto ao longo do seu ciclo de vida. Os resultados desta análise são utilizados para escolher alternativas favoráveis para uma aplicação específica. Este artigo utilizou as ferramentas de ACV, apoiada pelo software Umberto, para comparar o processo de obtenção de concretos de cimento Portland com o de concretos geopoliméricos, obtidos da ativação alcalina de aluminossilicatos. O impacto ambiental foi avaliado considerando 1 m³ de cada concreto, sendo (i) as emissões de CO2 (kg CO2/ m³) e (ii) a demanda energética (MJ/m³) as variáveis para determinar o potencial sustentável de ambos materiais. O objetivo principal foi avaliar se os concretos geopoliméricos são mais sustentáveis do que os concretos tradicionais. Os resultados obtidos mostraram que o consumo energético é reduzido em 45,8% na produção do concreto geopolimérico, quando comparado à produção do concreto de cimento Portland de desempenho mecânico equivalente. Com relação às emissões de CO2, o concreto geopolimérico reduz as emissões em 72,4%, em comparação ao concreto tradicional de cimento Portland CPII. Assim, o primeiro se mostra uma alternativa a ser considerada, na produção de materiais de construção de menor impacto ambiental

Long-term outcome of preterm infants treated with nasal continuous positive airway pressure

This study's aim was to assess neurodevelopmental and growth outcome until the age of 4 years of premature infants placed on early nCPAP, in the setting of the neonatal intensive care unit (NICU) and follow-up program of the Division of Neonatology of the Department of Pediatrics of the University Hospital, Lausanne, Switzerland. All consecutive inborn infants weighing <1500 g or <32 weeks of gestational age admitted to the NICU during two periods of 12 months-7.1996-6.1997 and 7.1998-6.1999-were compared before and after the systematic application of early nCPAP. Of 172 infants admitted to the NICU, 150 (87%) survived. 126 (84%) were tested at 6 months' corrected age, 121 (81%) at 18 months' corrected age, and 117 (78%) at the age of 4 years. Detailed perinatal data were collected. Follow-up included neurological examination, developmental testing and measurement of growth parameters. Statistical analyses were performed. Early application of nCPAP and avoidance of mechanical ventilation showed no adverse effects on neurodevelopment and growth. A significantly higher developmental quotient was found in the nCPAP group at 18 months' corrected age. Several trends were also noted in the nCPAP group with a decrease of intraventricular hemorrhage and in "abnormal neurodevelopment" at 6 months corrected age, a bigger head circumference at all different tested ages and a greater height at 6 and 18 months corrected ages. In conclusion, our study of developmental outcome documents the absence of any harmful effect of early application of nCPAP to treat respiratory failure in very low birthweight infants

CONSTRUCTIONOFAN FIA UNIT AND ITS USE IN THE INVESTIGATION OF IMMOBILISED LIGNIN PEROXIDASE

A flow injection analyser was designed to serve asa tool for the characterisation of enzymes. The original device was constructed from available laboratory equipment, and has subsequently been refined to a fully automated, stand alone unit. The hard- and software have been so conceived as to enable a wide range of applications. All system components are controlled by a microprocessor, which also takes over data acquisition, peak integration and evaluation, and provides a convenientinterface to the user via a key-board and display. We have used this FIA system to investigate the enzymatic properties of lignin peroxidase. This enzyme is believed to play a key role in the biodegradation oflignin by white-rot fungi, and has attracted interest for use in various industrial processes. Lignin peroxidase has a very similar mechanism of action to horse radish peroxidase, butdiffers in its ability to oxidise organic compoundsof higher oxidation potential, and in its extreme sensitivity to inactivation by excess H2O2. The enzyme can be successfully immobilised on a variety of carriers. However when investigated in batch assays, the loss of activity is such that repeated experimentation is impossible. FIA is characterised by small sample volumes, and thus low contact times when working with an immobilised enzyme. We have exploited this to enable investigation of an essentially unstable enzyme system