Deep brain stimulation in Bassen-Kornzweig syndrome: Still effective after 22 years.

Introduction: Bassen-Kornzweig syndrome or abetalipoproteinemia is a rare autosomal recessive disorder characterized by a malabsorption of dietary fat and fat-soluble vitamins. This deficiency can lead to a variety of symptoms, including hematological (acanthocytosis, bleeding tendency), neurological (tremor, spinocerebellar ataxia), neuromuscular (myopathy), ophthalmological symptoms (retinitis pigmentosa). The thalamic ventral intermediate nucleus (VIM) is a well-established target for deep brain stimulation (DBS) in the treatment of refractory tremor. Research question: We evaluated the clinical long-term follow-up (22 years) after VIM-DBS for refractory tremor in abetalipoproteinemia. We also evaluated the adjustments of stimulation settings and medication balance after DBS procedure. Material and methods: We report a 53-year-old male who suffers from abetalipoproteinemia since the age of 17. He underwent bilateral VIM-DBS to treat his disabling refractory intentional tremor at the age of 31. He still has a very good response to his tremor with limited stimulation adaptations over 22 years. For more than two decades follow-up, the treatment significantly improved his ADL functions and therefore also the QoL. Discussion and conclusion: The VIM target for DBS in the treatment of refractory tremor has been extensively reported in the literature. Thalamic VIM-DBS is a safe and effective treatment for a severe, refractory tremor as a neurological symptom caused by abetalipoproteinemia. It also highlights the importance of a multidisciplinary follow-up, to adjust and optimize the stimulation/medication balance after VIM-DBS surgery.

Regional environmental pressure influences population differentiation in turbot (Scophthalmus maximus).

Unravelling the factors shaping the genetic structure of mobile marine species is challenging due to the high potential for gene flow. However, genetic inference can be greatly enhanced by increasing the genomic, geographical or environmental resolution of population genetic studies. Here, we investigated the population structure of turbot (Scophthalmus maximus) by screening 17 random and gene-linked markers in 999 individuals at 290 geographical locations throughout the northeast Atlantic Ocean. A seascape genetics approach with the inclusion of high-resolution oceanographical data was used to quantify the association of genetic variation with spatial, temporal and environmental parameters. Neutral loci identified three subgroups: an Atlantic group, a Baltic Sea group and one on the Irish Shelf. The inclusion of loci putatively under selection suggested an additional break in the North Sea, subdividing southern from northern Atlantic individuals. Environmental and spatial seascape variables correlated marginally with neutral genetic variation, but explained significant proportions (respectively, 8.7% and 10.3%) of adaptive genetic variation. Environmental variables associated with outlier allele frequencies included salinity, temperature, bottom shear stress, dissolved oxygen concentration and depth of the pycnocline. Furthermore, levels of explained adaptive genetic variation differed markedly between basins (3% vs. 12% in the North and Baltic Sea, respectively). We suggest that stable environmental selection pressure contributes to relatively strong local adaptation in the Baltic Sea. Our seascape genetic approach using a large number of sampling locations and associated oceanographical data proved useful for the identification of population units as the basis of management decisions.

Recombinant expression of trypanosome surface glycoproteins in Pichia pastoris for the diagnosis of Trypanosoma evansi infection.

Serodiagnosis of surra, which causes vast economic losses in livestock, is still based on native antigens purified from bloodstream form Trypanosoma (T.) evansi grown in rodents. To avoid the use of laboratory rodents in antigen preparation we expressed fragments of the invariant surface glycoprotein (ISG) 75, cloned from T. brucei gambiense cDNA, and the variant surface glycoprotein (VSG) RoTat 1.2, cloned from T. evansi gDNA, recombinantly in Pichia (P.) pastoris. The M5 strain of this yeast has an engineered N-glycosylation pathway resulting in homogenous Man5GlcNAc2 N-glycosylation which resembles the predominant Man9-5GlcNAc2 oligomannose structures in T. brucei. The secreted recombinant antigens were affinity purified with yields of up to 10mg and 20mg per liter cell culture of rISG 7529-465-E and rRoTat 1.223-385-H respectively. In ELISA, both recombinant proteins discriminated between pre-immune and immune serum samples of 25 goats experimentally infected with T. evansi. The diagnostic potential of rRoTat 1.223-385-H but not of rISG 7529-465-E was confirmed with sera of naturally infected and control dromedary camels. The results suggest that rRoTat 1.223-385-H expressed in P. pastoris requires further evaluation before it could replace native RoTat 1.2 VSG for serodiagnosis of surra, thus eliminating the use of laboratory animals for antigen production.

Renal replacement therapy in acute renal failure in children.

Acute renal failure in children differs from adult patients in incidence, pathogenesis and size of the patient, but outcome is significantly better. Specific problems are access and haemodynamic stability. Where increasing reporting on the use of CRRT in children seems to convince that CRRT is the treatment of choice, we have to stress that there is no evidence for this statement. Part of this misunderstanding is that both peritoneal and haemodialysis techniques from chronic renal replacement therapy (RRT) are simply extrapolated to intensive care setting. In this paper we want to elaborate on several adaptations in the dialysis-prescription of both peritoneal dialysis and haemodialysis in the ARF setting, which may improve efficacy and outcome. Introduction of new peritoneal dialysis catheter techniques, the cyclers, bicarbonate solutions, combined glucose/amino acid solutions, and low sodium-solutions have overcome many of the inconveniences of the old CAPD-technique. Slow SLED haemodialysis, with an ambulant Genius haemodialyser, with the use of ultra pure water adds to the benefits of conventional haemodialysis (monitoring, safetyness) to better haemodynamic stability of CRRT techniques.

RNA diversity has profound effects on the translation of neuronal nitric oxide synthase.

A comprehensive analysis of the structure of neuronal nitric oxide synthase (nNOS; EC 1.14.13.39) mRNA species revealed NOS1 to be the most structurally diverse human gene described to date in terms of promoter usage. Nine unique exon 1 variants are variously used for transcript initiation in diverse tissues, and each is expressed from a unique 5'-flanking region. The dependence on unique genomic regions to control transcription initiation in a cell-specific fashion burdens the transcripts with complex 5'-mRNA leader sequences. Elaborate splicing patterns that involve alternatively spliced leader exons and exon skipping have been superimposed on this diversity. Highly structured nNOS mRNA 5'-untranslated regions, which have profound effects on translation both in vitro and in cells, contain cis RNA elements that modulate translational efficiency in response to changes in cellular phenotype.

Regional diastolic wall motion dynamics in anterior myocardial infarction: analysis and quantification with magnetic resonance imaging.

BACKGROUND: Regional variability in systolic and diastolic cardiac function occurs in most cardiac disorders. The influence of this regional functional heterogeneity on global function is not well understood and is difficult to study with the common imaging modalities. METHODS: A midventricular short axis slice of the left ventricle was obtained with ECG-triggered magnetic resonance imaging in eight infarct patients and 10 control volunteers. The variation in wall thickness and slice cavity volume during the cycle was studied using the centreline method. RESULTS: The peak filling rate was significantly decreased in the infarct group (96 versus 58 cm3/s, P < 0.005). In addition, a small contribution of other parameters, such as the time to end systole, the isovolumic relaxation time, and the duration and extent of early filling, was also shown by linear discriminant analysis. Analysis of the regional parameters demonstrated an increased asynchronicity of contraction (64 versus 37 ms, P < 0.01) as well as relaxation (88 versus 51 ms, P < 0.01) in patients with myocardial infarction. On comparison of the anterior (infarcted) and inferior (non-infarcted) parts of the left ventricle, the difference was present only in the infarct region. CONCLUSION: Magnetic resonance imaging of the heart allows evaluation of the relationship between regional differences in wall motion dynamics and global parameters of diastolic function in infarct patients.