Radiostrontium sorption on natural glauconite sands of the Neogene-Paleogene formations in Belgium.

The Neogene-Paleogene glauconite sands are investigated for radionuclide sorption in the framework of the Belgian radioactive waste disposal program. This study was set up to measure the adsorption of radiostrontium (85Sr) on the sands and on glauconite fractions to identify factors explaining variable sorption among different formations. Batch 85Sr sorption experiments were set up with 45 different glauconite sands and glauconite fractions (125-250 µm) in a background solution of 1 mM CaCl2.H2O and 0.5 mM KCl. The distribution coefficients (KD) for 85Sr2+ ranged 23-65 L kg-1 for the intact sands and ranged 50-144 L kg-1 for the glauconite fractions. The KD values strongly correlated with the CEC (R2 = 0.62 for sands and 0.82 for glauconite fractions) and corresponded well with CEC based predictions based on two existing models calibrated to soils. The KD on the complete sand is proportional to the glauconite content and the KD of the glauconite fraction if no other clay minerals are present in significant amounts. Sorption equilibrium was reached within 48 h in the complete sands, in milled complete sands, in glauconite fractions and in milled glauconite fractions, suggesting no diffusive boundaries in the glauconite pellets. It is concluded that glauconite sands have a suitably high retention of radiostrontium and the sorption strength is in line with that of other geological barriers when judged from the CEC.

Spondylo-epiphyseal dysplasia in two sibs due to a homozygous splicing variant in COL2A1.

Type 2 collagenopathies encompass a large group of chondrodysplasias ranging from the perinatally lethal achondrogenesis type 2 and hypochondrogenesis at the severe end of the spectrum to early-onset osteoarthritis with normal stature at the milder end of the spectrum. With the exception of a few reported cases, these dysplasias are predominantly caused by heterozygous variants in the COL2A1 gene and hence show an autosomal dominant inheritance pattern. Here we report on two siblings, originating from a consanguineous family, who presented with disproportionate short stature, ocular abnormalities, cleft palate and hearing impairment. The radiographic study showed signs of a spondyloepiphyseal dysplasia, compatible with a type 2 collagen disorder. Indeed, both siblings were homozygous for a c.3111+2T > Cp.(Glu1033Lysfs*5) splice site variant in the COL2A1 gene. cDNA analysis performed on skin fibroblasts from the affected sibs revealed the co-occurrence of the wild-type transcript and an aberrant splice product, the latter believed to be degraded by nonsense-mediated mRNA decay. The parents who were heterozygous for this variant were phenotypically normal. This paper confirms that type 2 collagenopathies can show an autosomal recessive inheritance.

Radiocaesium sorption on natural glauconite sands is unexpectedly as strong as on Boom Clay.

The Neogene-Paleogene glauconite sands of Belgium cover the Boom Clay deposits that are candidate host for radioactive waste disposal. It is unclear if the highly permeable sand formations may act as an additional barrier for radiocesium (137Cs) or could be added as a complementary sorption sink in a surface disposal concept. Glauconite is an Fe-rich phyllosilicate that is mainly present as 250-125 µm sized pellets in sand, it is unknown to what extent and how fast these pellets may bind 137Cs. Pelletized clays embedded in sand may have poorly accessible high affinity sites for 137Cs. The 137Cs sorption on 11 different glauconite sands was measured in batch in a background solution of 0.1 M CaCl2 and 0.5 mM KCl. The log transformed 137Cs distribution coefficient Kd (L kg-1) after 30 days reaction ranged 3.4-4.3, surprisingly close to the Kd of the Boom Clay (3.5). Isolated glauconite fractions exhibited similar 137Cs sorption potentials (log Kd 4.1-4.3) as the reference Illite du Puy (4.4). The small Kd variation among the Neogene-Paleogene sands was explained by its glauconite content (r = 0.82). The 137Cs sorption kinetics (1-57 days) of milled pellets (<2 µm) confirmed slower reaction with intact pellets than with milled samples. Additionally, the Kd values of milled samples (57 days) sorption are 1.1-1.5 fold larger than the corresponding intact pellets, suggesting that not all Cs binding sites are accessible in intact pellets. Strongly weathered pellets exhibited cracks (visible with SEM). In these pellets the Kd was similar for milled and intact pellets suggesting that cracks increase the accessibility of the inner sorption sites. After 8.5 months the Kd values were 1.6-1.8-fold above corresponding 1 month data and these long-term reactions were more pronounced as total sand K content was larger. An adsorption-desorption experiment illustrated that 137Cs sorption is not fully reversible.

Overlapping but distinct roles for NOTCH receptors in human cardiovascular disease.

The NOTCH signalling pathway is an essential pathway, involved in many cellular processes, including cell fate decision, cell proliferation, and cell death and important in the development of most organs. Mutations in genes encoding components of the NOTCH signalling pathway lead to a spectrum of congenital disorders. Over the past decades, mutations in human NOTCH signalling genes have been identified in several diseases with cardiovascular involvement. NOTCH1 mutations have been described in bicuspid aortic valve disease, left-sided congenital heart disease, and Adams-Oliver syndrome. NOTCH2 mutations lead to the development of Alagille syndrome, while mutations in NOTCH3 cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. To date, mutations in NOTCH4 have not been associated with cardiovascular disease. This review focuses on the mutations described in NOTCH1, NOTCH2, and NOTCH3 and their associated cardiovascular phenotypes.

Treatment of boundary conditions in through-diffusion: A case study of (85)Sr(2+) diffusion in compacted illite.

Valuable techniques to measure effective diffusion coefficients in porous media are an indispensable prerequisite for a proper understanding of the migration of chemical-toxic and radioactive micropollutants in the subsurface and geosphere. The present article discusses possible pitfalls and difficulties in the classical through-diffusion technique applied to situations where large diffusive fluxes of cations in compacted clay minerals or clay rocks occur. The results obtained from a benchmark study, in which the diffusion of (85)Sr(2+) tracer in compacted illite has been studied using different experimental techniques, are presented. It is shown that these techniques may yield valuable results provided that an appropriate model is used for numerical simulations. It is further shown that effective diffusion coefficients may be systematically underestimated when the concentration at the downstream boundary is not taken adequately into account in modelling, even for very low concentrations. A criterion is derived for quasi steady-state situations, by which it can be decided whether the simplifying assumption of a zero-concentration at the downstream boundary in through-diffusion is justified or not. The application of the criterion requires, however, knowledge of the effective diffusion coefficient of the clay sample. Such knowledge is often absent or only approximately available during the planning phase of a diffusion experiment.

Genetics of sudden cardiac death in the young.

Sudden cardiac death (SCD) has an enormous impact on those who are left behind, evoking strong feelings of anxiety and incomprehension because such a dramatic event was not anticipated. Moreover, over the last decade a prominent genetic contribution to the pathogenesis of SCD has been unveiled. As many inherited cardiac diseases show an autosomal dominant pattern of inheritance, the risk of carrying the same inherited predisposition is a real concern for the relatives. In this article, we discuss the major causes of primary electrical disorders, cardiomyopathies and thoracic aortic dissection and address issues in genotype-phenotype correlation, personalized management and cardiogenetic counselling.

[Growth behavior after epiphyseal plate injury: importance of "watertight" osteosynthesis]. / Wachstumsverhalten nach Fugenverletzungen: Bedeutung von "wasserdichten" Osteosynthesen.

BACKGROUND: The frequency figures for epiphyseal plate injuries of long bones given in the literature are inexact and they probably occur with a frequency of 15% of all fractures of the growing skeleton. In order to be able to give correct figures in the future a classification system, such as the LiLa classification should be used, which does not attempt to be oriented to an assumed growth prognosis but is oriented to therapy and makes a strict differentiation between shaft and joint fractures. For epiphyseal joint fractures a differentiation must be made between those where the epiphysis is still open and those where the epiphysis has begun to close, in order to be able to incorporate all epiphyseal joint fractures and differentiate them from epiphyseal shaft fractures (epiphysiolysis). CLINICAL ASPECTS: The growth prognosis encompasses stimulatory and inhibitory growth disorders as well as spontaneous correction of residual axial deviations. The prognosis is fundamentally dependent on the biological age of the patient by fracture, on the localization in the skeleton and the localization in the segment because the growth components of epiphyses are asymmetrically distributed in the segment. Stimulatory growth disorders in the actual growth phase < 10 years of age are the obligatory growth disorders which lead to overgrowth of the section of the skeleton affected. In an age over 10 years they lead to an also obligatory premature closure of adjacent or affected epiphyses which is expressed as a slight shortening. Asymmetrical stimulations are most common in the upper extremities following intra-articular fractures of the radial condyle as the obligatory growth disorder at this site. Asymmetrical stimulation is rare in the lower extremities after extra-articular metaphyseal valgus fractures of the proximal and distal tibia. Asymmetrical premature closure of the epiphysis in the upper extremities is rare in contrast to partial stimulation with less than 5% after extra-articular fractures of the distal radius and proximal humerus. Conversely, asymmetrical inhibitory growth disorders are found significantly more often in the lower extremities after extra-articular and intra-articular fractures of the distal femur, proximal tibia and distal tibia between 50% and 20%. "Spontaneous corrections" of residual axial deviations and side to side shifts after epiphyseal shaft fractures occur reliably without resulting in growth disorders, provided the patient is young enough. THERAPEUTIC TARGETS: In cases of displacement the aim of therapy in epiphyseal shaft fractures is to reconstitute age-related and tolerable axes. For displaced epiphyseal joint fractures the aim is to reconstruct the joint surfaces. The basic principles of an efficient and targeted diagnostics and the therapeutic options for diminishing the clinical sequelae of growth disorders are discussed. CONCLUSION: No growth disorders, which are to be expected as a result of every epiphyseal injury, can primarily be therapeutically avoided; however, better foundations can be achieved to reduce the clinical sequelae of growth disorders. Therapy can only follow the differentiation into shaft and joint (and not an assumed growth prognosis) and should integrate a scientifically proven and reasonable spontaneous correction for the patient. A classification must achieve a therapy-related uncoupling of the epiphyseal injuries into shaft and joint fractures.

[Growth behavior after femoral shaft fractures: feasibility of patient therapy targets]. / Wachstumsverhalten nach Oberschenkelschaftfrakturen: Umsetzbarkeit von Patiententherapiezielen.

BACKGROUND: The treatment of femoral shaft fractures has increasingly become a domain of surgical therapy. On the one hand the possibilities of spontaneous correction of shaft axis deviation and rotation are limited and on the other hand leg length differences are often observed as a result of shaft fractures, which can lead to relevant consequences for spinal and pelvic statics. OBJECTIVES: Is there a benefit from the increasing trend towards surgical therapy and what treatment options are currently available for the treatment of femoral shaft fractures? MATERIAL AND METHODS: Analysis of treatment recommendations and a literature search of the last decades. RESULTS AND DISCUSSION: Newly developed implants currently provide a variety of methods for osteosynthesis for each age group and each fracture type. This allows a better fracture, weight and age adjusted retention of fractures with increased stability and a lower risk of post-traumatic leg length differences. Secondary effects are prompt mobilization and reintegration in the social environment of patients and hence a better achievement of their own therapeutic goals.

[Growth behaviour after fractures of the proximal radius: differences to the rest of the skeleton]. / Wachstumsverhalten nach Frakturen des proximalen Radiusendes: Unterschiede zum übrigen Skelett.

BACKGROUND: Fractures of the proximal end of the radius in the growth phase have three characteristics: the head of the radius articulates with two joint partners and is therefore indispensable for an undisturbed function of the elbow. The blood supply of the proximal end of the radius is via periosteal vessels in the sense of a terminal circulation which makes it extremely vulnerable. Severe trauma caused either by accidents or treatment, can result in partial or complete necrosis with deformity of the head and neck region of the radius. INJURY PATTERNS: Radioulnar synostosis and chronic epiphysiolysis are irreversible complications which can occur after excessive physiotherapy. Despite a low potency growth plate, in young patients the proximal end of the radius shows an enormous spontaneous correction of dislocations. Side to side shifts, however, will not be remodeled. THERAPY: Therapy should be as atraumatic as possible. Due to the blood supply situation, with the appropriate indications the spontaneous correction and a brief period of immobilization without physiotherapy should be integrated into the therapy concept. If an operation is necessary, repeated traumatic repositioning maneuvers should be avoided and in case of doubt closed or careful open repositioning can be achieved with intramedullary nailing. CONCLUSION: In order to take the special characteristics of the proximal radius into consideration, the vulnerability and correction potential must be weighed up against each other. Therapy must be as atraumatic as possible. The spontaneous correction potential should be integrated into the primary therapy without overestimating this potential with respect to the extent and age of the patient.

[Is there life after trauma surgery? Charitable activities after retirement]. / Gibt es ein Leben nach der Unfallchirurgie? Gemeinnützige Tätigkeiten nach der Pensionierung.

Every profession, even that of a doctor of traumatology has to be kept in motion by personal convictions and indignations. It is the only way to give the profession a profile and to get a profile back. This dynamic process also remains at the end of the professional career even when it is no longer the profession and refers"only" to one's own life, as (to be honest) it always was before anyway. So profession is life and life is profession, even afterwards.

Large scale mtDNA sequencing reveals sequence and functional conservation as major determinants of homoplasmic mtDNA variant distribution.

The mitochondrial DNA (mtDNA) is highly variable, containing large numbers of pathogenic mutations and neutral polymorphisms. The spectrum of homoplasmic mtDNA variation was characterized in 730 subjects and compared with known pathogenic sites. The frequency and distribution of variants in protein coding genes were inversely correlated with conservation at the amino acid level. Analysis of tRNA secondary structures indicated a preference of variants for the loops and some acceptor stem positions. This comprehensive overview of mtDNA variants distinguishes between regions and positions which are likely not critical, mainly conserved regions with pathogenic mutations and essential regions containing no mutations at all.

Inherited mitochondrial variants are not a major cause of age-related hearing impairment in the European population.

Mitochondrial DNA (mtDNA) mutations have been implicated in various age-related diseases. To further clarify the role of mtDNA variants in age-related hearing impairment (ARHI), we determined the DNA sequence of the entire mitochondrial genome of 400 individuals using the Affymetrix Human Mitochondrial Resequencing Array. These were the 200 worst hearing and the 200 best hearing from a collection of 947 Belgian samples. We performed association tests with individual mitochondrial variants, comparison of the mutation load, and association with European haplogroups and their interaction with environmental risk factors. We also tested the influence of rare variants on ARHI. None of these tests showed any association with ARHI.

I know the pain you feel-how the human brain's default mode predicts our resonance to another's suffering.

Introspective and self-referential in nature, the human brain's default mode network (DMN) is presumed to influence our behavior in response to the environment in predictive manner [Raichle ME, Gusnard DA (2005) J Comp Neurol 493:167-176; Bar M (2009) Philos Trans R Soc Lond B Biol Sci 364:1235-1243]. In the current study, we hypothesize that the strength of DMN-connectivity contributes to distinct introspective psychological processes in every-day social life such as the intuitive understanding of other people through inner representation of their affective states -e. g. his or her pain. 19 healthy individuals underwent functional MRI scanning, which consisted of a resting-state-scan followed by the presentation of visual stimuli depicting human limbs in painful and non-painful situations. After scanning, participants were asked to evaluate the stimuli in terms of pain intensity perceived from the first person perspective. Independent component analysis (ICA) demonstrated that higher integration of the left medial orbitofrontal cortex (BA 32) into the anterior default mode network (aDMN) was associated with higher post-scan pain ratings. Furthermore, the exposition to the "Pain"-pictures led to relative increases of aDMN-activity compared to "No Pain"-stimuli which were also correlated with the subjective pain intensity. The behaviorally predictive functional architecture during a task-free period supports the notion that the DMN serves as a "memory of the future" [Ingvar DH (1985) Hum Neurobiol 4:127-136] in terms of a neuronal cache, storing "a priori scripts," which are recalled to deal efficiently with upcoming environmental events. In addition, our results suggest that an individual predisposition to identify oneself with another's pain influences the automatic response of the DMN during the observation of painful situations.

Involvement of T-cell receptor-beta alterations in the development of otosclerosis linked to OTSC2.

Otosclerosis is a common form of hearing loss, characterized by disordered bone remodeling in the otic capsule. Within the otosclerotic foci, several immunocompetent cells and immune-modulating factors can be found. Different etiological theories involving the immune system have been suggested. However, a genetic component is clearly present. In large otosclerosis families, seven autosomal-dominant loci have been found, but none of the disease-causing genes has been identified. This study focused on the exploration of the second otosclerosis locus on chromosome 7q34-36 (OTSC2), holding the T-cell receptor beta locus (TRB locus). A significantly lower T-cell receptor-beta (TCR-beta) mRNA expression and percentage of blood circulating TCR-alphabeta(+) T cells was detected in OTSC2 patients compared with controls and patients with the complex form of the disease. Further analysis illustrated more significant disturbances in specific T-cell subsets, including an increased CD28(null) cell population, suggesting a disturbed T-cell development and ageing in OTSC2 patients. These disturbances could be associated with otosclerotic bone remodeling, given the known effects of immunocompetent cells on bone physiology. These data implicate the TRB locus as the causative gene in the OTSC2 region and represent an important finding in the elucidation of the disease pathology.

[Influence of exogenic factors on age-related hearing impairment]. / Einfluss exogener Faktoren auf Altersschwerhörigkeit

BACKGROUND: Age-related hearing impairment is a complex disorder, the causes for which have been insufficiently studied. Genetic and environmental factors all play a role. METHODS: A total of 406 persons aged between 53 and 67 years old were interviewed about various causes and audiometric data were collected. The audiometric pure tone data were adjusted for sex and age and tested for association with exposure to risk factors. RESULTS: Significant negative effects of noise exposure, painkillers, overweight, and cardiovascular diseases on hearing loss were found. A positive effect of moderate alcohol consumption could also be shown in the elderly. These results suggest that a healthy lifestyle can positively affect age-related hearing impairment.

Candidate gene association study for noise-induced hearing loss in two independent noise-exposed populations.

Millions of people are daily exposed to high levels of noise. Consequently, noise-induced hearing loss (NIHL) is one of the most important occupational health hazards worldwide. In this study, we performed an association study for NIHL based on a candidate gene approach. 644 Single Nucleotide Polymorphisms (SNPs) in 53 candidate genes were analyzed in two independent NIHL sample sets, a Swedish set and part of a Polish set. Eight SNPs with promising results were selected and analysed in the remaining part of the Polish samples. One SNP in PCDH15 (rs7095441), resulted in significant associations in both sample sets while two SNPs in MYH14 (rs667907 and rs588035), resulted in significant associations in the Polish sample set and significant interactions with noise exposure level in the Swedish sample set. Calculation of odds ratios revealed a significant association of rs588035 with NIHL in the Swedish high noise exposure level group. Our studies suggest that PCDH15 and MYH14 may be NIHL susceptibility genes, but further replication in independent sample sets is mandatory.

[Conservative treatment of fractures of the long bones during the growth phase]. / Die konservative Behandlung von Frakturen der langen Röhrenknochen im Wachstumsalter.

In the treatment of fractures of the long bones in children and adolescents, surgical and conservative methods are not mutually exclusive alternatives; rather, each can complement the other in the overall treatment strategy. Many operative procedures, such as fixation of juxtaarticular, metaphyseal fractures, need to be supplemented by conservative procedures, such as immobilization by means of casts. We refer to methods that are performed without anaesthesia and do not involve the implantation of osteosynthetic foreign material as conservative. These are: immobilization with no further treatment, plaster wedging, and functional treatment options. The indications for purely conservative treatment strategies are basically different for articular and nonarticular fractures. Whereas in the case of articular fractures only the nondisplaced fractures are treated by conservative methods, in the case of nonarticular (shaft) fractures those involving a degree of displacement, as long as it is not too pronounced to allow the integration of spontaneous corrections, can also be treated conservatively.

A new, easy, and rapid high-throughput detection method for the common GJB2 (CX26), 35delG mutation.

GJB2 (Gap Junction protein beta type 2; Connexin 26, CX26) is known for its contribution to nonsyndromic recessive deafness (NSRD). One particular mutation, 35delG, a deletion of one guanine from a stretch of six leading to a frame shift early in the gene, has a high prevalence in populations from European descent. 35delG testing therefore has become a standard test in genetic diagnostic laboratories. Most of the currently available methods for the detection of 35delG are relatively time consuming, and not suited for high-throughput diagnostic testing. Within this paper we present a real-time PCR genotyping assay based on melting curve analysis, requiring only a single preparation step before the actual analysis. The assay was optimized on a panel of 48 samples with known 35delG genotypes and subsequently tested using a large Belgian population (N = 460) with unknown 35delG status. For the latter set of samples, real-time PCR results were validated with SNAPShot, an assay used in our laboratory for diagnostic purposes. The real-time PCR genotyping method has proven to be highly reliable, rapid, cost-effective, and suitable for high-throughput screening. We believe that this genetic test for 35delG will find widespread applications in the DNA diagnostic field.