A New Statistical Image Analysis Approach and Its Application to Hippocampal Morphometry

In this work, we propose a novel and powerful image analysis framework for hippocampal morphometry in early mild cognitive impairment (EMCI), an early prodromal stage of Alzheimer’s disease (AD). We create a hippocampal surface atlas with subfield information, model each hippocampus using the SPHARM technique, and register it to the atlas to extract surface deformation signals. We propose a new alternative to standard random field theory (RFT) and permutation image analysis methods, Statistical Parametric Mapping (SPM) Distribution Analysis or SPM-DA, to perform statistical shape analysis and compare its performance with that of RFT methods on both simulated and real hippocampal surface data. The major strengths of our framework are twofold: (a) SPM-DA provides potentially more powerful algorithms than standard RFT methods for detecting weak signals, and (b) the framework embraces the important hippocampal subfield information for improved biological interpretation. We demonstrate the effectiveness of our method via an application to an AD cohort, where an SPM-DA method detects meaningful hippocampal shape differences in EMCI that are undetected by standard RFT methods

The Teleost Retina as a Model for Developmental and Regeneration Biology

Retinal development in teleosts can broadly be divided into three epochs. The first is the specification of cellular domains in the larval forebrain that give rise to the retinal primordia and undergo early morphogenetic movements. The second is the neurogenic events within the retina proper—proliferation, cell fate determination, and pattern formation—that establish neuronal identities and form retinal laminae and cellular mosaics. The third, which is unique to teleosts and occurs in the functioning eye, is stretching of the retina and persistent neurogenesis that allows the growth of the retina to keep pace with the growth of the eye and other tissues. The first two events are rapid, complete by about 3 days postfertilization in the zebrafish embryo. The third is life-long and accounts for the bulk of retinal growth and the vast majority of adult retinal neurons. In addition, but clearly related to the retina's developmental history, lesions that kill retinal neurons elicit robust neuronal regeneration that originates from cells intrinsic to the retina. This paper reviews recent studies of retinal development in teleosts, focusing on those that shed light on the genetic and molecular regulation of retinal specification and morphogenesis in the embryo, retinal neurogenesis in larvae and adults, and injury-induced neuronal regeneration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63365/1/zeb.2004.1.257.pd

Environmentally friendly analysis of emerging contaminants by pressurized hot water extraction-stir bar sorptive extraction-derivatization and gas chromatography-mass spectrometry

This work describes the development, optimiza- tion, and validation of a new method for the simultaneous determination of a wide range of pharmaceuticals (beta- blockers, lipid regulators ... ) and personal care products (fragrances, UV filters, phthalates ... ) in both aqueous and solid environmental matrices. Target compounds were extracted from sediments using pressurized hot water ex- traction followed by stir bar sorptive extraction. The first stage was performed at 1,500 psi during three static extrac- tion cycles of 5 min each after optimizing the extraction temperature (50 – 150 °C) and addition of organic modifiers (% methanol) to water, the extraction solvent. Next, aqueous extracts and water samples were processed using polydime- thylsiloxane bars. Several parameters were optimized for this technique, including extraction and desorption time, ionic strength, presence of organic modifiers, and pH. Fi- nally, analytes were extracted from the bars by ultrasonic irradiation using a reduced amount of solvent (0.2 mL) prior to derivatization and gas chromatography – mass spectrome- try analysis. The optimized protocol uses minimal amounts of organic solvents (<10 mL/sample) and time ( ≈ 8 h/sam- ple) compared to previous ex isting methodologies. Low standard deviation (usually below 10 %) and limits of de- tection (sub-ppb) vouch for the applicability of the method- ology for the analysis of target compounds at trace levels. Once developed, the method was applied to determin

Case report of MR perfusion imaging in Sinking Skin Flap Syndrome: growing evidence for hemodynamic impairment

<p>Abstract</p> <p>Background</p> <p>The syndrome of the sinking skin flap (SSSF) with delayed sensorimotor deficits after craniectomy is not well known and often neglected. Among various postulated causes, there is evidence that disturbed brain perfusion may be related to the observed symptoms, and that cranioplasty reliably alleviates these symptoms. We report a case of sinking skin flap syndrome (SSFS) with recovery from neurological sensorimotor deficits after cranioplasty correlated with pre- and postsurgical MR brain perfusion studies.</p> <p>Case Presentation</p> <p>A 42-year-old woman presented with slowly progressive sensorimotor paresis of her left arm after decompressive extensive craniectomy due to subarachnoid hemorrhage four months ago. Her right cranium showed a "sinking skin flap". After cranioplastic repair of her skull defect, the patient fully recovered from her symptoms. Before cranioplasty, reduced brain perfusion in the right central cortical region was observed in MR-perfusion images. After cranioplasty, a marked increase in brain perfusion was observed which correlated with objective clinical recovery.</p> <p>Conclusion</p> <p>There is increasing evidence that impaired blood flow is responsible for delayed motor deficits in patients with sinking skin flap syndrome in the area of compressed brain regions. Symptoms should be evaluated by brain perfusion imaging complementing surgical decision-making.</p

On the Generalizability of Experimental Results

The age-old question of the generalizability of the results of experiments that are conducted in artificial laboratory settings to more realistic inferential and decision making situations is considered in this paper. Conservatism in probability revision provides an example of a result that 1) has received wide attention, including attention in terms of implications for real-world decision making, on the basis of experiments conducted in artificial settings and 2) is now apparently thought by many to be highly situational and not at all a ubiquitous phenomenon, in which case its implications for real-world decision making are not as extensive as originally claimed. In this paper we consider the questions of generalizations from the laboratory to the real world in some detail, both within the context of the experiments regarding conservatism and within a more general context. In addition, we discuss some of the difficulties inherent in experimentation in realistic settings, suggest possible procedures for avoiding or at least alleviating such difficulties, and make a plea for more realistic experiments

A large animal model of RDH5-associated retinopathy recapitulates important features of the human phenotype

Pathogenic variants in retinol dehydrogenase 5 (RDH5) attenuate supply of 11-cis-retinal to photoreceptors leading to a range of clinical phenotypes including night blindness due to markedly slowed rod dark adaptation and in some patients, macular atrophy. Current animal models (such as Rdh5-/- mice) fail to recapitulate the functional or degenerative phenotype. Addressing this need for a relevant animal model we present a new domestic cat model with a loss-of-function missense mutation in RDH5 (c.542G > T; p.Gly181Val). As with patients, affected cats have a marked delay in recovery of dark adaptation. Additionally, the cats develop a degeneration of the area centralis (equivalent to the human macula). This recapitulates the development of macular atrophy that is reported in a subset of patients with RDH5 mutations and is shown in this paper in 7 patients with biallelic RDH5 mutations. There is notable variability in the age at onset of the area centralis changes in the cat, with most developing changes as juveniles but some not showing changes over the first few years of age. There is similar variability in development of macular atrophy in patients and while age is a risk factor, it is hypothesized that genetic modifying loci influence disease severity, and we suspect the same is true in the cat model. This novel cat model provides opportunities to improve molecular understanding of macular atrophy and test therapeutic interventions for RDH5-associated retinopathies

Overexpression of human kynurenine-3-monooxygenase protects against 3-hydroxykynurenine-mediated apoptosis through bidirectional non-linear feedback

Kynurenine 3-monooxygenase (KMO) is a critical regulator of inflammation. The preferred KMO substrate, kynurenine, is converted to 3-hydroxykynurenine (3HK), and this product exhibits cytotoxicity through mechanisms that culminate in apoptosis. Here, we report that overexpression of human KMO with orthotopic localisation to mitochondria creates a metabolic environment during which the cell exhibits increased tolerance for exogenous 3HK-mediated cellular injury. Using the selective KMO inhibitor Ro61-8048, we show that KMO enzyme function is essential for cellular protection. Pan-caspase inhibition with Z-VAD-FMK confirmed apoptosis as the mode of cell death. By defining expression of pathway components upstream and downstream of KMO, we observed alterations in other key kynurenine pathway components, particularly tryptophan-2,3-dioxygenase upregulation, through bidirectional nonlinear feedback. KMO overexpression also increased expression of inducible nitric oxide synthase (iNOS). These changes in gene expression are functionally relevant, because siRNA knockdown of the pathway components kynureninase and quinolinate phosphoribosyl transferase caused cells to revert to a state of susceptibility to 3HK-mediated apoptosis. In summary, KMO overexpression, and importantly KMO activity, have metabolic repercussions that fundamentally affect resistance to cell stress

Thrombus or tumor? a case of fibroelastoma as indicated during the submission process

We describe the case of a 50-year-old woman who was admitted to a pheriferal department for heart failure. The echocardiography revealed a small mass measuring about 1.3 × 1.0 cm adhering to the non-coronary cusp of the aortic valve, mild dilated cardiomiopathy and severe biventricular dysfunction. This mass had erroneously been considered a thrombotic lesion, so the patient was treated with thrombolysis and heparin e.v. Only after a transoesophageal echocardiography a tumour cardiac mass was suspected. The diagnosis of fibroelastoma was confirmed by MRI and then from the anatomic and histoligical definition after surgery

Gliosarcoma: a study of four cases

Gliosarcomas (GS) are highly malignant and rare tumors of the central nervous system with a poor prognosis. We report here on four patients with GS, the median survival for whom was 9.25 months. Prognosis of GS remains poor, and a multidisciplinary approach (surgery, radiation therapy, and chemotherapy) seems to be associated with slightly more prolonged survival times

Juvenile obesity and its association with utilisation and costs of pharmaceuticals - results from the KiGGS study

<p>Abstract</p> <p>Background</p> <p>According to a national reference, 15% of German children and adolescents are overweight (including obese) and 6.3% are obese. An earlier study analysed the impact of childhood overweight and obesity on different components of direct medical costs (physician, hospital and therapists). To complement the existing literature for Germany, this study aims to explore the association of body mass index (BMI) with utilisation of pharmaceuticals and related costs in German children and adolescents.</p> <p>Methods</p> <p>Based on data from 14, 836 respondents aged 3-17 years in the German Interview and Examination Survey for Children and Adolescents (KiGGS), drug intake and associated costs were estimated using a bottom-up approach. To investigate the association of BMI with utilisation and costs, univariate analyses and multivariate generalised mixed models were conducted.</p> <p>Results</p> <p>There was no significant difference between BMI groups regarding the probability of drug utilisation. However, the number of pharmaceuticals used was significantly higher (14%) for obese children than for normal weight children. Furthermore, there was a trend for more physician-prescribed medication in obese children and adolescents. Among children with pharmaceutical intake, estimated costs were 24% higher for obese children compared with the normal weight group.</p> <p>Conclusions</p> <p>This is the first study to estimate excess drug costs for obesity based on a representative cross-sectional sample of the child and adolescent population in Germany. The results suggest that obese children should be classified as a priority group for prevention. This study complements the existing literature and provides important information concerning the relevance of childhood obesity as a health problem.</p