Transcranial sonography for diagnosis of Parkinson's disease

<p>Abstract</p> <p>Background</p> <p>In idiopathic Parkinson's disease (IPD) transcranial sonography (TCS) represents an alternative diagnostic method to verify clinical diagnosis. Although the phenomenon of an increased echogenicity of the Substantia nigra (SN) is well known this method is still not widly used in the diagnostic workup. Until now reliability of this method is still a matter of debate, partly because data only existed from a few laboratories using the same ultrasound machine. Therefore our study was conducted to test the reliability of this method by using a different ultrasound device and examining a large population of control and IPD subjects by two examiners to calculate interobserver reliability.</p> <p>Method</p> <p>In this study echogenicity of SN was examined in 199 IPD patients and 201 control subjects. All individuals underwent a neurological assessment including Perdue pegboard test and Webster gait test. Using a Sonos 5500 ultrasound device area of SN was measured, echogenicity of raphe, red nuclei, thalamus, caudate and lenticular nuclei, width of third and lateral ventricle were documented.</p> <p>Results</p> <p>We found a highly characteristic enlargement of the SN echogenic signal in IPD. The cut-off value for the SN area was established using a ROC curve with a sensitivity of 95% corresponding to an area of SN of 0.2 cm²and was found to be equivalent to the cut-off values of other studies using different ultrasound devices.</p> <p>Conclusions</p> <p>Our study shows that TCS is a reliable and highly sensitive tool for differentiation of IPD patients from individuals without CNS disorders.</p

Psychometric properties of the IDS-SR30 for the assessment of depressive symptoms in spanish population

<p>Abstract</p> <p>Background</p> <p>Due to the high prevalence of depression, it is clinically relevant to improve the early identification and assessment of depressive episodes. The main objective of the present study was to examine the psychometric properties of the IDS-SR₃₀(Self-rated Inventory of Depressive Symptomatology) in a large Spanish sample of depressive patients.</p> <p>Methods</p> <p>This prospective, naturalistic, multicenter, nationwide epidemiological study conducted in Spain included 1595 adult patients (65.3% females) with a DSM-IV Major Depressive Disorder (MDD. IDS-SR₃₀and the Hamilton Depression Rating Scale (HDRS, 21 items)were administered to the sample. Data was collected during 2 routine visits. The second assessment was carried out after 10 ± 2 weeks after first assessment.</p> <p>Results</p> <p>The IDS-SR₃₀showed good internal consistency (α = 0.94) and high item total correlations (≥ 0.50) were found in 70% of the items. The convergent validity was 0.85. Results of the principal component analysis (PCA) and confirmatory factor analyses (CFA) showed that a three factor model (labelled mood/cognition, anxiety/somatic and sleep) is adequate for the current sample.</p> <p>Conclusions</p> <p>The Spanish version of the IDS-SR₃₀seems a reliable, valid and useful tool for measuring depression symptomatology in Spanish population.</p

Children's active play: self-reported motivators, barriers and facilitators

Physical activity has important benefits for children's physical health and mental wellbeing, but many children do not meet recommended levels. Research suggests that active play has the potential to make a valuable contribution to children's overall physical activity, whilst providing additional cognitive, social and emotional benefits. However, relatively little is known about the determinants of UK children's active play. Understanding these factors provides the critical first step in developing interventions to increase children's active play, and therefore overall physical activity. Eleven focus groups were conducted with 77, 10-11 year old children from four primary schools in Bristol, UK. Focus groups examined: (i) factors which motivate children to take part in active play; (ii) factors which limit children's active play and (iii) factors which facilitate children's active play. All focus groups were audio-taped and transcribed verbatim. Data were analysed using a thematic approach. Children were motivated to engage in active play because they perceived it to be enjoyable, to prevent boredom, to have physical and mental health benefits and to provide freedom from adult control, rules and structure. However, children's active play was constrained by a number of factors, including rainy weather and fear of groups of teenagers in their play spaces. Some features of the physical environment facilitated children's active play, including the presence of green spaces and cul-de-sacs in the neighbourhood. Additionally, children's use of mobile phones when playing away from home was reported to help to alleviate parents' safety fears, and therefore assist children's active play. Children express a range of motivational and environmental factors that constrain and facilitate their active play. Consideration of these factors should improve effectiveness of interventions designed to increase active play

Transcriptional regulatory program in wild-type and retinoblastoma gene-deficient mouse embryonic fibroblasts during adipocyte differentiation

<p>Abstract</p> <p>Background</p> <p>Although many molecular regulators of adipogenesis have been identified a comprehensive catalogue of components is still missing. Recent studies showed that the retinoblastoma protein (pRb) was expressed in the cell cycle and late cellular differentiation phase during adipogenesis. To investigate this dual role of pRb in the early and late stages of adipogenesis we used microarrays to perform a comprehensive systems-level analysis of the common transcriptional program of the classic 3T3-L1 preadipocyte cell line, wild-type mouse embryonic fibroblasts (MEFs), and retinoblastoma gene-deficient MEFs (Rb-/- MEFs).</p> <p>Findings</p> <p>Comparative analysis of the expression profiles of 3T3-L1 cells and wild-type MEFs revealed genes involved specifically in early regulation of the adipocyte differentiation as well as secreted factors and signaling molecules regulating the later phase of differentiation. In an attempt to identify transcription factors regulating adipogenesis, bioinformatics analysis of the promoters of coordinately and highly expressed genes was performed. We were able to identify a number of high-confidence target genes for follow-up experimental studies. Additionally, combination of experimental data and computational analyses pinpointed a feedback-loop between Pparg and Foxo1.</p> <p>To analyze the effects of the retinoblastoma protein at the transcriptional level we chose a perturbated system (Rb-/- MEFs) for comparison to the transcriptional program of wild-type MEFs. Gene ontology analysis of 64 deregulated genes showed that the Rb-/- MEF model exhibits a brown(-like) adipocyte phenotype. Additionally, the analysis results indicate a different or additional role for pRb family member involvement in the lineage commitment.</p> <p>Conclusion</p> <p>In this study a number of commonly modulated genes during adipogenesis in 3T3-L1 cells and MEFs, potential transcriptional regulation mechanisms, and differentially regulated targets during adipocyte differentiation of Rb-/- MEFs could be identified. These data and the analysis provide a starting point for further experimental studies to identify target genes for pharmacological intervention and ultimately remodeling of white adipose tissue into brown adipose tissue.</p

New technologies for examining neuronal ensembles in drug addiction and fear

Correlational data suggest that learned associations are encoded within neuronal ensembles. However, it has been difficult to prove that neuronal ensembles mediate learned behaviours because traditional pharmacological and lesion methods, and even newer cell type-specific methods, affect both activated and non-activated neurons. Additionally, previous studies on synaptic and molecular alterations induced by learning did not distinguish between behaviourally activated and non-activated neurons. Here, we describe three new approaches—Daun02 inactivation, FACS sorting of activated neurons and c-fos-GFP transgenic rats — that have been used to selectively target and study activated neuronal ensembles in models of conditioned drug effects and relapse. We also describe two new tools — c-fos-tTA mice and inactivation of CREB-overexpressing neurons — that have been used to study the role of neuronal ensembles in conditioned fear

UCP1 Induction during Recruitment of Brown Adipocytes in White Adipose Tissue Is Dependent on Cyclooxygenase Activity

Background The uncoupling protein 1 (UCP1) is a hallmark of brown adipocytes and pivotal for cold- and diet-induced thermogenesis. Methodology/Principal Findings Here we report that cyclooxygenase (COX) activity and prostaglandin E2 (PGE2) are crucially involved in induction of UCP1 expression in inguinal white adipocytes, but not in classic interscapular brown adipocytes. Cold-induced expression of UCP1 in inguinal white adipocytes was repressed in COX2 knockout (KO) mice and by administration of the COX inhibitor indomethacin in wild-type mice. Indomethacin repressed β-adrenergic induction of UCP1 expression in primary inguinal adipocytes. The use of PGE2 receptor antagonists implicated EP4 as a main PGE2 receptor, and injection of the stable PGE2 analog (EP3/4 agonist) 16,16 dm PGE2 induced UCP1 expression in inguinal white adipose tissue. Inhibition of COX activity attenuated diet-induced UCP1 expression and increased energy efficiency and adipose tissue mass in obesity-resistant mice kept at thermoneutrality. Conclusions/Significance Our findings provide evidence that induction of UCP1 expression in white adipose tissue, but not in classic interscapular brown adipose tissue is dependent on cyclooxygenase activity. Our results indicate that cyclooxygenase-dependent induction of UCP1 expression in white adipose tissues is important for diet-induced thermogenesis providing support for a surprising role of COX activity in the control of energy balance and obesity development

Advances in structure elucidation of small molecules using mass spectrometry

The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules