Learning a high-precision locomotor task in patients with Parkinson's disease.

We evaluated the acquisition and performance of a high-precision locomotor task in patients with Parkinson's disease (PD) and healthy subjects. All subjects walked on a treadmill and had to step repetitively as low as possible over an obstacle without touching it. During blocks 1 and 2, the subjects had full vision and received additional acoustic warning and feedback signals. During block 3, vision became restricted. Changes in foot clearance and the number of obstacle hits were evaluated. Initially, PD patients performed poorer and improved foot clearance slower. After task repetition, the groups performed similarly. Restricting vision deteriorated performance in both groups. The similar performance of PD patients after task repetition might indicate that adequate training could improve adaptive locomotor behavior in PD patients.     

Development of three parallel cytochrome P450 enzyme affinity detection systems coupled on-line to gradient high-performance liquid chromatography.

A high resolution screening (HRS) technology is described, in which gradient high-performance liquid chromatography (HPLC) is connected on-line to three parallel placed bioaffinity detection systems containing mammalian cytochromes P450 (P450s). The three so-called enzyme affinity detection (EAD) systems contained, respectively, liver microsomes from rats induced by beta-naphthoflavone (CYP1A activity), phenobarbital (CYP2B activity), and dexamethasone (CYP3A activity). Each P450-EAD system was optimized for enzyme, substrate, and organic modifier (isopropyl alcohol, methanol, and acetonitrile) in flow injection analysis mode. Characteristic P450 ligands were used to validate the P450-EAD systems. IC(50) values of the ligands were measured and found to be similar to those obtained with conventional microtiter plate reader assays. Detection limits (n = 3; signal-to-noise ratio = 3) of potent inhibitors ranged from 1 to 3 pmol for CYP1A activity, 4 to 17 pmol for CYP2B activity, and 4 to 15 pmol for CYP3A activity. The three optimized P450-EAD systems were subsequently coupled to gradient HPLC and used to screen compound mixtures for individual ligands. Finally, to increase analysis efficiency, a HRS system was constructed in which all three P450-EAD systems were coupled on-line and in parallel to gradient HPLC. The triple parallelized P450-EAD system was shown to enable rapid profiling of individual components in complex mixtures for inhibitory activity to three different P450s.     

Differentiating moderate and severe depression using the Montgomery-Asberg depression rating scale (MADRS)

BACKGROUND: MADRS cut-off scores for moderate and severe depression were estimated in relation to the Hamilton Depression Rating Scale (HAMD(17)) and the Clinical Global Impressions Scale (CGI). METHOD: HAMD(17), MADRS, and CGI ratings from patients with major depression (DSM-IV) were analyzed (N=85). Receiver operating characteristics (ROC) curves were applied. RESULTS: Mean age was 51.4+/-14.5 years, 69% were female. Mean MADRS scores were 23.4+/-13.2, HAMD(17), MADRS, and CGI scores were highly correlated (r>0.85; P<0.0001). Best separation between moderate and severe depression according to CGI criteria was achieved with a MADRS score of 31 (sensitivity 93.5%, specificity 83.3%). LIMITATIONS: Studies to validate severity gradations including DSM-IV or ICD-10 diagnostic severity categories are recommended. CONCLUSIONS: Empirically based MADRS cut-off scores to separate moderate from severe depression on the basis of HAMD(17) and CGI severity ratings in patients with major depression were yielded.     

NRE,the major nitrogen regulatory protein of Penicillium chrysogenum,binds specifically to elements in the intergenic promoter regions of nitrate assimilation and penicillin biosynthetic gene clusters

NRE, the nitrogen regulatory protein of Penicillium chrysogenum, contains a single Cys2/Cys2-type zinc-finger motif followed immediately by a highly basic region. The zinc-finger domain was expressed to Escherichia coli as a fusion protein with -galactosidase. In order to test the putative DNA-binding ability of NRE, the intergenic promoter region of the nitrate reductase/nitrite reductase gene cluster (niiA-niaD) of Penicillium was sequenced. Our results show that NRE is a DNA-binding protein and binds to the intergenic promoter regions of the P. chrysogenum niiA-niaD and acvA-pcbC gene cluster, encoding the first two enzymes in penicillin biosynthesis. Three of the four high-affinity NRE-binding sites contained two GATA core elements. In one of the recognition sites for NRE, one GATA motif was replaced by GATT. The two GATA elements showed all possible orientations, head-to-head, head-to-tail and tail-to-tail, and were separated by between 4 and 27 bp. Missing-contact analysis showed that all three purines in both of the GATA core sequences and the single adenine residue in each of the complementary TATC sequences were involved in the binding of NRE. Moreover, loss of purines in the flanking regions of the GATA elements also affect binding of NRE, as their loss causes reduced affinity.     

Recurrent pelvic neuroblastoma in an adult patient

BACKGROUND: Neuroblastoma is a common malignancy in children, but rarely occurs in adults. CASE REPORT: We report the case of a 39-year-old woman who was treated for her fourth recurrence of a pelvic neuroblastoma. CONCLUSIONS: Because of the rarity of these tumors during adolescence and adulthood, little information is available on the clinical course of patients with neuroblastoma in this age group. Currently there is no standard treatment for adult patients with neuroblastoma. Surgical resection and chemotherapy seem to be best of choice.     

Weitere Untersuchungen über eine objektive Feststellung des Bestehens einer C-Hypovitaminose

Zusammenfassung Bei natürlicher Vitamin C-armer Ernährung lassen sich bei Kaninchen und Ratten die gleichen Veränderungen des Stoffwechsels nachweisen wie bei Meerschweinchen, bestehend in einer Weckung oder Verstärkung der Fähigkeit zur Selbstsynthese des Vitamins und zugleich in einem Unfähigwerden, den Grundumsatz konstant zu halten.Diese Unfähigkeit ist, wie das Zurückbleiben des Wachstums zeigt, für jüngere noch wachsende Tiere als ein sicheres Mangelsymptom zu bewerten.Bereits ausgewachsene Tiere sind bei C-armer Ernährung weit besser im Stande, sowohl den Grundumsatz konstant zu halten als auch den Organbestand an Vitamin C zu wahren. Es wird dies auf die bessere Ausbildung eines zweiten Kompensationsmechanismus zurückgeführt, welcher die erste Gegenregulation mittels Eigensynthese verstärkt und weitgehend ablöst. Durch diesen zweiten Mechanismus sind bei ausgewachsenen und zumal bei alten Meerschweinchen die Schwankungen des Gaswechsels weniger gro\ als bei jüngeren Tieren. Bei der Ratte kann hierdurch der Grundumsatz nach einiger Zeit sogar völlig wieder zur normalen Konstanz zurückgebracht werden, wobei jedoch ein erhöhtes Niveau bleibt. Selbst für ausgewachsene Ratten ist somit eine an Vitamin C arme Ernährung zumindest nicht optimal ökonomisch. Für ausgewachsene Meerschweinchen bleibt sie direkt schädlich.Im Alter war weder bei Meerschweinchen noch Ratten ein Nachlassen der Regulationsmöglichkeit nachweisbar.Alle Befunde sprechen dafür, da\ die Unfähigkeit den Grundumsatz konstant halten zu können, als objektives Kennzeichen des Bestehens einer sonst noch latenten C-Hypovitaminose angesehen werden darf.     

Disgust and Self-Disgust in Eating Disorders: A Systematic Review and Meta-Analysis

Disgust and self-disgust are aversive emotions which are often encountered in people with eating disorders. We conducted a systematic review and meta-analysis of disgust and self-disgust in people with eating disorders using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The systematic review of the literature revealed 52 original research papers. There was substantial heterogeneity regarding the research question and outcomes. However, we found 5 articles on disgust elicited by food images, 10 studies on generic disgust sensitivity, and 4 studies on self-disgust, and we proceeded to a meta-analytic approach on these studies. We found that women with eating disorders have significantly higher momentary disgust feelings in response to food images (1.32; 95% CI 1.05, 1.59), higher generic disgust sensitivity (0.49; 95% CI 0.24, 0.71), and higher self-disgust (1.90; 95% CI 1.51, 2.29) compared with healthy controls. These findings indicate the potential clinical relevance of disgust and self-disgust in the treatment of eating disorders.     

Development of a home visitation programme for the early detection of health problems in potentially frail community-dwelling older people by general practices

The integration within existing health care systems of preventive initiatives to maintain independent living among older people is increasingly emphasized. This article describes the development and refinement of the [G]OLD home visitation programme: an eight-step programme, including a comprehensive geriatric assessment, for the early detection of health and well-being problems among older people (≥75 years) by general practices. A single group post-test study using a mixed model design is performed to evaluate (a) the feasibility of the home visitation programme in general practice, (b) the practical usefulness of the geriatric assessment instrument, and (c) programme implementation with respect to reinventions introduced by general practitioners (GPs) and practice nurses (PNs). Within 3 months time, 22 PNs of 18 participating general practices visited 240 community-dwelling older people (mean age = 82.0 years; SD 4.2) who had not been in contact with their general practice for more than 6 months. Mean time investment of the programme per older person was 118.1 min (SD 27.0) for GPs and PNs combined. Evaluation meetings revealed that GPs and PNs considered the home visitation programme to be feasible in daily practice. They judged the geriatric assessment to be useful, although minor adjustments are needed (e.g., lay-out, substitution of tests). PNs often failed to register follow-up actions for detected problems in a care and treatment plan. Future training for PNs should address this issue. No reinventions were introduced that threatened fidelity of implementation. The findings are used to improve the home visitation programme before its evaluation in a large-scale controlled trial.