Impaired Hippocampal Reactivation Preceding Robust Aß Deposition in a Model of Alzheimer's Disease.

Current therapeutic strategies for Alzheimer's disease (AD) target amyloid-beta (Aß) fibrils and high molecular weight protofibrils associated with plaques, but other bioactive species may directly contribute to neural systems failure in AD. Employing hippocampal electrophysiological recordings and dynamic calcium imaging across the sleep-wake cycle in young mice expressing human Aß and Aß oligomers, we reveal marked impairments of hippocampal function long before amyloid plaques predominate. In slow wave sleep (SWS), Aß increased the proportion of hypoactive cells and reduced place-cell reactivation. During awake behavior, Aß impaired theta-gamma phase-amplitude coupling (PAC) and drove excessive synchronization of place cell calcium fluctuations with hippocampal theta. Remarkably, the on-line impairment of hippocampal theta-gamma PAC correlated with the SWS impairment of place-cell reactivation. Together, these results identify toxic effects of Aß on memory encoding and consolidation processes before robust plaque deposition and support targeting soluble Aß-related species to treat and prevent AD.

Characterization of BioID tagging systems in budding yeast and exploring the interactome of the Ccr4-Not complex.

The modified E. coli biotin ligase BirA* was the first developed for proximity labeling of proteins (BioID). However, it has low activity at temperatures below 37°C, which reduces its effectiveness in organisms growing at lower temperatures, such as budding yeast. Multiple derivatives of the enzymes have been engineered, but a comparison of these variations of biotin ligases has not been reported in Saccharomyces cerevisiae. Here, we designed a suite of vectors to compare the activities of biotin ligase enzymes in yeast. We found that the newer TurboID versions were the most effective at labeling proteins, but they displayed low constitutive activity from biotin contained in the culture medium. We describe a simple strategy to express free BioID enzymes in cells that can be used as an appropriate control in BioID studies to account for the promiscuous labeling of proteins caused by random interactions between bait-BioID enzymes in cells. We also describe chemically-induced BioID systems exploiting the rapamycin-stabilized FRB-FKBP interaction. Finally, we used the TurboID version of the enzyme to explore the interactome of different subunits of the Ccr4-Not gene regulatory complex. We find that Ccr4-Not predominantly labeled cytoplasmic mRNA regulators, consistent with its function in mRNA decay and translation quality control in this cell compartment.

Inducing perceived group variability triggers the incorporation of counter-stereotypic information into a generalized stereotype change.

Perceived variability is the extent to which individuals perceive group members as being similar to one another. Previous research has focused on how: group variability is perceived (and measured); information indicative of group heterogeneity can lead to reductions in stereotypicality; or how stereotype-inconsistent information can result into increased perceived variability. The present combines the three lines of research into a single research venue. In previous studies the stereotypicality of a group representation was influenced by priming stereotype-unrelated traits in an unrelated-context, prior to stereotype measurement; but priming counter-stereotypic traits had no effect on stereotypicality, although it boosted perceptions of group's variability. The present study examines whether highlighting dissimilarities among members of the same professional groups results in subsequent changes in the reported stereotype for a, not yet mentioned, group. The more the dissimilarity among group members, the more likely individuals were to incorporate counter-stereotypic information into the targeted-group, described as less stereotypic, even in central tendency measures. Importantly, the generating mechanism may involve a modification of participants' overall perception of variability. When members within professional groups are perceived as dissimilar, the well-known resistance of stereotypes to counter-stereotypic information is lessened making the group representations more flexible and less biased.

LRRC8A anion channels modulate vascular reactivity via association with myosin phosphatase rho interacting protein.

Leucine-rich repeat containing 8A (LRRC8A) volume regulated anion channels (VRACs) are activated by inflammatory and pro-contractile stimuli including tumor necrosis factor alpha (TNFα), angiotensin II and stretch. LRRC8A associates with NADPH oxidase 1 (Nox1) and supports extracellular superoxide production. We tested the hypothesis that VRACs modulate TNFα signaling and vasomotor function in mice lacking LRRC8A exclusively in vascular smooth muscle cells (VSMCs, Sm22α-Cre, Knockout). Knockout (KO) mesenteric vessels contracted normally but relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) was enhanced compared to wild type (WT). Forty-eight hours of ex vivo exposure to TNFα (10 ng/mL) enhanced contraction to norepinephrine (NE) and markedly impaired dilation to ACh and SNP in WT but not KO vessels. VRAC blockade (carbenoxolone, CBX, 100 µM, 20 min) enhanced dilation of control rings and restored impaired dilation following TNFα exposure. Myogenic tone was absent in KO rings. LRRC8A immunoprecipitation followed by mass spectroscopy identified 33 proteins that interacted with LRRC8A. Among them, the myosin phosphatase rho-interacting protein (MPRIP) links RhoA, MYPT1 and actin. LRRC8A-MPRIP co-localization was confirmed by confocal imaging of tagged proteins, Proximity Ligation Assays, and IP/western blots. siLRRC8A or CBX treatment decreased RhoA activity in VSMCs, and MYPT1 phosphorylation was reduced in KO mesenteries suggesting that reduced ROCK activity contributes to enhanced relaxation. MPRIP was a target of redox modification, becoming oxidized (sulfenylated) after TNFα exposure. Interaction of LRRC8A with MPRIP may allow redox regulation of the cytoskeleton by linking Nox1 activation to impaired vasodilation. This identifies VRACs as potential targets for treatment or prevention of vascular disease.

LRRC8A anion channels modulate vasodilation via association with Myosin Phosphatase Rho Interacting Protein (MPRIP).

Background: In vascular smooth muscle cells (VSMCs), LRRC8A volume regulated anion channels (VRACs) are activated by inflammatory and pro-contractile stimuli including tumor necrosis factor alpha (TNFα), angiotensin II and stretch. LRRC8A physically associates with NADPH oxidase 1 (Nox1) and supports its production of extracellular superoxide (O 2 -• ). Methods and Results: Mice lacking LRRC8A exclusively in VSMCs (Sm22α-Cre, KO) were used to assess the role of VRACs in TNFα signaling and vasomotor function. KO mesenteric vessels contracted normally to KCl and phenylephrine, but relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) was enhanced compared to wild type (WT). 48 hours of ex vivo exposure to TNFα (10ng/ml) markedly impaired dilation to ACh and SNP in WT but not KO vessels. VRAC blockade (carbenoxolone, CBX, 100 µM, 20 min) enhanced dilation of control rings and restored impaired dilation following TNFα exposure. Myogenic tone was absent in KO rings. LRRC8A immunoprecipitation followed by mass spectroscopy identified 35 proteins that interacted with LRRC8A. Pathway analysis revealed actin cytoskeletal regulation as the most closely associated function of these proteins. Among these proteins, the Myosin Phosphatase Rho-Interacting protein (MPRIP) links RhoA, MYPT1 and actin. LRRC8A-MPRIP co-localization was confirmed by confocal imaging of tagged proteins, Proximity Ligation Assays, and IP/western blots which revealed LRRC8A binding at the second Pleckstrin Homology domain of MPRIP. siLRRC8A or CBX treatment decreased RhoA activity in cultured VSMCs, and MYPT1 phosphorylation at T853 was reduced in KO mesenteries suggesting that reduced ROCK activity contributes to enhanced relaxation. MPRIP was a target of redox modification, becoming oxidized (sulfenylated) after TNFα exposure. Conclusions: Interaction of Nox1/LRRC8A with MPRIP/RhoA/MYPT1/actin may allow redox regulation of the cytoskeleton and link Nox1 activation to both inflammation and vascular contractility.

Long-term health sequelae and quality of life at least 6 months after infection with SARS-CoV-2: design and rationale of the COVIDOM-study as part of the NAPKON population-based cohort platform (POP).

PURPOSE: Over the course of COVID-19 pandemic, evidence has accumulated that SARS-CoV-2 infections may affect multiple organs and have serious clinical sequelae, but on-site clinical examinations with non-hospitalized samples are rare. We, therefore, aimed to systematically assess the long-term health status of samples of hospitalized and non-hospitalized SARS-CoV-2 infected individuals from three regions in Germany. METHODS: The present paper describes the COVIDOM-study within the population-based cohort platform (POP) which has been established under the auspices of the NAPKON infrastructure (German National Pandemic Cohort Network) of the national Network University Medicine (NUM). Comprehensive health assessments among SARS-CoV-2 infected individuals are conducted at least 6 months after the acute infection at the study sites Kiel, Würzburg and Berlin. Potential participants were identified and contacted via the local public health authorities, irrespective of the severity of the initial infection. A harmonized examination protocol has been implemented, consisting of detailed assessments of medical history, physical examinations, and the collection of multiple biosamples (e.g., serum, plasma, saliva, urine) for future analyses. In addition, patient-reported perception of the impact of local pandemic-related measures and infection on quality-of-life are obtained. RESULTS: As of July 2021, in total 6813 individuals infected in 2020 have been invited into the COVIDOM-study. Of these, about 36% wished to participate and 1295 have already been examined at least once. CONCLUSION: NAPKON-POP COVIDOM-study complements other Long COVID studies assessing the long-term consequences of an infection with SARS-CoV-2 by providing detailed health data of population-based samples, including individuals with various degrees of disease severity. TRIAL REGISTRATION: Registered at the German registry for clinical studies (DRKS00023742).

Inactivation of Tsc2 in Abcg2 lineage-derived cells drives the appearance of polycystic lesions and fibrosis in the adult kidney.

Tuberous sclerosis complex 2 (TSC2), or tuberin, is a pivotal regulator of the mechanistic target of rapamycin signaling pathway that controls cell survival, proliferation, growth, and migration. Loss of Tsc2 function manifests in organ-specific consequences, the mechanisms of which remain incompletely understood. Recent single cell analysis of the kidney has identified ATP-binding cassette G2 (Abcg2) expression in renal proximal tubules of adult mice as well as a in a novel cell population. The impact in adult kidney of Tsc2 knockdown in the Abcg2-expressing lineage has not been evaluated. We engineered an inducible system in which expression of truncated Tsc2, lacking exons 36-37 with an intact 3' region and polycystin 1, is driven by Abcg2. Here, we demonstrate that selective expression of Tsc2fl36-37 in the Abcg2pos lineage drives recombination in proximal tubule epithelial and rare perivascular mesenchymal cells, which results in progressive proximal tubule injury, impaired kidney function, formation of cystic lesions, and fibrosis in adult mice. These data illustrate the critical importance of Tsc2 function in the Abcg2-expressing proximal tubule epithelium and mesenchyme during the development of cystic lesions and remodeling of kidney parenchyma.

Robot-assisted laparoscopic excision of prostatic utricle in a 3-year old.

Prostatic utricles have traditionally been excised via the open approach or laparoscopically. Recently, the robot-assisted laparoscopic approach has been described in a 19-year-old male. the case of a 3-year-old male with a disorder of sex development (mosaic 45X/46 XY), with multiple associated anomalies, who presented with recurrent UTI is presented. Renal/bladder ultrasound revealed normal bilateral kidneys, and a 4.3 × 2.8 × 3.3 cm cystic mass in the midline posterior to the bladder. Voiding cystourethrogram demonstrated a large cystic mass behind the bladder, concerning for large prostatic utricle. The patient was brought to the operating room and placed in lithotomy. The urethra was examined cystoscopically. The os of the utricle was identified, an open-ended catheter was advanced, the cystoscope was removed, and a Foley was placed. The camera port was introduced supraumbilically, and robotic ports were introduced inferolaterally. Irrigation of the catheter and distension of the utricle allowed manipulation of the utricle to facilitate identification of a plane of dissection. The neck of the utricle was identified and incised. The catheter was removed, transection was completed, and the stump was oversewn. CONCLUSION: Combined cystoscopic and robotic approach to prostatic utricle excision is feasible, safe, and effective in this patient population.

Deceased donor uterus retrieval: A novel technique and workflow.

Uterus transplantation has proven successful when performed with a living donor. Subsequently, interest in the novel field of reproductive transplantation is growing. The procedure is still considered experimental, with fewer than 25 cases performed worldwide, and the techniques of both uterus procurement and transplantation are still developing. We detail a new approach to deceased donor uterus procurement. In contrast to reported techniques and our own initial experience, in which the deceased donor uterus was procured post cross-clamp and after other organs were procured, our approach now is to perform the uterus procurement prior to the procurement of other organs in a multiorgan donor and hence prior to cross-clamp. We describe our practical experience in developing and implementing the logistical workflow for deceased donor uterus procurement in a deceased multiorgan donor setting.

A new computer-based pediatric vision-screening test.

BACKGROUND: We developed and validated the Jaeb Visual Acuity Screener (JVAS), a computerized visual acuity-based screening program for children that employs a rapid, age-specific, standardized algorithm for vision screening in the medical home that is available for download at no cost. METHODS: A total of 175 children aged 3 to <8 (median, 6) years were screened with the JVAS before undergoing a complete eye examination (gold standard). The JVAS presented 2 large single surround optotypes (20/100 and 20/80) and then 5 optotypes at a predetermined, age-specific normal threshold. Failure on the gold standard examination was determined using recently published referral criteria and published visual acuity norms for age. We evaluated the sensitivity and specificity of the JVAS for detecting reduced visual acuity, amblyopia, and amblyopia risk factors. JVAS pass/fail paradigms evaluated were inability to identify 3 of 4, 3 of 5, and 4 of 5 age-appropriate optotype presentations. RESULTS: Screening testability for the JVAS was high, at 100%. Sensitivity of the JVAS ranged from 88% to 91%, and specificity from 73% to 86%, with positive predictive value ranging from 66% to 79% and negative predictive value from 92% to 93% (ranges reflect different pass/fail paradigms). CONCLUSIONS: The new JVAS provides an effective and practical method for screening 3- to 7-year-olds using any Windows-based computer. Providing the JVAS free-of-charge to pediatricians and school systems would standardize currently fragmented visual acuity-based screening practices.

Catecholamine-resistant hypotension and myocardial performance following patent ductus arteriosus ligation.

OBJECTIVE: We performed a multicenter study of preterm infants, who were about to undergo patent ductus arteriosus ligation, to determine whether echocardiographic indices of impaired myocardial performance were associated with subsequent development of catecholamine-resistant hypotension following ligation. STUDY DESIGN: A standardized treatment approach for hypotension was followed at each center. Infants were considered to have catecholamine-resistant hypotension if their dopamine infusion was > 15 µg kg(-1)min(-1). Echocardiograms and cortisol measurements were obtained between 6 and 14 h after the ligation (prior to the presence of catecholamine-resistant hypotension). RESULT: Forty-five infants were enrolled, 10 received catecholamines (6 were catecholamine-responsive and 4 developed catecholamine-resistant hypotension). Catecholamine-resistant hypotension was not associated with decreased preload, shortening fraction or ventricular output. Infants with catecholamine-resistant hypotension had significantly lower levels of systemic vascular resistance and postoperative cortisol concentration. CONCLUSION: We speculate that low cortisol levels and impaired vascular tone may have a more important role than impaired cardiac performance in post-ligation catecholamine-resistant hypotension.

Gastrointestinal ostomies and sexual outcomes: a comparison of colorectal cancer patients by ostomy status.

PURPOSE: Research examining effects of ostomy use on sexual outcomes is limited. Patients with colorectal cancer were compared on sexual outcomes and body image based on ostomy status (never, past, and current ostomy). Differences in depression were also examined. METHODS: Patients were prospectively recruited during clinic visits and by tumor registry mailings. Patients with colorectal cancer (N = 141; 18 past ostomy; 25 current ostomy; and 98 no ostomy history) completed surveys assessing sexual outcomes (medical impact on sexual function, Female Sexual Function Index, International Index of Erectile Function), body image distress (Body Image Scale), and depressive symptoms (Center for Epidemiologic Studies Depression Scale-Short Form). Clinical information was obtained through patient validated self-report measures and medical records. RESULTS: Most participants reported sexual function in the dysfunctional range using established cut-off scores. In analyses adjusting for demographic and medical covariates and depression, significant group differences were found for ostomy status on impact on sexual function (p < .001), female sexual function (p = .01), and body image (p < .001). The current and past ostomy groups reported worse impact on sexual function than those who never had an ostomy (p < .001); similar differences were found for female sexual function. The current ostomy group reported worse body image distress than those who never had an ostomy (p < .001). No differences were found across the groups for depressive symptoms (p = .33) or male sexual or erectile function (p values ≥ .59). CONCLUSIONS: Colorectal cancer treatment puts patients at risk for sexual difficulties and some difficulties may be more pronounced for patients with ostomies as part of their treatment. Clinical information and support should be offered.

Evaluation of late vegetative and reproductive stage soybeans for resistance to soybean aphid (Hemiptera: Aphididae).

The soybean aphid, Aphis glycines Matsumura, has become the most significant soybean [Glycine max (L.) Merrill] insect pest in the north central soybean production region of North America. The objectives of this research were to measure selected genotypes for resistance to the soybean aphid in the later vegetative and reproductive stages under field conditions, and confirm the presence of tolerance in KS4202. The results from 2007 to 2011 indicate that KS4202 can support aphid populations with minimal yield loss at levels where significant yield loss would be expected in most other genotypes. The common Nebraska cultivar, 'Asgrow 2703', appears to show signs of tolerance as well. None of the yield parameters were significantly different between the aphid infested and noninfested treatments. Based on our results, genotypes may compensate for aphid feeding in different ways. Asgrow 2703 appears to produce a similar number of seeds as its noninfested counterpart, although the seeds produced are slightly smaller. Field evaluation of tolerance in KS4202 indicated a yield loss of only 13% at 34,585-53,508 cumulative aphid-days, when 24-36% yield loss would have been expected.

The Oklahoma Thrombotic Thrombocytopenic Purpura-haemolytic Uraemic Syndrome Registry. A model for clinical research, education and patient care.

The Oklahoma Thrombotic Thrombocytopenic Purpura-Haemolytic Uraemic Syndrome (TTP-HUS) Registry has a 24 year record of success for collaborative clinical research, education, and patient care. This article tells the story of how the Registry began and it describes the Registry's structure and function. The Registry provides a model for using a cohort of consecutive patients to investigate a rare disorder. Collaboration between Oklahoma, United States and Bern, Switzerland has been the basis for successful interpretation of Registry data. Registry data have provided new insights into the evaluation and management of TTP. Because recovery from acute episodes of TTP has been assumed to be complete, the increased prevalence of hypertension, diabetes, depression, and death documented by long-term follow-up was unexpected. Registry data have provided opportunities for projects for students and trainees, education of physicians and nurses, and also for patients themselves. During our follow-up, patients have also educated Registry investigators about problems that persist after recovery from an acute episode of TTP. Most important, Registry data have resulted in important improvements for patient care.

EFNS/MDS-ES/ENS [corrected] recommendations for the diagnosis of Parkinson's disease.

BACKGROUND: A Task Force was convened by the EFNS/MDS-ES Scientist Panel on Parkinson's disease (PD) and other movement disorders to systemically review relevant publications on the diagnosis of PD. METHODS: Following the EFNS instruction for the preparation of neurological diagnostic guidelines, recommendation levels have been generated for diagnostic criteria and investigations. RESULTS: For the clinical diagnosis, we recommend the use of the Queen Square Brain Bank criteria (Level B). Genetic testing for specific mutations is recommended on an individual basis (Level B), taking into account specific features (i.e. family history and age of onset). We recommend olfactory testing to differentiate PD from other parkinsonian disorders including recessive forms (Level A). Screening for pre-motor PD with olfactory testing requires additional tests due to limited specificity. Drug challenge tests are not recommended for the diagnosis in de novo parkinsonian patients. There is an insufficient evidence to support their role in the differential diagnosis between PD and other parkinsonian syndromes. We recommend an assessment of cognition and a screening for REM sleep behaviour disorder, psychotic manifestations and severe depression in the initial evaluation of suspected PD cases (Level A). Transcranial sonography is recommended for the differentiation of PD from atypical and secondary parkinsonian disorders (Level A), for the early diagnosis of PD and in the detection of subjects at risk for PD (Level A), although the technique is so far not universally used and requires some expertise. Because specificity of TCS for the development of PD is limited, TCS should be used in conjunction with other screening tests. Conventional magnetic resonance imaging and diffusion-weighted imaging at 1.5 T are recommended as neuroimaging tools that can support a diagnosis of multiple system atrophy (MSA) or progressive supranuclear palsy versus PD on the basis of regional atrophy and signal change as well as diffusivity patterns (Level A). DaTscan SPECT is registered in Europe and the United States for the differential diagnosis between degenerative parkinsonisms and essential tremor (Level A). More specifically, DaTscan is indicated in the presence of significant diagnostic uncertainty such as parkinsonism associated with neuroleptic exposure and atypical tremor manifestations such as isolated unilateral postural tremor. Studies of [(123) I]MIBG/SPECT cardiac uptake may be used to identify patients with PD versus controls and MSA patients (Level A). All other SPECT imaging studies do not fulfil registration standards and cannot be recommended for routine clinical use. At the moment, no conclusion can be drawn as to diagnostic efficacy of autonomic function tests, neurophysiological tests and positron emission tomography imaging in PD. CONCLUSIONS: The diagnosis of PD is still largely based on the correct identification of its clinical features. Selected investigations (genetic, olfactory, and neuroimaging studies) have an ancillary role in confirming the diagnosis, and some of them could be possibly used in the near future to identify subjects in a pre-symptomatic phase of the disease.

Effects of thiamethoxam seed treatments on soybean aphid (Hemiptera: Aphididae) feeding behavior.

Since its discovery in North America in 2000, the soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), has rapidly become an important pest of soybean [Glycine max (L.) Merrill], sometimes resulting in significant yield losses. Previous research has documented the toxicity of neonicotinoid seed treatments to soybean aphids, but control under field conditions has been inconsistent. Imidacloprid, a popular neonicotinoid insecticide, has been shown to exhibit antifeedant effects on aphids. Antifeedant activity has not been demonstrated for other neonicotinoids, including thiamethoxam. This research investigated the effects of a thiamethoxam seed treatment on soybean aphid feeding behavior by using electronic penetration graphs (EPG) to visualize stylet penetration behavior. Soybean aphid feeding behavior was assessed for 9 h on thiamethoxam-treated and untreated soybeans (V2 and V4 stages). Because results were inconclusive from initial experiments, a study was conducted to document the effects of thiamethoxam-treated soybeans on soybean aphid survival. The seed treatment was shown to negatively affect aphid survival at 4, 8, and 11 d after aphid introduction. A subsequent EPG study then was designed to document soybean aphid feeding behavior for 15 h, after an initial exposure of 9 h to thiamethoxam-treated soybeans. In this study, the exposed aphids exhibited significant differences in feeding behavior compared with those aphids feeding on untreated soybeans. Soybean aphids on thiamethoxam-treated soybeans spent significantly less time feeding in the sieve element phase, with a greater duration of nonprobing events. These studies suggest soybean aphids are unable to ingest phloem sap, which may be another important element in seed treatment protection.

A characterization of aerosolized Sudan virus infection in African green monkeys, cynomolgus macaques, and rhesus macaques.

Filoviruses are members of the genera Ebolavirus, Marburgvirus, and "Cuevavirus". Because they cause human disease with high lethality and could potentially be used as a bioweapon, these viruses are classified as CDC Category A Bioterrorism Agents. Filoviruses are relatively stable in aerosols, retain virulence after lyophilization, and can be present on contaminated surfaces for extended periods of time. This study explores the characteristics of aerosolized Sudan virus (SUDV) Boniface in non-human primates (NHP) belonging to three different species. Groups of cynomolgus macaques (cyno), rhesus macaques (rhesus), and African green monkeys (AGM) were challenged with target doses of 50 or 500 plaque-forming units (pfu) of aerosolized SUDV. Exposure to either viral dose resulted in increased body temperatures in all three NHP species beginning on days 4-5 post-exposure. Other clinical findings for all three NHP species included leukocytosis, thrombocytopenia, anorexia, dehydration, and lymphadenopathy. Disease in all of the NHPs was severe beginning on day 6 post-exposure, and all animals except one surviving rhesus macaque were euthanized by day 14. Serum alanine transaminase (ALT) and aspartate transaminase (AST) concentrations were elevated during the course of disease in all three species; however, AGMs had significantly higher ALT and AST concentrations than cynos and rhesus. While all three species had detectable viral load by days 3-4 post exposure, Rhesus had lower average peak viral load than cynos or AGMs. Overall, the results indicate that the disease course after exposure to aerosolized SUDV is similar for all three species of NHP.

[Health-economic burden of Parkinson's disease in Portugal: a cohort study]. / Estudio de cohortes sobre la carga socioeconomica de la enfermedad de Parkinson en Portugal.

INTRODUCTION: Parkinson's disease (PD) is a common neurodegenerative disorder with a considerable socioeconomic burden. Health-economic evaluations of PD in the Southern European countries are limited. AIM: To evaluate the costs of PD in an outpatient cohort in Portugal. PATIENTS AND METHODS: 49 consecutive PD patients were recruited at the neurological outpatient clinic of the University of Lisbon between October 2004 and December 2005. Clinical status was evaluated using the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr stages. Costs were assessed from the societal perspective using health-economic questionnaires. Human capital approach was used to estimate indirect costs. Health-related quality of life was evaluated by means of the EQ-5D. RESULTS: Direct costs were 2,717 euros (95% CI = 1,147-3,351) per patient for a six-month period. Main contributors to the direct costs included drugs (544 euros; 95% CI = 426-6,940) and hospitalizations (690 euros; 95% CI = 229-1,944). Indirect costs amounted to 850 euros (95% CI = 397-1,529), whereas patient expenditures constituted 12% of direct costs. Assistance by family and other relatives played a major role. In general, costs were lower than in other Western countries. CONCLUSIONS: The economic burden of PD in Portugal is considerable. Important cost components include medications and hospitalizations. More research is needed in order to describe a comprehensive health service patterns in Portugal and to guide health policy decisions more effectively.

Normative data collection of the Marburg Concentration Test for Pre-school Children (German: MKVK).

OBJECTIVE: The objective of this study was the standardization of the Marburg Concentration Test for Pre-school Children (German: MKVK) for 3- to 6-year-old children as an instrument for the early diagnosis of lack of concentration in connection with language development disorders. PATIENTS AND METHODS: We conducted the MKVK on 309 children in 15 day-care centres. The MKVK is a matter of a simple sorting task of 80 cards according to pictures. The ascertainment of the concentration performance is conducted using the criteria processing time and error count. The results are analysed in seven age groups. RESULTS: An age dependence is seen in the execution time and a tendency in the amount of errors. Three-year-olds require more time and make more errors than 4.5- and 5-year-olds. Two groups become apparent in the 3-year-olds: children with whom the test is easy to take and children who are still overwhelmed with the instructions and processing. CONCLUSION: The MKVK is easy to conduct and shows children's ability to concentrate at pre-school ages. It proves to be of particular value for the 4- and 5-year-olds. The study gives hints on different work methods of the children. Indications for a differentiated facilitation could be deduced from that.