Functional specialization and dynamic resource allocation in visual cortex

We studied the spatiotemporal characteristics of cortical activity in early visual areas and the fusiform gyri (FG) by means of magnetoencephalography (MEG). Subjects performed a visual classification task, in which letters and visually similar pseudoletters were presented in different surrounds and under different task demands. The stimuli appeared in a cued half of the visual field (VF). We observed prestimulus effects on amplitudes in V1 and Cuneus relating to VF and task demands, suggesting a combination of active anticipation and specialized routing of activity in visual processing. Amplitudes in the right FG between 150 and 350 ms after stimulus onset reflected task demands, while those in the left FG between 300 and 400 ms showed selectivity for graphemes. The contrasting stimulus‐evoked effects in the right and left FG show that the former area is sensitive to task demands irrespective of stimulus content, whereas the left FG is sensitive to stimulus content irrespectively of task demand. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

Bye-bye urinary gonadotrophins? Reply to debate

Dear Sir, Drs Matorras and Crosignani have recently published a debateon urinary gonadotrophins: ‘Bye-bye gonadotrophins,’(Matorras et al., 2002; Crosignani, 2002) in which both authorssuggested a potential risk of prion infectivity to which I wouldlike to respond. Discouraging the use of urinary gonadotrophinssolely on the grounds of potential risks associated with prion     

The effect of repeated exposure to fruit drinks on intake, pleasantness and boredom in young and elderly adults

The effect of a repeated monotonous exposure on ad libitum intake, pleasantness and boredom in elderly people in a real life situation is unclear. We therefore investigated the effects of repeated exposure to ad libitum intake of three orange-based drinks on boredom and acceptance in young and elderly people. Young (n=32) and elderly women (n=36) participated in a randomized within subjects cross over trial with three intervention periods of 12 days each followed by a 2-day wash out period. During each intervention period, the participants received 1 L of one type of drink per day. The three drinks varied in sweetness intensity. Intake was measured by weighing the returned packets and pleasantness, boredom and sweetness were rated on a 10-point scale. For the young women, mean consumption of the three drinks (p<0.01) and pleasantness decreased (p<0.01) and boredom increased (p<0.001). For the elderly women, consumption increased (p=0.03) whereas pleasantness (p=0.34) and boredom (p=0.40) were stable. In the young women, the orange peach drink which had the highest sugar content contributed the most to the effect of the repeated exposure. The consumption and pleasantness ratings for this drink decreased (r=-1.05, p=0.01 and r=-0.07, p=0.007, respectively) and boredom increased (r=0.12, p<0.001). In conclusion, elderly women experienced no increased boredom whereas young women did.     

High prevalence of eating disorders in narcolepsy with cataplexy: a case-control study

STUDY OBJECTIVES: To study the prevalence of and symptoms of eating disorders in patients with narcolepsy. DESIGN: We performed a case-control study comparing symptoms of eating disorders in patients with narcolepsy versus healthy population controls, using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN 2.1). To study whether an increased body mass index (BMI) could be responsible for symptoms of an eating disorder, we also compared patients with BMI-matched controls, using the SCAN as well as the Eating Disorder Examination-Questionnaire. SETTING: University hospital. PATIENTS AND PARTICIPANTS: Patients with narcolepsy/cataplexy (n = 60) were recruited from specialized sleep centers. Healthy controls (n = 120) were drawn from a population study previously performed in the Netherlands. Separately, 32 BMI-matched controls were recruited. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: In total, 23.3% of the patients fulfilled the criteria for a clinical eating disorder, as opposed to none of the control subjects. Most of these were classified as Eating Disorder-Not Otherwise Specified, with an incomplete form of binge eating disorder. On the symptom level, half of the patients reported a persistent craving for food, as well as binge eating. Twenty-five percent of patients even reported binging twice a week or more often. When compared with BMI-matched controls, the significant increases persisted in symptoms of eating disorders among patients with narcolepsy. Except for a higher level of interference in daily activities due to eating problems in patients using antidepressants, medication use did not influence our findings. CONCLUSIONS: The majority of patients with narcolepsy experience a number of symptoms of eating disorders, with an irresistible craving for food and binge eating as the most prominent features. Eating disorder symptomatology interfered with daily activities. These findings justify more attention for eating disorders in the treatment of patients with narcolepsy.     

Complement Activation Is Involved in Renal Damage in Human Antineutrophil Cytoplasmic Autoantibody Associated Pauci-Immune Vasculitis

Objective  This study was to investigate the evidence for complement activation in renal biopsy specimens of patients with myeloperoxidase (MPO)-antineutrophil cytoplasmic autoantibody (ANCA)-associated pauci-immune vasculitis. Methods  Renal biopsy specimens from seven patients with MPO-ANCA positive pauci-immune necrotizing crescentic glomerulonephritis (NCGN) were used to detect the staining of membrane attack complex (MAC), C3d, C4d, mannose-binding lectin (MBL), factor B and factor P using immunohistochemistry and immunofluorescence. Renal tissue from seven patients with minimal change disease (MCD) and two normal renal tissue were used as controls. Results  MAC, C3d, factor B and factor P could be detected in glomeruli and small blood vessels with active vasculitis of patients with pauci-immune AAV, but not or scarcely in patients with MCD and in normal renal tissue. C3d and factor B co-localized with MAC, factor P colocalized with C3d. MBL and C4d were not detected in patients with AAV. Conclusion  The alternative pathway of the complement system is involved in renal damage of human pauci-immune AAV.     

Circulating uncarboxylated matrix Gla protein,a marker of vitamin K status,as a risk factor of cardiovascular disease

Objectives

Vitamin K plays a pivotal role in the synthesis of Matrix Gla protein (MGP), a calcification inhibitor in vascular tissue. Vascular calcification has become an important predictor of cardiovascular disease. The aim of the current study was to examine the potential association of circulating desphospho-carboxylated and -uncarboxylated MGP (dp-cMGP and dp-ucMGP), reflecting vitamin K status, with the incidence of cardiovascular events and disease (CVD) in older individuals.

Study design

The study was conducted in 577 community-dwelling older men and women of the Longitudinal Aging Study Amsterdam (LASA), aged >55 year, who were free of cardiovascular disease at baseline. Multivariate Cox proportional hazards models were used to analyze the data.

Main outcome measures

Incidence of CVD.

Results

After a mean follow-up of 5.6 ± 1.2 year, we identified 40 incident cases of CVD. After adjustment for classical confounders and vitamin D status, we observed a more than 2-fold significantly higher risk of CVD for the highest tertile of dp-ucMGP with a HR of 2.69 (95% CI, 1.09–6.62) as compared with the lowest tertile. Plasma dp-cMGP was not associated with the risk of CVD.

Conclusions

Vitamin K insufficiency, as assessed by high plasma dp-ucMGP concentrations is associated with an increased risk for cardiovascular disease independent of classical risk factors and vitamin D status. Larger epidemiological studies on dp-ucMGP and CVD incidence are needed followed by clinical trials to test whether vitamin K-rich diets will lead to a decreased risk for cardiovascular events.     

Decision making about medical interventions in the end-of-life care of people with intellectual disabilities: A national survey of the considerations and beliefs of GPs,ID physicians and care staff

Objective

This paper explores the personal beliefs and specific considerations of professionals regarding decisions about potentially burdensome medical interventions in the end-of-life care for people with intellectual disabilities (ID).

Methods

A survey questionnaire covering decision making about potentially burdensome medical interventions was sent to nationally representative samples of 294 ID care staff-members, 273 ID physicians and 1000 GPs.

Results

Professionals predominantly believed that considerations about quality of life are most important. Quality of life and wellbeing were also frequently considered in both decisions to start/continue an intervention and decisions to forgo/withdraw an intervention. Seventy percent believed that people with ID should always be informed about interventions, and 61% would respect a refusal by the person. The family's wishes were explicitly considered more often than the wishes of the person with ID.

Conclusion

Although respondents agree that the quality of life is highly important, the wishes of people with ID (especially of those with severe/profound ID) were often not considered in decisions about potentially burdensome medical interventions.

Practice implications

To enhance the active involvement of people with ID in decision making we recommend that professionals integrate collaborative principles in decision making and make use of pictorial and easy reading resources.     

Copy number variants in patients with short stature

Height is a highly heritable and classic polygenic trait. Recent genome-wide association studies (GWAS) have revealed that at least 180 genetic variants influence adult height. However, these variants explain only about 10% of the phenotypic variation in height. Genetic analysis of short individuals can lead to the discovery of novel rare gene defects with a large effect on growth. In an effort to identify novel genes associated with short stature, genome-wide analysis for copy number variants (CNVs), using single-nucleotide polymorphism arrays, in 162 patients (149 families) with short stature was performed. Segregation analysis was performed if possible, and genes in CNVs were compared with information from GWAS, gene expression in rodents'' growth plates and published information. CNVs were detected in 40 families. In six families, a known cause of short stature was found (SHOX deletion or duplication, IGF1R deletion), in two combined with a de novo potentially pathogenic CNV. Thirty-three families had one or more potentially pathogenic CNVs (n=40). In 24 of these families, segregation analysis could be performed, identifying three de novo CNVs and nine CNVs segregating with short stature. Four were located near loci associated with height in GWAS (ADAMTS17, TULP4, PRKG2/BMP3 and PAPPA). Besides six CNVs known to be causative for short stature, 40 CNVs with possible pathogenicity were identified. Segregation studies and bioinformatics analysis suggested various potential candidate genes.     

Postprandial ghrelin responses are associated with the intermeal interval in time-blinded normal weight men,but not in obese men

ObjectiveTo investigate the relation between ghrelin responses and meal initiation and the effects of BMI and energy status on this.DesignThe experiment had a randomised, cross-over design.Setting and subjectsNine normal-weight (age: 33.2 ± 4.8 y, BMI: 23.2 ± 0.5 kg/m²) and eleven obese (age: 40.8 ±4.7 y, BMI: 33.2 ± 0.8 kg/m²) healthy men were recruited from a pool of volunteers and by advertisements.InterventionsSubjects followed a three-day energy restrictive and a three-day energy balanced diet separated by one month. Each diet was followed by a time-blinded (overnight) stay at the research facility. Subjects received a breakfast (preload) and were instructed to ask for lunch when they felt hungry. Ghrelin, insulin, glucose, free fatty acids, appetite, IMI and energy intake during lunch were assessed.ResultsPostprandial decreases in ghrelin (r = ? 0.54; p < 0.05) and the AUC of the ghrelin response (r = ? 0.57, p = 0.01) were associated with the intermeal interval, independent of diet, but in normal weight subjects only. Lunch request was preceded by an increase in ghrelin, reaching at least 93% of fasting values. These preprandial increases in ghrelin were correlated with IMI, after energy restriction only. Ghrelin concentrations but not changes in ghrelin were correlated with appetite.ConclusionMeal-related changes in ghrelin are correlated with the IMI in normal weight subjects only, independent of diet. Ghrelin concentrations may need to reach a certain threshold level before the next meal is initiated.SponsorshipSupported by Dutch Ministry of Education, Culture and Science, Dutch Ministry of Health, Welfare and Sport and Danone Research.     

Unbearability of suffering at the end of life: the development of a new measuring device, the SOS-V

Background  

Unbearable suffering is an important issue in end-of-life decisions. However, there has been no systematic, prospective, patient-oriented research which has focused on unbearable suffering, nor is there a suitable measurement instrument. This article describes the methodological development of a quantitative instrument to measure the nature and intensity of unbearable suffering, practical aspects of its use in end-stage cancer patients in general practice, and studies content validity and psychometric properties.