Cerebral activations related to ballistic, stepwise interrupted and gradually modulated movements in parkinson patients

Patients with Parkinson's disease (PD) experience impaired initiation and inhibition of movements such as difficulty to start/stop walking. At single-joint level this is accompanied by reduced inhibition of antagonist muscle activity. While normal basal ganglia (BG) contributions to motor control include selecting appropriate muscles by inhibiting others, it is unclear how PD-related changes in BG function cause impaired movement initiation and inhibition at single-joint level. To further elucidate these changes we studied 4 right-hand movement tasks with fMRI, by dissociating activations related to abrupt movement initiation, inhibition and gradual movement modulation. Initiation and inhibition were inferred from ballistic and stepwise interrupted movement, respectively, while smooth wrist circumduction enabled the assessment of gradually modulated movement. Task-related activations were compared between PD patients (N = 12) and healthy subjects (N = 18). In healthy subjects, movement initiation was characterized by antero-ventral striatum, substantia nigra (SN) and premotor activations while inhibition was dominated by subthalamic nucleus (STN) and pallidal activations, in line with the known role of these areas in simple movement. Gradual movement mainly involved antero-dorsal putamen and pallidum. Compared to healthy subjects, patients showed reduced striatal/SN and increased pallidal activation for initiation, whereas for inhibition STN activation was reduced and striatal-thalamo-cortical activation increased. For gradual movement patients showed reduced pallidal and increased thalamo-cortical activation. We conclude that PD-related changes during movement initiation fit the (rather static) model of alterations in direct and indirect BG pathways. Reduced STN activation and regional cortical increased activation in PD during inhibition and gradual movement modulation are better explained by a dynamic model that also takes into account enhanced responsiveness to external stimuli in this disease and the effects of hyper-fluctuating cortical inputs to the striatum and STN in particular

Prolonged Antibiotic Treatment does not Prevent Intra-Abdominal Abscesses in Perforated Appendicitis

Contains fulltext : 89619.pdf (publisher's version ) (Open Access)BACKGROUND: Children with perforated appendicitis have a relatively high risk of intra-abdominal abscesses. There is no evidence that prolonged antibiotic treatment after surgery reduces intra-abdominal abscess formation. We compared two patient groups with perforated appendicitis with different postoperative antibiotic treatment protocols. METHODS: We retrospectively reviewed patients younger than age 18 years who underwent appendectomy for perforated appendicitis at two academic hospitals between January 1992 and December 2006. Perforation was diagnosed during surgery and confirmed during histopathological evaluation. Patients in hospital A received 5 days of antibiotics postoperatively, unless decided otherwise on clinical grounds. Patients in hospital B received antibiotics for 5 days, continued until serum C-reactive protein (CRP) was <20 mg/l. Univariate logistic regression analysis was performed on intention-to-treat basis. p < 0.05 was considered significant. RESULTS: A total of 149 children underwent appendectomy for perforated appendicitis: 68 in hospital A, and 81 in hospital B. As expected, the median (range) use of antibiotics was significantly different: 5 (range, 1-16) and 7 (range, 2-32) days, respectively (p < 0.0001). However, the incidence of postoperative intra-abdominal abscesses was similar (p = 0.95). Regression analysis demonstrated that sex (female) was a risk factor for abscess formation, whereas surgical technique and young age were not. CONCLUSIONS: Prolonged use of antibiotics after surgery for perforated appendicitis in children based on serum CRP does not reduce postoperative abscess formation.1 december 201

(Cost)-effectiveness of family meetings on indicated prevention of anxiety and depressive symptoms and disorders of primary family caregivers of patients with dementia: design of a randomized controlled trial

Contains fulltext : 70773.pdf (publisher's version ) (Open Access)BACKGROUND: Dementia is a major public health problem with enormous costs to society and major consequences for both patients and their relatives. Family members of persons with dementia provide much of the care for older adults with dementia in the community. Caring for a demented relative is not easy and fraught with emotional strain, distress, and physical exhaustion. Family caregivers of dementia patients have an extremely high risk developing affective disorders such as major depression and anxiety disorder. Family meetings appear to be among the most powerful psychosocial interventions to reduce depression in caregivers.An American landmark study reported substantial beneficial effects of a multifaceted intervention where family meetings had a central place on depression in family caregivers as well as on delay of institutionalization of patients. These effects were not replicated in other countries yet. We perform the first trial comparing only structured family meetings with significant others versus usual care among primary family caregivers of community dwelling demented patients and measure the effectiveness on both depression and anxiety in the primary caregiver, both on disorder and symptom levels. METHODS/DESIGN: In this randomized controlled trial effectiveness as well as cost-effectiveness of family meetings is evaluated. The intervention group receives four family meetings with family and close friends of the primary family caregiver of a community dwelling patient with a clinical diagnosis of dementia. Dyads of patients and their primary caregiver are followed up to one year after baseline assessment. The main outcome measures are the incidence of anxiety and depressive disorders assessed with the Mini-International Neuropsychiatric Interview (MINI) and the severity of anxiety and depressive symptoms in caregivers is measured by validated self report instruments: the Centre for Epidemiologic Studies Depression Scale (CES-D) for depression and the anxiety scales of the Hospital Anxiety and Depression scales (HADS) for anxiety. The economic evaluation is performed from a societal perspective. DISCUSSION: By evaluating the effectiveness of only structured family meetings organized in the Netherlands, this study will contribute to the existing literature about the value of psychosocial interventions for dementia caregivers. TRIAL REGISTRATION: Dutch Trial Registry ISRCTN90163486

Representation of Time-Varying Stimuli by a Network Exhibiting Oscillations on a Faster Time Scale

Sensory processing is associated with gamma frequency oscillations (30–80 Hz) in sensory cortices. This raises the question whether gamma oscillations can be directly involved in the representation of time-varying stimuli, including stimuli whose time scale is longer than a gamma cycle. We are interested in the ability of the system to reliably distinguish different stimuli while being robust to stimulus variations such as uniform time-warp. We address this issue with a dynamical model of spiking neurons and study the response to an asymmetric sawtooth input current over a range of shape parameters. These parameters describe how fast the input current rises and falls in time. Our network consists of inhibitory and excitatory populations that are sufficient for generating oscillations in the gamma range. The oscillations period is about one-third of the stimulus duration. Embedded in this network is a subpopulation of excitatory cells that respond to the sawtooth stimulus and a subpopulation of cells that respond to an onset cue. The intrinsic gamma oscillations generate a temporally sparse code for the external stimuli. In this code, an excitatory cell may fire a single spike during a gamma cycle, depending on its tuning properties and on the temporal structure of the specific input; the identity of the stimulus is coded by the list of excitatory cells that fire during each cycle. We quantify the properties of this representation in a series of simulations and show that the sparseness of the code makes it robust to uniform warping of the time scale. We find that resetting of the oscillation phase at stimulus onset is important for a reliable representation of the stimulus and that there is a tradeoff between the resolution of the neural representation of the stimulus and robustness to time-warp. Author Summary Sensory processing of time-varying stimuli, such as speech, is associated with high-frequency oscillatory cortical activity, the functional significance of which is still unknown. One possibility is that the oscillations are part of a stimulus-encoding mechanism. Here, we investigate a computational model of such a mechanism, a spiking neuronal network whose intrinsic oscillations interact with external input (waveforms simulating short speech segments in a single acoustic frequency band) to encode stimuli that extend over a time interval longer than the oscillation's period. The network implements a temporally sparse encoding, whose robustness to time warping and neuronal noise we quantify. To our knowledge, this study is the first to demonstrate that a biophysically plausible model of oscillations occurring in the processing of auditory input may generate a representation of signals that span multiple oscillation cycles.National Science Foundation (DMS-0211505); Burroughs Wellcome Fund; U.S. Air Force Office of Scientific Researc

Characterizing genomic alterations in cancer by complementary functional associations.

Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes

Morphological features in a Xhosa schizophrenia population

BACKGROUND: Demonstrating an association between physical malformation and schizophrenia could be considered supportive of a neurodevelopmental origin of schizophrenia and may offer insights into a critical period for the development of this illness. The aim of our study was to investigate whether differences in the presence of minor physical anomalies could be demonstrated between schizophrenia sufferers and normal controls in a Xhosa population with a view to identifying a means of subtyping schizophrenia for use in future genetic studies. METHODS: Sixty-three subjects with schizophrenia (21 sibling pairs, 1 sibship of four and a group of probands with an affected non-participating sibling (n = 17)), 81 normal controls (37 singletons and 22 sibling pairs) of Xhosa ethnicity were recruited. Each participant was then examined for minor physical anomalies using the Modified Waldrop scale. The relationship between each of the morphological features and the presence of an affected sib was examined using the Chi-squared test, followed by an intra-pair concordance analysis in the sibling pairs. RESULTS: Gap between first and second toes was significantly more common in the affected sib pair group when compared to the non-affected sib pair group (p = 0.019) and non-affected singleton control group (p = 0.013). Concordance analysis also revealed increased concordance for this item in the affected sib pair group. CONCLUSION: These findings offer an intriguing possibility that in the Xhosa population, affected sib pair status may be linked to a neurodevelopmental insult during a specific period of the fetal developmental