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Striatal signaling in the treatment of Parkinson's disease

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by typical motor symptoms that are caused by depletion of dopamine (DA) in the striatum. These symptoms are treated with the DA precursor L-DOPA, or with DA receptor (DAR) agonists. L-DOPA is the most efficacious treatment, but causes complications that limit its utility, in particular, dyskinesia (involuntary movements). Model

500 år med humlesuga, Betonica officinalis L., i Skåne och Danmark

Humlesugan, Betonica officinalis L., är en av den skandinaviska florans sällsyntaste växter och samtidigt en av de arter som har den längsta dokumenterade historien. Den rapporterades från Stehag väster om Ringsjön i Skåne av Christiern Pedersen redan 1534, Skånes äldsta litteraturuppgift där en växtart knyts till en lokal. I övriga Danmark beskrevs den med lokaluppgift första gången av Peder Laur

Identifying carriers at high risk for negative reactions when performing prenatal diagnosis of haemophilia

The aim of the current study was to determine which pregnant carriers of haemophilia are at particularly high risk for having notably negative psychological reactions in association with prenatal diagnosis (PND) by fetal blood sampling of offspring haemophilia. Among 29 carriers of haemophilia A or B, notable psychiatric or psychosomatic symptoms in association with PND were significantly related

Characterization and criteria of embryonic stem and induced pluripotent stem cells for a dopamine replacement therapy

Human pluripotent stem cells provide new choices for sources of A9-type dopaminergic (DA) neurons in clinical trials of neural transplantation for patients with Parkinson's disease (PD). For example, "self" and HLA-matched A9 DA neurons may improve the patient-to-patient variability observed in previous clinical trials using fetal DA neurons and obviate the need for long-term immunosuppression in

α-Synuclein induced toxicity in brain stem serotonin neurons mediated by an AAV vector driven by the tryptophan hydroxylase promoter

We studied the impact of α-synuclein overexpression in brainstem serotonin neurons using a novel vector construct where the expression of human wildtype α-synuclein is driven by the tryptophan hydroxylase promoter, allowing expression of α-synuclein at elevated levels, and with high selectivity, in serotonergic neurons. α-Synuclein induced degenerative changes in axons and dendrites, displaying a

An age structured cell cycle model with crowding

We study a two compartment, nonlinear, age structured model for the cell cycle. The phases of the cell cycle G1, S, G2 and M are grouped into two phases, which we call Phase 1 and Phase 2, where Phase 1 consists of the phase G1 and Phase 2 consists of the phases S, G2 and M. It is assumed that Phase 1 has a variable duration while the duration of Phase 2 is fixed. The model consists of a system of

Changes in El Niño – Southern Oscillation (ENSO) conditions during the Greenland Stadial 1 (GS-1) chronozone revealed by New Zealand tree-rings

The warming trend at the end of the last glacial was disrupted by rapid cooling clearly identified in Greenland (Greenland Stadial 1 or GS-1) and Europe (Younger Dryas Stadial or YD). This reversal to glacial-like conditions is one of the best known examples of abrupt change but the exact timing and global spatial extent remain uncertain. Whilst the wider Atlantic region has a network of high-reso

Gaucher disease and comorbidities : B-cell malignancy and parkinsonism

Data emerging from the International Collaborative Gaucher Group (ICGG) Gaucher Registry together with other contemporary clinical surveys have revealed a close association between Gaucher disease and non-Hodgkin's B-cell lymphoma and myeloma and Gaucher disease and Parkinson's disease. Several possible explanations for increased B-cell proliferation and neoplasia in Gaucher disease have been prop

Progress in Huntington's disease : the search for markers of disease onset and progression

Unlike most neurodegenerative disorders, individuals at risk from Huntington's disease can be identified prior to the onset of clinical signs of the disease by virtue of it being an autosomal dominant condition. This provides the hypothetical opportunity to delay disease onset and/or slow down the progression of the disease in the very early stages ahead of overt features of disease. To help prepa

Which patients with Parkinson's disease participate in clinical trials? : One centre's experiences with a new cell based therapy trial (TRANSEURO)

BACKGROUND: There is currently little evidence regarding the selection of patients for clinical trials in Parkinson's Disease (PD), especially those involving experimental therapies delivered using invasive techniques.OBJECTIVE: Understanding which patients are recruited will increase awareness of issues regarding parity of access to clinical trials and have an impact on the wider applicability of

Hippocampal dysfunction defines disease onset in Huntington's disease

BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterised by a triad of motor, psychiatric and cognitive deficits with the latter classically attributed to disruption of frontostriatal networks. However, emerging evidence from animal models of HD suggests that some of the early cognitive deficits may have a hippocampal basis. The objective of this stud

The effect of multidisciplinary rehabilitation on brain structure and cognition in Huntington's disease : an exploratory study

BACKGROUND: There is a wealth of evidence detailing gray matter degeneration and loss of cognitive function over time in individuals with Huntington's disease (HD). Efforts to attenuate disease-related brain and cognitive changes have been unsuccessful to date. Multidisciplinary rehabilitation, comprising motor and cognitive intervention, has been shown to positively impact on functional capacity,

Cholelithiasis during the first year of life : Case reports and literature review

Five cases are reported of children with gallstones diagnosed by ultrasound during their first 7 months of life. Of the four with symptomatic gallstones, one subsequently developed vitamin K deficiency syndrome with profuse bleedings. The children, who belonged to a defined population, were all diagnosed within an 18-month span, suggesting the frequency of early gallstone formation to be higher th

Mutant huntingtin is present in neuronal grafts in Huntington disease patients

OBJECTIVE: Huntington disease (HD) is caused by a genetically encoded pathological protein (mutant huntingtin [mHtt]), which is thought to exert its effects in a cell-autonomous manner. Here, we tested the hypothesis that mHtt is capable of spreading within cerebral tissue by examining genetically unrelated fetal neural allografts within the brains of patients with advancing HD.METHODS: The presen

Selective serotonin reuptake inhibition modulates response inhibition in Parkinson's disease

Impulsivity is common in Parkinson's disease even in the absence of impulse control disorders. It is likely to be multifactorial, including a dopaminergic 'overdose' and structural changes in the frontostriatal circuits for motor control. In addition, we proposed that changes in serotonergic projections to the forebrain also contribute to response inhibition in Parkinson's disease, based on precli

Clinical risk profile score predicts all cause mortality but not implantable cardioverter defibrillator intervention rate in a large unselected cohort of patients with congestive heart failure

BACKGROUND: Primary prophylactic implantable cardioverter defibrillator (ICD) therapy is indicated for patients with reduced left ventricular ejection fraction (LVEF). We aimed to determine if preoperative clinical risk profiling can predict long-term benefit, and if clinical risk scores can be applied and improved in a patient cohort outside the clinical trial setting.METHODS: Using registry data