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A regulatable AAV vector mediating GDNF biological effects at clinically-approved sub-antimicrobial doxycycline doses

Preclinical and clinical data stress the importance of pharmacologically-controlling glial cell line-derived neurotrophic factor (GDNF) intracerebral administration to treat PD. The main challenge is finding a combination of a genetic switch and a drug which, when administered at a clinically-approved dose, reaches the brain in sufficient amounts to induce a therapeutic effect. We describe a highl

Comparison of rating scales used to evaluate L-DOPA-induced dyskinesia in the 6-OHDA lesioned rat

Abnormal involuntary movement (AIM) rating scales are frequently used to study the mechanisms underlying L-DOPA-induced dyskinesia (LID) in 6-OHDA lesioned rodents and the propensity of novel treatments for Parkinson's disease to induce or alleviate similar abnormal behaviours. Despite the existence of at least one well validated method, other AIM scales are also in use. Moreover, there have been

Pharmacological modulation of amphetamine-induced dyskinesia in transplanted hemi-parkinsonian rats

Foetal cell transplantation in patients with Parkinson's disease can induce motor complications independent of L-DOPA administration, known as graft-induced dyskinesia. In the 6-OHDA lesioned rat model of Parkinson's disease, post-transplantation abnormal movements can develop in response to an amphetamine challenge, a behaviour which is used to model graft-induced dyskinesia. Although L-DOPA-indu

Premonitory urges and Touretting volcanoes : Force construal in personal narratives on Tourette Syndrome

Causative meaning including, but not limited to, causation, prevention, and enabling is realized in language use through force construal. Force is explored in this article through consideration of narratives on Tourette Syndrome, a disorder that is largely characterized by its constitutive actions (i.e. vocal and motor tics). To account for force construal, the article proposes a merger of a vecto

The states of water in Norway spruce (Picea abies (L.) Karst.) studied by low-field nuclear magnetic resonance (LFNMR) relaxometry : Assignment of free-water populations based on quantitative wood anatomy

LFNMR relaxometry was applied to determine the spin-spin relaxation time (T2) of water saturated Norway spruce samples cut from mature sapwood and mature and juvenile heartwood where earlywood and latewood were separated. In combination with quantitative wood anatomy data focusing on the void volumes in various morphological regions, the NMR data served for a more reliable assignment of free waterLow-field nuclear magnetic resonance (LFNMR) relaxometry was applied to determine the spin-spin relaxation time (T2) of water-saturated Norway spruce (Picea abies (L.) Karst.) specimens cut from mature sapwood (sW) and mature and juvenile heartwood (hW), where earlywood (EW) and latewood (LW) were separated. In combination with quantitative wood anatomy data focusing on the void volumes in various

RIFM fragrance ingredient safety assessment, p-Isopropylbenzyl acetate, CAS Registry Number 59230-57-8

The use of this material under current use conditions is supported by the existing information.This material was evaluated for genotoxicity, repeated dose toxicity, developmental toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity, skin sensitization, as well as environmental safety. Data from the suitable read across analog, benzyl acetate (CAS # 140-11-4), show that this m

Structural Mechanism of Allosteric Activity Regulation in a Ribonucleotide Reductase with Double ATP Cones

Summary Ribonucleotide reductases (RNRs) reduce ribonucleotides to deoxyribonucleotides. Their overall activity is stimulated by ATP and downregulated by dATP via a genetically mobile ATP cone domain mediating the formation of oligomeric complexes with varying quaternary structures. The crystal structure and solution X-ray scattering data of a novel dATP-induced homotetramer of the Pseudomonas aer

Pupil dilation : a fingerprint of temporal selection during the “attentional blink"

Pupil dilation indexes cognitive events of behavioral relevance, like the storage of information to memory and the deployment of attention. Yet, given the slow temporal response of the pupil dilation, it is not known from previous studies whether the pupil can index cognitive events in the short time scale of ∼100 ms. Here we measured the size of the pupil in the Attentional Blink (AB) experiment,

Did Jupiter's core form in the innermost parts of the Sun's protoplanetary disc?

Jupiter's core is generally assumed to have formed beyond the snow line. Here we consider an alternative scenario that Jupiter's core may have accumulated in the innermost part of the protoplanetary disc. A growing body of research suggests that small particles ('pebbles') continually drift inward through the disc. If a fraction of drifting pebbles is trapped at the inner edge of the disc, several

Vitamin B12 deficiency is associated with cardiovascular autonomic neuropathy in patients with type 2 diabetes

AIMS: Vitamin B12 deficiency could be associated with cardiovascular autonomic neuropathy (CAN) in diabetes patients. We aim to investigate the association between serum levels of vitamin B12 and CAN in type 2 diabetes patients.METHODS: 469 ambulatory type 2 diabetes patients (mean diabetes duration 10.0years (IQR 5.0;17.0), mean age 59.0years (SD 11.6), 63% men, mean B12 289.0pmol/l (IQR 217;390)

Potential positive impact of group-based diabetes dialogue meetings on diabetes distress and glucose control in people with type 1 diabetes

OBJECTIVE: To evaluate the effect of group-based diabetes dialogue meetings (DDMs) on diabetes distress, perceived competence and glycaemic control.METHODS: Patients with type 1 diabetes (T1D) were invited to DDMs with peers and healthcare professionals. The impact of participation was evaluated by change in diabetes distress measured by Problem Areas in Diabetes (PAID), diabetes competence measur

Changes in HbA1c and Weight Following Transition to Continuous Subcutaneous Insulin Infusion Therapy in Adults With Type 1 Diabetes

BACKGROUND: Historically, intensive insulin therapy for type 1 diabetes (T1D) has improved glycemic control at the risk of adverse weight gain. The impact of continuous subcutaneous insulin infusion therapy (CSII) on weight in the current era remains unknown. We assessed changes in hemoglobin A1c (HbA1c) and weight in adults with T1D transitioning to CSII at 2 diabetes centers in Denmark and the U

Group-based Parental Support in Child Health Service. Development and evaluation of a group leadership course for nurses.

The close relationship between young children’s living conditions and their healthlater in life is well documented and a safe and healthy environment during earlychildhood promotes cognitive functions and social development during the wholelifespan. Becoming a parent is a major life transition and it is sometimes described as a stressful and vulnerable time involving changes to lifestyle and routi

The Impacts of Contextual Factors on Social Media Crises : Implications for crisis communication strategy selection

The prescriptive approach to crisis communication strategy (CCS) selection has long been criticized for lack of flexibility and adaptability. To address this issue, this study proposes an emergent approach to strategy formulation by focusing on contextual impacts on social media crises and their implications for CCS. An online discussion on Sina Weibo, a Chinese microblogging platform, about a hig