Tolerability of non-ergot oral and transdermal dopamine agonists in younger and older Parkinson's disease patients: an European multicentre survey.

In older patients with Parkinson's disease (PD), the use of dopamine agonists (DA) has been limited due to uncertainties related to their tolerability in spite of potential gains with the advent of longer acting or transdermal therapies. Comparative real-life data addressing the tolerability of DA therapy across age ranges are currently sparse. This study addressed the tolerability (Shulman criteria, continued intake of DA therapy for at least 6 months) in PD patients across several European centres treated with long-acting and transdermal DA (Rotigotine skin patch, Ropinirole extended release, or Pramipexole prolonged release) as part of routine clinical care in younger and older PD patients. A medical record-based retrospective data capture and clinical interview-based follow-up survey of patients initiating or initiated on DA treatment (short and long acting) in a real-life setting. 425 cases were included [mean age 68.3 years (range 37-90), mean duration of disease 7.5 years (range 0-37), 31.5% older age (≥ 75 years of age)]. Tolerability was above 90% irrespective of age, with no significant differences between younger and older patients. Based on our findings, we suggest that long-acting/transdermal DA are tolerated in non-demented older patients, as well as in younger patients, however, with lower daily dose in older patients.

Cranial nerve deficits in giant cavernous carotid aneurysms and their relation to aneurysm morphology and location.

BACKGROUND: Giant cavernous carotid aneurysms (GCCAs) usually exert substantial mass effect on adjacent intracavernous cranial nerves. Since predictors of cranial nerve deficits (CNDs) in patients with GCCA are unknown, we designed a study to identify associations between CND and GCCA morphology and the location of mass effect. METHODS: This study was based on data from the prospective clinical and imaging databases of the Giant Intracranial Aneurysm Registry. We used magnetic resonance imaging and digital subtraction angiography to examine GCCA volume, presence of partial thrombosis (PT), GCCA origins, and the location of mass effect. We also documented whether CND was present. RESULTS: We included 36 GCCA in 34 patients, which had been entered into the registry by eight participating centers between January 2009 and March 2016. The prevalence of CND was 69.4%, with one CND in 41.7% and more than one in 27.5%. The prevalence of PT was 33.3%. The aneurysm origin was most frequently located at the anterior genu (52.8%). The prevalence of CND did not differ between aneurysm origins (p = 0.29). Intracavernous mass effect was lateral in 58.3%, mixed medial/lateral in 27.8%, and purely medial in 13.9%. CND occurred significantly more often in GCCA with lateral (81.0%) or mixed medial/lateral (70.0%) mass effect than in GCCA with medial mass effect (20.0%; p = 0.03). After adjusting our data for the effects of the location of mass effect, we found no association between the prevalence of CND and aneurysm volume (odds ratio (OR) 1.30 (0.98-1.71); p = 0.07), the occurrence of PT (OR 0.64 (0.07-5.73); p = 0.69), or patient age (OR 1.02 (95% CI 0.95-1.09); p = 0.59). CONCLUSIONS: Distinguishing between medial versus lateral location of mass effect may be more helpful than measuring aneurysm volumes or examining aneurysm thrombosis in understanding why some patients with GCCA present with CND while others do not. CLINICAL TRIAL REGISTRATION NO: NCT02066493 ( clinicaltrials.gov ).

High-energy, high-fat lifestyle challenges an Arctic apex predator, the polar bear.

Regional declines in polar bear (Ursus maritimus) populations have been attributed to changing sea ice conditions, but with limited information on the causative mechanisms. By simultaneously measuring field metabolic rates, daily activity patterns, body condition, and foraging success of polar bears moving on the spring sea ice, we found that high metabolic rates (1.6 times greater than previously assumed) coupled with low intake of fat-rich marine mammal prey resulted in an energy deficit for more than half of the bears examined. Activity and movement on the sea ice strongly influenced metabolic demands. Consequently, increases in mobility resulting from ongoing and forecasted declines in and fragmentation of sea ice are likely to increase energy demands and may be an important factor explaining observed declines in body condition and survival.

A European multicentre survey of impulse control behaviours in Parkinson's disease patients treated with short- and long-acting dopamine agonists.

BACKGROUND AND PURPOSE: Impulse control disorders (ICDs) in Parkinson's disease (PD) are associated primarily with dopamine agonist (DA) use. Comparative surveys of clinical occurrence of impulse control behaviours on longer acting/transdermal DA therapy across age ranges are lacking. The aim of this study was to assess the occurrence of ICDs in PD patients across several European centres treated with short- or long-acting [ropinirole (ROP); pramipexole (PPX)] and transdermal [rotigotine skin patch (RTG)] DAs, based on clinical survey as part of routine clinical care. METHODS: A survey based on medical records and clinical interviews of patients initiating or initiated on DA treatment (both short- and long-acting, and transdermal) across a broad range of disease stages and age groups was performed. RESULTS: Four hundred and twenty-five cases were included [mean age 68.3 years (range 37-90), mean duration of disease 7.5 years (range 0-37)]. ICD frequencies (as assessed by clinical interview) were significantly lower with RTG (4.9%; P < 0.05) compared with any other assessed DAs except for prolonged release PPX (PPX-PR). The rate of ICDs for PPX-PR (6.6%) was significantly lower than for immediate release PPX (PPX-IR) (19.0%; P < 0.05). Discontinuation rates of DA therapy due to ICDs were low. CONCLUSION: Our data suggest a relatively low rate of ICDs with long-acting or transdermal DAs, however these preliminary observational data need to be confirmed with prospective studies controlling for possible confounding factors.

Animal physiology. Summer declines in activity and body temperature offer polar bears limited energy savings.

Polar bears (Ursus maritimus) summer on the sea ice or, where it melts, on shore. Although the physiology of "ice" bears in summer is unknown, "shore" bears purportedly minimize energy losses by entering a hibernation-like state when deprived of food. Such a strategy could partially compensate for the loss of on-ice foraging opportunities caused by climate change. However, here we report gradual, moderate declines in activity and body temperature of both shore and ice bears in summer, resembling energy expenditures typical of fasting, nonhibernating mammals. Also, we found that to avoid unsustainable heat loss while swimming, bears employed unusual heterothermy of the body core. Thus, although well adapted to seasonal ice melt, polar bears appear susceptible to deleterious declines in body condition during the lengthening period of summer food deprivation.

Axially chiral amidinium ions as inducers of enantioselectivity in Diels-Alder reactions

[reaction: see text] Enantioselective catalysis of Diels-Alder reactions is mostly achieved by coordinating the dienophile to relatively strong chiral Lewis acids. Here we report on a novel approach employing the hydrogen-bond-mediated association of dienophiles to chiral host molecules. In a reaction forming the steroid skeleton of norgestrel, chiral amidinium ions induce 5:ent-5 ratios of up to 2.5:1. Improved and simplified amidinium catalysts may become interesting candidates to perform stereoselective transformations.