Diagnostic and therapeutic challenges in PD-associated non-motor symptoms: the roles of neurologists and consultant physicians.

In addition to their motor symptoms, almost all Parkinson's disease patients report non-motor symptoms (NMS) and, in the later course of the disease, non-motor fluctuations as well. These NMS encompass e.g. neuropsychiatric, gastrointestinal, urogenital, cardiovascular symptoms and pain. For a long time, these symptoms received no or at best very little attention, but there is a growing trend towards their recognition and treatment. Despite this progress, significant gaps remain, particularly due to the sometimes-limited expertise among neurologists regarding these symptoms. The clinical need to consequently treat these NMS raises the question of whether Movement Disorder specialists should and can address them sufficiently or if additional consultant physicians have to be enrolled. Therefore, our objective is to establish benchmarking criteria to outline a potential way forward. Ideally, Movement Disorder specialists should take on greater responsibility when treating non-motor PD symptoms, integrating diagnostic and therapeutic pathways from other medical disciplines where feasible.

Increased risk of acute stroke among patients with severe COVID-19: a multicenter study and meta-analysis.

BACKGROUND AND PURPOSE: Recent observations linked coronavirus disease 2019 (COVID-19) to thromboembolic complications possibly mediated by increased blood coagulability and inflammatory endothelial impairment. We aimed to define the risk of acute stroke in patients with severe and non-severe COVID-19. METHODS: We performed an observational, multicenter cohort study in four participating hospitals in Saxony, Germany to characterize consecutive patients with laboratory-confirmed COVID-19 who experienced acute stroke during hospitalization. Furthermore, we conducted a systematic review using PubMed/MEDLINE, Embase, Cochrane Library and bibliographies of identified papers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines including data from observational studies of acute stroke in COVID-19 patients. Data were extracted by two independent reviewers and pooled with multicenter data to calculate risk ratios (RRs) and 95% confidence intervals (95% CIs) for acute stroke related to COVID-19 severity using a random-effects model. Between-study heterogeneity was assessed using Cochran's Q and I2 statistics. International Prospective Register of Systematic Reviews registration number: CRD42020187194. RESULTS: Of 165 patients hospitalized for COVID-19 (49.1% males, median age = 67 years [57-79 years], 72.1% severe or critical) included in the multicenter study, overall stroke rate was 4.2% (95% CI: 1.9-8.7). Systematic literature search identified two observational studies involving 576 patients that were eligible for meta-analysis. Amongst 741 pooled COVID-19 patients, overall stroke rate was 2.9% (95% CI: 1.9-4.5). Risk of acute stroke was increased for patients with severe compared to non-severe COVID-19 (RR = 4.18, 95% CI: 1.7-10.25; P = 0.002) with no evidence of heterogeneity (I2  = 0%, P = 0.82). CONCLUSIONS: Synthesized analysis of data from our multicenter study and previously published cohorts indicates that severity of COVID-19 is associated with an increased risk of acute stroke.

Levodopa/carbidopa intestinal gel (LCIG) infusion as mono- or combination therapy.

Levodopa/carbidopa intestinal gel (LCIG) infusion is an effective escalating therapy in patients with Parkinson disease (PD) suffering from motor fluctuations and dyskinesia. Levodopa/carbidopa given continuously as infusion provides an optimized application of the most effective and best tolerable antiparkinsonian drug. It has been proven to have a superior motor effect compared with oral levodopa and to improve also non-motor symptoms. However, invasiveness, discomfort resulting from carrying an external device, and side effects associated with the way of administration limit its application in PD patients. At present, there are no guidelines that delineate to which patients LCIG should be offered as monotherapy, in combination with oral and/or transdermal medication, or as additional therapy to deep brain stimulation (DBS). Based on clinical studies, we propose an expert consensus for neurologists addressing the question when LCIG therapy should be recommended and in which cases LCIG infusion is suggested in combination with other antiparkinsonian drugs and/or DBS. We describe how LCIG should be initiated and what we consider necessary for clinical follow-up. We suggest an algorithm facilitating decision-making with respect to the currently available invasive PD therapies, namely infusion with subcutaneous apomorphine, LCIG, and DBS.

Epitaxial Growth of GaN Nanowires with High Structural Perfection on a Metallic TiN Film.

Vertical GaN nanowires are grown in a self-induced way on a sputtered Ti film by plasma-assisted molecular beam epitaxy. Both in situ electron diffraction and ex situ ellipsometry show that Ti is converted to TiN upon exposure of the surface to the N plasma. In addition, the ellipsometric data demonstrate this TiN film to be metallic. The diffraction data evidence that the GaN nanowires have a strict epitaxial relationship to this film. Photoluminescence spectroscopy of the GaN nanowires shows excitonic transitions virtually identical in spectral position, line width, and decay time to those of state-of-the-art GaN nanowires grown on Si. Therefore, the crystalline quality of the GaN nanowires grown on metallic TiN and on Si is equivalent. The freedom to employ metallic substrates for the epitaxial growth of semiconductor nanowires in high structural quality may enable novel applications that benefit from the associated high thermal and electrical conductivity as well as optical reflectivity.

[The Geriatric Patient with Parkinson's Disease - a Neurological Challenge]. / Der geriatrische Parkinson-Patient - eine neurologische Herausforderung.

Geriatric patients with Parkinson's disease (PD) represent a particular challenge in terms of diagnostics and treatment. This overview article addresses age-related characteristics of this patient group and discusses particularities in PD symptoms in this age group, frequent comorbidities and the resulting polypharmacy. Questions regarding the availability of specialist and therapist care as well as end-of-life aspects are discussed. While comprehensive care structures are not always available, this patient group requires a multidisciplinary treatment team supervised by neurologists with ample experience in PD treatment.

[Executive task performance under deep brain stimulation of the subthalamic nucleus in Parkinson's disease revisited: the modulating influence of apathy, depression and mood]. / Einfluss der Tiefen Hirnstimulation des Nucleus subthalamicus auf exekutive Funktionen bei Patienten mit idiopathischem Parkinson-Syndrom unter Berücksichtigung von Apathie, Depressivität und Stimmung.

We investigated the moderating influence of apathy, depression and transient mood changes on executive functions under best medical treatment and under postoperative stimulation-on and -off conditions in a sample of 33 patients with Parkinson's disease (PD) after deep brain stimulation of the subthalamic nucleus (STN), 33 PD patients with pharmacological treatment only and 34 healthy controls. In comparison to clinical and healthy control groups, DBS patients showed worse executive task performance and also more severe symptoms of depression and apathy. Apathy accounted for differences in stroop interference between groups. The effects of DBS on stroop interference were explained by increased state anxiety in the -off, so that DBS STN had no significant influence on test performance. Consideration of neuropsychiatric symptoms and acute mood changes is an important aspect when evaluating neuropsychological deficits in DBS patients.

Current path in light emitting diodes based on nanowire ensembles.

Light emitting diodes (LEDs) have been fabricated using ensembles of free-standing (In, Ga)N/GaN nanowires (NWs) grown on Si substrates in the self-induced growth mode by molecular beam epitaxy. Electron-beam-induced current analysis, cathodoluminescence as well as biased µ-photoluminescence spectroscopy, transmission electron microscopy, and electrical measurements indicate that the electroluminescence of such LEDs is governed by the differences in the individual current densities of the single-NW LEDs operated in parallel, i.e. by the inhomogeneity of the current path in the ensemble LED. In addition, the optoelectronic characterization leads to the conclusion that these NWs exhibit N-polarity and that the (In, Ga)N quantum well states in the NWs are subject to a non-vanishing quantum confined Stark effect.

Correlation between In content and emission wavelength of In(x)Ga(1-x)N/GaN nanowire heterostructures.

GaN nanowire ensembles with axial In(x)Ga(1-x)N multi-quantum-wells (MQWs) were grown by molecular beam epitaxy. In a series of samples we varied the In content in the MQWs from almost zero to around 20%. Within the nanowire ensemble, the MQWs fluctuate strongly in composition and size. Statistical information about the composition was obtained from x-ray diffraction and Raman spectroscopy. Photoluminescence at room temperature was obtained in the range of 2.2 to 2.5 eV, depending on In content. Contrary to planar MQWs, the intensity increases with increasing In content. We compare the observed emission energies with transition energies obtained from a one-dimensional model, and conclude that several mechanisms for carrier localization affect the luminescence of these three-dimensional structures.

Creation of equal-spin triplet superconductivity at the Al/EuS interface.

In conventional superconductors, electrons of opposite spins are bound into Cooper pairs. However, when the superconductor is in contact with a non-uniformly ordered ferromagnet, an exotic type of superconductivity can appear at the interface, with electrons bound into three possible spin-triplet states. Triplet pairs with equal spin play a vital role in low-dissipation spintronics. Despite the observation of supercurrents through ferromagnets, spectroscopic evidence for the existence of equal-spin triplet pairs is still missing. Here we show a theoretical model that reveals a characteristic gap structure in the quasiparticle density of states which provides a unique signature for the presence of equal-spin triplet pairs. By scanning tunnelling spectroscopy we measure the local density of states to reveal the spin configuration of triplet pairs. We demonstrate that the Al/EuS interface causes strong and tunable spin-mixing by virtue of its spin-dependent transmission.

Effects of a low molecular weight heparin (Fragmin) and of unfractionated heparin on coagulation activation at the site of plug formation in vivo.

The clinical benefits of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have been shown in many trials. However, the mode of action of heparin has not been fully elucidated. Thus, we wanted to study the effects of UFH and LMWH in vivo by measuring coagulation activation markers in blood obtained directly from a vascular injury site. In a double-blind, randomized, 3-way, cross-over study 18 healthy volunteers were given UFH (150 U/kg s.c.) and 2 doses of LMWH [35 U/kg s.c. (low dose, ld), 75 U/kg s.c. (high dose, hd)]. Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT) and fibrinopeptide A (FPA) were measured in bleeding time blood and in venous blood before and after drug application. In addition, the effects of UFH and LMWH on in vitro coagulation tests were studied. Compared to base line, UFH and both ldLMWH and hdLMWH caused significant reductions of F1+2, TAT and FPA in bleeding time blood at 2 h. A marked effect of UFH and of hdLMWH was also seen at 5 h. The inhibition of FPA generation was more pronounced after hdLMWH compared to ldLMWH. In venous blood, UFH and LMWH caused reductions of F1+2, but not of TAT and FPA. In vitro, UFH predominantly affected the anti-IIa assays (activated partial thromboplastin time, thrombin time) and LMWH mainly the anti-Xa test system. Using a technique that investigates the activated coagulation system in vivo, a time- and dose dependent inhibitory effect of heparin on coagulation activation was detectable.(ABSTRACT TRUNCATED AT 250 WORDS)

Longitudinally measured blood pressure, antihypertensive medication use, and cognitive performance: the Framingham Study.

The relation of longitudinally measured blood pressure to cognitive performance in the absence of clinically diagnosed cerebrovascular disease was investigated in the Framingham Study. In 1976-1978, neuropsychologic testing was administered to 1993 participants aged 55-89 years. Performance on an education-adjusted composite of these tests was examined in relation to measures of chronicity of hypertension as well as the average systolic and average diastolic blood pressure. All analyses were stratified by antihypertensive medication use during the 2 years prior to cognitive testing and adjusted for age, sex, occupation, alcohol consumption, and participation rate in prior examination cycles. Among subjects on drug therapy for hypertension, there was no association between cognitive performance and longitudinally measured blood pressure. The proportion of cycles in which hypertension was present and average systolic and diastolic blood pressure had a significant inverse relation with cognitive performance only in the group not on antihypertensive drug therapy. However, among subjects on antihypertensive medication at earlier cycles, there was a highly significant graded relation between cognitive impairment and the probability of being off medication at the time of testing. These results suggest that hypertension-related subclinical vascular disease is not an important cause of cognitive impairment in the elderly. Cognitive impairment may, however, be associated with a reduced adherence to drug treatment regimens.

The difficult venous ulcer: case series of 177 ulcers referred for vascular surgical opinion following failure of conservative management.

Venous leg ulcers are common, chronic, debilitating, and expensive. Evidence supports use of compression bandaging, with superficial venous surgery in selected cases, but these interventions frequently fail to achieve healing. We describe a series of 152 consecutive referrals from a nurse-led specialist dermatology clinic to a vascular surgical service; a group posing particularly challenging problems. This observational study, with median follow-up of 18 months, describes outcomes in a number of important clinically identifiable subgroups. Its findings may assist service planning and discussion of the surgical role within multidisciplinary ulcer management.

[Malignant epithelioma of the retinal pigment epithelium (author's transl)]. / Malignes epitheliom des retinalen pigmentepithels.

Description of clinical and histopathologic findings in a case of malignant epithelioma of the retinal pigment epithelium. This very rare neoplasm usually develops at the equator of the globe or more peripherally and is practically always mistaken for a malignant melanoma of the choroid. Metastasis of this tumor, revealing an infiltrative and destructive growth pattern, has not been described unequivocally.

Alcohol problems and the availability of alcohol.

This study assesses the statistical effects of the physical availability of alcohol as measured by the number of liquor store employees per 100,000 persons. Controlling for the effects of per capita income and urbanism, it is found that there are effects of physical availability on current tangible consequences but not on alcoholism rates or frequent heavy drinking.

The prevention of alcoholism: an empirical report on the effects of outlet availability.

Recent studies suggest that alcohol availability as measured by outlet rates is unrelated to per capita consumption or rates of alcoholism in the United States. Drawing from the same data bases, this article assesses the effects of outlet rates while controlling for the effects of per capita income, urbanism, and limitations by population on the number of sales outlets. The analysis discloses strong effects of outlet availability on per capita consumption and alcoholism rates in states that do not have restrictions on the number of outlets per unit of population.