Neuropathological diagnostic considerations in hyperkinetic movement disorders

Neuropathology of hyperkinetic movement disorders can be very challenging. This paper starts with basic functional anatomy of the basal ganglia in order to appreciate that focal lesions like for instance tumor or infarction can cause hyperkinetic movement disorders like (hemi)ballism. The neuropathology of different causes of chorea (amongst others Huntington’s disease, neuroacanthosis, and HLD-2) and dystonia (DYT1, PD, and Dopa-Responsive Dystonia) are described. Besides the functional anatomy of the basal ganglia a wider anatomical network view is provided. This forms the basis for the overview of the neuropathology of different forms of tremor

Double Sivers effect asymmetries and their impact on transversity measurements at RHIC

We study double transverse spin asymmetries in the Drell-Yan process at measured transverse momentum of the lepton pair. Contrary to what a collinear factorization approach would suggest, a nonzero double transverse spin asymmetry in the laboratory frame a priori does not imply nonzero transversity. TMD effects, such as the double Sivers effect, in principle form a background. Using the current knowledge of the relevant TMDs we estimate their contribution in the laboratory frame for Drell-Yan and W production at RHIC and point out a cross check asymmetry measurement to bound the TMD contributions. We also comment on the transverse momentum integrated asymmetries that only receive power suppressed background contributions.Comment: 12 pages, 11 eps figures, minor changes, matches the published versio

The Potential of Ferroptosis-Targeting Therapies for Alzheimer's Disease:From Mechanism to Transcriptomic Analysis

Alzheimer’s disease (AD), the most common form of dementia, currently affects 40–50 million people worldwide. Despite the extensive research into amyloid β (Aβ) deposition and tau protein hyperphosphorylation (p-tau), an effective treatment to stop or slow down the progression of neurodegeneration is missing. Emerging evidence suggests that ferroptosis, an iron-dependent and lipid peroxidation-driven type of programmed cell death, contributes to neurodegeneration in AD. Therefore, how to intervene against ferroptosis in the context of AD has become one of the questions addressed by studies aiming to develop novel therapeutic strategies. However, the underlying molecular mechanism of ferroptosis in AD, when ferroptosis occurs in the disease course, and which ferroptosis-related genes are differentially expressed in AD remains to be established. In this review, we summarize the current knowledge on cell mechanisms involved in ferroptosis, we discuss how these processes relate to AD, and we analyze which ferroptosis-related genes are differentially expressed in AD brain dependant on cell type, disease progression and gender. In addition, we point out the existing targets for therapeutic options to prevent ferroptosis in AD. Future studies should focus on developing new tools able to demonstrate where and when cells undergo ferroptosis in AD brain and build more translatable AD models for identifying anti-ferroptotic agents able to slow down neurodegeneration

Corrigendum:The Potential of Ferroptosis-Targeting Therapies for Alzheimer's Disease: From Mechanism to Transcriptomic Analysis

[This corrects the article DOI: 10.3389/fnagi.2021.745046.].</p

Recruitment of bone marrow derived cells during anti-angiogenic therapy in GBM:The potential of combination strategies

Glioblastoma (GBM) is a highly vascular tumor characterized by rapid and invasive tumor growth, followed by oxygen depletion, hypoxia and neovascularization, which generate a network of disorganized, tortuous and permeable vessels. Recruitment of bone marrow derived cells (BMDC) is crucial for vasculogenesis. These dells may act as vascular progenitors by integrating into the newly formed blood vessels or as vascular modulators by releasing pro-angiogenic factors. In patients with recurrent GBM, anti-vascular endothelial growth factor (VEGF) therapy has been evaluated in combination with chemotherapy, yielding improvements in progression-free survival (PFS). However, benefits are temporary as vascular tumors acquire angiogenic pathways independently of VEGF. Specifically, acute hypoxia following prolonged VEGF depletion induces the recruitment of certain myeloid cell subpopulations, which highly contribute to treatment refractoriness. Here we review the molecular mechanisms of neovascularization in relation to bevacizumab therapy with special emphasis on the recruitment of BMDCs and possible combination therapies for GBM patients. (C) 2014 Elsevier Ireland Ltd. All rights reserved

Conservative treatment of CMC-1 osteoarthritis

Initially, osteoarthritis of the carpometacarpal joint of the thumb (CMC-1) should be conservatively treated. However, literature concerning this topic is absent. Therefore, 39 patients (71 hands) with conservatively treated osteoarthritis of the carpometacarpal joint of the thumb were reviewed. The minimum follow-up period was I year; the average follow-up period was 8.8 years. Thirty-two women had bilateral CMC-I osteoarthritis; the remaining seven patients had unilateral CMC-1 osteoarthritis. Although suggested by others, long-term pain relief was not observed in this study. Moreover, patient satisfaction, thumb strength, and mobility were not influenced by the duration of the CMC-1 osteoarthritis. In conservatively treated patients, worse results are achieved than in operated patients, especially concerning their subjective experiences. The authors therefore advise surgery, especially in the case of pain which hampers the activities of daily life

The Influence of a Fibrin-Coating Inside a Biodegradable Poly(DL-Lactide-ε-Caprolactone) Nerve Guide on Peripheral Nerve Regeneration

The aim of this study was to evaluate the effect of a fibrin-coating on the inner surface of a biodegradable poly(DL-lactide-E-caprolactone) nerve guide on the speed and quality of the nerve regeneration. The nerve regeneration and orientation of the nerve fibers, as well as the fibrous tissue formation were evaluated. On the short term, nerve regeneration was slightly faster in the non-coated nerve guide. After longer implantation periods (≥ 4 weeks), nerve regeneration in the fibrin-coated nerve guides was characterized by a severe inflammatory response with large numbers of macrophages and polymorphonuclear cells (PMN\u27s). This study clearly demonstrates that nerve regeneration in a fibrin-coated nerve guide is not faster when compared with a non-coated nerve guide, and that nerve regeneration in the fibrin-coated nerve guide is even worse after longer implantation periods

An aggressive poorly differentiated plurihormonal Pit-1-positive adenoma

In July 2017, a 35-year-old woman was referred to our care for treatment of a large pituitary mass with an unusually high growth rate. She presented with right-sided ptosis and diplopia (n. III palsy), increasing retrobulbar pain and vertigo. Although laboratory investigations were consistent with acromegaly, she exhibited no clear phenotypic traits. During transsphenoidal surgery aimed at biopsy, typical adenomatous tissue was encountered, upon which it was decided to proceed to debulking. Histopathological analysis demonstrated a poorly differentiated plurihormonal Pit-1-positive adenoma with focal growth hormone (GH) and prolactin positivity, positive SSTR2 staining and a Ki-67 of 20–30%. Postoperative magnetic resonance imaging (MRI) examination revealed a large tumour remnant within the sella invading the right cavernous sinus with total encasement of the internal carotid artery and displacement of the right temporal lobe. As a consequence, she was treated additionally with radiotherapy, and a long-acting first-generation somatostatin analogue was prescribed. Subsequently, the patient developed secondary hypocortisolism and diabetes mellitus despite adequate suppression of GH levels. In September 2019, her symptoms recurred. Laboratory evaluations indicated a notable loss of biochemical control, and MRI revealed tumour progression. Lanreotide was switched to pasireotide, and successful removal of the tumour remnant and decompression of the right optic nerve was performed. She received adjuvant treatment with temozolomide resulting in excellent biochemical and radiological response after three and six courses. Symptoms of right-sided ptosis and diplopia remained. Evidence for systemic therapy in case of tumour progression after temozolomide is currently limited, although various potential targets can be identified in tumour tissue

Tuning Hydrophobicity of Platinum by Small Changes in Surface Morphology

Catalysis and Surface Chemistr