Huntington's disease is a multi-system disorder.

Huntingtons disease (HD) is one of the most common non-curable rare diseases and is characterized by choreic movements, psychiatric symptoms, and slowly progressive dementia. HD is inherited as an autosomal dominant disorder with complete penetrance. Although brain pathology has become a hallmark of HD, there is a critical mass of new studies suggesting peripheral tissue pathology as an important factor in disease progression. In particular, recently published studies about skeletal muscle malfunction and HD-related cardiomyopathy in HD mouse models strongly suggest their important roles, leading to upcoming preclinical and clinical trials. One might conclude that therapeutic approaches in HD should not be restricted only to the brain pathology but instead major efforts should also be made to understand the cross-talk between diseased tissues like the CNS-Heart or CNS-skeletal muscle axes

Rayleigh surface waves propagating in (111) Si substrate decorated with Ni phononic nanostructure

The paper reports results of the Surface Brillouin Light Scattering at the silicon (111) surface loaded with a periodic 2D nickel nanostructure. Measurements were made for samples loaded with nanostructures of different period (different size) but of the same height. The relation between the nanostructure size and the velocity of surface Rayleigh waves was proved to be nonlinear. Anisotropy of the surface Rayleigh wave velocity was compared with the results of theoretical modelling based on the Finite Element Method

Dispersion of the surface phonons in semiconductor/topological insulator Si/Bi2Te3 heterostructure studied by high resolution Brillouin spectroscopy

The dynamics and dispersion of surface phonons in heterostructure semiconductor/ topological insulator Si/Bi2Te3 was investigated using high resolution Brillouin light scattering method in the GHz frequency range. Both Rayleigh and Sezawa surface acoustic waves have been observed for wave vectors ranging from 0.006 to 0.023 nm−1. Anomaly in dispersion relations ω(q) for both surface waves were detected for the wave vector q = 0.016 nm−1. The finite element method (FEM) was used to simulate the observed shapes of ω(q) and to find the deformation profiles of surface acoustic waves. We attribute the observed changes to the coupling between low energy electrons and surface phonons. The coupling between helical Dirac states and surface phonons is discussed in the frame of accessible theoretical models

Structural abnormalities of the optic nerve and retina in Huntington’s disease pre-clinical and clinical settings

Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin protein. HD-related pathological remodelling has been reported in HD mouse models and HD carriers. In this study, we studied structural abnormalities in the optic nerve by employing Spectral Domain Optical Coherence Tomography (SD-OCT) in pre-symptomatic HD carriers of Caucasian origin. Transmission Electron Microscopy (TEM) was used to investigate ultrastructural changes in the optic nerve of the well-established R6/2 mouse model at the symptomatic stage of the disease. We found that pre-symptomatic HD carriers displayed a significant reduction in the retinal nerve fibre layer (RNFL) thickness, including specific quadrants: superior, inferior and temporal, but not nasal. There were no other significant irregularities in the GCC layer, at the macula level and in the optic disc morphology. The ultrastructural analysis of the optic nerve in R6/2 mice revealed a significant thinning of the myelin sheaths, with a lamellar separation of the myelin, and a presence of myelonoid bodies. We also found a significant reduction in the thickness of myelin sheaths in peripheral nerves within the choroids area. Those ultrastructural abnormalities were also observed in HD photoreceptor cells that contained severely damaged membrane disks, with evident vacuolisation and swelling. Moreover, the outer segment of retinal layers showed a progressive disintegration. Our study explored structural changes of the optic nerve in pre- and clinical settings and opens new avenues for the potential development of biomarkers that would be of great interest in HD gene therapies

Conditioning Intensity, Pre-Transplant Flow Cytometric Measurable Residual Disease, and Outcome in Adults with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

How conditioning intensity is related to outcomes of AML patients undergoing allografting in morphologic remission is an area of great ongoing interest. We studied 743 patients in morphologic remission and known pre-transplant measurable residual disease (MRD) status determined by multiparameter flow cytometry (MFC) who received a first allograft after myeloablative, reduced intensity, or nonmyeloablative conditioning (MAC, RIC, and NMA). Overall, relapse-free survival (RFS) and overall survival (OS) were longer after MAC than RIC or NMA conditioning, whereas relapse risks were not different. Among MRD(pos)patients, 3-year estimates of relapse risks and survival were similar across conditioning intensities. In contrast, among MRD(neg)patients, 3-year RFS and OS were longer for MAC (69% and 71%) than RIC (47% and 55%) and NMA conditioning (47% and 52%). Three-year relapse risks were lowest after MAC (18%) and highest after NMA conditioning (30%). Our data indicate an interaction between conditioning intensity, MFC-based pre-transplant MRD status, and outcome, with benefit of intensive conditioning primarily for patients transplanted in MRD(neg)remission. Differing from recent findings from other studies that indicated MAC is primarily beneficial for some or all patients with MRD(pos)pre-HCT status, our data suggest MAC should still be considered for MRD(neg)AML patients if tolerated