New therapeutic approaches to Parkinson's disease targeting GBA, LRRK2 and Parkin.

Parkinson's disease (PD) is defined as a complex disorder with multifactorial pathogenesis, yet a more accurate definition could be that PD is not a single entity, but rather a mixture of different diseases with similar phenotypes. Attempts to classify subtypes of PD have been made based on clinical phenotypes or biomarkers. However, the most practical approach, at least for a portion of the patients, could be to classify patients based on genes involved in PD.

Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study.

Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS).

Objective: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion.

Methods: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14).

Outcomes and toxicity of allogeneic hematopoietic cell transplantation in chronic myeloid leukemia patients previously treated with second-generation tyrosine kinase inhibitors: a prospective non-interventional study from the Chronic Malignancy Working Party of the EBMT.

Allogeneic hematopoietic cell transplantation (allo-HCT) remains a treatment option for patients with chronic myeloid leukemia (CML) who fail to respond to tyrosine kinase inhibitors (TKIs). While imatinib seems to have no adverse impact on outcomes after transplant, little is known on the effects of prior use of second-generation TKI (2GTKI). We present the results of a prospective non-interventional study performed by the EBMT on 383 consecutive CML patients previously treated with dasatinib or nilotinib undergoing allo-HCT from 2009 to 2013.

SORL1 mutation in a Greek family with Parkinson's disease and dementia.

Whole exome sequencing and linkage analysis were performed in a three generational pedigree of Greek origin with a broad phenotypic spectrum spanning from Parkinson's disease and Parkinson's disease dementia to dementia of mixed type (Alzheimer disease and vascular dementia). We identified a novel heterozygous c.G1135T (p.

Incidence of the Diagnosis of Anxiety Disorders in the Russian Federation: Results of a Web-Based Survey of Psychiatrists.

Introduction: According to the official Russian source, in 2017 only 0.27% of the population of Russia was diagnosed with International Classification of Diseases, tenth revision (ICD-10) F4 category disorders (neurotic, stress-related and somatoform disorders), despite these disorders being among the most prevalent mental disorders worldwide. Here we report the results of a large-scale survey among Russian psychiatrists with the primary objective to assess the proportion of psychiatrists who use the diagnoses of interest (mixed anxiety and depression disorder [MADD], adjustment disorder [AdD], panic disorder [PD], agoraphobia, generalized anxiety disorder [GAD], social phobia, simple phobia, acute stress disorder and posttraumatic stress disorder) and compare results with those of a recent World Psychiatric Association (WPA) and World Health Organization (WHO) survey.

Deep negative volume segmentation.

Clinical examination of three-dimensional image data of compound anatomical objects, such as complex joints, remains a tedious process, demanding the time and the expertise of physicians. For instance, automation of the segmentation task of the TMJ (temporomandibular joint) has been hindered by its compound three-dimensional shape, multiple overlaid textures, an abundance of surrounding irregularities in the skull, and a virtually omnidirectional range of the jaw's motion-all of which extend the manual annotation process to more than an hour per patient. To address the challenge, we invent a new workflow for the 3D segmentation task: namely, we propose to segment empty spaces between all the tissues surrounding the object-the so-called negative volume segmentation.

Parkinson's Disease Associated with GBA Gene Mutations: Molecular Aspects and Potential Treatment Approaches.

Parkinson's disease (PD) is a multifactorial neurodegenerative disease. To date, genome-wide association studies have identified more than 70 loci associated with the risk of PD. Variants in the gene encoding glucocerebrosidase are quite often found in PD patients in all populations across the world, which justifies intensive investigation of this gene.

Heavy Alcohol Use Among Women and Men Living With HIV in Uganda, Russia, and the United States.

Objective: We examined whether gender is associated with heavy drinking in three cohorts of people living with HIV (PLWH) in Mbarara, Uganda; St. Petersburg, Russia; and Boston, Massachusetts.

Method: We conducted secondary analyses of baseline data collected from three cohorts in the Uganda Russia Boston Alcohol Network for Alcohol Research Collaboration on HIV/AIDS (URBAN ARCH) consortium.

Understanding the Process and Challenges for Return-to-Work Post-Hematopoietic Cell Transplantation from a Musculoskeletal Perspective: A Narrative Review.

The current paper seeks to inform healthcare professionals on how adapting various components of return to work (RTW) programs that are already in use by other musculoskeletal rehabilitation settings can help optimize return to work process for patients with or without musculoskeletal manifestations, posthematopoietic cell transplantation. Since there is no universally agreed RTW structure for hematopoietic cell transplant patients, a narrative approach has been taken utilizing evidence from the existing musculoskeletal return to work assessment publications to help draw parallel for the hematopoietic cell transplant patients. Databases were searched including PUBMED, CINHAL, AMED, SCOPUS, and Cochrane using keywords RTW, functional restoration program, hematopoietic cell transplant, bone marrow transplant, stem cell transplant, and musculoskeletal functional assessment.

Impact of prior JAK-inhibitor therapy with ruxolitinib on outcome after allogeneic hematopoietic stem cell transplantation for myelofibrosis: a study of the CMWP of EBMT.

JAK1/2 inhibitor ruxolitinib (RUX) is approved in patients with myelofibrosis but the impact of pretreatment with RUX on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) remains to be determined. We evaluated the impact of RUX on outcome in 551 myelofibrosis patients who received HSCT without (n = 274) or with (n = 277) RUX pretreatment. The overall leukocyte engraftment on day 45 was 92% and significantly higher in RUX responsive patients than those who had no or lost response to RUX (94% vs.

Recommendations for the use of corrective makeup after dermatological procedures.

Introduction: The number of dermatological or cosmetic procedures carried out has continuously increased over the last decades. Almost all may cause transient local skin reactions such as erythema, blistering, crusts, scaling, hypo- or hyperpigmentation, or hemorrhagic lesions. One issue of dermatological procedures is the downtime, during which patients need to hide their skin, due to these local reactions.

Outcomes of Unmanipulated Haploidentical Transplantation Using Post-Transplant Cyclophosphamide (PT-Cy) in Pediatric Patients With Acute Lymphoblastic Leukemia.

HLA-haploidentical transplantation (haplo-HCT) using post-transplantation-cyclophosphamide (PT-Cy) is a feasible procedure in children with malignancies. However, large studies on Haplo-HCT with PT-Cy for childhood acute lymphoblastic leukemia (ALL) are lacking. We analyzed haplo-HCT outcomes in 180 children with ALL.

[Plasma Exosomes in Inherited Forms of Parkinson's Disease].

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Alpha-synuclein misfolding and aggregation resulting in neurototoxicity is a hallmark of PD. The prion properties of alpha-synuclein are still under discussion.

Albumin covering maintains endothelial function upon magnetic iron oxide nanoparticles intravenous injection in rats.

Magnetic iron oxide nanoparticles (IONP) present the promising instrument for broad-spectrum of clinical applications, for example, targeted drug delivery. Reactivity of nanoparticles depends on their surface area and material. In the blood plasma IONP are getting covered with an albumin crown, so it was decided to test this shell for biocompatibility.

Per-protocol analysis of the ZINC trial for HIV disease among alcohol users.

Background: The Zinc for INflammation and Chronic disease in HIV (ZINC) trial randomized person who live with HIV (PLWH) who engage in heavy drinking to either daily zinc supplementation or placebo. The primary outcome was change in the Veterans Aging Cohort Study (VACS) index, a predictor of mortality, between baseline and 18 months. Because adherence and follow-up were suboptimal, the intention-to-treat analysis, which was not statistically significant, may have underestimated the effect of the zinc supplementation.

The Hepatitis C Continuum of Care Among HIV-Positive Persons with Heavy Alcohol Use in St. Petersburg, Russia.

This study describes the self-reported prevalence of hepatitis C virus (HCV) coinfection and the HCV care continuum among persons enrolled in the St PETER HIV Study, a randomized controlled trial of medications for smoking and alcohol cessation in HIV-positive heavy drinkers and smokers in St. Petersburg, Russia. Baseline health questionnaire data were used to calculate proportions and 95% confidence intervals for self-reported steps along the HCV continuum of care.

Dependence of seasonal dynamics of hemorrhagic and ischemic strokes on the climate of a region: A meta-analysis.

Background: Cardiovascular events occur more often in winter than in summer; however, the dependence of strokes on various meteorological factors remains unclear.

Aims: The purpose of this meta-analysis was to determine the dependence of the circannual dynamics of hospitalizations for hemorrhagic stroke and ischemic stroke on seasonal fluctuations in meteorological factors.

Summary Of Review And Conclusions: For our meta-analysis, we selected 20 and 26 publications examining the seasonal dynamics of hemorrhagic stroke and ischemic stroke, respectively .

Pilot study of tolerability and safety of opioid receptor antagonists as novel therapies for chronic pain among persons living with HIV with past year heavy drinking: a randomized controlled trial.

ClinicalTrials.gov identifier: NCT03278886.

Eculizumab in Asian patients with anti-aquaporin-IgG-positive neuromyelitis optica spectrum disorder: A subgroup analysis from the randomized phase 3 PREVENT trial and its open-label extension.

Background Eculizumab, a terminal complement inhibitor, significantly reduced the risk of relapse compared with placebo in patients with anti-aquaporin-4 immunoglobulin G-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) in the PREVENT trial. We report efficacy and safety analyses in Asian patients in PREVENT and its open-label extension (OLE). Methods PREVENT was a double-blind, randomized, phase 3 trial.

Ambroxol increases glucocerebrosidase (GCase) activity and restores GCase translocation in primary patient-derived macrophages in Gaucher disease and Parkinsonism.

Mutations in the glucocerebrosidase gene (GBA) encoding the lysosomal enzyme glucocerebrosidase (GCase) cause Gaucher disease (GD) and are the most commonly known genetic risk factor for Parkinson disease (PD). Ambroxol is one of the most effective pharmacological chaperones of GCase. Fourteen GD patients, six PD patients with mutations in the GBA gene (GBA-PD), and thirty controls were enrolled.

Addition of Rituximab in Reduced Intensity Conditioning Regimens for B-Cell Malignancies Does Not Influence Transplant Outcomes: EBMT Registry Analyses Following Allogeneic Stem Cell Transplantation for B-Cell Malignancies.

Rituximab (R) is increasingly incorporated in reduced intensity conditioning (RIC) regimens for allogeneic hematopoietic cell transplantation (alloHCT) in patients with B-cell malignancies, not only to improve disease control, but also to prevent graft-versus-host disease (GVHD). There are no randomized prospective data to validate this practice, although single center data and the CIBMTR analysis have shown promising results. We aimed at validation of these findings in a large registry study.

Layer-by-Layer technique as a versatile tool for gene delivery applications.

: Gene therapy is a breakthrough medical field which focuses on the therapeutic delivery of recombinant nucleic acids in order to treat or prevent a broad spectrum of diseases. However, a number of important obstacles remain before its wide introduction into clinical practice can be envisaged. One of the biggest bottlenecks is the lack of efficient and safe delivery technologies, particularly, for distribution.