The human priondiseases comprise Creutzfeldt-Jakob disease, variably protease-sensitive prionopathy, Gerstmann-Sträussler-Scheinker disease, fatalfamilialinsomnia, and kuru ... The majority of cases of human priondiseases occur worldwide in the form of sporadic Creutzfeldt-Jakob disease ... termed PRNP, in the forms of genetic Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, and fatalfamilialinsomnia.
Gerstmann-Sträussler-Scheinker disease (GSS) is an autosomal, dominantly inherited priondisease. In this study, we present different complicated brain pathologies determined postmortem of monozygotic GSS twin sisters. Case 1 showed cerebellar ataxia at the age of 58 years, and died at 66 years. Case 2 became symptomatic at the age of 75 years, and died at 79 years.
The article presents epidemiological data on the prevalence of Creutzfeldt-Jakob disease in the world and modern techniques for the rapid accurate diagnosis. The author discusses a national approach to this subject.
Three decades after the discovery of prions as the cause of Creutzfeldt-Jakob disease and other transmissible spongiformencephalopathies, we are still nowhere close to finding an effective therapy. Numerous pharmacological interventions have attempted to target various stages of disease progression, yet none has significantly ameliorated the course of disease.
Prion Diseases (2), Creutzfeldt-Jakob Syndrome (1), more mentions
The notion that prion-like spreading of misfolded α-synuclein (α-SYN) causes Parkinson's disease (PD) has received a great deal of attention. Although attractive in its simplicity, the hypothesis is difficult to reconcile with postmortem analysis of human brains and connectome-mapping studies. An alternative hypothesis is that PD pathology is governed by regional or cell-autonomous factors. Although these factors provide an explanation for the pattern of neuronal loss in PD, they do not readily explain the apparently staged distribution of Lewy pathology in many PD brains, the feature of the disease that initially motivated the spreading hypothesis by Braak and colleagues. While each hypothesis alone has its shortcomings, a synthesis of the two can explain much of what we know about the etiopathology of PD.Dual Perspectives Companion Paper: Prying into the Prion Hypothesis for Parkinson's Disease, by Patrik Brundin and Ronald Melki.
Neurological and Central Nervous System Diseases (3) Parkinson Disease (3), more mentions
Chronic neurodegenerative diseases, such as priondiseases or Alzheimer's disease, are associated with progressive accumulation of host proteins which misfold and aggregate. Neurodegeneration is restricted to specific neuronal populations which show clear accumulation of misfolded proteins, whilst neighbouring neurons remain unaffected. Such data raise interesting questions about the vulnerability of specific neuronal populations to neurodegeneration and much research has concentrated ...
Combinations of three or more drugs are used to treat many diseases, including tuberculosis. Thus, it is important to understand how synergistic or antagonistic drug interactions affect the efficacy of combination therapies. However, our understanding of high-order drug interactions is limited because of the lack of both efficient measurement methods and theoretical framework for analysis and interpretation. We developed an efficient experimental sampling and scoring method [diagonal measurement of n-way drug interactions (DiaMOND)] to measure drug interactions for combinations of any number of drugs. DiaMOND provides an efficient alternative to checkerboard assays, which are commonly used to measure drug interactions. We established a geometric framework to factorize high-order drug interactions into lower-order components, thereby establishing a road map of how to use lower-order measurements to predict high-order interactions. Our framework is a generalized Loewe additivity model for high-order drug interactions. Using DiaMOND, we identified and analyzed synergistic and antagonistic antibiotic combinations against Mycobacteriumtuberculosis. Efficient measurement and factorization of high-order drug interactions by DiaMOND are broadly applicable to other cell types and disease models.
Cardiovascular Diseases (2), Infectious Diseases (1) Tuberculosis (2), more mentions
BACKGROUND: Low back pain is one of the most important causes of morbidity.
OBJECTIVE: This study was designed to evaluate the effect of Kinesio® taping on pain, functionality, mobility and endurance in chronic low back pain treatment.
METHODS: Patients with chronic low back pain were randomly divided into three groups. Therapeutic ultrasound, hot packs, and transcutaneous electrical nerve stimulation were applied to each group for ten sessions during two weeks, and therapeutic exercises were applied in the clinic under physiotherapist supervision starting from the sixth session. Kinesio® tape was applied to the patients in the first group after each treatment session, and placebo tape was applied to the patients in the second group. No taping was applied to the third group, which constituted the control group. All the patients were evaluated pre and post-treatment in respect of pain, functional status (Oswestry scale), flexibility and endurance.
RESULTS: The study included 60 patients (32 females). When the initial demographic and clinical characteristics of the groups were evaluated, all assessment results, except the Oswestry scores, were similar (p= 0.000). When the average changes in the clinical evaluations were evaluated after the treatment, a statistically significant improvement demonstrating the superiority of the taping group was observed in pain, functionality, flexibility and endurance values (p= 0.000, 0.000, 0.000, 0.000).
CONCLUSIONS: Kinesio® taping in chronic low back pain is an easy and effective method which increases the effectiveness of the treatment significantly in a short period when applied in addition to exercise and electrotherapy methods.
We screened anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies among 42 patients who had undiagnosed chronic myopathy from six national hospitals. Anti-SRP and anti-HMGCR antibodies were determined by RNA immuneprecipitation and enzyme-linked immune-sorbent assay (ELISA), respectively. We identified two patients with anti-SRP antibodies (4.7%) and, two with anti-HMGCR antibodies (4.7%). Both of anti-SRP-positive patients showed dysphagia with a high level of creatine kinase. Anti-HMGCR antibodies were associated with mild muscle weakness with a relatively late disease onset. Our study suggests the importance of autoantibody testing among undiagnosed chronic myopathy.
Acute bilateral foot drop is a rare clinical presentation. A 77-year-old male presented with acute bilateral weakness of the foot and ankle dorsiflexion. Magnetic resonance imaging of the lumbar spine revealed ligamentum flavum hypertrophy as well as a mass lesion that appeared hyperintense on T1-weighted images and hypointense on T2-weighted images. Emergent decompressive laminectomy and hemorrhagic synovial cyst excision were performed. Histopathological examination of the tissue revealed a synovial cyst with hemorrhage. Here, we describe a unique case of a hemorrhagic synovial cyst with a presenting symptom of bilateral foot drop.
Synovial Cysts (4), Hypertrophy (1), Hemorrhage (1), more mentions
PURPOSE: The aims of our study were to determine the incidence of axillary recurrence and arm morbidity in T1-2 invasive breast cancer patients with macrometastases on the sentinel lymph node (SLN) who underwent breast-conserving therapy (BCT), with or without axillary lymph node dissection (ALND).
METHODS: One hundred and nine T1-2 invasive breast cancer patients with macrometastases on the SLN who underwent BCT in our institution were included in the study. Patients with 1-2 positive SLN and without extra nodal extension (ENE) on the SLN did not undergo ALND (SLN-only group) and patients with ENE or patients who had >2 metastatic nodes underwent level I, II ALND (ALND group). The SLN-only group received radiotherapy to three axillary levels, the supraclavicular fossa, and ± mammaria interna. ALND group received radiotherapy to axillary level III, the supraclavicular fossa, and ± mammaria interna. The incidence of axillary recurrence and arm morbidity were investigated.
RESULTS: Of the 109 patients, 18 patients with >2 metastatic SLNs and 10 with ENE on the SLN underwent ALND and 81 patients underwent SLN only. Median follow-up time was 37 months (3-77). There was no axillary recurrence in SLN-only group. However, in the ALND group 1 patient had developed axillary metastasis. There were 2 objective lymphoedema and 3 arm-shoulder restriction cases in the SLN-only group, and 2 and 3 in the ALND group, respectively.
CONCLUSIONS: Axillary dissection could safely be omitted in patients with 1-2 macrometastatic SLN and without ENE who undergo BCT and axillary radiotherapy.
Abstract: All of the common neurodegenerative disorders-Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and priondiseases-are characterized by accumulation of misfolded proteins that trigger activation of microglia; brain-resident mononuclear phagocytes. This chronic form of neuroinflammation is earmarked by increased release of myriad cytokines and chemokines in patient brains and biofluids.
Neurological and Central Nervous System Diseases (2), Neuroscience (1) Neurodegenerative Diseases (4), Prion Diseases (1), Parkinson Disease (1), more mentions
Priondiseases are fatal neurodegenerative disorders of the central nervous system characterized by the accumulation of a protease resistant form (PrP(Sc)) of the cellular prion protein (PrP(C)) in the brain. Two types of cellular prion (PrP(C)) compounds have been identified that appear to affect prion conversion are known as Effective Binders (EBs) and Accelerators (ACCs.
Prion Diseases (1), Neurodegenerative Diseases (1), more mentions
Interestingly, the pathological molecular processes of these IDPs share multiple common features with those of protein misfolding diseases, such as transmissible spongiformencephalopathy (PrPsc) and AL-amyloidosis (VL-domain of γ-immunoglobulin. This review provides an overview of solution NMR techniques that can help analyze the early and transient events of conformational equilibrium of IDPs and folded proteins.
Neurological and Central Nervous System Diseases (1), Neuroscience (1), Oncology (1) Prion Diseases (1), Neoplasms (1), Parkinson Disease (1), more mentions