Mitchellhussein5774
To investigate diagnostic accuracy of a nerve ultrasound (US) protocol that is individualized to a patient's clinical deficits for the differentiation of amyotrophic lateral sclerosis with predominant lower motoneuron disease (ALS/LMND) and multifocal motor neuropathy (MMN).
Single-center, prospective, examiner-blinded, diagnostic study in two cohorts. Cohort I (model development) Convenience sample of subjects with ALS/LMND or MMN according to revised El-Escorial or EFNS guidelines. Cohort II (model validation) Consecutively recruited treatment-naïve subjects with suspected diagnosis of ALS/LMND or MMN. Cutoffs for 28 different US values were determined by Receiver Operating Curve (ROC) in cohort I. Area Under The Curve (AUC) of US was compared to nerve conduction studies (NCS). Diagnostic accuracy of US protocols, individualized according to clinical deficits, was compared to former rigid non-individualized protocols and to random examination site selection in cohort II.
48 patients were recruited. In cohort I (28 patients), US had higher ROC AUCs than NCS, US 0.82 (0.12)(mean (standard deviation)), NCS (compound muscle action potential (CMAP) 0.60 (0.09), p < .001; two-sided t-test). US models based on the nerve innervating the clinically most affected muscles had higher correct classification rates (CCRs, 93%) in cohort II than former rigid protocols (85% and 80%), or models with random measurement site selection (66% and 80%).
Clinically guided US protocols for differentiation of ALS/LMND from MMN increase diagnostic accuracy when compared to clinically unguided protocols. They also require less measurements sites to achieve this accuracy.
Clinically guided US protocols for differentiation of ALS/LMND from MMN increase diagnostic accuracy when compared to clinically unguided protocols. They also require less measurements sites to achieve this accuracy.
Mounting evidence supports the existence of an important feedforward cycle between sleep and neurodegeneration, wherein neurodegenerative diseases cause sleep and circadian abnormalities, which in turn exacerbate and accelerate neurodegeneration. If so, sleep therapies bear important potential to slow progression in these diseases.
This cycle is challenging to study, as its bidirectional nature renders cause difficult to disentangle from effect. Likewise, well-controlled intervention studies are often impractical in the setting of established neurodegenerative disease. Zilurgisertib fumarate clinical trial It is this that makes understanding sleep and circadian abnormalities in Huntington's disease (HD) important as a monogenic fully penetrant neurodegenerative condition presenting in midlife, it provides a rare opportunity to study sleep and circadian abnormalities longitudinally, prior to and throughout disease manifestation, and in the absence of confounds rendered by age and comorbidities. It also provides potential to trial sleep therapieneration cyclical relationship in HD. We conclude by outlining key directions of current and future investigation by which to advance the sleep-neurodegeneration field via studies in HD.
We aimed to determine (1) the test-retest reliability of a newly developed portable fixed dynamometer (PFD) as compared to the hand-held dynamometer (HHD) in patients with motor neuron disease (MND) and (2) the PFD's ability to reduce possible examiner-induced ceiling effects.
Test-retest reliability of isometric muscle strength of the quadriceps was measured in patients with MND and non-neurological controls using the HHD and PFD. Reliability was estimated by the intraclass correlation coefficient (ICC) and standard error of measurement (SEM) using linear mixed effects models, and the Bland-Altman method of agreement.
In total, 45 patients with MND and 43 healthy controls were enrolled in this study. The ICC of the PFD was excellent and similar in both patients and controls (ICC
99.5% vs. ICC
98.6%) with a SEM of 6.2%. A strong examiner-induced ceiling effect in HHD was found when the participant's strength exceeded that of examiner. Employing the PFD increased the range of muscle strength measurements across individuals nearly twofold from 414 to 783N.
Portable fixed dynamometry may significantly reduce examiner-induced ceiling effects, optimize the standardization of muscle strength testing, and maximize reliability. Ultimately, PFD may improve the delivery of care due to its potential for unsupervised, home-based assessments and reduce the burden to the patient of participating in clinical trials for MND or other neuromuscular diseases.
Portable fixed dynamometry may significantly reduce examiner-induced ceiling effects, optimize the standardization of muscle strength testing, and maximize reliability. Ultimately, PFD may improve the delivery of care due to its potential for unsupervised, home-based assessments and reduce the burden to the patient of participating in clinical trials for MND or other neuromuscular diseases.The cell membrane, which is lipid-rich, is not only a simple mechanical barrier but also an important and complex component of the cell. It also communicates with the external environment. Sphingomyelin is an important class of phospholipids in the membrane that performs many functions. Interest in sphingomyelin-based liposomes, which are a critical component of cell membranes, have become the focus of intense study in recent years. Through additional research, the function of sphingomyelin and its derivatives in diseases can be gradually elucidated. Sphingomyelin consists of ceramide and its derivatives including ceramide-1-phosphate glucosylceramide and sphingosine-1-phosphate. The metabolism of glucosylceramide is regulated by glucosylceramide synthase (EC 2.4.1.80) which is the key enzyme in the glycosylation of ceramide. link2 The activity of glucosylceramide synthase directly affects the level of glucosylceramide in cells which in turn affects the function of cells and may eventually lead to diseases. Recently, the relationship between glucosylceramide and its metabolic enzymes, with diseases has become a relatively new area of study. The purpose of this paper is to address the relationship between glucosylceramide, glucosylceramide synthase, and their possible association with liver diseases at the theoretical level.
To study the features of the bronchial mucosa lesion in relation to centrally growing lung cancer (LC) according to diagnostic fibrobronchoscopy in comparison with the results of cytomorphological data to determine the possible origin of tumor growth (histogenesis).
The data of fibrobronchoscopy and cytological findings based on the materials of 75patients with a clinical diagnosis of LC were studied and compared. By the sum of the numerous cytomorphological features of epithelial cells and their components, the cells of the cylindrical epithelium and LC of various histological types were identified. The cells in bronchial smears and bronchial lavage were stained by Pappenheim and Papanicolau. Diagnostic material was examined by light microscopy.
We have found that in a part of the patients (49%), the tumors with exophytic growth in the bronchus are covered with a cylindrical epithelium, which indirectly indicates the origin of cancer growth under the epithelial layer. In cytological preparations of 51% patients, cancer cells were found, which confirms the tumor invasion into the bronchial mucosa. In 48 (64%) patients, fibrobronchoscopy revealed that the examined bronchus was compressed from 50% to pinpoint width, evidencing that tumor growth develops from the outside, peribronchially.
The obtained data indirectly confirm the development of central LC from type II pneumocytes, which are found in the glands of the submucous membrane of the bronchus. However, it does not exlude the development of this type of LC from the basal cell of the bronchial epithelium.
The obtained data indirectly confirm the development of central LC from type II pneumocytes, which are found in the glands of the submucous membrane of the bronchus. However, it does not exlude the development of this type of LC from the basal cell of the bronchial epithelium.Pericellular plasmin generation triggers apoptosis/anoikis in normal adherent cells. However, cancer cells are notoriously resistant to anoikis, enabling metastasis and new tumor growth beyond their original environment. Autophagy can be a major contributor to anoikis resistance in cancer.
To investigate if protective autophagy can be induced in lung adenocarcinoma cells in response to plasminogen treatment.
Human lung adenocarcinoma A549cells were incubated with Glu-plasminogen (0.1-1.0µM) for 24h. Pericellular plasmin activity was monitored spectrophotometrically by a cleavage of the specific chromogenic- substrate S-2251. Cell survival was assessed by 3-[4,5-dimethyl thiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT)-test. Degradation of fibronectin, levels of autophagy markers (beclin-1and light chain 3 (LC3)) and glycolysis regulator (TIGAR) were evaluated by western blot. Intracellular localization of LC-3was visualized by immunocytochemistry.
It was shown that plasminogen is converted into plasmI conversion in plasminogen-treated A549cells are the hallmarks of autophagy induction. According to immunocytochemistry data, increased LC3puncta and autophagosome formation after exposure to plasminogen could reflect autophagy activation.
Therefore, we showed stimulation of prosurvival signals and induction of autophagy in plasminogen-treated adenocarcinoma cells rendering them resistant to apoptosis/anoikis. Based on the obtained data, autophagy has a great potential for novel targets that affect cancer cell death, in addition to the current cytotoxic agents.
Therefore, we showed stimulation of prosurvival signals and induction of autophagy in plasminogen-treated adenocarcinoma cells rendering them resistant to apoptosis/anoikis. Based on the obtained data, autophagy has a great potential for novel targets that affect cancer cell death, in addition to the current cytotoxic agents.Turner syndrome (TS) is a chromosomal condition that affects development in females. link3 The case of TS in the mother whose child was diagnosed with acute leukemia at the age of 1.5 years is presented. FANCI gene in child was detected among 94 genes associated- with hematologic malignancies. Acute lymphoblastic leukemia, common-B ІІ, L1, associated with t(12;21)(p13;q22), TEL/AML1 (ETV6/RUNX1) in a child was detected during a prophylactic examination. During the treatment of the baby, the mother had a second pregnancy, which ended in miscarriage at 8 weeks. Upon cytogenetic examination in the mother TS was revealed - mos45,Х[23]/46, ХХ[7], and the father's karyotype was without abnormalities (46, ХУ). After chemotherapy, the child is in clinical-hematological remission. It could be suggested that chromosomal abnormalities in mother with TS may cause the chromosomal instability and hematological malignancy in offspring.
Previous studies have pointed out the role of dickkopf-related protein 1 (DKK1)- Wnt inhibitor, which is essential for osteoblast functioning, in the development of osteolytic lesions in multiple myeloma (MM).
To assess the DKK1expression displayed by myeloma cells in bone marrow trephine biopsies of patients with and without osteolytic lesions, and in different malignancy grades of the disease.
The expression level of DKK1was assessed immunohistochemically in bone marrow of 49MM patients presented with and without osteolytic lesions (the 1
and the 2
group, respectively).
Levels of weak, moderate, and strong DKK1expression were distributed- as 43.33, 27.78and 25.56%, and 63.91, 18.80, and 1.50%, respectively when evaluating the samples obtained from the 1
and the 2
group. Statistically significant differences were found when the levels of DKK1expression in the 1
and the 2
group were compared (χ
= 51; df= 3; p< 0.001).
DKK1contributes to the development of osteolytic lesions in MM. The present study provides morphological evidence that inhibition in Wnt signaling may lead to bone damage observed in the advanced stage of the disease.
