Transcranial Magnetic Stimulation Measures, Pyramidal Score on Expanded Disability Status Scale and Magnetic Resonance Imaging of Corticospinal Tract in Multiple Sclerosis.

Probing the cortic ospinal tract integrity by transcranial magnetic stimulation (TMS) could help to understand the neurophysiological correlations of multiple sclerosis (MS) symptoms. Therefore, the study objective was, first, to investigate TMS measures (resting motor threshold-RMT, motor evoked potential (MEP) latency, and amplitude) of corticospinal tract integrity in people with relapsing-remitting MS (pwMS). Then, the study examined the conformity of TMS measures with clinical disease-related (Expanded Disability Status Scale-EDSS) and magnetic resonance imaging (MRI) results (lesion count) in pwMS. The e-field navigated TMS, MRI, and EDSS data were collected in 23 pwMS and compared to non-clinical samples. The results show that pwMS differed from non-clinical samples in MEP latency for upper and lower extremity muscles. Also, pwMS with altered MEP latency (prolonged or absent MEP response) had higher EDSS, general and pyramidal, functional scores than pwMS with normal MEP latency finding. Furthermore, the RMT intensity for lower extremity muscles was predictive of EDSS functional pyramidal scores. TMS/MEP latency findings classified pwMS as the same as EDSS functional pyramidal scores in 70-83% of cases and were similar to the MRI results, corresponding to EDSS functional pyramidal scores in 57-65% of cases. PwMS with altered MEP latency differed from pwMS with normal MEP latency in the total number of lesions in the brain corticospinal and cervical corticospinal tract. The study provides preliminary results on the correspondence of MRI and TMS corticospinal tract evaluation results with EDSS functional pyramidal score results in MS.

Expression of CD40 and CD192 in Classical Monocytes in Multiple Sclerosis Patients Assessed with Transcranial Magnetic Stimulation.

Expression of CD40 and CD192 markers in different monocyte subpopulations has been reported to be altered in people with MS (pwMS). Also, functional connectivity of the corticospinal motor system pathway alterations has been proved by transcranial magnetic stimulation (TMS). The study objective was to investigate the expression of CD40 and CD192 in classical (CD14++CD16-), intermediate CD14++CD16+ and non-classical (CD14+CD16++) blood monocyte subpopulations in pwMS, undergoing neurophysiological TMS assessment of the corticospinal tract integrity by recording motor-evoked potentials (MEPs). Radiological examination on lesion detection with MRI was performed for 23 patients with relapsing-remitting MS treated with teriflunomide. Then, immunological analysis was conducted on peripheral blood samples collected from the patients and 10 healthy controls (HC). The blood samples were incubated with anti-human CD14, CD16, CD40 and CD192 antibodies. Next, pwMS underwent neurological testing of functional disability (EDSS) and TMS assessment with recording MEPs from upper and lower extremity muscles. The results show that in comparison to HC subjects, both pwMS with normal and altered MEP findings (prolonged MEP latency or absent MEP response) had significantly decreased surface receptor expression measured (MFIs) of CD192 and increased CD40 MFI in classical monocytes, and significantly increased percentages of classical and total monocytes positive for CD40. Knowing CD40's pro-inflammatory action, and CD192 as a molecule that enables the passing of monocytes into the brain, decreased CD192 in classical monocytes could represent a beneficial anti-inflammatory parameter.

Dynamic of Circulating DNAM-1+ Monocytes and NK Cells in Patients with STEMI Following Primary Percutaneous Coronary Intervention.

Although the role of inflammation and adverse cardiac remodeling in myocardial infarction (MI) have been extensively explored, gaps in knowledge on the complex interaction between these processes still exist. Data suggest that DNAX accessory molecule-1 (DNAM-1), an activating receptor implicated in NK cell education, may be involved in cardiac remodeling following coronary artery occlusion. In the present study, we aimed to explore the dynamic of DNAM-1+ monocytes and NK cells in peripheral blood in the early phase following reperfusion in patients with ST-elevation MI (STEMI). The study enrolled 49 patients older than 18 years of age diagnosed with STEMI, referred to primary percutaneous coronary intervention (pPCI). Blood samples were obtained at three distinct points (at admission, 3 h, and 24 h after pPCI) and analyzed using flow cytometry. The number of circulating DNAM-1+ monocytes (CD16++ and CD14++) and CD56dimCD16++NK cells was significantly reduced 3 h after pPCI and subsequently returned to initial levels 24 h after procedure (p = 0.003, p < 0.001, and p = 0.002, respectively). Notably, such dynamic was dependent on age of patients. A positive correlation between high sensitivity troponin I levels and number of CD16++DNAM-1+ monocytes in peripheral blood 3 h after pPCI was observed (r = 0.431, p = 0.003). In conclusion, in the present study we delineated the post-reperfusion dynamic of DNAM-1-expresing leukocytes. Additionally, we demonstrated that the number of CD16++ DNAM-1+ monocytes correlate with the extent of myocardial injury.

Psychometric Properties of the HADS Measure of Anxiety and Depression Among Multiple Sclerosis Patients in Croatia.

Depression and anxiety are common complaints in patients with multiple sclerosis (MS). The study objective was to investigate the factor structure, internal consistency, and correlates of the Croatian version of the Hospital Anxiety and Depression Scale (HADS) in patients with MS. A total of 179 patients with MS and 999 controls were included in the online survey. All subjects completed the HADS and self-administered questionnaires capturing information of demographic, education level, disease-related variables, and the Multiple Sclerosis Impact Scale-29 (MSIS-29). Psychometric properties were examined by estimating the validity, reliability, and factor structure of the HADS in patients with MS. The two HADS subscales (anxiety and depression) had excellent internal consistencies (Cronbach's α value 0.82-0.83), and factor analysis confirmed a two-factor structure. The convergent validity of the HADS subscales appeared to be good due to the significant correlations between HADS and MSIS-29. Receiver operating characteristic (ROC) analysis indicates that the HADS subscales have a significant diagnostic validity for group differentiation. Hierarchical regression analysis using MSIS-29 subscales as criterion variables showed consistent evidence for the incremental validity of the HADS. The HADS is a reliable and valid self-assessment scale in patients with MS and is suggested to be used in clinical monitoring of the psychiatric and psychological status of patients with MS.

Thieno[2,3-b]Pyridine Derivative Targets Epithelial, Mesenchymal and Hybrid CD15s+ Breast Cancer Cells.

The adhesion of cancer cells to vascular endothelium is a critical process in hematogenous metastasis and might be similar to the recruitment of leukocytes at the site of inflammation. It is mediated by E-selectin and its ligands, of which the most stereospecific is a glycoconjugate sialyl Lewis x (CD15s), which may be expressed as an oligosaccharide branch of the CD44 glycoprotein, as well as a self-contained glycosphingolipid. It is also known that increased sialylation of glycoconjugates is a feature of malignant cells. The aim of the study was to analyse the effect of a novel thieno[2,3-b]pyridine, compound 1, in MDA-MB-231 triple-negative breast cancer cells (TNBCs) upon CD15s and CD44 expression in different cell subpopulations using flow cytometry. CD15s expression was compared between mesenchymal-like cancer stem cells (CSC, CD44+CD24-), epithelial cells without CD44 (CD44-CD24+ and CD44-CD24-), and CD44+CD24+ cells that exhibit mesenchymal and epithelial features. In addition, expression of CD44 in CD15s+CSC and CD15s-CSC was determined. Compound 1 significantly decreased the percentage of CD15s+CSC, CD15s+CD44+CD24+, and CD15s+CD44- subpopulations, as well as the expression of CD15s in CD44+CD24+ and CD44- cells, and therefore shows potential as a treatment for TNBC.

Obstructive Sleep Apnea Syndrome: A Preliminary Navigated Transcranial Magnetic Stimulation Study.

PURPOSE: An increase in resting motor threshold (RMT), prolonged cortical silent period duration (CSP), and reduced short-latency afferent inhibition (SAI), confirmed with previous transcranial magnetic stimulation (TMS), suggest decreased cortical excitability in obstructive sleep apnea syndrome (OSAS). The present study included MRI of OSAS patients for navigated TMS assessment of the RMT, as an index of the threshold for corticospinal activation at rest, and SAI as an index of cholinergic neurotransmission. We hypothesize to confirm findings on SAI and RMT with adding precision in the targeting of motor cortex in OSAS. SUBJECTS AND METHODS: After acquiring head MRIs for 17 severe right-handed OSAS and 12 healthy subjects, the motor cortex was mapped with nTMS to assess the RMT and SAI, with motor evoked potentials (MEPs) recorded from the abductor-pollicis brevis (APB) muscle. The 120%RMT intensity was used for the SAI by a paired-pulse paradigm in which the electrical stimulation to the median nerve is followed by magnetic stimulation of the motor cortex at inter-stimulus intervals (ISIs) of 18-28 ms (ISIs18-28). The SAI control condition included a recording of MEPs without peripheral stimulation. Latency and amplitude of MEP at RMT at 120%RMT for eleven different at ISIs18-28 were analyzed. RESULTS: The study showed a significantly lower percentage deviation of MEP amplitude at ISIs(18-28ms) from the control condition between OSAS and healthy subjects (U=44.0, p=0.01). The intensity of stimulation at RMT was significantly higher in OSAS subjects (U=55.0, p=0.04*). Correlation analysis showed that BMI significantly negatively correlated (ρ=-0.47) with MEP amplitude percentage deviation in OSAS patients. CONCLUSION: The nTMS study results in increased RMT, and reduced cortical afferent inhibition in OSAS patients for SAI at ISIs18-28, confirming previous findings of impaired cortical afferent inhibition in OSAS. Future nTMS studies are desirable to elucidate the role of RMT and SAI in diagnostics and treatment of OSAS, and to elucidate the usefulness of nTMS in OSAS research.

Glycosphingolipid expression at breast cancer stem cells after novel thieno[2,3-b]pyridine anticancer compound treatment.

Glycosphingolipid expression differs between human breast cancer stem cells (CSC) and cancer non-stem cells (non-CSC). We performed studies of viability, type of cell death, cancer stem cell percent and glycosphingolipid expression on CSC and non-CSC after treatment of MDA-MB-231 and MDA-MB-453 triple-negative breast cancer cells with a newly developed thienopyridine anticancer compound (3-amino-N-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide, 1). Compound 1 was cytotoxic for both breast cancer cell lines and the majority of cells died by treatment-induced apoptosis. The percent of cancer stem cells and number of formed mammospheres was significantly lower. Glycosphingolipids IV6Neu5Ac-nLc4Cer and GalNAc-GM1b (IV3Neu5Ac-Gg5Cer) not reported previously, were identified in both CSCs and non-CSCs. IV6Neu5Ac-nLc4Cer had increased expression in both CSCs and non-CSCs of both cell lines after the treatment with 1, while GM3 (II3Neu5Ac-LacCer) had increased expression only on both cell subpopulations in MDA-MB-231 cell line. GalNAc-GM1b, Gb4Cer (GalNAcß1-3Galα1-4Galß1-4Glcß1-1Cer) and GM2 (II3Neu5Ac-GalNAcß1-4Galß1-4Glcß1-1Cer) were increased only in CSCs of both cell lines while GD3 was decreased in CSC of MDA-MB-231 cell line. Due to its effect in reducing the percentage of cancer stem cells and number of mammospheres, and its influence upon several glycosphingolipid expressions, it can be concluded that compound 1 deserves attention as a potential new drug for triple-negative breast cancer therapy.

Expression of adhesion molecules on granulocytes and monocytes following myocardial infarction in rats drinking white wine.

Neutrophils and monocytes through their CD15s, CD11b and CD44 adhesion molecules are implicated in the initiation and resolution of cardiac inflammation as well as in healing processes after the myocardial infarction (MI). The aim of this study was to determine the effect of white wine consumption on granulocyte and monocyte CD15s, CD11b, and CD44 expression 24h after the surgically inflicted MI. Granulocytes and monocytes were analyzed by flow cytometry, using whole blood of male Sprague-Dawley rats that consumed white wine for 4 weeks. This group was compared with water only drinking controls, sham animals (subject to surgery without myocardial infarction) and baseline group (intact animals that received no intervention prior to being sacrificed). Sham animals did not differ from baseline animals in CD11b+CD44+ percentage and CD44+ median fluorescence intensity. Wine drinking was associated with striking increase in CD44 expression on monocyte subpopulations. Its expression was three and fourfold increased on monocytes and large monocytes, respectively, relative to the water only drinking controls. Because of known role of CD44 on suppression of post-infarction inflammation, its upregulation on granulocytes and monocytes may significantly contribute to the microenvironment favourable for the cardiac regeneration.

Glycophenotype of breast and prostate cancer stem cells treated with thieno[2,3-b]pyridine anticancer compound.

Tumor progression may be driven by a small subpopulation of cancer stem cells (CSCs characterized by CD44+/CD24- phenotype). We investigated the influence of a newly developed thienopyridine anticancer compound (3-amino-5-oxo-N-naphthyl-5,6,7, 8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide, 1) on the growth, survival and glycophenotype (CD15s and GM3 containing neuraminic acid substituted with acetyl residue, NeuAc) of breast and prostate cancer stem/progenitor-like cell population. MDA-MB-231 and Du-145 cells were incubated with compound 1 alone or in combination with paclitaxel. The cellular metabolic activity was determined by the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. The type of cell death induced by 48-h treatment was assessed using a combination of Annexin-V-FITC and propidium iodide staining. Flow cytometric analysis was performed to detect the percentage of CD44+/CD24- cells, and GM3 and CD15s positive CSCs, as well as the expression of GM3 and CD15s per one CSC, in both cell lines. Compound 1 produces a dose- and time-dependent cytotoxicity, mediated mainly by apoptosis in breast cancer cells, and slightly (2.3%) but statistically significant lowering breast CSC subpopulation. GM3 expression per one breast CSC was increased, and the percentage of prostate GM3+ CSC subpopulation was decreased in cells treated with compound 1 compared with non-treated cells. The percentage of CD15s+ CSCs was lower in both cell lines after treatment with compound 1. Considering that triple-negative breast cancers are characterized by an increased percentage of breast CSCs and knowing their association with an increased risk of metastasis and mortality, compound 1 is a potentially effective drug for triple-negative breast cancer treatment.