Diagnosis of Progressive Multiple Sclerosis From the Imaging Perspective: A Review.

Importance: Although magnetic resonance imaging (MRI) is useful for monitoring disease dissemination in space and over time and excluding multiple sclerosis (MS) mimics, there has been less application of MRI to progressive MS, including diagnosing primary progressive (PP) MS and identifying patients with relapsing-remitting (RR) MS who are at risk of developing secondary progressive (SP) MS. This review addresses clinical application of MRI for both diagnosis and prognosis of progressive MS.

Observations: Although nonspecific, some spinal cord imaging features (diffuse abnormalities and lesions involving gray matter [GM] and ≥2 white matter columns) are typical of PPMS.

Translation step-cut osteotomy for posttraumatic Cubitus Varus in adults: a retrospective study.

Background: Cubitus varus is a complex three-dimensional deformity. Various osteotomies have been introduced to correct this complex deformity. The objective of the present study was to evaluate clinical and functional outcomes of adult cubitus varus deformity treated with translation step-cut osteotomy.

Obesity and GLP-1.

Obesity is an important public health issue that has been on the rise over the last decades. It calls for effective prevention and treatment. Bariatric surgery is the most effective medical therapy for weight loss in morbid obesity, but we are in need for less aggressive treatments.

Inhibition of SIRT6 potentiates the anti-tumor effect of doxorubicin through suppression of the DNA damage repair pathway in osteosarcoma.

Background: SIRT6 has diverse roles in cells, and the role of SIRT6 in tumorigenesis is controversial. Considering the role of SIRT6 as an inducer of DNA damage repair, it might be involved in resistance to anti-cancer therapy.

Methods: We evaluated the prognostic significance of SIRT6 in 37 osteosarcomas and investigated the therapeutic efficacy of SIRT6 on the anticancer effects of doxorubicin, olaparib, and ATM inhibitor.

Osteoblasts/Osteocytes sirtuin6 Is Vital to Preventing Ischemic Osteonecrosis Through Targeting VDR-RANKL Signaling.

Ischemic osteonecrosis (ION) can produce permanent deformity and osteoarthritis in the femoral head and other joints. No biologic treatment has been established, and the molecular mechanisms involved in the pathogenesis of ION have not been elucidated. In this work, we found that treatment with sirtuin6 (Sirt6) suppressed inflammatory cytokines, bone resorption, progression of osteoarthritis, and reduced bone deformity in an ION mouse model.

Advances in hepatitis B therapeutics.

Despite the availability of both effective preventive vaccines and oral antivirals, over 250 million people are chronically infected with the hepatitis B virus (HBV). Globally, chronic hepatitis B is the leading cause of hepatocellular carcinoma, which represents the third cause of cancer mortality, accounting for nearly 1 million annual deaths. Current oral nucleos(t)ide therapy with tenofovir or entecavir suppresses serum HBV-DNA in most treated patients, but rarely is accompanied by HBsAg loss.

H NMR serum metabolomic profiling of patients at risk of cardiovascular diseases performing stress test.

Cardiovascular diseases are the leading cause of death worldwide. Changes in lifestyle and/or pharmacological treatment are able to reduce the burden of coronary artery diseases (CAD) and early diagnosis is crucial for the timely and optimal management of the disease. Stress testing is a good method to measure the burden of CAD but it is time consuming and pharmacological testing may not fully mimic exercise test.

Macrophages promote endothelial-to-mesenchymal transition via MT1-MMP/TGFβ1 after myocardial infarction.

Macrophages (Mφs) produce factors that participate in cardiac repair and remodeling after myocardial infarction (MI); however, how these factors crosstalk with other cell types mediating repair is not fully understood. Here we demonstrated that cardiac Mφs increased the expression of (MT1-MMP) 7 days post-MI. We selectively inactivated the gene in Mφs using a genetic strategy (:-Cre).

Comprehensive flow cytometric reference intervals of leukocyte subsets from six study centers across Europe.

A group of European FOCIS Centers of Excellence adapted panels of the Human Immunophenotyping Consortium (HIPC) for whole blood analysis. Using four core panels [T/regulatory T cell/B/natural killer (T/T /B/NK) and myeloid cells] the main leukocyte populations were analyzed in a clinical-diagnostic setting in a harmonized manner across different platforms. As a first step, the consortium presents here the absolute and relative frequencies of the leukocyte subpopulations in the peripheral blood of more than 300 healthy volunteers across six different European centers.

Identifying Progression in Multiple Sclerosis: New Perspectives.

The identification of progression in multiple sclerosis is typically retrospective. Given the profound burden of progressive multiple sclerosis, and the recent development of effective treatments for these patients, there is a need to establish measures capable of identifying progressive multiple sclerosis early in the disease course. Starting from recent pathological findings, this review assesses the state of the art of potential measures able to predict progressive multiple sclerosis.

An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells.

Interferon-α (IFNα), a type I interferon, is expressed in the islets of type 1 diabetic individuals, and its expression and signaling are regulated by T1D genetic risk variants and viral infections associated with T1D. We presently characterize human beta cell responses to IFNα by combining ATAC-seq, RNA-seq and proteomics assays. The initial response to IFNα is characterized by chromatin remodeling, followed by changes in transcriptional and translational regulation.

Analytical techniques for multiplex analysis of protein biomarkers.

Introduction: The importance of biomarkers for pharmaceutical drug development and clinical diagnostics is more significant than ever in the current shift toward personalized medicine. Biomarkers have taken a central position either as companion markers to support drug development and patient selection, or as indicators aiming to detect the earliest perturbations indicative of disease, minimizing therapeutic intervention or even enabling disease reversal. Protein biomarkers are of particular interest given their central role in biochemical pathways.

Pancreatic β-cells in type 1 and type 2 diabetes mellitus: different pathways to failure.

Loss of functional β-cell mass is the key mechanism leading to the two main forms of diabetes mellitus - type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Understanding the mechanisms behind β-cell failure is critical to prevent or revert disease. Basic pathogenic differences exist in the two forms of diabetes mellitus; T1DM is immune mediated and T2DM is mediated by metabolic mechanisms.

Connexin 43 Deficiency Is Associated with Reduced Myocardial Scar Size and Attenuated TGFβ1 Signaling after Transient Coronary Occlusion in Conditional Knock-Out Mice.

Previous studies demonstrated a reduction in myocardial scar size in heterozygous Cx43 mice subjected to permanent coronary occlusion. However, patients presenting with ST segment elevation myocardial infarction often undergo rapid coronary revascularization leading to prompt restoration of coronary flow. Therefore, we aimed to assess changes in scar size and left ventricular remodeling following transient myocardial ischemia (45 min) followed by 14 days of reperfusion using Cx43 (controls) and Cx43 inducible knock-out (Cx43 content: 50%) mice treated with vehicle or 4-hydroxytamoxifen (4-OHT) to induce a Cre-ER(T)-mediated global deletion of the Cx43 floxed allele.

Enhancing Glycolysis Protects against Ischemia-Reperfusion Injury by Reducing ROS Production.

After myocardial ischemia-reperfusion, fatty acid oxidation shows fast recovery while glucose oxidation rates remain depressed. A metabolic shift aimed at increasing glucose oxidation has shown to be beneficial in models of myocardial ischemia-reperfusion. However, strategies aimed at increasing glucose consumption in the clinic have provided mixed results and have not yet reached routine clinical practice.

Tuberculosis in a Spanish cohort of children living with HIV: the CHOTIS study (Childhood HIV & TB study).

Tuberculosis (TB) is the leading opportunistic infection in children with human immunodeficiency virus (HIV), but is uncommon in low prevalence regions. We aim to describe the changing epidemiology and clinical presentation of TB-HIV co-infection in a cohort of HIV-infected children in Spain. Children diagnosed with TB between 1995 and 2016 in the paediatric HIV cohort were identified.

Mitochondrial and mitochondrial-independent pathways of myocardial cell death during ischaemia and reperfusion injury.

Acute myocardial infarction causes lethal injury to cardiomyocytes during both ischaemia and reperfusion (IR). It is important to define the precise mechanisms by which they die in order to develop strategies to protect the heart from IR injury. Necrosis is known to play a major role in myocardial IR injury.

Ratio of T1-Weighted to T2-Weighted Signal Intensity as a Measure of Tissue Integrity: Comparison with Magnetization Transfer Ratio in Patients with Multiple Sclerosis.

The study aim was to compare the ratio of T1WI to T2WI signal intensity (T1/T2) with magnetization transfer ratio, a marker of myelin integrity, in patients with multiple sclerosis. A moderate correlation ( = 0.50, = .

Immunological Pattern in IgA Nephropathy.

The current gold-standard diagnostic technique for IgA nephropathy (IgAN), the leading form of primary glomerulonephritis, is renal biopsy. CD89 (the main IgA receptor) is expressed on the surface of monocytes and plays a role in disease pathogenesis. Immunocomplexes formed by sCD89 (soluble form) and Gd-IgA1 are related to disease prognosis.

PLGA protein nanocarriers with tailor-made fluorescence/MRI/PET imaging modalities.

Designing theranostic nanocarriers with high protein payload and multimodality tracking without cross interferences between the different imaging probes and the delicate protein cargo is challenging. Here, chemical modifications of poly(lactic-co-glycolic acid) (PLGA) to produce nanocapsules (NCs) that incorporate several imaging moieties are reported. The biocompatible and biodegradable PLGA-NCs can be endowed with a magnetic resonance imaging (MRI) reporter, two fluorescence imaging probes (blue/NIR) and a positron emission tomography (PET) reporter.

Metformin coordinates osteoblast/osteoclast differentiation associated with ischemic osteonecrosis.

In this study, we aimed to identify a candidate drug that can activate endogenous Angiopoietin 1 (Ang1) expression via drug repositioning as a pharmacological treatment for avascular osteonecrosis. After incubation with 821 drugs from the Food and Drug Administration (FDA)-approved drug library, Ang1 expression in U2OS cell culture media was examined by ELISA. Metformin, the first-line medication for treatment of type 2 diabetes, was selected as a candidate for in vitro and in vivo experimental evaluation.