Human CD4+CD25+ Cells in Combination with CD34+ Cells and Thymoglobulin to Prevent Anti-hematopoietic Stem Cell T Cell Alloreactivity

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Updates on Quantitative MRI of Diffuse Liver Disease. A Narrative Review

Diffuse liver diseases are highly prevalent conditions around the world, including pathological liver changes that occur when hepatocytes are damaged and liver function declines, often leading to a chronic condition. In the last years, Magnetic Resonance Imaging (MRI) is reaching an important role in the study of diffuse liver diseases moving from qualitative to quantitative assessment of liver parenchyma. In fact, this can allow noninvasive accurate and standardized assessment of diffuse liver diseases and can represent a concrete alternative to biopsy which represents the current reference standard. MRI approach already tested for other pathologies include diffusion-weighted imaging (DWI) and radiomics, able to quantify different aspects of diffuse liver disease. New emerging MRI quantitative methods include MR elastography (MRE) for the quantification of the hepatic stiffness in cirrhotic patients, dedicated gradient multiecho sequences for the assessment of hepatic fat storage, and iron overload. Thus, the aim of this review is to give an overview of the technical principles and clinical application of new quantitative MRI techniques for the evaluation of diffuse liver disease

Effects of pre-harvest techniques in the control of berry ripening in grapevine cv. Sauvignon blanc

Due to a variety of reasons (changing climatic conditions, higher photosynthetic efficiency of newly established vineyards, yield restriction imposed by production protocols), there is currently a tendency towards early ripening in grapevines, combined with the production of berries characterized by high sugar content. This tendency conflicts with the general market demand for wines (mostly white wines) with low alcohol level and characterised by a fresh, easy-to-drink taste. We tested two different techniques applied to the canopy (defoliation and the use of an antitranspirant product) with the aim of delaying the ripening process and improving the berry quality of the white cultivar Sauvignon blanc. The defoliation performed at veraison allowed postponement of the ripening process by about 5 days as compared to undefoliated vines, without altering the sugar/acid ratio of the berries. The antitranspirant product delayed ripening by 10 to 15 days. Brix was reduced by 1.5-2.5 degrees in the 2 considered seasons, whereas the effect on acidity was contradicting and needs further research for a full understanding of the mechanisms involved in the process

CSF levels of CXCL12 and osteopontin as early markers of primary progressive multiple sclerosis

Background and objectives: To evaluate the extent of intrathecal inflammation in patients with primary progressive MS (PPMS) at the time of diagnosis and to define markers and a specific inflammatory profile capable of distinguishing progressive from relapsing-remitting multiple sclerosis (RRMS). Methods: Levels of 34 pro- and anti-inflammatory cytokines and chemokines in the CSF were evaluated at the diagnosis in 16 patients with PPMS and 80 with RRMS. All patients underwent clinical evaluation, including Expanded Disability Status Scale assessment and a 3T brain MRI to detect white matter and cortical lesion number and volume and global and regional cortical thickness. Results: Higher levels of CXCL12 (odds ratio [OR] = 3.97, 95% CI [1.34-11.7]) and the monocyte-related osteopontin (OR = 2.24, 95% CI [1.01-4.99]) were detected in patients with PPMS, whereas levels of interleukin-10 (IL10) (OR = 0.28, 95% CI [0.09-0.96]) were significantly increased in those with RRMS. High CXCL12 levels were detected in patients with increased gray matter lesion number and volume (p = 0.001, r = 0.832 and r = 0.821, respectively). Pathway analysis confirmed the chronic inflammatory processes occurring in PPMS. Conclusions: At the time of diagnosis, a specific CSF protein profile can recognize the presence of early intrathecal inflammatory processes, possibly stratifying PPMS with respect to RRMS. Elevated CSF levels of CXCL12 and osteopontin suggested a key role of brain innate immunity and glia activity in MS. These molecules could represent useful candidate markers of MS progression, with implications for the pathogenesis and treatment of progressive MS. Classification of evidence: This study provides Class III evidence that CXCL12 and monocyte-related osteopontin may be correlated with PPMS, and IL-10 may be related to RRMS. It is may be correlated due to Bonferroni correction negating the statistical correlations found in the study

Chest CT Features of COVID-19 in Rome, Italy

Background The standard for diagnosis of SARS-CoV-2 virus is reverse transcription polymerase chain reaction (RT-PCR) test, but chest CT may play a complimentary role in the early detection of COVID-19 pneumonia. Purpose To investigate CT features of patients with COVID-19 in Rome, Italy, and to compare the accuracy of CT with RT-PCR. Methods In this prospective study from March 4, 2020, until March 19, 2020, consecutive patients with suspected COVID-19 infection and respiratory symptoms were enrolled. Exclusion criteria were: chest CT with contrast medium performed for vascular indications, patients who refused chest CT or hospitalization, and severe CT motion artifact. All patients underwent RT-PCR and chest CT. Diagnostic performance of CT was calculated using RT-PCR as reference. Chest CT features were calculated in a subgroup of RT-PCR-positive and CT-positive patients. CT features of hospitalized patients and patient in home isolation were compared by using Pearson chi squared test. Results Our study population comprised 158 consecutive study participants (83 male and 75 female, mean age 57 y ±17). Fever was observed in 97/158 (61%), cough in 88/158 (56%), dyspnea in 52/158 (33%), lymphocytopenia in 95/158 (60%), increased C-reactive protein level in 139/158 (88%), and elevated lactate dehydrogenase in 128/158 (81%) study participants. Sensitivity, specificity, and accuracy of CT were 97% (60/62)[95% IC, 88-99%], 56% (54/96)[95% IC,45-66%] and 72% (114/158)[95% IC 64-78%], respectively. In the subgroup of RT-PCR-positive and CT-positive patients, ground-glass opacities (GGO) were present in 58/58 (100%), multilobe and posterior involvement were both present in 54/58 (93%), bilateral pneumonia in 53/58 (91%), and subsegmental vessel enlargement (> 3 mm) in 52/58 (89%) of study participants. Conclusion The typical pattern of COVID-19 pneumonia in Rome, Italy, was peripherally ground-glass opacities with multilobe and posterior involvement, bilateral distribution, and subsegmental vessel enlargement (> 3 mm). Chest CT sensitivity was high (97%) but with lower specificity (56%)

t cell mediated rejection of human cd34 cells is prevented by costimulatory blockade in a xenograft model

Abstract A xenograft model of stem cell rejection was developed by co-transplantating human CD34 + and allogeneic CD3 + T cells into NOD-scid ɣ-chain null mice. T cells caused graft failure when transplanted at any CD34/CD3 ratio between 1:50 and 1:.1. Kinetics experiments showed that 2 weeks after transplantation CD34 + cells engrafted the marrow and T cells expanded in the spleen. Then, at 4 weeks only memory T cells populated both sites and rejected CD34 + cells. Blockade of T cell costimulation was tested by injecting the mice with abatacept (CTLA4-IgG1) from day –1 to +27 (group A), from day –1 to +13 (group B), or from day +14 to +28 (group C). On day +56 groups B and C had rejected the graft, whereas in group A graft failure was completely prevented, although with lower stem cell engraftment than in controls ( P  = .03). Retransplantation of group A mice with same CD34 + cells obtained a complete reconstitution of human myeloid and B cell lineages and excluded latent alloreactivity. In this first xenograft model of stem cell rejection we showed that transplantation of HLA mismatched CD34 + cells may be facilitated by treatment with abatacept and late stem cell boost

The prognostic value of white-matter selective double inversion recovery mri sequence in multiple sclerosis: an exploratory study

Using a white-matter selective double inversion recovery sequence (WM-DIR) that suppresses both grey matter (GM) and cerebrospinal fluid (CSF) signals, some white matter (WM) lesions appear surrounded by a dark rim. These dark rim lesions (DRLs) seem to be specific for multiple sclerosis (MS). They could be of great usefulness in clinical practice, proving to increase the MRI diagnostic criteria specificity. The aims of this study are the identification of DRLs on 1.5 T MRI, the exploration of the relationship between DRLs and disease course, the characterization of DRLs with respect to perilesional normal-appearing WM using magnetization transfer imaging, and the investigation of possible differences in the underlying tissue properties by assessing WM-DIR images obtained at 3.0 T MRI. DRLs are frequent in primary progressive MS (PPMS) patients. Amongst relapsing-remitting MS (RRMS) patients, DRLs are associated with a high risk of the disease worsening and secondary progressive MS (SPMS) conversion after 15 years. The mean magnetization transfer ratio (MTR) of DRLs is significantly different from the lesion without the dark rim, suggesting that DRLs correspond to more destructive lesions

Radiomics analysis in gastrointestinal imaging: a narrative review

Background and Objective: To present an overview of radiomics radiological applications in major gastrointestinal oncological non-oncologic diseases, such as colorectal cancer, pancreatic cancer, gastro- oesophageal cancer, gastrointestinal stromal tumor (GIST), hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and non-oncologic diseases, such as liver fibrosis, nonalcoholic steatohepatitis, and inflammatory bowel disease. Methods: A search of PubMed databases was performed for the terms “radiomic”, “radiomics”, “liver”, “small bowel”, “colon”, “GI tract”, and “gastrointestinal imaging” for English articles published between January 2013 and July 2022. A narrative review was undertaken to summarize literature pertaining to application of radiomics in major oncological and non-oncological gastrointestinal diseases. The strengths and limitation of radiomics, as well as advantages and major limitations and providing considerations for future development of radiomics were discussed. Key Content and Findings: Radiomics consists in extracting and analyzing a vast amount of quantitative features from medical datasets, Radiomics refers to the extraction and analysis of large amounts of quantitative features from medical images. The extraction of these data, integrated with clinical data, allows the construction of descriptive and predictive models that can build disease-specific radiomic signatures. Texture analysis has emerged as one of the most important biomarkers able to assess tumor heterogeneity and can provide microscopic image information that cannot be identified with the naked eye by radiologists. Conclusions: Radiomics and texture analysis are currently under active investigation in several institutions worldwide, this approach is being tested in a multitude of anatomical areas and diseases, with the final aim to exploit personalized medicine in diagnosis, treatment planning, and prediction of outcomes. Despite promising initial results, the implementation of radiomics is still hampered by some limitations related to the lack of standardization and validation of image acquisition protocols, feature segmentation, data extraction, processing, and analysi

Impact of Natalizumab on Cognitive Performances and Fatigue in Relapsing Multiple Sclerosis: A Prospective, Open-Label, Two Years Observational Study

Background and Objectives: Natalizumab reduces the relapse rate and magnetic resonance imaging activity in patients with Relapsing-Remitting Multiple Sclerosis (RRMS). So far the influence of natalizumab on cognitive functions and fatigue in MS remains uncertain. The aim of this prospective, open-label, observational study was to evaluate the possible effects of natalizumab on cognition and fatigue measures in RRMS patients treated for up to two years. Methods: Cognitive performances were examined by the Rao’s Brief Repeatable Battery (BRB), the Stroop test (ST) and the Cognitive Impairment Index (CII), every 12 months. Patients who failed in at least 3 tests of the BRB and the ST were classified as cognitively impaired (CI). Fatigue Severity Scale (FSS) was administered every 12 months to assess patient’s selfreported fatigue. One hundred and 53 patients completed 1 and 2 year-natalizumab treatment, respectively. Results: After 1 year of treatment the percentage of CI patients decreased from 29 % (29/100) at baseline to 19 % (19/100) (p = 0.031) and the mean baseline values of CII (13.5266.85) and FSS (4.0161.63) scores were significantly reduced (10.4867.12, p,0.0001 and 3.6161.56, p = 0.008). These significant effects were confirmed in the subgroup of patients treated up to two years. Conclusions: These results demonstrate that a short-term NTZ treatment may significantly improve cognitive performance

Enantiomeric Separation and Molecular Modelling of Bioactive 4-Aryl-3,4-dihydropyrimidin-2(1H)-one Ester Derivatives on Teicoplanin-Based Chiral Stationary Phase

The enantiomeric separation of 15 racemic 4-aryl-3,4-dihydropyrimidin-2(1H)-one (DHP) alkoxycarbonyl esters, some of which proved to be highly active as A2B adenosine receptor antagonists, was carried out by HPLC on ChirobioticTM TAG, a chiral stationary phase (CSP) bearing teicoplanin aglycone (TAG) as the chiral selector. The racemic compounds were separated under polar organic (PO) conditions. Preliminarily, the same selectands were investigated on three different Pirkle-type CSPs in normal-phase (NP) conditions. A baseline separation was successfully obtained on TAG-based CSPs for the majority of compounds, some of which achieved high enantioselectivity ratios ( > 2) in contrast with the smaller values (1–1.5) and the lack of baseline resolution observed with the Pirkle-type CSPs. In particular, the racemic tetrazole-fused DHP ester derivatives, namely compounds 8 and 9, were separated on TAG-based HPLC columns with noteworthy values (8.8 and 6.0, respectively), demonstrating the potential of the method for preparative purposes. A competition experiment, carried out with a racemic analyte (6) by adding N-acetyl-D-alanine (NADA) to the mobile phase, suggested that H-bonding interactions involved in the recognition of the natural dipeptide ligand D-Ala-D-Ala into the TAG cleft should be critical for enantioselective recognition of 4-aryl DHPs by TAG. The X-ray crystal structure of TAG was elucidated at a 0.77 Å resolution, whereas the calculation of molecular descriptors of size, polar, and H-bond interactions, were complemented with molecular docking and molecular dynamics calculations, shedding light on repulsive (steric effects) and attractive (H-bond—polar and apolar) interactions between 4-aryl DHP selectands and TAG chiral selectors