Muscle mass estimation on breast magnetic resonance imaging in breast cancer patients: comparison between psoas muscle area on computer tomography and pectoralis muscle area on MRI.

Objectives: To evaluate the correlation between psoas muscle area (TPA) on CT images and pectoralis muscle area (PMA) on MRI in breast cancer patients.

Methods: This retrospective study was institutional review board approved and women involved gave written informed consent. Twenty six patients with both body CT and breast MRI available were evaluated.

Acyl Glucuronide Metabolites of 6-Chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1 H-indole-3-carboxylic Acid (PF-06409577) and Related Indole-3-carboxylic Acid Derivatives are Direct Activators of Adenosine Monophosphate-Activated Protein Kinase (AMPK).

Studies on indole-3-carboxylic acid derivatives as direct activators of human adenosine monophosphate-activated protein kinase (AMPK) α1β1γ1 isoform have culminated in the identification of PF-06409577 (1), PF-06885249 (2), and PF-06679142 (3) as potential clinical candidates. Compounds 1-3 are primarily cleared in animals and humans via glucuronidation. Herein, we describe the biosynthetic preparation, purification, and structural characterization of the glucuronide conjugates of 1-3.

MRI of cortical lesions and its use in studying their role in MS pathogenesis and disease course.

Cortical grey matter (GM) demyelination is present from the earliest stages of multiple sclerosis (MS) and is associated with physical deficits and cognitive impairment. In particular, the rate of disability progression in MS, both in the relapsing and progressive phases, appears to be strictly associated with degenerative GM demyelination and diffuse cortical atrophy. In the last decade, several histopathological studies and advanced radiological methodologies have contributed to better identify the exact involvement/load of cortical pathology in MS, even if the specific inflammatory features and the precise cell and molecular mechanisms of GM demyelination and neurodegeneration in MS remain still not fully understood.

Delineating the role of cooperativity in the design of potent PROTACs for BTK.

Proteolysis targeting chimeras (PROTACs) are heterobifunctional small molecules that simultaneously bind to a target protein and an E3 ligase, thereby leading to ubiquitination and subsequent degradation of the target. They present an exciting opportunity to modulate proteins in a manner independent of enzymatic or signaling activity. As such, they have recently emerged as an attractive mechanism to explore previously "undruggable" targets.

Urgent challenges in quantification and interpretation of brain grey matter atrophy in individual MS patients using MRI.

Atrophy of the brain grey matter (GM) is an accepted and important feature of multiple sclerosis (MS). However, its accurate measurement is hampered by various technical, pathological and physiological factors. As a consequence, it is challenging to investigate the role of GM atrophy in the disease process as well as the effect of treatments that aim to reduce neurodegeneration.

The effect of fingolimod on focal and diffuse grey matter damage in active MS patients.

Introduction: The mechanism of action of fingolimod within the central nervous system and its efficacy in reducing/preventing both focal and diffuse grey matter (GM) damage in active multiple sclerosis (MS) are not completely understood.

Methods: In this longitudinal, 2-year prospective, phase IV, single-blind study, 40 MS patients treated with fingolimod and 39 untreated age, gender, and disability-matched MS patients were enrolled. Each patient underwent a neurological examination every 6 months and a 3T MRI at the beginning of the treatment and after 24 months.

Detecting Branching in Wormlike Micelles via Dynamic Scattering Methods.

Topological differences in a model series of wormlike micelles (WLMs) with varying degrees of branching are investigated via neutron spin echo (NSE) and dynamic light scattering (DLS). Branching was previously verified via microscopy, scattering methods, and rheology. NSE measurements reveal that on the shortest length scales, where WLMs are topologically similar, the dynamic behavior is independent of branching level.

The cortical damage, early relapses, and onset of the progressive phase in multiple sclerosis.

Objective: To investigate the relationship among cortical radiologic changes, the number of early relapses (ERs), and the long-term course of multiple sclerosis (MS).

Methods: In this cohort study, we assessed the number of cortical lesions (CLs) and white matter (WM) lesions and the cortical thickness (Cth) at clinical onset and after 7.9 mean years among 219 patients with relapsing remitting (RR) MS with 1 (Low-ER), 2 (Mid-ER), and ≥3 (High-ER) ERs during the first 2 years.

An exploratory radiomics analysis on digital breast tomosynthesis in women with mammographically negative dense breasts.

Purpose: To compare Digital Breast Tomosynthesis (DBT) for cancers and normal screens in women with dense breasts and negative mammography using a Radiomics approach.

Materials And Methods: A substudy (N = 40) of the 'Adjunct Screening With Tomosynthesis or Ultrasound in Women With Mammography-Negative Dense Breasts (ASTOUND)' trial was done based on 20 women who had DBT-detected, histology-proven, breast cancer and 20 controls matched for age and density. Using a Radiomics approach normal and pathological breast parenchyma were evaluated, and correlations among Radiomics features and clinical and prognostic parameters were investigated.

A multicentRE observational analysiS of PErsistenCe to Treatment in the new multiple sclerosis era: the RESPECT study.

In this independent, multicenter, retrospective study, we investigated the short-term persistence to treatment with first-line self-injectable or oral disease-modifying treatments (DMTs) in patients with relapsing-remitting multiple sclerosis. Data of patients regularly attending 21 Italian MS Centres who started a self-injectable or an oral DMT in 2015 were collected to: (1) estimate the proportion of patients discontinuing the treatment; (3) explore reasons for discontinuation; (3) identify baseline predictors of treatment discontinuation over a follow-up period of 12 months. We analyzed data of 1832 consecutive patients (1289 women, 543 men); 374 (20.

Inflammatory intrathecal profiles and cortical damage in multiple sclerosis.

Objective: Gray matter (GM) damage and meningeal inflammation have been associated with early disease onset and a more aggressive disease course in multiple sclerosis (MS), but can these changes be identified in the patient early in the disease course?

Methods: To identify possible biomarkers linking meningeal inflammation, GM damage, and disease severity, gene and protein expression were analyzed in meninges and cerebrospinal fluid (CSF) from 27 postmortem secondary progressive MS and 14 control cases. Combined cytokine/chemokine CSF profiling and 3T magnetic resonance imaging (MRI) were performed at diagnosis in 2 independent cohorts of MS patients (35 and 38 subjects) and in 26 non-MS patients.

Results: Increased expression of proinflammatory cytokines (IFNγ, TNF, IL2, and IL22) and molecules related to sustained B-cell activity and lymphoid-neogenesis (CXCL13, CXCL10, LTα, IL6, and IL10) was detected in the meninges and CSF of postmortem MS cases with high levels of meningeal inflammation and GM demyelination.

Biophysical Interactions of Direct AMPK Activators.

Protein-ligand interactions can be evaluated by a number of different biophysical methods. Here we describe some of the experimental methods that we have used to generate AMPK protein reagents and characterize its interactions with direct synthetic activators. Recombinant heterotrimeric AMPK complexes were generated using standard molecular biology methods by expression either in insect cells via infection with three different viruses or more routinely in Escherichia coli with a tricistronic expression vector.

Optimization of Metabolic and Renal Clearance in a Series of Indole Acid Direct Activators of 5'-Adenosine Monophosphate-Activated Protein Kinase (AMPK).

Optimization of the pharmacokinetic (PK) properties of a series of activators of adenosine monophosphate-activated protein kinase (AMPK) is described. Derivatives of the previously described 5-aryl-indole-3-carboxylic acid clinical candidate (1) were examined with the goal of reducing glucuronidation rate and minimizing renal excretion. Compounds 10 (PF-06679142) and 14 (PF-06685249) exhibited robust activation of AMPK in rat kidneys as well as desirable oral absorption, low plasma clearance, and negligible renal clearance in preclinical species.

Vacuum assisted breast biopsy (VAB) excision of subcentimeter microcalcifications as an alternative to open biopsy for atypical ductal hyperplasia.

Objective: Atypical ductal hyperplasia (ADH) is a proliferative lesion associated with a variable increased risk of breast malignancy, but the management of the patients is still not completely defined, with mandatory surgical excision in most cases. To report the results of the conservative management with mammographic checks of patients with ADH diagnosed by vacuum assisted breast biopsy (VAB), without residual calcifications.

Methods: The authors accessed the institutional database of radiological, surgical and pathological anatomy.

The Impact of Aging on Cardio and Cerebrovascular Diseases.

A growing number of evidences report that aging represents the major risk factor for the development of cardio and cerebrovascular diseases. Understanding Aging from a genetic, biochemical and physiological point of view could be helpful to design a better medical approach and to elaborate the best therapeutic strategy to adopt, without neglecting all the risk factors associated with advanced age. Of course, the better way should always be understanding risk-to-benefit ratio, maintenance of independence and reduction of symptoms.

Potential neuroprotective effect of Fingolimod in multiple sclerosis and its association with clinical variables.

Introduction: Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disease of the central nervous system affecting both white matter and grey matter in the earliest phases of its course. The crucial role of neurodegeneration in disability progression in MS, regardless of white matter damage, has been confirmed by several imaging and neuropathological studies. Fingolimod is an effective immunomodulator of the sphingosine 1-phosphate receptor, approved in relapsing remitting MS and able to cross the blood-brain barrier and to slow disability progression and brain volume loss.

Rapid review: radiomics and breast cancer.

Purpose: To perform a rapid review of the recent literature on radiomics and breast cancer (BC).

Methods: A rapid review, a streamlined approach to systematically identify and summarize emerging studies was done (updated 27 September 2017). Clinical studies eligible for inclusion were those that evaluated BC using a radiomics approach and provided data on BC diagnosis (detection or characterization) or BC prognosis (response to therapy, morbidity, mortality), or provided data on technical challenges (software application: open source, repeatability of results).

Future Considerations for the Evaluation of Hepatitis C Virus Treatments in Pan-Genotypic Therapy for Noncirrhotic Treatment-Naive Patients.

Unlabelled: Given the recent approval of the first pan-genotypic chronic hepatitis C virus (HCV) therapy, managed care, health systems, and clinicians will need to evaluate current practices related to essential laboratory assessments used to select therapy. Historically, clinicians and payers required a battery of tests to determine HCV genotype, viral load, degree of fibrosis, and organ function. In light of current and forthcoming approvals of pan-genotypic therapy, clinicians and payers can expect a more competitive marketplace and a downward curve in the price of therapy.

Physical rehabilitation modulates microRNAs involved in multiple sclerosis: a case report.

This study shows that neuromuscular taping improves gait, balance, pain and ability to walk and conduct daily activities in a multiple sclerosis patient. It is the first study to identify a panel of miRNAs modulated throughout rehabilitation using neuromuscular taping in a multiple sclerosis patient.

COPD management as a model for all chronic respiratory conditions: report of the 4 Consensus Conference in Respiratory Medicine.

Background: Non-communicable diseases (NCDs) kill 40 million people each year. The management of chronic respiratory NCDs such as chronic obstructive pulmonary disease (COPD) is particularly critical in Italy, where they are widespread and represent a heavy burden on healthcare resources. It is thus important to redefine the role and responsibility of respiratory specialists and their scientific societies, together with that of the whole healthcare system, in order to create a sustainable management of COPD, which could become a model for other chronic respiratory conditions.

Circulating Endothelial Progenitor Cells in Type 1 Diabetic Patients: Relation with Patients' Age and Disease Duration.

Objectives: Circulating endothelial progenitor cells (cEPCs) have been reported to be dysfunctional in diabetes mellitus (DM) patients, accounting for the vascular damage and the ensuing high risk for cardiovascular disease (CVD) characteristic of this disease. The aim of the present study was to evaluate the number of circulating cEPCs in type 1 DM (T1DM) patients, without clinical vascular damage, of different ages and with different disease duration.

Methods: An observational, clinical-based prospective study was performed on T1DM patients enrolled in two clinical centers.

Flat epithelial atypia: conservative management of patients without residual microcalcifications post-vacuum-assisted breast biopsy.

Objective: To determine the malignancy rate (defined in this study as stability or absence of malignancy developed on close imaging follow-up post-biopsy) of conservative management in patients with a vacuum-assisted breast biopsy (VAB) diagnosis of flat epithelial atypia (FEA), performed on single group of microcalcifications, completely removed during procedure.

Methods: This is a retrospective, monocentric, observational study, approved by IRB. Inclusion criteria were: VAB performed on a single group of microcalcifications; the absence of residual calcifications post-VAB; diagnosis of isolated FEA as the most advanced proliferative lesion; radiological follow-up at least of 12 months.