Validation of Motor Outcome Measures in Myotonic Dystrophy Type 2

Introduction: Myotonic dystrophy type 2 (DM2) lacks disease-specific, validated, motor outcome measures (OMs), and patients' reported outcomes (PROs). This represents a limit for the monitoring of disease progression and treatment response. Our aim was to identify the most appropriate OMs to be translated in clinical practice and clinical trials on DM2. This study has been registered on clinicaltrials.gov NCT03603171 (https://clinicaltrials.gov/ct2/show/NCT03603171). Methods: Sixty-six patients with genetically confirmed DM2 underwent a baseline and a follow-up visit after 1 year. The tested OMs included: hand opening time, pressure pain threshold (PPT), manual muscle testing (MMT), hand held dynamometry (HHD), scale for the assessment and rating of ataxia (SARA), quantitative motor function test (QMFT), gait stairs Gowers chair (GSGC), 30-s sit to stand test, functional index 2 (FI-2) and 6MWT. The PROs included DM1-Active-C, Rasch-built Pompe-specific activity scale (R-Pact), fatigue and daytime sleepiness (FDSS), brief pain inventory short form (BPI-sf), myotonia behavior scale (MBS), and the McGill pain questionnaire. Results: All patients completed the MBS and the results correlated well with the hand-opening time. The PPT showed a low reliability, no correlation with pain questionnaires, and did not differentiate patients with or without myalgia. Both muscle strength assessments, MMT and HHD, showed good construct validity. The QMFT showed an acceptable ceiling effect (14.5%), good convergent and differential validity and performed overall better than GSGC. The SARA score showed high flooring effect and is not useful in DM2. 6MWT proved a valid outcome measure in DM2. The 30-s sit to stand is a feasible test with good convergent validity, showing a flooring effect of 20% as it cannot be used in more severely affected patients. The FI-2 is time-consuming and has a high ceiling effect. At the 1-year visit the only assessments able to detect a worsening of DM2 were HHD, QMFT, and 6MWT, which are the most sensitive to change, and therefore clinically meaningful OMs in DM2. Conclusion: The clinical meaningful motor outcome measures that best depict the multifaceted phenotype of DM2 and its slow progression are MBS, MMT, or HHD (depending on the clinical setting), QMFT, and the 6MWT

Recognition of cooking activities through air quality sensor data for supporting food journaling

Abstract Unhealthy behaviors regarding nutrition are a global risk for health. Therefore, the healthiness of an individual's nutrition should be monitored in the medium and long term. A powerful tool for monitoring nutrition is a food diary; i.e., a daily list of food taken by the individual, together with portion information. Unfortunately, frail people such as the elderly have a hard time filling food diaries on a continuous basis due to forgetfulness or physical issues. Existing solutions based on mobile apps also require user's effort and are rarely used in the long term, especially by elderly people. For these reasons, in this paper we propose a novel architecture to automatically recognize the preparation of food at home in a privacy-preserving and unobtrusive way, by means of air quality data acquired from a commercial sensor. In particular, we devised statistical features to represent the trend of several air parameters, and a deep neural network for recognizing cooking activities based on those data. We collected a large corpus of annotated sensor data gathered over a period of 8 months from different individuals in different homes, and performed extensive experiments. Moreover, we developed an initial prototype of an interactive system for acquiring food information from the user when a cooking activity is detected by the neural network. To the best of our knowledge, this is the first work that adopts air quality sensor data for cooking activity recognition

New Hybrid Pyrazole and Imidazopyrazole Antinflammatory Agents Able to Reduce ROS Production in Different Biological Targets

Several anti-inflammatory agents based on pyrazole and imidazopyrazole scaffolds and a large library of substituted catechol PDE4D inhibitors were reported by us in the recent past. To obtain new molecules potentially able to act on different targets involved in inflammation onset we designed and synthesized a series of hybrid compounds by linking pyrazole and imidazo-pyrazole scaffolds to differently decorated catechol moieties through an acylhydrazone chain. Some compounds showed antioxidant activity, inhibiting reactive oxygen species (ROS) elevation in neutrophils, and a good inhibition of phosphodiesterases type 4D and, particularly, type 4B, the isoform most involved in inflammation. In addition, most compounds inhibited ROS production also in platelets, confirming their ability to exert an antiinflammatory response by two independent mechanism. Structure-activity relationship (SAR) analyses evidenced that both heterocyclic scaffolds (pyrazole and imidazopyrazole) and the substituted catechol moiety were determinant for the pharmacodynamic properties, even if hybrid molecules bearing to the pyrazole series were more active than the imidazopyrazole ones. In addition, the pivotal role of the catechol substituents has been analyzed. In conclusion the hybridization approach gave a new serie of multitarget antiinflammatory compounds, characterized by a strong antioxidant activity in different biological targets

Solitary Fibrous Tumours of the Pleura

Solitary fibrous tumours of the pleura (SFTP) are rare neoplasms originating from one of the components of the sub-mesothelial connective layer underlying the pleura. They are the most common non-mesothelial primary pleural neoplasms but still remain relatively rare. Their behaviour is mostly indolent; however, some may de-differentiate into malignant and aggressive tumours. Surgical resection is the mainstay treatment for SFTP, even more so in case of voluminous masses, due to compression onto lung, mediastinum and great vessels. In this chapter, we discuss the disease characteristics reported in the literature with respect to clinical presentation, diagnosis and treatment; also, we will discuss the results of patients treated for SFTP who underwent a surgical treatment in our unit of thoracic surgery

Automatic Detection of Myotonia using a Sensory Glove with Resistive Flex Sensors and Machine Learning Techniques

This paper deals with the automatic detection of Myotonia from a task based on the sudden opening of the hand. Data have been gathered from 44 subjects, divided into 17 controls and 27 myotonic patients, by measuring a 2-point articulation of each finger thanks to a calibrated sensory glove equipped with a Resistive Flex Sensor (RFS). RFS gloves are proven to be reliable in the analysis of motion for myotonic patients, which is a relevant task for the monitoring of the disease and subsequent treatment. With the focus on a healthy VS pathological comparison, customized features were extracted, and several classifications entailing motion data from single fingers, single articulations and aggregations were prepared. The pipeline employed a Correlation-based feature selector followed by a SVM classifier. Results prove that it’s possible to detect Myotonia, with aggregated data from four fingers and upper/lower articulations providing the most promising accuracies (91.1%

Integration of tumour infiltrating lymphocytes, programmed cell-death ligand-1, CD8 and FOXP3 in prognostic models for triple-negative breast cancer: Analysis of 244 stage I-III patients treated with standard therapy.

Tumour infiltrating lymphocytes (TILs) are an established prognostic biomarker for triple-negative breast cancer (TNBC). We evaluated the role of programmed cell-death ligand-1 (PD-L1), CD8 and FOXP3 expression in refining a prognostic model for non-metastatic TNBC beyond classic factors and TILs.Primary tumour samples from 244 early patients with TNBC, all treated with surgery and chemotherapy, were collected. Stromal TILs were evaluated on haematoxylin-eosin slides according to guidelines. PD-L1, CD8 and FOXP3 were assessed by immunohistochemistry and evaluated by digital pathology.TILs, PD-L1, CD8 and FOXP3 were positively correlated with each other (P 0.001). TILs were confirmed as an independent prognostic factor. When PD-L1, CD8 and FOXP3 were added to multivariable models including classic factors (age, stage, histologic grade) and TILs, PD-L1 provided the largest amount of additional prognostic information: likelihood ratio χBeyond clinicopathological factors and TILs, other immune biomarkers may add prognostic information for early TNBC. The increased PD-L1 expression on residual disease after neoadjuvant chemotherapy strengthens the rationale of testing immune checkpoint inhibitors in the post-neoadjuvant setting