Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Assessing Stiffness, Joint Torque and ROM for Paretic and Non-Paretic Lower Limbs during the Subacute Phase of Stroke Using Lokomat Tools

The efficacy of Lokomat on motor recovery in stroke patients is well known. However, few studies have examined Lokomat tools to assess stiffness, joint torque and range of motion (ROM) during the subacute phase of stroke. The purpose of this retrospective observational study is to assess the changes of joint torque, ROM and stiffness that were estimated with Lokomat tools, namely L-FORCE (lower limb-force), L-ROM (lower limb-range of motion)and L-STIFF (lower limb-stiff), for paretic and non-paretic lower limbs in the subacute phase of stroke, assuming that the tools were able to measure these changes. The data come from 10 subjects in the subacute phase who had their first ever-stroke and followed a treatment that included Lokomat. The measurements came from basal assessments (T0) and one-month follow-up (T1). The measures were compared between paretic and non-paretic legs, and between T0 and T1. Significant differences in stiffness, joint torque and ROM were obtained between the paretic and non-paretic limbs at both T0 and T1. A non-significant trend was obtained for reduced stiffness and increased torque and ROM between T0 and T1 of the paretic limbs. The Lokomat tools were able to measure the changes between paretic and non-paretic legs and the small changes between T0 and T1 measurements

Clinical scales for measuring stroke rehabilitation promote functional recovery by supporting teamwork

The growing interest in documenting the effectiveness of rehabilitation has led to a progressive increasing focus on clinical tools to measure stroke-survivors disability and recovery. In clinical practice a general agreement on the instruments to be used seems to be lacking and clinical scales are often limited to the assessment of global function

Blockchain-as-a-Service and Blockchain-as-a-Partner: Implementation options for supply chain optimization

Smart contracts show a high potential to make supply chain management strategies epochally leap towards higher levels of productivity, not only in the functioning of production processes but also in terms of product innovation and overall economic returns. This article illustrates the principle of Income Sharing as a highly performing economic strategy for supply chains with a natural implementation in blockchain smart contracts. It proposes a blockchain-based architecture that uses smart contracts to implement various algorithmic versions of the Income Sharing principle among companies participating in a supply chain. The formation of the total income and its consequent redistribution are calculated taking into account the role of the technological platform automating these procedures, which therefore becomes a party to the inter-company business project of a supply chain in the alternative roles, as feasible in business practice, of Blockchain-as-a-Service and Blockchain-as-a-Partner. The approach is implemented on Hyperledger Fabric, the most widespread platform for private and consortium blockchains. We compare and justify this design choice with the alternative given by public blockchains, with specific attention to Ethereum

Biofeedback rehabilitation of posture and weight-bearing distribution in stroke: a center of foot pressure analysis

Weight bearing on the paretic lower extremity and transfer of weight from one lower extremity to the other are important goals of stroke rehabilitation. Improvements in these limb loading and weight transfer abilities have been shown to relate to improved performance of many functional activities. Unfortunately, valid and practical clinical measures of paretic lower extremity loading and weight transfer have not been identified. The purpose of this study was to quantitatively assess, through center of foot pressure (CoP) analysis of quiet upright stance control, recovery of paretic limb loading as a measure of weight transfer in early stroke subjects, testing the effectiveness of a targeted rehabilitation intervention based on audio-visual biofeedback. Thirty-seven adults with lower extremity motor impairment following unilateral, non-cerebellar stroke, were tested twice, at an interval of at least one month post stroke and following rehabilitation intervention aimed at correcting their asymmetrical weight bearing. The intervention was performed with (Study Group, SG) or without (Control Group, CG) a postural audio-visual biofeedback approach. Indices of postural stability and of balance control asymmetry were estimated by acquiring the movements of the CoP during quiet upright stance condition with or without visual input (eyes open, EO and eyes closed, EC). Clinical scales were also administered. Both the CG and the SG subjects showed improved control in upright stance posture as documented by significant improvements in the scale scores and indices of stability during both the EO and the EC condition. Only the SG showed a significantly reduced CoP index of asymmetry. The CoP index of asymmetry, correlating with clinical motor scales, is a valid measure of paretic limb loading during stroke recovery. Postural audio-visual biofeedback represented the more effective approach for reducing weight loading asymmetry of the lower limbs in stroke

Arm weight support training improves functional motor outcome and movement smoothness after stroke

The aim of this study was to compare the effectiveness in acute stroke patients of a rehabilitation program performed with or without an arm weight support device. Twenty-eight acute, first-ever unilateral stroke patients were enrolled in a single-blind, randomized controlled trial. Clinical evaluation included Fugl-Mayer Assessment, Functional Independence Measure and kinematic analysis [maximum and mean hand velocity, maximum range of motion (Max RoM), normalized jerk (NJ)]. Patients received 12 daily 30-minute sessions (6/week) of additional upper limb therapy performed using an arm weight support device (study group) or additional traditional physiotherapy (control group). The patients were evaluated on admission and at the end of the rehabilitation intervention. The two groups were clinically comparable on admission (p>0.05). Both groups showed significant improvements in clinical scale scores and in Max RoM in flexion-extension, while only the study group showed improvements in NJ and in Max RoM in adduction-abduction. Rehabilitation training using an arm weight support device appears to be a useful method to supplement conventional therapy in acute stroke patients, increasing smoothness of movement and motor function

Prognostic Value of Colorectal Cancer Biomarkers

Despite the large amount of data in cancer biology and many studies into the likely survival of colorectal cancer (CRC) patients, knowledge regarding the issue of CRC prognostic biomarkers remains poor. The Tumor-Node-Metastasis (TNM) staging system continues to be the most powerful and reliable predictor of the clinical outcome of CRC patients. The exponential increase of knowledge in the field of molecular genetics has lead to the identification of specific alterations involved in the malignant progression. Many of these genetic alterations were proposed as biomarkers which could be used in clinical practice to estimate CRC prognosis. Recently there has been an explosive increase in the number of putative biomarkers able to predict the response to specific adjuvant treatment. In this review we explore and summarize data concerning prognostic and predictive biomarkers and we attempt to shed light on recent research that could lead to the emergence of new biomarkers in CRC

Deep Underground Neutrino Experiment (DUNE), Far Detector Technical Design Report, Volume I Introduction to DUNE

International audienceThe preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. This TDR is intended to justify the technical choices for the far detector that flow down from the high-level physics goals through requirements at all levels of the Project. Volume I contains an executive summary that introduces the DUNE science program, the far detector and the strategy for its modular designs, and the organization and management of the Project. The remainder of Volume I provides more detail on the science program that drives the choice of detector technologies and on the technologies themselves. It also introduces the designs for the DUNE near detector and the DUNE computing model, for which DUNE is planning design reports. Volume II of this TDR describes DUNE's physics program in detail. Volume III describes the technical coordination required for the far detector design, construction, installation, and integration, and its organizational structure. Volume IV describes the single-phase far detector technology. A planned Volume V will describe the dual-phase technology