Precision-based exercise as a new therapeutic option for children and adolescents with haematological malignancies

Children and adolescents with haematological malignancies (pedHM) are characterized by a severe loss of exercise ability during cancer treatment, lasting throughout their lives once healed and impacting their social inclusion prospects. The investigation of the effect of a precision-based exercise program on the connections between systems of the body in pedHM patients is the new frontier in clinical exercise physiology. This study is aimed at evaluating the effects of 11 weeks (3 times weekly) of combined training (cardiorespiratory, resistance, balance and flexibility) on the exercise intolerance in PedHM patients. Two-hundred twenty-six PedHM patients were recruited (47% F). High or medium frequency participation (HAd and MAd) was considered when a participant joined; > 65% or between 30% and < 64% of training sessions, respectively. The \u201cup and down stairs\u2019\u2019 test (TUDS), \u201c6 min walking\u201d test (6MWT), the \u201c5 Repetition Maximum strength\u201d leg extension and arm lateral raise test (5RM-LE and 5RM-ALR), flexibility (stand and reach), and balance (stabilometry), were performed and evaluated before and after training. The TUDS, the 5RM-LE and 5RM-ALR, and the flexibility exercises showed an increase in HAd and MAd groups (P < 0.05), while the 6MWT and balance tests showed improvement only in HAd group (P < 0.0001). these results support the ever\u2010growing theory that, in the case of the treatment of PedHM, \u2018exercise is medicine\u2019 and it has the potential to increase the patient\u2019s chances of social inclusion

TCA cycle rewiring fosters metabolic adaptation to oxygen restriction in skeletal muscle from rodents and humans

In mammals, hypoxic stress management is under the control of the Hypoxia Inducible Factors, whose activity depends on the stabilization of their labile \uce\ub1 subunit. In particular, the skeletal muscle appears to be able to react to changes in substrates and O2 delivery by tuning its metabolism. The present study provides a comprehensive overview of skeletal muscle metabolic adaptation to hypoxia in mice and in human subjects exposed for 7/9 and 19 days to high altitude levels. The investigation was carried out combining proteomics, qRT-PCR mRNA transcripts analysis, and enzyme activities assessment in rodents, and protein detection by antigen antibody reactions in humans and rodents. Results indicate that the skeletal muscle react to a decreased O2 delivery by rewiring the TCA cycle. The first TCA rewiring occurs in mice in 2-day hypoxia and is mediated by cytosolic malate whereas in 10-day hypoxia the rewiring is mediated by Idh1 and Fasn, supported by glutamine and HIF-2\uce\ub1 increments. The combination of these specific anaplerotic steps can support energy demand despite HIFs degradation. These results were confirmed in human subjects, demonstrating that the TCA double rewiring represents an essential factor for the maintenance of muscle homeostasis during adaptation to hypoxia

Peripheral Arterial and Venous Response to Tilt Test after a 60-Day Bedrest with and without Countermeasures (ES-IBREP)

We quantified the impact of 60-day head-down bed rest (HDBR) with countermeasures on arterial and venous response to tilt. Methods: Twenty-one males: 7 control (Con), 7 resistive vibration exercise (RVE) and 7 Chinese herb (Herb) were assessed. Subjects were identified as finisher (F) or non-finishers (NF) at the post-HDBR 20-min tilt test. The cerebral (MCA), femoral (FEM) arterial flow velocity and leg vascular resistance (FRI), the portal vein section (PV), the flow redistribution ratios (MCA/FEM; MCA/PV), the tibial (Tib), gastrocnemius (Gast), and saphenous (Saph) vein sections were measured by echography and Doppler ultrasonography. Arterial and venous parameters were measured at 3-min pre-tilt in the supine position, and at 1 min before the end of the tilt. Results: At post-HDBR tilt, MCA decreased more compared with pre-HDBR tilt in the Con, RVE, and Herb groups, the MCA/FEM tended to decrease in the Con and Herb groups (not significant) but remained stable in the RVE gr. FRI dropped in the Con gr, but remained stable in the Herb gr and increased in the RVE gr. PV decreased less in the Con and Herb groups but remained unchanged in the RVE gr. MCA/PV decreased in the Con and Herb groups, but increased to a similar extent in the RVE gr. Gast section significantly increased more in the Con gr only, whereas Tib section increased more in the Con and Herb groups but not in the RVE gr. The percent change in Saph section was similar at pre- and post-HDBR tilt. Conclusion: In the Con gr, vasoconstriction was reduced in leg and splanchnic areas. RVE and Herb contributed to prevent the loss of vasoconstriction in both areas, but the effect of RVE was higher. RVE and Herb contributed to limit Gast distension whereas only RVE had a protective effect on the Tib

Magnetic resonance imaging (MRI) contrast agents for tumor diagnosis

10.1260/2040-2295.4.1.23Journal of Healthcare Engineering4123-4

Analytical methods to support continuous improvements at Scania

Considerable effort is usually devoted by companies to ensure the competitiveness of their manufacturing systems. This makes continuous improvement a central topic in production management activities. Less attention is given to the methods that drive improvement and to the way actions are defined and selected. In the literature, analytical models and simulation are the most widely used tools for manufacturing systems’ performance evaluation and improvement. In practice, simple approaches, mainly based on experience, seems to be the best compromise to face this problem. In a collaboration project between Politecnico di Milano (Milano, Italy), Kungliga Tekniska ho¨ gskolan (Stockholm, Sweden) and Scania CV AB (So¨ derta¨ lje, Sweden) within the European Network of Excellence VRL-KCiP we proposed a new methodology, based on analytical methods, to support the company in manufacturing system productivity improvement through re-configuration. The application of this approach to the Scania six-cylinder engine-block machining line enabled a remarkable increment in throughput by selecting analytically the most suitable improvement actions

Differential proteome analysis in col6a1-/- mouse model of gastrocnemious, tibialis and diaphragm muscles and effects of Ciclosporin A treatment

Ullrich Congenital Muscular Dystrophy (UCMD) and Bethlem Myopathy (BM) are congenital muscular dystrophies caused by abnormalities of Collagen VI due to COLVI gene mutations. The absence of Collagen VI has a major impact inside fibres by triggering a short circuit in the cell\u2019s energy generators, the mitochondria. This short circuit is caused by opening of a channel called the \u201cPermeability Transition Pore\u201d (PTP), which can be inhibited by the drug cyclosporin A (CsA). To better understand the molecular consequences of collagen VI absence in muscles, the proteome of functionally different and differentially affected muscles such as tibialis, diaphragm and gastrocnemius was investigated. Differential proteome was assessed by 2D-DIGE, De Cyder software analysis and MALDI Tof/Tof and ESI MS/MS. Results indicates that different categories of dysregulated proteins. A specific set of proteins was differentially regulated in diaphragm compared to tibialis and gastrocnemius suggesting that disease progression could be influenced by fiber type distribution, by muscle metabolism and by specific muscle function. The effects of CsA treatment were assessed in the same muscles adopting the same proteomic approach indicated above. Changes induced by CsA in muscle tissue were assessed by two-way ANOVA. A set of molecules, as putative targets of CsA treatment, were identified. A partial recovery of dysregulated proteins, more evident in gastronemious muscle, was observed according to muscle functional recovery. Moreover, CsA efficacy over time is not determined in this study, results highlight the relevance of the proposed approach to monitor effects of pharmacological treatments targeting muscle