Glyco-metabolic Effects of Ranolazine: A truly Multifaceted Drug?

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Can off-training physical behaviors influence recovery in athletes? A sccoping review

Recently, the attention on recovery in sport increased enormously although there is lack of scientific evidence on the role of lifestyle in terms of movement [i.e., physical behaviors (PBs)], apart from sleep. Few studies assessed physical activity (PA) and sedentary behavior (SB) in athletes. The aims of this scoping review were to answer to the following scientific questions: (1) How active/inactive are competitive athletes out of training? (2) Do off-training PBs affect recovery, performance, and health? (3) What strategies can be implemented to improve recovery using off-training PBs, apart from sleep? From 1,116 potentially relevant articles, nine were eligible for inclusion in this review. The main issues identified were related to the heterogeneity concerning the types of sports, age category, gender, competitive level, sample size, and instruments/devices adopted, the paucity of studies investigating the effects of PBs while awake on recovery, and the lack of experimental designs manipulating PBs while awake to accelerate recovery. Furthermore, PA and SB domains were rarely investigated, while no research articles focused on the combined effect of 24-h PBs. Eight out of nine studies measured PA, seven SB, and two included sleep. Three studies included training practice into PA measurement by the means of accelerometry. Overall, almost the totality of the athletes achieved recommended PA levels although they sustained prolonged SB. In conclusion, more descriptive researches are needed in different athletic populations and settings. Furthermore, experimental designs aimed at investigating the effects of PBs manipulation on recovery and the putative mechanisms are encouraged

Use of uteroglobin for the engineering of polyvalent, polyspecific fusion proteins

We report a novel strategy to engineer and express stable and soluble human recombinant polyvalent/polyspecific fusion proteins. The procedure is based on the use of a central skeleton of uteroglobin, a small and very soluble covalently linked homodimeric protein that is very resistant to proteolytic enzymes and to pH variations. Using a human recombinant antibody (scFv) specific for the angiogenesis marker domain B of fibronectin, interleukin 2, and an scFv able to neutralize tumor necrosis factor-α, we expressed various biologically active uteroglobin fusion proteins. The results demonstrate the possibility to generate monospecific divalent and tetravalent antibodies, immunocytokines, and dual specificity tetravalent antibodies. Furthermore, compared with similar fusion proteins in which uteroglobin was not used, the use of uteroglobin improved properties of solubility and stability. Indeed, in the reported cases it was possible to vacuum dry and reconstitute the proteins without any aggregation or loss in protein and biological activity

Brainstem NTCP and dose constraints for carbon ion RT—Application and translation from Japanese to European RBE-weighted dose

Background and Purpose: The Italian National Center of Oncological Hadrontherapy (CNAO) has applied dose constraints for carbon ion RT (CIRT) as defined by Japan’s National Institute of Radiological Sciences (NIRS). However, these institutions use different models to predict the relative biological effectiveness (RBE). CNAO applies the Local Effect Model I (LEM I), which in most clinical situations predicts higher RBE than NIRS’s Microdosimetric Kinetic Model (MKM). Equal constraints therefore become more restrictive at CNAO. Tolerance doses for the brainstem have not been validated for LEM I-weighted dose (DLEM I). However, brainstem constraints and a Normal Tissue Complication Probability (NTCP) model were recently reported for MKM-weighted dose (DMKM), showing that a constraint relaxation to DMKM|0.7 cm3 <30 Gy (RBE) and DMKM|0.1 cm3 <40 Gy (RBE) was feasible. The aim of this work was to evaluate the brainstem NTCP associated with CNAO’s current clinical practice and to propose new brainstem constraints for LEM I-optimized CIRT at CNAO. Material and Methods: We reproduced the absorbed dose of 30 representative patient treatment plans from CNAO. Subsequently, we calculated both DLEM I and DMKM, and the relationship between DMKM and DLEM I for various brainstem dose metrics was analyzed. Furthermore, the NTCP model developed for DMKM was applied to estimate the NTCPs of the delivered plans. Results: The translation of CNAO treatment plans to DMKM confirmed that the former CNAO constraints were conservative compared with DMKM constraints. Estimated NTCPs were 0% for all but one case, in which the NTCP was 2%. The relationship DMKM/DLEM I could be described by a quadratic regression model which revealed that the validated DMKM constraints corresponded to DLEM I|0.7 cm3 <41 Gy (RBE) (95% CI, 38–44 Gy (RBE)) and DLEM I|0.1 cm3 <49 Gy (RBE) (95% CI, 46–52 Gy (RBE)). Conclusion: Our study demonstrates that RBE-weighted dose translation is of crucial importance in order to exchange experience and thus harmonize CIRT treatments globally. To mitigate uncertainties involved, we propose to use the lower bound of the 95% CI of the translation estimates, i.e., DLEM I|0.7 cm3 <38 Gy (RBE) and DLEM I|0.1 cm3 <46 Gy (RBE) as brainstem dose constraints for 16 fraction CIRT treatments optimized with LEM I.publishedVersio

Impact of NOx and NH3 Emission Reduction on Particulate Matter across Po Valley: A LIFE-IP-PREPAIR Study

Air quality in Europe continues to remain poor in many areas, with regulation limits often exceeded by many countries. The EU Life-IP PREPAIR Project, involving administrations and environmental protection agencies of eight regions and three municipalities in Northern Italy and Slovenia, was designed to support the implementation of the regional air quality plans in the Po Valley, one of the most critical areas in Europe in terms of pollution levels. In this study, four air quality modelling systems, based on three chemical transport models (CHIMERE, FARM and CAMx) were applied over the Po Valley to assess the sensitivity of PM2.5 concentrations to NOx and NH3 emission reductions. These two precursors were reduced (individually and simultaneously) from 25% up to 75% for a total of 10 scenarios, aimed at identifying the most efficient emission reduction strategies and to assess the non-linear response of PM2.5 concentrations to precursor changes. The multi-model analysis shows that reductions across multiple emission sectors are necessary to achieve optimal results. In addition, the analysis of non-linearities revealed that during the cold season, the efficiency of PM2.5 abatement tends to increase by increasing the emission reductions, while during summertime, the same efficiency remains almost constant, or slightly decreases towards higher reduction strengths. Since the concentrations of PM2.5 are greater in winter than in summer, it is reasonable to infer that significant emission reductions should be planned to maximise reduction effectiveness

Unpredictability of Intravenous Busulfan Pharmacokinetics in Children Undergoing Hematopoietic Stem Cell Transplantation for Advanced Beta Thalassemia: Limited Toxicity with a Dose-Adjustment Policy

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Neuropsychological and psychological functioning aspects in myotonic dystrophy type 1 patients in Italy

Introduction: Myotonic Dystrophy Type 1 (DM1) is an autosomal dominant genetic illness, characterized by a progressive loss of strength. Important deficits in cognitive functioning and a significant prevalence of psychiatric disorders have been previously reported. Methods: A neuropsychological and psychological assessment was carried out in 31 DM1 patients (61% males) in order to measure the cognitive functioning and explore their personality profiles. The MMSE Mini-Mental State Examination, Frontal Assessment Battery (FAB), ENB-2 Battery assessing memory (short term, long term and working memory), integration capacities, visual-spatial ability, attention (selective, divided, shifting/switching) executive functions, praxis, discrimination and logic capabilities and psychopathology Symptom Check List 90-R (SCL-90-R) were administered. The neuropsychological and psychological evaluation of DM1 patients was carried out taking into consideration the clinical parameters (CTG repeat, age at onset, disease duration, Muscular Impairment Rate Scale (MIRS), Medical Research Council Scale (MRC) and the Epworth Sleepiness Scales (EPS)). Results: Regarding psychopathology 19.4% of patients scored a moderate or high level of symptoms intensity index (GSI), 12.9% reported a high number of symptoms (PST) and 16.1% reported a high intensity level of the perceived symptoms (PSDI). Fatigue and daytime sleepiness resulted as being associated with higher levels of psychoticism (PSY). Only 1 patient reported a severe impairment in the spatial and temporal orientation, memory, language, praxis, attention and calculation. Longer disease duration was also associated with cognitive impairment evaluated through ENB-2 (p < 0.05). Discussions and Conclusions: There are indications of the utility of neuropsychological and psychological screening and support for these patients and their families due to the link between disease duration and cognitive performances. A proposal of a clinical protocol, with an illustration of a clinical case report of a family is presented

Can Off-Training Physical Behaviors Influence Recovery in Athletes? A Scoping Review

Recently, the attention on recovery in sport increased enormously although there is lack of scientific evidence on the role of lifestyle in terms of movement [i.e., physical behaviors (PBs)], apart from sleep. Few studies assessed physical activity (PA) and sedentary behavior (SB) in athletes. The aims of this scoping review were to answer to the following scientific questions: (1) How active/inactive are competitive athletes out of training? (2) Do off-training PBs affect recovery, performance, and health? (3) What strategies can be implemented to improve recovery using off-training PBs, apart from sleep? From 1,116 potentially relevant articles, nine were eligible for inclusion in this review. The main issues identified were related to the heterogeneity concerning the types of sports, age category, gender, competitive level, sample size, and instruments/devices adopted, the paucity of studies investigating the effects of PBs while awake on recovery, and the lack of experimental designs manipulating PBs while awake to accelerate recovery. Furthermore, PA and SB domains were rarely investigated, while no research articles focused on the combined effect of 24-h PBs. Eight out of nine studies measured PA, seven SB, and two included sleep. Three studies included training practice into PA measurement by the means of accelerometry. Overall, almost the totality of the athletes achieved recommended PA levels although they sustained prolonged SB. In conclusion, more descriptive researches are needed in different athletic populations and settings. Furthermore, experimental designs aimed at investigating the effects of PBs manipulation on recovery and the putative mechanisms are encouraged