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Patient preferences are gaining recognition among key stakeholders involved in benefit-risk decision-making along the medical product lifecycle. However, one of the main challenges of integrating patient preferences in benefit-risk decision-making is understanding differences in patient preference, which may be attributable to clinical characteristics (eg age, medical history) or psychosocial factors. Measuring the latter may provide valuable information to decision-makers but there is limited guidance regarding which psychological dimensions may influence patient preferences and which psychological instruments should be considered for inclusion in patient preference studies. This paper aims to provide such guidance by advancing evidence and consensus-based recommendations and considerations. Findings of a recent systematic review on psychological constructs having an impact on patients’ preferences and health-related decisions were expanded with input from an expert group (n = 11). These data were then used as the basis for final recommendations developed through two rounds of formal evaluation via an online Delphi consensus process involving international experts in the field of psychology, medical decision-making, and risk communication (n = 27). Three classes of recommendations emerged. Eleven psychological constructs reached consensus to be recommended for inclusion with the strongest consensus existing for health literacy, numeracy, illness perception and treatment-related beliefs. We also proposed a set of descriptive and check-list criteria to appraise available psychological measures to assist researchers and other stakeholders in including psychological assessment when planning patient preference studies. These recommendations can guide researchers and other stakeholders when designing and interpreting patient preference studies with a potential high impact in clinical practice and medical product benefit-risk decision-making processes.

Health locus of control (HLOC) may influence people’s behavior regarding their health as well as their desires to be involved in the medical decision-making. Our study aimed to examine HLOC’s relations with people’s control preferences about the medical decision-making. A total of 153 people filled out the self-administered version of the Control Preference Scale and the Multidimensional Health Locus of Control Scale–form C. The most preferred role is the collaborative one. However, HLOC explained heterogeneity in people’s control preferences: lower scores in external HLOC were related to a greater preference for the active and the collaborative role. From the personalized medicine perspective, an accurate evaluation of the patient’s HLOC could help tailoring the decision-making process within the clinical context.

Background: Patient preferences regarding their involvement in shared treatments decisions is fundamental in clinical practice. Previous evidences demonstrated a large heterogeneity in these preferences. However, only few studies have analysed the influence of patients’ individual differences, contextual and situational qualities, and their complex interaction in explaining this variability. Methods: We assessed the role of the interaction of patient’s sociodemographic and psychological factors with a physician’s gender. Specifically, we focused on patient gender and attitudes toward male or female physicians. One hundred fifty-three people participated in this randomised controlled study and were randomly assigned to one of two experimental conditions in which they were asked to imagine discussing their treatment with a male and a female doctor. Results: Analyses showed an interplay between attitude towards women and the gender of patients and doctors, explaining interindividual variability in patient preferences. Conclusions: In conclusion, patients’ attitudes toward the physicians’ gender constitutes a relevant characteristic that may influence the degree of control patients want to have and the overall patient-physician relationship.

L'attuale pandemia CoViD-19 minaccia il benessere sia fisico che psicologico. Secondo il modello bio-psico-sociale, le Unità di Psicologia Clinica degli Ospedali della Lombardia (Italia) hanno reagito a questo rischio, offrendo interventi diversificati, descritti nel presente contributo. Lo staff medico ha operato in prima linea durante l'emergenza: gli psicologi hanno affrontato le loro esigenze attraverso lavori clinici individuali, sessioni di decompressione e debriefing. Allo stesso tempo, le Unità di Psicologia Clinica hanno supportato i pazienti positivi ospedalizzati conducendo consultazioni psicologiche, sia in reparto che tramite dispositivi. Inoltre, alcuni ospedali hanno attivato linee di assistenza telefonica per rispondere ai bisogni della popolazione e dei familiari, particolarmente vulnerabili durante la malattia del parente e dopo il lutto., The current CoViD-19 pandemic threatens both physical and psychological well-being. According to the bio-psycho-social model, Units of Clinical Psychology of the Hospitals in Lombardy (Italy) reacted to this risk, offering diversified interventions, described in the present contribution. The medical staff operated on the front line during the emergency: psychologists addressed their needs through individual clinical work, sessions of decompression and debriefing. At the same time, Units of Clinical Psychology supported the hospitalized positive patients by conducting psychological consultations, either on the ward or through devices. Moreover, some hospitals activated helplines to address the needs of the population and family members, who were particularly vulnerable during the relative's illness and after the mourning.

The sandwich panel structures have been widely used in many industrial applications because of their high mechanical properties. The middle layer of these structures is very important factor in controlling and enhancing their mechanical performance under various loading scenarios. The re-entrant lattice configurations, are prominent candidates that can be used as the middle layer in such sandwich structures because of several reasons namely the simplicity in tuning their elastic (e.g., values of Poisson’s ratio and elastic stiffness) and plastic (e.g., high strength-to-weight ratio) properties by only adjusting the geometrical features of the constituting unit cells. Here, we investigated the response of a three-layered sandwich plate with a re-entrant core lattice under flexural bending using analytical (i.e., zig-zag theory), computational (i.e., finite element) and experimental tests. We also analyzed the effects of different geometrical parameters (e.g., angle, thicknesses, and length to the height ratio of unit cells) of re-entrant lattice structures on the overall mechanical behavior of sandwich structures. We found that the core structures with auxetic behavior (i.e., negative Poisson’s ratio) resulted in a higher bending strength and a minimum out-of-plane shear stress as compared to those with conventional lattices. Our results can pave way in designing advanced engineered sandwich structures with architected core lattices for aerospace and biomedical applications., Biomaterials & Tissue Biomechanics

Cancer is a deadly disease that can lead to psychological suffering and decreased quality of life (QoL). Personality has been proven to have an effect on QoL and, in particular, Dispositional Optimism (DO) has been studied in relation to overcoming health crisis. The aim of this systematic review is to deepen the state of art of the relationship between QoL and DO in cancer patients. PubMed and Embase databases were systematically searched. Fifteen studies were included with a total of 5,249 cancer patients. All of the studies consider the relationship between DO and QoL, some studies analyze the correlation between the two variables and found a positive association. The majority of the studies investigate the predictive power of DO over QoL and most of them found DO to be predictive of a higher QoL. Results confirmed the association between DO and QoL in a sample of cancer patients. These results could influence the clinical practice as DO has been proven to have a beneficial effect on mental and physical health.

In recent years, virtual reality (VR) has been effectively employed in several settings, ranging from health care needs to leisure and gaming activities. A new application of virtual stimuli appeared in social media: in the documentary ‘I met you’ from the South-Korean Munhwa Broadcasting, a mother made the experience of interacting with the avatar of the seven-year-old daughter, who died four years before. We think that this new application of virtual stimuli should open a debate on its possible implications: it represents contents related to grief, a dramatic and yet natural experience, that can have deep psychological impacts on fragile subjects put in virtual environments. In the present work, possible side-effects, as well as hypothetical therapeutical application of VR for the treatment of mourning, are discussed.

Background: The COVID-19 pandemic is a traumatic individual and collective chronic experience, with tremendous consequences on mental and psychological health that can also be reflected in people's use of words. Psycholinguistic analysis of tweets from Twitter allows obtaining information about people's emotional expression, analytical thinking, and somatosensory processes, which are particularly important in traumatic events contexts. Objective: We aimed to analyze the influence of official Italian COVID-19 daily data (new cases, deaths, and hospital discharges) and the phase of managing the pandemic on how people expressed emotions and their analytical thinking and somatosensory processes in Italian tweets written during the first phases of the COVID-19 pandemic in Italy. Methods: We retrieved 1,697,490 Italian COVID-19-related tweets written from February 24, 2020 to June 14, 2020 and analyzed them using LIWC2015 to calculate 3 summary psycholinguistic variables: emotional tone, analytical thinking, and somatosensory processes. Official daily data about new COVID-19 cases, deaths, and hospital discharges were retrieved from the Italian Prime Minister's Office and Civil Protection Department GitHub page. We considered 3 phases of managing the COVID-19 pandemic in Italy. We performed 3 general models, 1 for each summary variable as the dependent variable and with daily data and phase of managing the pandemic as independent variables. Results: General linear models to assess differences in daily scores of emotional tone, analytical thinking, and somatosensory processes were significant (F6,104=21.53, P<.001, R2= .55; F5,105=9.20, P<.001, R2= .30; F6,104=6.15, P<.001, R2=.26, respectively). Conclusions: The COVID-19 pandemic affects how people express emotions, analytical thinking, and somatosensory processes in tweets. Our study contributes to the investigation of pandemic psychological consequences through psycholinguistic analysis of social media textual

Risk propensity is a multifaced construct that influences many aspects of life, such as decision making. In the present study, the psychometric characteristics of the Risk Propensity Scale (RPS) have been explored for the first time in an Italian sample. The RPS is a 7 item self-report questionnaire measuring people's tendency to take risks. The English RPS has been translated following the forward-backwards translation method, and it was filled out by 199 participants. Since its dimensionality has never been explored before, its factor structure has been analysed with exploratory factor analysis that confirmed the one-factor structure of the questionnaire and the retention of all the items. The Italian version of the RPS has high internal consistency (Cronbach alphas .78), and almost all the items were positively and significantly correlated. The convergent and discriminant validity, analysed by considering the associations with decision-making styles and an implicit measure of risk propensity, were satisfactory. Overall, the Italian version of the RPS is a valid and quick questionnaire useful to measure propensity to take risks in the Italian context.

Background: Psychological health has been one of the aspects affected by the recent COVID-19 pandemic. We aim to evaluate the patterns of Google search for mental distress symptoms of Italian citizens during the various phases of the COVID-19 pandemic. Methods: We assessed Google searches for psychological-health related words. We gathered and analyzed data on daily search queries on depression, anxiety, and insomnia from Google Trends, in a time ranging from the Pre-COVID phase (beginning 25th January 2020) up to the second wave phase (ending 17th October 2020). We performed three general linear models on search trends of the three words and tested whether and to what extent official data about new cases of COVID-19, information searching on new cases, and the government health measures impacted on these trends. Results: Average daily search queries were higher for anxiety, followed by depression and insomnia. General linear models performed to assess differences in daily search queries for anxiety, depression and insomnia were significant, respectively [F(13, 253) = 6.80, P <.001]; [F(13, 253) = 10.25, P <.001]; [F(13, 253) = 6.61, P <.001]. Specifically, daily search queries differed among different phases of managing the COVID-19 outbreak: anxiety [F(5, 253) = 10.35, P <.001, np2 =.17]; depression [F(5, 253) = 13.59, P <.001, np2 =.21]; insomnia [F(5, 253) = 3.52, P =.004, np2 =.07]. Conclusions: Our study contributed to the investigation of online information-seeking behaviors of Italians regarding mental health throughout the entire phase of the pandemic and provides insights on the possible future trends of mental distress during upcoming pandemic phases.

Bone quantity and quality are considered the main predictors of bone mechanical properties (i.e., strength and fracture resistance). These factors deal with the morphology and chemical composition of bone and can be assessed by non-invasive techniques such as dual-energy x-ray absorptiometry (DXA), providing the bone mineral density (BMD) and the trabecular bone score (TBS). These parameters, and in particular BMD, are currently used as clinical predictors of fracture risk but do not provide information regarding the fatigue life. Bone is continuously subjected to fatigue loading and fatigue-induced damage can be crucial in fragility fractures. To probe the effect of fatigue-induced damage on bone microarchitecture and elucidate the effect of such damage on the bone clinical parameters, we combined fatigue testing on ex-vivo porcine trabecular bone samples with DXA measurements and μCT imaging. In addition, we performed interrupted cyclic tests at different load levels and measured fatigue-induced damage accumulation in the form of stiffness degradation. We also highlighted the change of clinical and microstructural parameters during the accumulation of fatigue-induced damage in interrupted fatigue tests. Our results suggest that the parameters obtained from the current non-invasive diagnostic protocols (i.e. μCT and DXA) are not able to assess the amount of fatigue-induced damage. This can be due to the fact that such techniques provide global parameters, whereas fatigue-induced damage is a local phenomenon, closely connected to the microarchitecture., Accepted Author Manuscript, Biomaterials & Tissue Biomechanics

Health locus of control (HLOC) may influence people’s behavior regarding their health as well as their desires to be involved in the medical decision-making. Our study aimed to examine HLOC’s relations with people’s control preferences about the medical decision-making. A total of 153 people filled out the self-administered version of the Control Preference Scale and the Multidimensional Health Locus of Control Scale–form C. The most preferred role is the collaborative one. However, HLOC explained heterogeneity in people’s control preferences: lower scores in external HLOC were related to a greater preference for the active and the collaborative role. From the personalized medicine perspective, an accurate evaluation of the patient’s HLOC could help tailoring the decision-making process within the clinical context.

Background: Patient preferences regarding their involvement in shared treatments decisions is fundamental in clinical practice. Previous evidences demonstrated a large heterogeneity in these preferences. However, only few studies have analysed the influence of patients’ individual differences, contextual and situational qualities, and their complex interaction in explaining this variability. Methods: We assessed the role of the interaction of patient’s sociodemographic and psychological factors with a physician’s gender. Specifically, we focused on patient gender and attitudes toward male or female physicians. One hundred fifty-three people participated in this randomised controlled study and were randomly assigned to one of two experimental conditions in which they were asked to imagine discussing their treatment with a male and a female doctor. Results: Analyses showed an interplay between attitude towards women and the gender of patients and doctors, explaining interindividual variability in patient preferences. Conclusions: In conclusion, patients’ attitudes toward the physicians’ gender constitutes a relevant characteristic that may influence the degree of control patients want to have and the overall patient-physician relationship.

Objectives: To investigate stakeholder perspectives on how patient preference studies (PPS) should be designed and conducted to allow for inclusion of patient preferences in decision-making along the medical product life cycle (MPLC), and how patient preferences can be used in such decision-making. Methods: Two literature reviews and semi-structured interviews (n = 143) with healthcare stakeholders in Europe and the US were conducted; results of these informed the design of focus group guides. Eight focus groups were conducted with European patients, industry representatives and regulators, and with US regulators and European/Canadian health technology assessment (HTA) representatives. Focus groups were analyzed thematically using NVivo. Results: Stakeholder perspectives on how PPS should be designed and conducted were as follows: 1) study design should be informed by the research questions and patient population; 2) preferred treatment attributes and levels, as well as trade-offs among attributes and levels should be investigated; 3) the patient sample and method should match the MPLC phase; 4) different stakeholders should collaborate; and 5) results from PPS should be shared with relevant stakeholders. The value of patient preferences in decision-making was found to increase with the level of patient preference sensitivity of decisions on medical products. Stakeholders mentioned that patient preferences are hardly used in current decision-making. Potential applications for patient preferences across industry, regulatory and HTA processes were identified. Four applications seemed most promising for systematic integration of patient preferences: 1) benefit-risk assessment by industry and regulators at the marketing-authorization phase; 2) assessment of major contribution to patient care by European regulators; 3) cost-effectiveness analysis; and 4) multi criteria decision analysis in HTA. Conclusions: The value of patient preferences for decision-making depends on

From an interview with Nucci Moneta, and the discover of his precious scarabook, born this work.

From an interview with two artist Borondo and Tresoldi born the narrative of a masterpiece: Chained

from an interview with Luca Bigazzi, the photographer, born this text.

A brief story about Fondazione Cineteca Italiana and MIC interactive cinema museum

Objectives: To investigate stakeholder perspectives on how patient preference studies (PPS) should be designed and conducted to allow for inclusion of patient preferences in decision-making along the medical product life cycle (MPLC), and how patient preferences can be used in such decision-making. Methods: Two literature reviews and semi-structured interviews (n = 143) with healthcare stakeholders in Europe and the US were conducted; results of these informed the design of focus group guides. Eight focus groups were conducted with European patients, industry representatives and regulators, and with US regulators and European/Canadian health technology assessment (HTA) representatives. Focus groups were analyzed thematically using NVivo. Results: Stakeholder perspectives on how PPS should be designed and conducted were as follows: 1) study design should be informed by the research questions and patient population; 2) preferred treatment attributes and levels, as well as trade-offs among attributes and levels should be investigated; 3) the patient sample and method should match the MPLC phase; 4) different stakeholders should collaborate; and 5) results from PPS should be shared with relevant stakeholders. The value of patient preferences in decision-making was found to increase with the level of patient preference sensitivity of decisions on medical products. Stakeholders mentioned that patient preferences are hardly used in current decision-making. Potential applications for patient preferences across industry, regulatory and HTA processes were identified. Four applications seemed most promising for systematic integration of patient preferences: 1) benefit-risk assessment by industry and regulators at the marketing-authorization phase; 2) assessment of major contribution to patient care by European regulators; 3) cost-effectiveness analysis; and 4) multi criteria decision analysis in HTA. Conclusions: The value of patient preferences for decision-making depends on

Mechanical metamaterials are a sub-category of designer materials where the geometry of the material at the small-scale is rationally designed to give rise to unusual properties and functionalities. Here, we propose the concept of "action-at-a-distance" metamaterials where a specific pattern of local deformation is programmed into the fabric of (cellular) materials. The desired pattern of local actuation could then be achieved simply through the application of one single global and far-field force. We proposed graded designs of auxetic and conventional unit cells with changing Poisson's ratios as a way of making "action-at-a-distance" metamaterials. We explored five types of graded designs including linear, two types of radial gradients, checkered, and striped. Specimens were fabricated with indirect additive manufacturing and tested under compression, tension, and shear. Full-field strain maps measured with digital image correlation confirmed different patterns of local actuation under similar far-field strains. These materials have potential applications in soft (wearable) robotics and exosuits., Biomaterials & Tissue Biomechanics

Architectured materials with rationally designed geometries could be used to create mechanical metamaterials with unprecedented or rare properties and functionalities. Here, we introduce "shape-matching" metamaterials where the geometry of cellular structures comprising auxetic and conventional unit cells is designed so as to achieve a pre-defined shape upon deformation. We used computational models to forward-map the space of planar shapes to the space of geometrical designs. The validity of the underlying computational models was first demonstrated by comparing their predictions with experimental observations on specimens fabricated with indirect additive manufacturing. The forward-maps were then used to devise the geometry of cellular structures that approximate the arbitrary shapes described by random Fourier's series. Finally, we show that the presented metamaterials could match the contours of three real objects including a scapula model, a pumpkin, and a Delft Blue pottery piece. Shape-matching materials have potential applications in soft robotics and wearable (medical) devices., Biomaterials & Tissue Biomechanics

Up until recently, the rational design of mechanical metamaterials has usually involved devising geometrical arrangements of micro-architectures that deliver unusual properties on the macro-scale. A less explored route to rational design is spatially distributing materials with different properties within lattice structures to achieve the desired mechanical properties. Here, we used computational models and advanced multi-material 3D printing techniques to rationally design and additively manufacture multi-material cellular solids for which the elastic modulus and Poisson's ratio could be independently tailored in different (anisotropic) directions. The random assignment of a hard phase to originally soft cellular structures with an auxetic, zero Poisson's ratio, and conventional designs allowed us to cover broad regions of the elastic modulus-Poisson's ratio plane. Patterned designs of the hard phase were also used and were found to be effective in the independent tuning of the elastic properties. Close inspection of the strain distributions associated with the different types of material distributions suggests that locally deflected patterns of deformation flow and strain localizations are the main underlying mechanisms driving the above-mentioned adjustments in the mechanical properties., Biomaterials & Tissue Biomechanics

Architectured materials with rationally designed geometries could be used to create mechanical metamaterials with unprecedented or rare properties and functionalities. Here, we introduce "shape-matching" metamaterials where the geometry of cellular structures comprising auxetic and conventional unit cells is designed so as to achieve a pre-defined shape upon deformation. We used computational models to forward-map the space of planar shapes to the space of geometrical designs. The validity of the underlying computational models was first demonstrated by comparing their predictions with experimental observations on specimens fabricated with indirect additive manufacturing. The forward-maps were then used to devise the geometry of cellular structures that approximate the arbitrary shapes described by random Fourier's series. Finally, we show that the presented metamaterials could match the contours of three real objects including a scapula model, a pumpkin, and a Delft Blue pottery piece. Shape-matching materials have potential applications in soft robotics and wearable (medical) devices., Biomaterials & Tissue Biomechanics

Mechanical metamaterials are a sub-category of designer materials where the geometry of the material at the small-scale is rationally designed to give rise to unusual properties and functionalities. Here, we propose the concept of "action-at-a-distance" metamaterials where a specific pattern of local deformation is programmed into the fabric of (cellular) materials. The desired pattern of local actuation could then be achieved simply through the application of one single global and far-field force. We proposed graded designs of auxetic and conventional unit cells with changing Poisson's ratios as a way of making "action-at-a-distance" metamaterials. We explored five types of graded designs including linear, two types of radial gradients, checkered, and striped. Specimens were fabricated with indirect additive manufacturing and tested under compression, tension, and shear. Full-field strain maps measured with digital image correlation confirmed different patterns of local actuation under similar far-field strains. These materials have potential applications in soft (wearable) robotics and exosuits., Biomaterials & Tissue Biomechanics

Crumpled-based materials are relatively easy to fabricate and show robust mechanical properties for practical applications, including meta-biomaterials design aimed for improved tissue regeneration. For such requests, however, the structure needs to be porous. We introduce a crumpled holey thin sheet as a robust bio-metamaterial and measure the mechanical response of a crumpled holey thin Mylar sheet as a function of the hole size and hole area fraction. We also study the formation of patterns of crease lines and ridges. The area fraction largely dominated the crumpling mechanism. We also show, the crumpling exponents slightly increases with increasing the hole area fraction and the total perimeter of the holes. Finally, hole edges were found to limit and guide the propagation of crease lines and ridges., Biomaterials & Tissue Biomechanics

The elastic properties of mechanical metamaterials are direct functions of their topological designs. Rational design approaches based on computational models could, therefore, be used to devise topological designs that result in the desired properties. It is of particular importance to independently tailor the elastic modulus and Poisson's ratio of metamaterials. Here, we present patterned randomness as a strategy for independent tailoring of both properties. Soft mechanical metamaterials incorporating various types of patterned randomness were fabricated using an indirect additive manufacturing technique and mechanically tested. Computational models were also developed to predict the topology-property relationship in a wide range of proposed topologies. The results of this study show that patterned randomness allows for independent tailoring of the elastic properties and covering a broad area of the elastic modulus-Poisson's ratio plane. The uniform and homogenous topologies constitute the boundaries of the covered area, while topological designs with patterned randomness fill the enclosed area., Biomaterials & Tissue Biomechanics

Crumpled-based materials are relatively easy to fabricate and show robust mechanical properties for practical applications, including meta-biomaterials design aimed for improved tissue regeneration. For such requests, however, the structure needs to be porous. We introduce a crumpled holey thin sheet as a robust bio-metamaterial and measure the mechanical response of a crumpled holey thin Mylar sheet as a function of the hole size and hole area fraction. We also study the formation of patterns of crease lines and ridges. The area fraction largely dominated the crumpling mechanism. We also show, the crumpling exponents slightly increases with increasing the hole area fraction and the total perimeter of the holes. Finally, hole edges were found to limit and guide the propagation of crease lines and ridges., Biomaterials & Tissue Biomechanics

The elastic properties of mechanical metamaterials are direct functions of their topological designs. Rational design approaches based on computational models could, therefore, be used to devise topological designs that result in the desired properties. It is of particular importance to independently tailor the elastic modulus and Poisson's ratio of metamaterials. Here, we present patterned randomness as a strategy for independent tailoring of both properties. Soft mechanical metamaterials incorporating various types of patterned randomness were fabricated using an indirect additive manufacturing technique and mechanically tested. Computational models were also developed to predict the topology-property relationship in a wide range of proposed topologies. The results of this study show that patterned randomness allows for independent tailoring of the elastic properties and covering a broad area of the elastic modulus-Poisson's ratio plane. The uniform and homogenous topologies constitute the boundaries of the covered area, while topological designs with patterned randomness fill the enclosed area., Biomaterials & Tissue Biomechanics

Crumpled-based materials are relatively easy to fabricate and show robust mechanical properties for practical applications, including meta-biomaterials design aimed for improved tissue regeneration. For such requests, however, the structure needs to be porous. We introduce a crumpled holey thin sheet as a robust bio-metamaterial and measure the mechanical response of a crumpled holey thin Mylar sheet as a function of the hole size and hole area fraction. We also study the formation of patterns of crease lines and ridges. The area fraction largely dominated the crumpling mechanism. We also show, the crumpling exponents slightly increases with increasing the hole area fraction and the total perimeter of the holes. Finally, hole edges were found to limit and guide the propagation of crease lines and ridges.

Basalt reinforced composites are recently developed materials. These mineral amorphousfibres are a valid alternative to carbon fibres for their lower cost, and to glass fibres for their strength.In order to use basalt reinforced composites for structural applications, it is necessary to perform amechanical characterization. With this aim in the present work experimental results of several staticand fatigue tests are described. Two polymeric matrices are taken into account, vinylester and epoxy,to assess their influence on the evaluated parameters. In parallel to these mechanical tests, also thethermal answer of the specimens to mechanical loads is evaluated by means of thermography. Thisexperimental technique allows defining the composite local heating during the application ofmechanical loads and its behaviour in details. Final discussion on obtained results is proposedfocussing the attention on basalt fibre composite behaviour, and comparing mechanical properties ofBFRP with other composite materials in glass and carbon fibres., QC 20120316. Updated from in press to published.

QC 20111128

QC 20111125

Decreased fatty acid beta-oxidation in riboflavin-responsive, multiple acylcoenzyme A dehydrogenase-deficient patients is associated with an increase in uncoupling protein-3. Russell AP, Schrauwen P, Somm E, Gastaldi G, Hesselink MK, Schaart G, Kornips E, Lo SK, Bufano D, Giacobino JP, Muzzin P, Ceccon M, Angelini C, Vergani L. Department of Medical Biochemistry, University of Geneva Medical Center, 1206 Geneva, Switzerland. aaron.russell@crr-suva.ch Riboflavin-responsive, multiple acylcoenzyme A dehydrogenase deficiency (RR-MAD), a lipid storage myopathy, is characterized by, among others, a decrease in fatty acid (FA) beta-oxidation capacity. Muscle uncoupling protein 3 (UCP3) is up-regulated under conditions that either increase the levels of circulating free FA and/or decrease FA beta-oxidation. Using a relatively large cohort of seven RR-MAD patients, we aimed to better characterize the metabolic disturbances of this disease and to explore the possibility that it might increase UCP3 expression. A battery of biochemical and molecular tests were performed, which demonstrated decreases in FA beta-oxidation and in the activities of respiratory chain complexes I and II. These metabolic alterations were associated with increases of 3.1- and 1.7-fold in UCP3 mRNA and protein expression, respectively. All parameters were restored to control values after riboflavin treatment. We postulate that the up-regulation of UCP3 in RR-MAD is due to the accumulation of muscle FA/acylCoA. RR-MAD is an optimal model to support the hypothesis that UCP3 is involved in the outward translocation of an excess of FA from the mitochondria and to show that, in humans, the effects of FA on UCP3 expression are direct and independent of fatty acid beta-oxidation.

Decreased fatty acid beta-oxidation in riboflavin-responsive, multiple acylcoenzyme A dehydrogenase-deficient patients is associated with an increase in uncoupling protein-3. Russell AP, Schrauwen P, Somm E, Gastaldi G, Hesselink MK, Schaart G, Kornips E, Lo SK, Bufano D, Giacobino JP, Muzzin P, Ceccon M, Angelini C, Vergani L. Department of Medical Biochemistry, University of Geneva Medical Center, 1206 Geneva, Switzerland. aaron.russell@crr-suva.ch Riboflavin-responsive, multiple acylcoenzyme A dehydrogenase deficiency (RR-MAD), a lipid storage myopathy, is characterized by, among others, a decrease in fatty acid (FA) beta-oxidation capacity. Muscle uncoupling protein 3 (UCP3) is up-regulated under conditions that either increase the levels of circulating free FA and/or decrease FA beta-oxidation. Using a relatively large cohort of seven RR-MAD patients, we aimed to better characterize the metabolic disturbances of this disease and to explore the possibility that it might increase UCP3 expression. A battery of biochemical and molecular tests were performed, which demonstrated decreases in FA beta-oxidation and in the activities of respiratory chain complexes I and II. These metabolic alterations were associated with increases of 3.1- and 1.7-fold in UCP3 mRNA and protein expression, respectively. All parameters were restored to control values after riboflavin treatment. We postulate that the up-regulation of UCP3 in RR-MAD is due to the accumulation of muscle FA/acylCoA. RR-MAD is an optimal model to support the hypothesis that UCP3 is involved in the outward translocation of an excess of FA from the mitochondria and to show that, in humans, the effects of FA on UCP3 expression are direct and independent of fatty acid beta-oxidation.

Item does not contain fulltext, Two unrelated adult males, aged 36 (patient 1) and 25 (patient 2) years, presented with subacute carnitine-deficient lipid storage myopathy that was totally and partly responsive to riboflavin supplementation in the two patients, respectively. Plasma acyl-carnitine and urinary organic acid profiles indicated multiple acyl coenzyme A dehydrogenase deficiency, which was mild in patient 1 and severe in patient 2. The activities of short-chain and medium-chain acyl coenzyme A dehydrogenases in mitochondrial fractions were decreased, especially in patient 2. This was in agreement with Western blotting results. Flavin-dependent complexes I and II were studied by immunoblotting and densitometric quantification of two-dimensional electrophoresis with comparable results. Complex I was present in normal amounts in both patients, whereas complex II was decreased only in the pretherapy muscle of patient 2. Flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) concentrations in muscle and isolated mitochondria, and the activity of mitochondrial FAD pyrophosphatase, showed that patient 1 had low levels of FAD (46%) and FMN (49%) in mitochondria, with a significant increase (P < 0.01) in mitochondrial FAD pyrophosphatase (273%) compared with controls. Patient 2 had similar low levels of FAD and FMN in both total muscle (FAD and FMN 22% of controls) and mitochondria (FAD 26%; FMN 16%) and normal activity of mitochondrial FAD pyrophosphatase. All of these biochemical parameters were either totally or partly corrected after riboflavin therapy.

Item does not contain fulltext, Two unrelated adult males, aged 36 (patient 1) and 25 (patient 2) years, presented with subacute carnitine-deficient lipid storage myopathy that was totally and partly responsive to riboflavin supplementation in the two patients, respectively. Plasma acyl-carnitine and urinary organic acid profiles indicated multiple acyl coenzyme A dehydrogenase deficiency, which was mild in patient 1 and severe in patient 2. The activities of short-chain and medium-chain acyl coenzyme A dehydrogenases in mitochondrial fractions were decreased, especially in patient 2. This was in agreement with Western blotting results. Flavin-dependent complexes I and II were studied by immunoblotting and densitometric quantification of two-dimensional electrophoresis with comparable results. Complex I was present in normal amounts in both patients, whereas complex II was decreased only in the pretherapy muscle of patient 2. Flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) concentrations in muscle and isolated mitochondria, and the activity of mitochondrial FAD pyrophosphatase, showed that patient 1 had low levels of FAD (46%) and FMN (49%) in mitochondria, with a significant increase (P < 0.01) in mitochondrial FAD pyrophosphatase (273%) compared with controls. Patient 2 had similar low levels of FAD and FMN in both total muscle (FAD and FMN 22% of controls) and mitochondria (FAD 26%; FMN 16%) and normal activity of mitochondrial FAD pyrophosphatase. All of these biochemical parameters were either totally or partly corrected after riboflavin therapy.

Wobbler mice display forelimb weakness, altered paw positioning, reduced running speed, muscle atrophy and motor neuron loss; co-treatment with glycosaminoglycans and insulin-like growth factor-I counteracts the progression of the disease. Reportedly, treatment with glycosaminoglycans or insulin-like growth factor-I slows the early stages of progressive forelimb dysfunction in wobbler mice. Our aim was to study whether the combination of these two drugs would result in greater neuroprotective effects. In a group of wobbler mice, combined treatment with daily s.c. administration of 20 microg/kg insulin-like growth factor-I and 1 mg/kg glycosaminoglycans was begun upon diagnosis at three weeks of age and continued for the next six weeks. This treatment halted motor neuron loss and markedly reduced the decay of forelimb muscle morphometry and function. Moreover, the mouse phenotype itself was strikingly improved. The effect of the combination treatment was significantly higher than that of the single drugs, even at a dosage as high as 1 mg/kg insulin-like growth factor-I. The ability of the insulin-like growth factor-I/glycosaminoglycans pharmacological cocktail to arrest the progression of motor neuron disease in wobbler mice and the safety of the low dose of insulin-like growth factor-I used hold promise that this combination might represent a novel approach for the treatment of motor neuron disease and peripheral neuropathies.

The present study shows that sciatic nerve crush in 2-day-old rats causes extensor digitorum longus (EDL) muscle atrophy and motor neuron loss and that treatment with glycosaminoglycans (GAGs) promotes muscle reinnervation, motor neuron survival, and markedly increases insulin-like growth factor-I (IGF-I) content in the denervated muscles. EDL muscle denervation-induced atrophy in saline-treated rats is progressive and reaches the greatest extent at 42 days after birth, which correlates with reduced EDL weight growth. There is also a partial reinnervation as shown by the number of reinnervated EDL muscle fibers (65.4% of control) and by the poor restoration of the indirect isometric twitch tension (62% of control) that is further reduced under tetanic stimulation (34% of control). The number of surviving motor neurons that innervate EDL muscle drops from 55 +/- 3 to 29 +/- 8. In GAGs-treated 42-day-old rats, the effects of neonatal nerve lesioning on EDL muscle atrophy and denervation are successfully reversed, and the isometric twitch tension and the capacity to hold tetanic stimulation are restored to almost control levels. The number of surviving EDL motor neurons is also increased to 43 +/- 4. Treatment with GAGs selectively affects IGF-I content in denervated hindlimb muscles, which is augmented from 7.02 +/- 0.71 ng/mg tissue to 25.72 +/- 0.7 in the EDL and from 3.2 +/- 0.18 to a robust 211 +/- 9.6 in the soleus.

This study shows that glycosaminoglycans promote muscle reinnervation following neonatal sciatic nerve injury. Such an effect appears to be mediated by insulin-like growth factor-1. The glycosaminoglycan moiety of proteoglycans is a constituent of the basal lamina active on nerve regeneration by means of the interaction with laminin and with several growth factors. We have previously shown that supplementation of glycosaminoglycans affects neuronal degeneration and regeneration. In this study we report that following neonatal lesion of the rat sciatic nerve glycosaminoglycan treatment promoted extensor digitorum longus muscle reinnervation with consequent improvement of muscle morphology. In saline-treated rats, reinnervation was only partial and there was a marked muscle fibre atrophy. In addition glycosaminoglycan treatment of lesioned rats increased insulin-like growth factor-I messenger RNA and protein in the reinnervated muscle, and insulin-like growth factor-I and insulin-like growth factor binding protein-3 plasma levels. Similarly, treatment of nerve lesioned rats with insulin-like growth factor-I promoted muscle reinnervation and prevention of muscle fibre atrophy, higher levels of insulin-like growth factor-I in the reinnervated muscle and of insulin-like growth factor-I and insulin-like growth factor binding proteins in plasma. These data suggest that glycosaminoglycans are potent stimulants of muscle reinnervation and that their effects may be mediated by increased levels of insulin-like growth factor-I.