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Additive Manufacturing provides unprecedented opportunities for designing and producing intricate, architected materials with exceptional properties while maintaining reduced weight. One of the most straightforward ways to create such structures is to mimic the lattice geometries of crystals. New approaches are now exploring how to influence the behaviour of these structures by mimicking not only the crystal arrangement but also peculiar mechanisms occurring at the crystallographic scale. In such a context, this study first presents a hexagonal close-packed (HCP) lattice derived from the homonymous crystal structures of Ti or Zr metals. Subsequently, the twinning phenomenon responsible for the plastic deformation of these metals is reproduced geometrically into this structure to improve its energy absorption capability. Compressive tests conducted on 3D-printed samples confirm such a hypothesis: the specific energy absorption of twinned structures is significantly higher than that of the equivalent HCP ones, with an increase of up to 24.3%. Introducing twinned regions stabilises the plastic deformation despite a limited reduction of the peak stress. Therefore, replicating the twinning metallurgical mechanism within an HCP-inspired metamaterial proves successful, further validating the approach of mimicking and transferring atomic phenomena at a different scale to tailor the properties of architected materials.

Aging represents a decline in function over time. Polyphenols are dietary antioxidants that could exert beneficial effects on aging. This study investigated the effects of dietary supplementation with two extracts from Thymbra spicata L. aerial parts on the lifespan, body-weight control, and antioxidant responses of Drosophila melanogaster cohorts distinguished for age and sex. The aqueous extract extended the lifespan of young female flies, and this pro-longevity potential was associated with a reduction in the body-weight gain. Furthermore, the aqueous extract promoted the antioxidant defense when young females were exposed to Paraquat by reducing oxidative stress and mortality. This study provides the first insight into the beneficial effects of T. spicata supplementation in an animal model, suggesting that the healthy effect could mainly depend on strengthening the antioxidant defenses which reflect on the lifespan. Further investigations will better clarify the mechanisms and potential of T. spicata as nutraceutics in anti-aging strategies.

Plants and plant extracts are a relevant source of bioactive compounds widely employed as functional foods. In the Mediterranean area, the shrub Sarcopoterium spinosum is traditionally used as an herbal medicine for weight loss and a diabetes treatment. Inflammation is a protective mechanism involved in the development of many pathological conditions, including cardiovascular diseases. The present study aimed to investigate in vitro the antioxidant and cytoprotective properties of an ethanolic extract from S. spinosum fruits (SEE) in a cellular model of endothelium dysfunction. Corilagin and quercetin are two polyphenols abundant in SEE and were tested for comparison. The exposure of HECV cells for 24 h to 30 µM hydrogen peroxide (H2O2) lead to an oxidative stress condition. When HECV cells were treated with 10 µg/mL of SEE or single compounds after or before the oxidative insult, the results showed their ability to (i) decrease the reactive oxygen species (ROS) production quantified using fluorometric analysis and the lipid peroxidation measured with a spectrophotometric assay; (ii) rescue both the glutathione reduced to oxidized (GSH/GSSG) ratio and nitric oxide impair and the protein denaturation; and (iii) accelerate the wound repair measured using a T-scratch assay. Taken together, our findings indicate that the ethanolic extract from S. spinosum fruits could be a potential candidate for nutraceutical application.

Abstract 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

Interest in plant-based food has grown in recent years due to their primary prevention potential. Za’atar, an ancient and popular Lebanese herbal mixture, might disclose relevant clinical interest, due to the well-known intrinsic properties of its individual components. Za’atar mixture contain Origanum syriacum (Lebanese thyme), Thymbra spicata (Wild thyme), Rhus coriaria (Sumac), and Sesamum indicum (Sesame). Here we explored the history, composition, general employment, and bio-active aspects of Za’atar through available in vitro, animal, and clinical trials evidence to depict its possible role as an innovative nutraceutical tool. The combined action of Za’atar constituents is able to generate comprehensive beneficial effects on several common pathogenic pathways underlying chronic cardio-metabolic diseases and cancer. However, main available evidence derives from animal and in vitro studies. Thus, further human studies are needed to fully characterize Za’atar as a preventive and curative tool.

Sumac (Rhus coriaria L.) is a commonly used spice in the Mediterranean region and considered as healthy food ingredients. The beneficial value of sumac is well documented in folk medicine. Accumulating data explored the phytochemical, nutritional and therapeutic proprieties suggesting sumac as a potential functional food. Here, we discuss the general and scientific aspects of sumac. Sumac is rich in different polyphenolic compounds such as flavonoids, tannins, and phenolic acids. The potential therapeutic effects of sumac have been studied in various cellular and animal models, as well as in human. These reports suggest that Sumac has potential effect against oxidative stress, inflammation, obesity, hyperglycemia, hypercholesterolemia, and hyperlipidemia, which represent key pathogenic mechanisms contributing to cardio-metabolic, liver, and cancer diseases. Clinical studies using sumac or its major compounds, suggest that this herbal product may represent a useful therapeutic tool in the management of metabolic-related conditions such as liver-atherosclerosis complications.

Objective: The study aimed to explore the psychological symptoms and the readiness to fight the pandemic of the new generation of healthcare professionals: medical and other healthcare degree students.Methods: We enrolled 509 medical and healthcare-related degree students during the second outbreak of COVID-19 in Italy. We have examined their psychological symptoms using the 12-item General Health Questionnaire (GHQ-12) and their readiness to fight the pandemic together with their academic career status, their relationship with the university, and their emotional reactions to the pandemic with Visual Analog Scales.Results: We retrieved a GHQ mean of 21.65 (SD = 40.63) and readiness to fight the pandemic mean of 53.58 (SD = 31.49). Perceived control affects variables: a negative effect on psychological symptoms and a positive effect on the willingness to fight the pandemic. The other variables with an impact were stress, loneliness, and anger that had a significant and positive impact on psychological symptoms. Age and concern for patients had a significant positive impact on readiness to fight for the pandemic, while years of attendance had a significant but negative impact.Conclusion: Universities and Institutions should consider the impact of the pandemic on students, in particular, for its effect on their mental health.

BackgroundThe 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. ObjectiveWe 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. MethodsWe 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. ResultsGeneral linear models to assess differences in daily scores of emotional tone, analytical thinking, and somatosensory processes were significant (F6,104=21.53, P

Plants or plant extracts are widely investigated for preventing/counteracting several chronic disorders. The oral route is the most common route for nutraceutical and drug administration. Currently, it is still unclear as to whether and how the pattern of phenolic compounds (PCs) found in the plants as well as their bioactivity could be modified during the gastrointestinal transit. Recent studies have revealed antioxidant and anti-steatotic properties of Thymbra spicata. Here, we investigated the possible loss of phytochemicals that occurs throughout the sequential steps of a simulated in vitro gastrointestinal (GI) digestion of aqueous and ethanolic extracts of aerial parts of T. spicata. Crude, digested, and dialyzed extracts were characterized in terms of their phenolic profile and biological activities. Total contents of carbohydrates, proteins, PCs, flavonoids, and hydroxycinnamic acids were quantified. The changes in the PC profile and in bioactive compounds upon the simulated GI digestion were monitored by HPLC–MS/MS analysis. The antioxidant activity was measured by different spectrophotometric assays, and the antiproliferative potential was assessed by using three representative human cancer cell lines. We observed that the simulated GI digestion reduced the phytochemical contents in both aqueous and ethanolic T. spicata extracts and modified the PC profile. However, T. spicata extracts improved their antioxidant potential after digestion, while a partial reduction in the antiproliferative activity was observed for the ethanolic extract. Therefore, our results could provide a scientific basis for the employment of T. spicata extract as valuable nutraceutical.

Numerous plants, plant extracts, and plant-derived compounds are being explored for their beneficial effects against overweight and liver diseases. Obesity is associated with the increased prevalence of non-alcoholic fatty liver disease (NAFLD), becoming the most common liver disease in Western countries. Obesity and NAFLD are closely associated with many other metabolic alternations such as insulin resistance, diabetes mellitus, and cardiovascular diseases. Many herbs of the Lamiaceae family are widely employed as food and spices in the Mediterranean area, but also in folk medicine, and their use for the management of metabolic disorders is well documented. Hereby, we summarized the scientific results of the medicinal and nutraceutical potential of plants from the Lamiaceae family for prevention and mitigation of overweight and fatty liver. The evidence indicates that Lamiaceae plants may be a cost-effective source of nutraceuticals and/or phytochemicals to be used in the management of metabolic-related conditions such as obesity and NAFLD. PubMed, Google Scholar, Scopus, and SciFinder were accessed to collect data on traditional medicinal plants, compounds derived from plants, their reported anti-obesity mechanisms, and therapeutic targets.

In mammalian cells, the content of polyamines is tightly regulated. Polyamines, including spermine, spermidine and putrescine, are involved in many cellular processes. Spermine oxidase specifically oxidizes spermine, and its deregulated activity has been reported to be linked to brain pathologies involving neuron damage. Spermine is a neuromodulator of a number of ionotropic glutamate receptors and types of ion channels. In this respect, the Dach-SMOX mouse model overexpressing spermine oxidase in the neocortex neurons was revealed to be a model of chronic oxidative stress, excitotoxicity and neuronal damage. Reactive astrocytosis, chronic oxidative and excitotoxic stress, neuron loss and the susceptibility to seizure in the Dach-SMOX are discussed here. This genetic model would help researchers understand the linkage between polyamine dysregulation and neurodegeneration and unveil the roles of polyamines in the crosstalk between astrocytes and neurons in neuroprotection or neurodegeneration.

This study aimed at exploring the emotional reaction that medical students (MS) and professionals have faced during the COVID-19 pandemic and investigating the differences between the two groups. A total of 362 MS and 330 professionals filled in an online survey during the second outbreak of the COVID-19 pandemic in Italy. The outcome measures were psychological distress with the General Health Questionnaire, stress, fear for themselves, fear for family members and cohabitants, perceived control, anger, loneliness, and feeling abandoned by institutions with Visual Analog Scales (VAS) and two open-ended questions about their perceived difficulties and the perceived consequences of the pandemic. The results showed that the level of distress among the two groups was above the threshold (MS mean: 21.85; professionals mean: 21.25). The means of the VAS of MS and professionals showed different results for the two groups, and we analyzed them with independent samples t-tests and linear regressions. MS reported higher levels of perceived loneliness (t(673.177) = −1.970, p < 0.05), while physicians reported more fear for themselves (t(655.183) = 4.799, p < 0.001), anger (t(690) = 2.096, p < 0.05), and feeling abandoned by the institutions (t(690) = 7.296, p < 0.001). The open questions were analyzed considering the most frequent words used to describe their perceived difficulties and consequences; the specificity analysis emphasizes the differences in the words used by the two groups. In conclusion, MS and physicians reported similar levels of psychological symptoms. Physicians were mostly worried about themselves, they were afraid of getting infected, while MS suffered from loneliness and the missed possibilities concerning their education.

Obesity is a major risk factor for metabolic dysfunction such as non-alcoholic fatty liver disease (NAFLD). The NAFLD spectrum ranges from simple steatosis, to steatohepatitis, fibrosis, and cirrhosis. The aim of this study is to characterize the grade of steatosis being associated with overnutrition and obesity, both at the level of single hepatocyte and whole liver, and to correlate it with the hepatocyte/liver stiffness and dysfunction. For the in vivo study, 60 subjects were enrolled and grouped based on the stage of liver steatosis/fibrosis according to biochemical analyses, liver ultrasonography (USG) and acoustic radiation force impulse shear wave elastography (ARFI-SWE). For single hepatocyte analyses we employed in vitro models of moderate and severe steatosis on which to assess the single cell biomechanics by Single Cell Force Spectroscopy (SCFS) and Quantitative Phase Microscopy (QPM). Results show that in vivo liver stiffness depends mainly on the extent of fat accumulation and not on fibrosis. These results parallel the in vitro observations showing that hepatocyte stiffness and dysfunction increase with increasing fat accumulation and lipid droplet enlargement. Our findings indicate that the extent of steatosis markedly affects the biomechanical properties of both liver and single hepatocytes thus proving insights about the role of modulation of liver/hepatocyte elasticity as a physical mechanism transducing the obesity-dependent excess of plasmatic lipids towards liver steatosis and dysfunction.

ObjectiveThe study aimed to investigate the mental health and emotional reaction of physicians working during phase 1 of the COVID-19 pandemic in Italy.MethodsA total of 458 Italian Health Care Workers (HCWs) working during phases 1 of the COVID-19 outbreak were voluntarily enlisted in the study and recruited with the snowball technique through an online survey. We examined our variables with the General Health Questionnaire – 12 and with Visual Analog Scales.ResultsThe sample has a high level of psychological distress 21.26 (SD = 4.46), the emotional reaction was characterized by high level of fear for family members and cohabitants (M = 77.67, SD = 27.16) and patients (M = 67.16, SD = 27.71). Perceived control, fear for patients, and for family members and cohabitants, feeling alone and anger all contribute to a decreased mental health in Italian physicians (R2 = 0.285, p < 0.001).ConclusionItalian HCWs’ mental health and emotional reaction have to be considered to prevent high risk of burnout and post-traumatic stress disorder (PTSD). It becomes pivotal in the next months to implement a tailored psychological intervention to take care of HCWs and to prevent costly consequences for them, patients, and the healthcare system.

Aim of the study: Genetic testing is becoming increasingly common in clinical practice and health management; nonetheless, little is known about how the population approaches genetic services through private companies. Our study aims to describe socio-demographic aspects, health-related habits, and overall beliefs and knowledge about genetic risk and testing in a population of Italian citizens who decided to undergo a genetic examination through a private genetic company.Study design: A sample of 152 clients from an Italian private genetic company completed an ad-hoc survey from September 2016 to February 2018, addressing socio-demographic data, health habits, psycho-physic condition, perceived utility of genetic results, decision purposes about data sharing, and behavioral changes after results.Results: Participants (mean age 42.4) were predominantly female (82.2%) and were overall well-educated. Their main source of information were physicians (77%), and 41.1% entrusted the management of results to the same. Thirty-eight percentage underwent genetic analysis for cancer predisposition, 31.3% for fertility problems, 24% for dietary or intolerance issues in the period of enrolment. More than half of them (62.7%) reported a family history of the disease, and overall 69% had a current or past experience with a disease. Clients perceived the genetic screening as useful to adopt behaviors that may prevent disease onset (37.7%), to know their “real health status” (27.4%), and to adopt health-related behaviors (23.3%). 62.8% claimed they were motivated to change behaviors after results (healthier diet, practice exercise, medical checks), and they wanted to share results with their physician and family members.Discussion/Conclusion: The overview of consumers' profiles in Italy and other European countries can contribute to tailoring and regulating genetic services in a way that could be efficient in terms of healthy choices, behaviors, and health resource expenditures for the general public.

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 the level of collaboration across stakeholders; the match between the research question, MPLC phase, sample, and preference method used in PPS; and the sensitivity of the decision regarding a medical product to patient preferences. Promising applications for patient preferences should be further explored with stakeholders to optimize their inclusion in decision-making.

Background: In the brain, polyamines are mainly synthesized in neurons, but preferentially accumulated in astrocytes, and are proposed to be involved in neurodegenerative/neuroinflammatory disorders and neuron injury. A transgenic mouse overexpressing spermine oxidase (SMOX, which specifically oxidizes spermine) in the neocortex neurons (Dach-SMOX mouse) was proved to be a model of increased susceptibility to excitotoxic injury. Methods: To investigate possible alterations in synapse functioning in Dach-SMOX mouse, both cerebrocortical nerve terminals (synaptosomes) and astrocytic processes (gliosomes) were analysed by assessing polyamine levels, ezrin and vimentin content, glutamate AMPA receptor activation, calcium influx, and catalase activity. Results: The main findings are as follows: (i) the presence of functional calcium-permeable AMPA receptors in synaptosomes from both control and Dach-SMOX mice, and in gliosomes from Dach-SMOX mice only; (ii) reduced content of spermine in gliosomes from Dach-SMOX mice; and (iii) down-regulation and up-regulation of catalase activity in synaptosomes and gliosomes, respectively, from Dach-SMOX mice. Conclusions: Chronic activation of SMOX in neurons leads to major changes in the astrocyte processes including reduced spermine levels, increased calcium influx through calcium-permeable AMPA receptors, and stimulation of catalase activity. Astrocytosis and the astrocyte process alterations, depending on chronic activation of polyamine catabolism, result in synapse dysregulation and neuronal suffering.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in industrialized countries and is associated with increased risk of cardiovascular, hepatic and metabolic diseases. Molecular mechanisms on the root of the disrupted lipid homeostasis in NAFLD and potential therapeutic strategies can benefit of in vivo and in vitro experimental models of fatty liver. Here, we describe the high fat diet (HFD)-fed rat in vivo model, and two in vitro models, the primary cultured rat fatty hepatocytes or the FaO rat hepatoma fatty cells, mimicking human NAFLD. Liver steatosis was invariably associated with increased number/size of lipid droplets (LDs) and modulation of expression of genes coding for key genes of lipid metabolism such as peroxisome proliferator-activated receptors (Ppars) and perilipins (Plins). In these models, we tested the anti-steatotic effects of 3,5-L-diiodothyronine (T2), a metabolite of thyroid hormones. T2 markedly reduced triglyceride content and LD size acting on mRNA expression of both Ppars and Plins. T2 also stimulated mitochondrial oxidative metabolism of fatty acids. We conclude that in vivo and especially in vitro models of NAFLD are valuable tools to screen a large number of compounds counteracting the deleterious effect of liver steatosis. Because of the high and negative impact of liver steatosis on human health, ongoing experimental studies from our group are unravelling the ultimate translational value of such cellular models of NAFLD.

Dual Energy X-Ray Absorptiometry (DXA) is currently the most widely adopted non-invasive clinical technique to assess bone mineral density and bone mineral content in human research and represents the primary tool for the diagnosis of osteoporosis. DXA measures areal bone mineral density, BMD, which does not account for the three-dimensional structure of the vertebrae and for the distribution of bone mass. The result is that longitudinal DXA can only predict about 70% of vertebral fractures. This study proposes a complementary tool, based on Finite Element (FE) models, to improve the DXA accuracy. Bone is simulated as elastic and inhomogeneous material, with stiffness distribution derived from DXA greyscale images of density. The numerical procedure simulates a compressive load on each vertebra to evaluate the local minimum principal strain values. From these values, both the local average and the maximum strains are computed over the cross sections and along the height of the analysed bone region, to provide a parameter, named Strain Index of Bone (SIB), which could be considered as a bone fragility index. The procedure is initially validated on 33 cylindrical trabecular bone samples obtained from porcine lumbar vertebrae, experimentally tested under static compressive loading. Comparing the experimental mechanical parameters with the SIB, we could find a higher correlation of the ultimate stress, σULT, with the SIB values (R2adj = 0.63) than that observed with the conventional DXA-based clinical parameters, i.e. Bone Mineral Density, BMD (R2adj = 0.34) and Trabecular Bone Score, TBS (R2adj = -0.03). The paper finally presents a few case studies of numerical simulations carried out on human lumbar vertebrae. If our results are confirmed in prospective studies, SIB could be used-together with BMD and TBS-to improve the fracture risk assessment and support the clinical decision to assume specific drugs for metabolic bone diseases.

Neuroblastoma (NB) is a heterogeneous developmental tumor occurring in childhood, which arises from the embryonic sympathoadrenal cells of the neural crest. Although the recent progress that has been done on this tumor, the mechanisms involved in NB are still partially unknown. Despite some genetic aberrations having been identified, the sporadic cases represent the majority. Due to its wide heterogeneity in clinical behavior and etiology, NB represents a challenge in terms of prevention and treatment. Since a definitive therapy is lacking so far, there is an urgent necessity to unveil the molecular mechanisms behind NB onset and progression to develop new therapeutic approaches. Long non-coding RNAs (lncRNAs) are a group of RNAs longer than 200 nucleotides. Whether lncRNAs are destined to become a protein or not, they exert multiple biological functions such as regulating gene expression and functions. In recent decades, different research has highlighted the possible role of lncRNAs in the pathogenesis of many diseases, including cancer. Moreover, lncRNAs may represent potential markers or targets for diagnosis and treatment of diseases. This mini-review aimed to briefly summarize the most recent findings on the involvement of some lncRNAs in NB disease by focusing on their mechanisms of action and possible role in unveiling NB onset and progression.

S-adenosylmethionine (SAMe) is an endogenous methyl donor derived from ATP and methionine that has pleiotropic functions. Most SAMe is synthetized and consumed in the liver, where it acts as the main methylating agent and in protection against the free radical toxicity. Previous studies have shown that the administration of SAMe as a supernutrient exerted many beneficial effects in various tissues, mainly in the liver. In the present study, we aimed to clarify the direct effects of SAMe on fatty acid-induced steatosis and oxidative stress in hepatic and endothelial cells. Hepatoma FaO cells and endothelial HECV cells exposed to a mixture of oleate/palmitate are reliable models for hepatic steatosis and endothelium dysfunction, respectively. Our findings indicate that SAMe was able to significantly ameliorate lipid accumulation and oxidative stress in hepatic cells, mainly through promoting mitochondrial fatty acid entry for β-oxidation and external triglyceride release. SAMe also reverted both lipid accumulation and oxidant production (i.e., ROS and NO) in endothelial cells. In conclusion, these outcomes suggest promising beneficial applications of SAMe as a nutraceutical for metabolic disorders occurring in fatty liver and endothelium dysfunction.

Bone's resistance to fracture depends on several factors, such as bone mass, microarchitecture, and tissue material properties. The clinical assessment of bone strength is generally performed by Dual-X Ray Photon Absorptiometry (DXA), measuring bone mineral density (BMD) and trabecular bone score (TBS). Although it is considered the major predictor of bone strength, BMD only accounts for about 70% of fragility fractures, while the remaining 30% could be described by bone "quality" impairment parameters, mainly related to tissue microarchitecture. The assessment of bone microarchitecture generally requires more invasive techniques, which are not applicable in routine clinical practice, or X-Ray based imaging techniques, requiring a longer post-processing. Another important aspect is the presence of local damage in the bony tissue that may also affect the prediction of bone strength and fracture risk. To provide a more comprehensive analysis of bone quality and quantity, and to assess the effect of damage, here we adopt a framework that includes clinical, morphological, and mechanical analyses, carried out by means of DXA, μCT and mechanical compressive testing, respectively. This study has been carried out on trabecular bones, taken from porcine trabecular vertebrae, for the similarity with human lumbar spine. This study confirms that no single method can provide a complete characterization of bone tissue, and the combination of complementary characterization techniques is required for an accurate and exhaustive description of bone status. BMD and TBS have shown to be complementary parameters to assess bone strength, the former assessing the bone quantity and resistance to damage, and the latter the bone quality and the presence of damage accumulation without being able to predict the risk of fracture.

Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity and mortality. Oxidative stress and release of pro-inflammatory cytokines, such as tumor necrosis factor α (TNFα), are major consequences of hepatic lipid overload, which can contribute to progression of NAFLD to non-alcoholic steatohepatitis (NASH). Also, mitochondria are involved in the NAFLD pathogenesis for their role in hepatic lipid metabolism. Definitive treatments for NAFLD/NASH are lacking so far. Silybin, the extract of the milk thistle seeds, has previously shown beneficial effects in NAFLD. Sequential exposure of hepatocytes to high concentrations of fatty acids (FAs) and TNFα resulted in fat overload and oxidative stress, which mimic in vitro the progression of NAFLD from simple steatosis (SS) to steatohepatitis (SH). The exposure to 50 µM silybin for 24 h reduced fat accumulation in the model of NAFLD progression. The in vitro progression of NAFLD from SS to SH resulted in reduced hepatocyte viability, increased apoptosis and oxidative stress, reduction in lipid droplet size, and up-regulation of IκB kinase β-interacting protein and adipose triglyceride lipase expressions. The direct action of silybin on SS or SH cells and the underlying mechanisms were assessed. Beneficial action of silybin was sustained by changes in expression/activity of peroxisome proliferator-activated receptors and enzymes for FA oxidation. Moreover, silybin counteracted the FA-induced mitochondrial damage by acting on complementary pathways: (i) increased the mitochondrial size and improved the mitochondrial cristae organization; (ii) stimulated mitochondrial FA oxidation; (iii) reduced basal and maximal respiration and ATP production in SH cells; (iv) stimulated ATP production in SS cells; and (v) rescued the FA-induced apoptotic signals and oxidative stress in SH cells. We provide new insights about the direct protective effects of the nutraceutic silybin on hepatocytes mimicking in vitro NAFLD progression.

Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease reflecting degeneration of upper and lower motoneurons (MNs). The cause of ALS and the mechanisms of neuronal death are still largely obscure, thus impairing the establishment of efficacious therapies. Glutamate (Glu)-mediated excitotoxicity plays a major role in MN degeneration in ALS. We recently demonstrated that the activation of Group I metabotropic Glu autoreceptors, belonging to both type 1 and type 5 receptors (mGluR1 and mGluR5), at glutamatergic spinal cord nerve terminals, produces excessive Glu release in mice over-expressing human superoxide-dismutase carrying the G93A point mutation (SOD1G93A), a widely used animal model of human ALS. To establish whether these receptors are implicated in ALS, we generated mice expressing half dosage of mGluR1 in the SOD1G93A background (SOD1G93AGrm1crv4/+), by crossing the SOD1G93A mutant mouse with the Grm1crv4/+ mouse, lacking mGluR1 because of a spontaneous recessive mutation. SOD1G93AGrm1crv4/+ mice showed prolonged survival probability, delayed pathology onset, slower disease progression and improved motor performances compared to SOD1G93A mice. These effects were associated to reduction of mGluR5 expression, enhanced number of MNs, decreased astrocyte and microglia activation, normalization of metallothionein and catalase mRNA expression, reduced mitochondrial damage, and decrease of abnormal Glu release in spinal cord of SOD1G93AGrm1crv4/+compared to SOD1G93A mice. These results demonstrate that a lower constitutive level of mGluR1 has a significant positive impact on mice with experimental ALS, thus providing the rationale for future pharmacological approaches to ALS by selectively blocking Group I metabotropic Glu receptors.

Background/Aims: Fatty acids are the main energy stores and the major membrane components of the cells. In the hepatocyte, fatty acids are esterified to triacylglycerols (TAGs) and stored in lipid droplets (LDs). The lipid lowering action of 3,5-diiodo-L-thyronine (T2) on an in vitro model of hepatosteatosis was investigated in terms of fatty acid and protein content of LDs, lipid oxidation and secretion. Methods: FaO cells were exposed to oleate/palmitate, then treated with T2. Results: T2 reduced number and size of LDs, and modified their acyl composition by decreasing the content of saturated (SFA) vs monounsaturated (MUFA) fatty acids thus reversing the SFA/MUFA ratio. The expression of the LD-associated proteins adipose differentiation-related protein (ADRP), oxidative tissue-enriched PAT protein (OXPAT), and adipose triglyceride lipase (ATGL) was increased in ‘steatotic' cells and further up-regulated by T2. Moreover, T2 stimulated the mitochondrial oxidation by up-regulating carnitine-palmitoyl-transferase (CPT1), uncoupling protein 2 (UCP2) and very long-chain acyl-coenzyme A dehydrogenase (VLCAD). Conclusions: T2 leads to mobilization of TAGs from LDs and stimulates mitochondrial oxidative metabolism of fatty acids, in particular of SFAs, and thus enriches of MUFAs the LDs. This action may protect the hepatocyte from excess of SFAs that are more toxic than MUFAs.

The aim of this work is a review of scientific results in the literature, related to the application of thermographic techniques to composite materials. Thermography is the analysis of the surface temperature of a body by infrared rays detection via a thermal-camera. The use of this technique is mainly based on the modification of the surface temperature of a material, when it is stimulated by means of a thermal or mechanical external source. The presence of defects, in fact, induces a localized variation in its temperature distribution and, then, the measured values of the surface temperature can be used to localize and evaluate the dimensions and the evolution of defects. In the past, many applications of thermography were proposed on homogeneous materials, but only recently this technique has also been extended to composites. In this work several applications of thermography to fibres reinforced plastics are presented. Thermographic measurements are performed on the surface of the specimens, while undergoing static and dynamic tensile loading. The joint analysis of thermal and mechanical data allows one to assess the damage evolution and to study the damage phenomenon from both mechanical and energetic viewpoints. In particular, one of the main issues is to obtain information about the fatigue behaviour of composite materials, by following an approach successfully applied to homogenous materials. This approach is based on the application of infrared thermography on specimens subjected to static or stepwise dynamic loadings and on the definition of a damage stress, D, that is correlated to the fatigue strength of the material. A wide series of experimental fatigue tests has been carried out to verify if the value of the damage stress, D, is correlated with the fatigue strength of the material. The agreement between the different values is good, showing the reliability of the presented thermographic techniques, to the study of composite damage and their fatigue behaviour.

The aim of this work is a review of scientific results in the literature, related to the application of thermographic techniques to composite materials. Thermography is the analysis of the surface temperature of a body by infrared rays detection via a thermal-camera. The use of this technique is mainly based on the modification of the surface temperature of a material, when it is stimulated by means of a thermal or mechanical external source. The presence of defects, in fact, induces a localized variation in its temperature distribution and, then, the measured values of the surface temperature can be used to localize and evaluate the dimensions and the evolution of defects. In the past, many applications of thermography were proposed on homogeneous materials, but only recently this technique has also been extended to composites. In this work several applications of thermography to fibres reinforced plastics are presented. Thermographic measurements are performed on the surface of the specimens, while undergoing static and dynamic tensile loading. The joint analysis of thermal and mechanical data allows one to assess the damage evolution and to study the damage phenomenon from both mechanical and energetic viewpoints. In particular, one of the main issues is to obtain information about the fatigue behaviour of composite materials, by following an approach successfully applied to homogenous materials. This approach is based on the application of infrared thermography on specimens subjected to static or stepwise dynamic loadings and on the definition of a damage stress, ?D, that is correlated to the fatigue strength of the material. A wide series of experimental fatigue tests has been carried out to verify if the value of the damage stress, ?D, is correlated with the fatigue strength of the material. The agreement between the different values is good, showing the reliability of the presented thermographic techniques, to the study of composite damage and their fatigue behaviour.