699 research outputs found
Damage Detection in Composite Materials by Flexural Dynamic Excitation and Accelerometer-Based Acquisition
Composite materials provide many advantages over more conventional materials.
However, their susceptibility to impact damage can question their use in critical load-bearing
structures, and efficient methods are needed for early damage detection. To this purpose, the
nonlinear vibro-acoustic modulation (VAM) technique applies a low-frequency pump excitation
and a high-frequency probe excitation to exploit the onset of harmonic components around the
probe frequency of the damaged structural response. The VAM technique has been widely
studied on structures instrumented with piezoceramic transducers used for both actuation and
sensing, but few attempts have been made to use equipment typical of modal testing, such as
shakers and accelerometers. In this study, the VAM technique is applied to a composite laminate
beam by employing an electro-dynamic shaker to generate low-frequency flexural excitation, a
low-profile piezoceramic transducer to introduce the probe wave, and a micro-accelerometer to
sense the structural response. Three resonance low frequencies and two acoustic frequencies are
considered in different testing scenarios, at increasing levels of excitation amplitude. The results
show a general good performance of the technique with the adopted experimental setup, the
choice of the probe frequency and the higher level of the pump excitation having a significant
impact on its sensitivity
Is it possible to compare inhibitory and excitatory intracortical circuits in face and hand primary motor cortex?
Face muscles are important in a variety of different functions, such as feeding, speech and communication of non-verbal affective states, which require quite different patterns of activity from those of a typical hand muscle. We ask whether there are differences in their neurophysiological control that might reflect this. Fifteen healthy individuals were studied. Standard single- and paired-pulse transcranial magnetic stimulation (TMS) methods were used to compare intracortical inhibitory (short interval intracortical inhibition (SICI); cortical silent period (CSP)) and excitatory circuitries (short interval intracortical facilitation (SICF)) in two typical muscles, the depressor anguli oris (DAO), a face muscle, and the first dorsal interosseous (FDI), a hand muscle. TMS threshold was higher in DAO than in FDI. Over a range of intensities, resting SICF was not different between DAO and FDI, while during muscle activation SICF was stronger in FDI than in DAO (P = 0.012). At rest, SICI was stronger in FDI than in DAO (P = 0.038) but during muscle contraction, SICI was weaker in FDI than in DAO (P = 0.034). We argue that although many of the difference in response to the TMS protocols could result from the difference in thresholds, some, such as the reduction of resting SICI in DAO, may reflect fundamental differences in the physiology of the two muscle groups
Spread of ductal carcinoma in situ into a phyllodes breast tumour: a case report
Phyllodes are uncommon fibroepithelial breast tumours. Here, we present the case of a 42-year-old woman who presented to our breast centre with a palpable breast mass, which was initially suspected and treated as fibroadenoma but was finally revealed to be a phyllodes tumour. Histopathological examination identified ductal carcinoma in situ (DCIS) within the entire volume of the fibroepithelial tumour. The literature on these transformations is still limited, and the treatment is not standardised
Inhibition of microglia overactivation restores neuronal survival in a mouse model of CDKL5 deficiency disorder
open9noFunding: This work was supported by the Telethon foundation (grant number GGP19045 to EC), by the Italian parent associations “CDKL5 insieme verso la cura” to EC and by the CARISBO foundation (grant number 2020.0400 to ST).CDKL5 deficiency disorder (CDD), a severe neurodevelopmental disorder characterized by early onset epilepsy, intellectual disability, and autistic features, is caused by mutations in the CDKL5 gene. Evidence in animal models of CDD showed that absence of CDKL5 negatively affects neuronal survival, as well as neuronal maturation and dendritic outgrowth; however, knowledge of the substrates underlying these alterations is still limited. Neuroinflammatory processes are known to contribute to neuronal dysfunction and death. Recent evidence shows a subclinical chronic inflammatory status in plasma from CDD patients. However, to date, it is unknown whether a similar inflammatory status is present in the brain of CDD patients and, if so, whether this plays a causative or exacerbating role in the pathophysiology of CDD.openGalvani, Giuseppe; Mottolese, Nicola; Gennaccaro, Laura; Loi, Manuela; Medici, Giorgio; Tassinari, Marianna; Fuchs, Claudia; Ciani, Elisabetta; Trazzi, StefaniaGalvani, Giuseppe; Mottolese, Nicola; Gennaccaro, Laura; Loi, Manuela; Medici, Giorgio; Tassinari, Marianna; Fuchs, Claudia; Ciani, Elisabetta; Trazzi, Stefani
Medical and surgical interventions to improve the quality of life for endometriosis patients: a systematic review
Endometriosis impairs the quality of life (QoL) of many women, including their social relationships, daily activity,
productivity at work, and family planning. The aim of this review was to determine the instruments used to
examine QoL in previous clinical studies of endometriosis and to evaluate the effect of medical and surgical
interventions for endometriosis on QoL. We conducted a systematic search and review of studies published
between January 2010 and December 2020 using MEDLINE. Search terms included “endometriosis” and “quality of
life.” We only selected studies that used a standardized questionnaire to evaluate QoL before and after medical or
surgical interventions. Only articles in the English language were examined. The initial search identified 720 results.
After excluding duplicates and applying inclusion criteria, 37 studies were selected for analysis. We found that the
two scales most frequently used to measure QoL were the Short Form-36 health survey questionnaire (SF-36) and
the Endometriosis Health Profile-30 (EHP-30). Many medical and surgical treatments demonstrated comparable
benefits in pain control and QoL improvement. There is no clear answer as to what is the best treatment for
improving QoL because each therapy must be personalized for the patient and depends on the woman’s goals. In
conclusion, women must be informed about endometriosis and given easily accessible information to improve
treatment adherence and their QoL
Meta-analysis of associations between five-factor personality traits and problematic social media use
This meta-analysis quantified the relationship between the five-factor model of personality and problematic social media use and identified moderators of this relationship. The analysis used a random-effects model to calculate a correlation for each factor and included 113 samples, with a total of 53,913 participants, identified from systematic searches of four databases. Moderator analyses were used to investigate potential causes of heterogeneity. The meta-analysis found that high neuroticism (r=.21,
Luteolin Treatment Ameliorates Brain Development and Behavioral Performance in a Mouse Model of CDKL5 Deficiency Disorder
CDKL5 deficiency disorder (CDD), a rare and severe neurodevelopmental disease caused by mutations in the X-linked CDKL5 gene, is characterized by early-onset epilepsy, intellectual disability, and autistic features. Although pharmacotherapy has shown promise in the CDD mouse model, safe and effective clinical treatments are still far off. Recently, we found increased microglial activation in the brain of a mouse model of CDD, the Cdkl5 KO mouse, suggesting that a neuroinflammatory state, known to be involved in brain maturation and neuronal dysfunctions, may contribute to the pathophysiology of CDD. The present study aims to evaluate the possible beneficial effect of treatment with luteolin, a natural flavonoid known to have anti-inflammatory and neuroprotective activities, on brain development and behavior in a heterozygous Cdkl5 (+/-) female mouse, the mouse model of CDD that best resembles the genetic clinical condition. We found that inhibition of neuroinflammation by chronic luteolin treatment ameliorates motor stereotypies, hyperactive profile and memory ability in Cdkl5 +/- mice. Luteolin treatment also increases hippocampal neurogenesis and improves dendritic spine maturation and dendritic arborization of hippocampal and cortical neurons. These findings show that microglia overactivation exerts a harmful action in the Cdkl5 +/- brain, suggesting that treatments aimed at counteracting the neuroinflammatory process should be considered as a promising adjuvant therapy for CDD
Early-onset brain alterations during postnatal development in a mouse model of CDKL5 deficiency disorder
Mutations in the CDKL5 gene are the cause of CDKL5 deficiency disorder (CDD), a rare and severe neurodevelopmental condition characterized by early-onset epilepsy, motor impairment, intellectual disability, and autistic features. A mouse model of CDD, the Cdkl5 KO mouse, that recapitulates several aspects of CDD symptomology, has helped to highlight brain alterations leading to CDD neurological defects. Studies of brain morphogenesis in adult Cdkl5 KO mice showed defects in dendritic arborization of pyramidal neurons and in synaptic connectivity, a hypocellularity of the hippocampal dentate gyrus, and a generalized microglia over-activation. Nevertheless, no studies are available regarding the presence of these brain alterations in Cdkl5 KO pups, and their severity in early stages of life compared to adulthood. A deeper understanding of the CDKL5 deficient brain during an early phase of postnatal development would represent an important milestone for further validation of the CDD mouse model, and for the identification of the optimum time window for treatments that target defects in brain development. In sight of this, we comparatively evaluated the dendritic arborization and spines of cortical pyramidal neurons, cortical excitatory and inhibitory connectivity, microglia activation, and proliferation and survival of granule cells of the hippocampal dentate gyrus in hemizygous Cdkl5 KO male (-/Y) mice aged 7, 14, 21, and 60 days. We found that most of the structural alterations in Cdkl5 -/Y brains are already present in pups aged 7 days and do not worsen with age. In contrast, the difference in the density of excitatory and inhibitory terminals between Cdkl5 -/Y and wild-type mice changes with age, suggesting an age-dependent cortical excitatory/inhibitory synaptic imbalance. Confirming the precocious presence of brain defects, Cdkl5 -/Y pups are characterized by an impairment in neonatal sensory-motor reflexes
Treatment with a GSK-3β/HDAC Dual Inhibitor Restores Neuronal Survival and Maturation in an In Vitro and In Vivo Model of CDKL5 Deficiency Disorder
open11noFunding: This research was funded by the Telethon foundation (grant number GGP19045, awarded to E.C.), and by the Italian parent association “CDKL5 insieme verso la cura” (to E.C.).Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene cause a rare neurodevelopmental disorder characterized by early-onset seizures and severe cognitive, motor, and visual impairments. To date there are no therapies for CDKL5 deficiency disorder (CDD). In view of the severity of the neurological phenotype of CDD patients it is widely assumed that CDKL5 may influence the activity of a variety of cellular pathways, suggesting that an approach aimed at targeting multiple cellular pathways simultaneously might be more effective for CDD. Previous findings showed that a single-target therapy aimed at normalizing impaired GSK-3β or histone deacetylase (HDAC) activity improved neurodevelopmental and cognitive alterations in a mouse model of CDD. Here we tested the ability of a first-in-class GSK-3β/HDAC dual inhibitor, Compound 11 (C11), to rescue CDD-related phenotypes. We found that C11, through inhibition of GSK-3β and HDAC6 activity, not only restored maturation, but also significantly improved survival of both human CDKL5-deficient cells and hippocampal neurons from Cdkl5 KO mice. Importantly, in vivo treatment with C11 restored synapse development, neuronal survival, and microglia over-activation, and improved motor and cognitive abilities of Cdkl5 KO mice, suggesting that dual GSK-3β/HDAC6 inhibitor therapy may have a wider therapeutic benefit in CDD patients.openLoi, Manuela; Gennaccaro, Laura; Fuchs, Claudia; Trazzi, Stefania; Medici, Giorgio; Galvani, Giuseppe; Mottolese, Nicola; Tassinari, Marianna; Giorgini, Roberto Rimondini; Milelli, Andrea; Ciani, ElisabettaLoi, Manuela; Gennaccaro, Laura; Fuchs, Claudia; Trazzi, Stefania; Medici, Giorgio; Galvani, Giuseppe; Mottolese, Nicola; Tassinari, Marianna; Giorgini, Roberto Rimondini; Milelli, Andrea; Ciani, Elisabett
Cardiac Functional and Structural Abnormalities in a Mouse Model of CDKL5 Deficiency Disorder
CDKL5 (cyclin-dependent kinase-like 5) deficiency disorder (CDD) is a severe neurodevelopmental disease that mostly affects girls, who are heterozygous for mutations in the X-linked CDKL5 gene. Mutations in the CDKL5 gene lead to a lack of CDKL5 protein expression or function and cause numerous clinical features, including early-onset seizures, marked hypotonia, autistic features, gastrointestinal problems, and severe neurodevelopmental impairment. Mouse models of CDD recapitulate several aspects of CDD symptomology, including cognitive impairments, motor deficits, and autistic-like features, and have been useful to dissect the role of CDKL5 in brain development and function. However, our current knowledge of the function of CDKL5 in other organs/tissues besides the brain is still quite limited, reducing the possibility of broad-spectrum interventions. Here, for the first time, we report the presence of cardiac function/structure alterations in heterozygous Cdkl5 +/- female mice. We found a prolonged QT interval (corrected for the heart rate, QTc) and increased heart rate in Cdkl5 +/- mice. These changes correlate with a marked decrease in parasympathetic activity to the heart and in the expression of the Scn5a and Hcn4 voltage-gated channels. Interestingly, Cdkl5 +/- hearts showed increased fibrosis, altered gap junction organization and connexin-43 expression, mitochondrial dysfunction, and increased ROS production. Together, these findings not only contribute to our understanding of the role of CDKL5 in heart structure/function but also document a novel preclinical phenotype for future therapeutic investigation
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