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Laser in situ keratomileusis (LASIK) is the most frequently used technique for the surgical correction of refractive errors on the cornea. It entails the creation of a superficial hinged corneal flap using a femtosecond laser, ablation of the underlying stromal bed using an excimer laser, and repositioning of the flap. A corneal flap with an angled side cut reduces the risk of flap dislocation and infiltration of epithelial cells and confers unique biomechanical properties to the cornea. A new laser software creating three-dimensional (3D) flaps using a custom angle side cut was retrospectively evaluated, comparing optical coherence tomography 3D (with intended 90° side cut) and 2D flaps (with tapered side cuts) as well as respective intra- and early postoperative complications. Four hundred consecutive eyes were included, two hundred for each group. In the 3D group, the mean edge angle was 92°, and the procedure was on average 5.2 s slower (p = 0). Non-visually significant flap folds were found in thirteen eyes of the 2D group and in seven eyes of the 3D group (p = 0.17). In conclusion, the creation of a LASIK flap using a 3D femtosecond laser cut, although slightly slower, was safe and effective. The side cut angle was predictable and accurate.

Information on the flyer deformation during laser impact welding (LIW) is an important aspect to consider when high reliability of the welded components is required. For this reason, accurate numerical models simulating thermal and mechanical aspects are needed. In the present work, the cross-section morphology during LIW of Ti/Brass joints at varying laser pulse energies is modeled by a 2D finite element (FE) model. A hydrodynamic plasma pressure model able to describe the evolution of the pressure load step by step, taking into account the progressive deformation of the flyer, was implemented. Hence, this paper proposes an alternative method to the conventional node concentrated forces or predefined velocity as flyer boundary conditions. The levels of the equivalent plastic strain (PEEQ), shear stress, and critical flyer velocity at the collision point were used as reference parameters to predict the success of the welding bond, distinguishing the welded area from the unwelded area. The model was validated by comparison with the experimental data, which showed the effectiveness of the proposed FE code in predicting the cross-section morphology of the welded materials. Moreover, practical industrial information such as variation in the flyer impact velocity, collision angle, and process temperatures was predicted by varying the process laser pulse energy according to the basic principle of the process.

The present review provides a comprehensive examination of the intricate dynamics between α-synuclein, a protein crucially involved in the pathogenesis of several neurodegenerative diseases, including Parkinson’s disease and multiple system atrophy, and endogenously-produced bioactive lipids, which play a pivotal role in neuroinflammation and neurodegeneration. The interaction of α-synuclein with bioactive lipids is emerging as a critical factor in the development and progression of neurodegenerative and neuroinflammatory diseases, offering new insights into disease mechanisms and novel perspectives in the identification of potential biomarkers and therapeutic targets. We delve into the molecular pathways through which α-synuclein interacts with biological membranes and bioactive lipids, influencing the aggregation of α-synuclein and triggering neuroinflammatory responses, highlighting the potential of bioactive lipids as biomarkers for early disease detection and progression monitoring. Moreover, we explore innovative therapeutic strategies aimed at modulating the interaction between α-synuclein and bioactive lipids, including the development of small molecules and nutritional interventions. Finally, the review addresses the significance of the gut-to-brain axis in mediating the effects of bioactive lipids on α-synuclein pathology and discusses the role of altered gut lipid metabolism and microbiota composition in neuroinflammation and neurodegeneration. The present review aims to underscore the potential of targeting α-synuclein-lipid interactions as a multifaceted approach for the detection and treatment of neurodegenerative and neuroinflammatory diseases.

This review focuses on the use of conventional gel or coil and “new” generation hydrogel used as an embolic agent in endovascular applications. In general, embolic agents have deep or multidistrict vascular penetration properties as they ensure complete occlusion of vessels by exploiting the patient’s coagulation system, which recognises them as substances foreign to the body, thus triggering the coagulation cascade. This is why they are widely used in the treatment of endovascular corrections (EV repair), arteriovenous malformations (AVM), endoleaks (E), visceral aneurysms or pseudo-aneurysms, and embolisation of pre-surgical or post-surgical (iatrogenic) lesions. Conventional gels such as Onyx or coils are now commercially available, both of which are frequently used in endovascular interventional procedures, as they are minimally invasive and have numerous advantages over conventional open repair (OR) surgery. Recently, these agents have been modified and optimised to develop new embolic substances in the form of hydrogels based on alginate, chitosan, fibroin and other polymers to ensure embolisation through phase transition phenomena. The main aim of this work was to expand on the data already known in the literature concerning the application of these devices in the endovascular field, focusing on the advantages, disadvantages and safety profiles of conventional and innovative embolic agents and also through some clinical cases reported. The clinical case series concerns the correction and exclusion of endoleak type I or type II appeared after an endovascular procedure of exclusion of aneurysmal abdominal aortic (EVAR) with a coil (coil penumbra released by a LANTERN microcatheter), the exclusion of renal arterial malformation (MAV) with a coil (penumbra coil released by a LANTERN microcatheter) and the correction of endoleak through the application of Onyx 18 in the arteries where sealing by the endoprosthesis was not guaranteed.

Background: The COVID-19 pandemic increased symptoms of stress and anxiety and induced changes in sleep quality, dream activity, and parasomnia episodes. It has been shown that stressful factors and/or bad sleep habits can affect parasomnia behaviors. However, investigations on how COVID-19 has affected sleep, dreams, and episode frequency in parasomnias are rare. The current study focuses on the impact of the pandemic on a specific parasomnia characterized by speech production (sleep talking, ST). Methods: We selected 27 participants with frequent ST episodes (STs) during the pandemic and compared them with 27 participants with frequent STs from a previous study conducted during a pre-pandemic period. All participants performed home monitoring through sleep logs and recorded their nocturnal STs for one week. Results: We observed a higher frequency of STs in the pandemic group. Moreover, STs were related to the emotional intensity of dreams, independent of the pandemic condition. The pandemic was associated with lower bizarreness of dreams in the pandemic group. There were no differences in sleep variables between the two groups. Conclusion: Overall, these results suggest a stressful effect of COVID-19 on the frequency of STs. Both the pandemic and the frequency of STs affect qualitative characteristics of dreams in this population.

Oligomeric alpha-synuclein (α-syn) in saliva and phosphorylated α-syn deposits in the skin have emerged as promising diagnostic biomarkers for Parkinson’s disease (PD). This study aimed to assess and compare the diagnostic value of these biomarkers in discriminating between 38 PD patients and 24 healthy subjects (HSs) using easily accessible biological samples. Additionally, the study sought to determine the diagnostic potential of combining these biomarkers and to explore their correlations with clinical features. Salivary oligomeric α-syn levels were quantified using competitive ELISA, while skin biopsies were analyzed through immunofluorescence to detect phosphorylated α-syn at Ser129 (p-S129). Both biomarkers individually were accurate in discriminating PD patients from HSs, with a modest agreement between them. The combined positivity of salivary α-syn oligomers and skin p-S129 aggregates differentiated PD patients from HSs with an excellent discriminative ability with an AUC of 0.9095. The modest agreement observed between salivary and skin biomarkers individually suggests that they may reflect different aspects of PD pathology, thus providing complementary information when combined. This study’s results highlight the potential of utilizing a multimodal biomarker approach to enhance diagnostic accuracy in PD.

Male infertility is a relevant public health problem, but there is no systematic review of the different machine learning (ML) models and their accuracy so far. The present review aims to comprehensively investigate the use of ML algorithms in predicting male infertility, thus reporting the accuracy of the used models in the prediction of male infertility as a primary outcome. Particular attention will be paid to the use of artificial neural networks (ANNs). A comprehensive literature search was conducted in PubMed, Scopus, and Science Direct between 15 July and 23 October 2023, conducted under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed a quality assessment of the included studies using the recommended tools suggested for the type of study design adopted. We also made a screening of the Risk of Bias (RoB) associated with the included studies. Thus, 43 relevant publications were included in this review, for a total of 40 different ML models detected. The studies included reported a good quality, even if RoB was not always good for all the types of studies. The included studies reported a median accuracy of 88% in predicting male infertility using ML models. We found only seven studies using ANN models for male infertility prediction, reporting a median accuracy of 84%.

Botulinum toxin (BoNT) is an effective and safe therapy for the symptomatic treatment of several neurological disturbances. An important line of research has provided numerous pieces of evidence about the mechanisms of action of BoNT in the central nervous system, especially in the context of dystonia and spasticity. However, only a few studies focused on the possible central effects of BoNT in Parkinson’s disease (PD). We performed a systematic review to describe and discuss the evidence from studies focused on possible central effects of BoNT in PD animal models and PD patients. To this aim, a literature search in PubMed and SCOPUS was performed in May 2023. The records were screened according to title and abstract by two independent reviewers and relevant articles were selected for full-text review. Most of the papers highlighted by our review report that the intrastriatal administration of BoNT, through local anticholinergic action and the remodulation of striatal compensatory mechanisms secondary to dopaminergic denervation, induces an improvement in motor and non-motor symptoms in the absence of neuronal loss in animal models of PD. In human subjects, the data are scarce: a single neurophysiological study in tremulous PD patients found that the change in tremor severity after peripheral BoNT administration was associated with improved sensory–motor integration and intracortical inhibition measures. Further clinical, neurophysiological, and neuroimaging studies are necessary to clarify the possible central effects of BoNT in PD.

Alpha-lipoic acid (ALA) is a natural antioxidant dithiol compound, exerting antiproliferative and antimetastatic effects in various cancer cell lines. In our study, we demonstrated that ALA reduces the cell growth of prostate cancer cells LNCaP and DU-145. Western blot results revealed that in both cancer cells, ALA, by upregulating pmTOR expression, reduced the protein content of two autophagy initiation markers, Beclin-1 and MAPLC3. Concomitantly, MTT assays showed that chloroquine (CQ) exposure, a well-known autophagy inhibitor, reduced cells’ viability. This was more evident for treatment using the combination ALA + CQ, suggesting that ALA can reduce cells’ viability by inhibiting autophagy. In addition, in DU-145 cells we observed that ALA affected the oxidative/redox balance system by deregulating the KEAP1/Nrf2/p62 signaling pathway. ALA decreased ROS production, SOD1 and GSTP1 protein expression, and significantly reduced the cytosolic and nuclear content of the transcription factor Nrf2, concomitantly downregulating p62, suggesting that ALA disrupted p62-Nrf2 feedback loop. Conversely, in LNCaP cells, ALA exposure upregulated both SOD1 and p62 protein expression, but did not affect the KEAP1/Nrf2/p62 signaling pathway. In addition, wound-healing, Western blot, and immunofluorescence assays evidenced that ALA significantly reduced the motility of LNCaP and DU-145 cells and downregulated the protein expression of TGFβ1 and vimentin and the deposition of fibronectin. Finally, a soft agar assay revealed that ALA decreased the colony formation of both the prostate cancer cells by affecting the anchorage independent growth. Collectively, our in vitro evidence demonstrated that in prostate cancer cells, ALA reduces cell growth and counteracts both migration and invasion. Further studies are needed in order to achieve a better understanding of the underlined molecular mechanisms.

Prostate cancer (PCa) is the second most common male cancer. Its incidence derives from the interaction between modifiable and non-modifiable factors. The progression of prostate cancer into a more aggressive phenotype is associated with chronic inflammation and increased ROS production. For their biological properties, some phytochemicals from fruits and vegetable emerge as a promise strategy for cancer progression delay. These bioactive compounds are found in the highest amounts in peels and seeds. Poncirus trifoliata (L.) Raf. (PT) has been widely used in traditional medicine and retains anti-inflammatory, anti-bacterial, and anticancer effects. The seeds of P. trifoliata were exhaustively extracted by maceration with methanol as the solvent. The cell proliferation rate was performed by MTT and flow cytometry, while the apoptosis signals were analyzed by Western blotting and TUNEL assay. P. trifoliata seed extract reduced LNCaP and PC3 cell viability and induced cell cycle arrest at the G0/G1phase and apoptosis. In addition, a reduction in the AKT/mTOR pathway has been observed together with the up-regulation of stress-activated MAPK (p38 and c-Jun N-terminal kinase). Based on the study, the anti-growth effects of PT seed extract on prostate tumor cells give indications on the potential of the phytochemical drug for the treatment of this type of cancer. However, future in-depth studies are necessary to identify which components are mainly responsible for the anti-neoplastic response.

Postural instability (PI) in Parkinson’s disease (PD) exposes patients to an increased risk of falls (RF). While dopaminergic therapy and deep brain stimulation (DBS) improve motor performance in advanced PD patients, their effects on PI and RF remain elusive. PI and RF were assessed using a stabilometric platform in six advanced PD patients. Patients were evaluated in OFF and ON dopaminergic medication and under four DBS settings: with DBS off, DBS bilateral, and unilateral DBS of the more- or less-affected side. Our findings indicate that dopaminergic medication by itself exacerbated PI and RF, and DBS alone led to a decline in RF. No combination of medication and DBS yielded a superior improvement in postural control compared to the baseline combination of OFF medication and the DBS-off condition. Yet, for ON medication, DBS significantly improved both PI and RF. Among DBS conditions, DBS bilateral provided the most favorable outcomes, improving PI and RF in the ON medication state and presenting the smallest setbacks in the OFF state. Conversely, the more-affected side DBS was less beneficial. These preliminary results could inform therapeutic strategies for advanced PD patients experiencing postural disorders.

Determining the walking ability of post-stroke patients is crucial for the design of rehabilitation programs and the correct functional information to give to patients and their caregivers at their return home after a neurorehabilitation program. We aimed to assess the convergent validity of three different walking tests: the Functional Ambulation Category (FAC) test, the 10-m walking test (10MeWT) and the 6-minute walking test (6MWT). Eighty walking participants with stroke (34 F, age 64.54 ± 13.02 years) were classified according to the FAC score. Gait speed evaluation was performed with 10MeWT and 6MWT. The cut-off values for FAC and walking tests were calculated using a receiver-operating characteristic (ROC) curve. Area under the curve (AUC) and Youden’s index were used to find the cut-off value. Statistical differences were found in all FAC subgroups with respect to walking speed on short and long distances, and in the Rivermead Mobility Index and Barthel Index. Mid-level precision (AUC > 0.7; p < 0.05) was detected in the walking speed with respect to FAC score (III vs. IV and IV vs. V). The confusion matrix and the accuracy analysis showed that the most sensitive test was the 10MeWT, with cut-off values of 0.59 m/s and 1.02 m/s. Walking speed cut-offs of 0.59 and 1.02 m/s were assessed with the 10MeWT and can be used in FAC classification in patients with subacute stroke between the subgroups able to walk with supervision and independently on uniform and non-uniform surfaces. Moreover, the overlapping walking speed registered with the two tests, the 10MeWT showed a better accuracy to drive FAC classification.

Paired associative stimulation (PAS) is a non-invasive brain stimulation technique that modulates synaptic plasticity in the human motor cortex (M1). Since previous studies have primarily used motor-evoked potentials (MEPs) as outcome measure, cortical correlates of PAS-induced plasticity remain unknown. Therefore, the aim of this observational study was to investigate cortical correlates of a standard PAS induced plasticity in the primary motor cortex by using a combined TMS-EEG approach in a cohort of eighteen healthy subjects. In addition to the expected long-lasting facilitatory modulation of MEPs amplitude, PAS intervention also induced a significant increase in transcranial magnetic stimulation-evoked potentials (TEPs) P30 and P60 amplitude. No significant correlation between the magnitude of PAS-induced changes in TEP components and MEP amplitude were observed. However, the linear regression analysis revealed that the combined changes in P30 and P60 component amplitudes significantly predicted the MEP facilitation after PAS. The findings of our study offer novel insight into the neurophysiological changes associated with PAS-induced plasticity at M1 cortical level and suggest a complex relationship between TEPs and MEPs changes following PAS.

Cardiac lipotoxicity is an important contributor to cardiovascular complications during obesity. Given the fundamental role of the endoplasmic reticulum (ER)-resident Selenoprotein T (SELENOT) for cardiomyocyte differentiation and protection and for the regulation of glucose metabolism, we took advantage of a small peptide (PSELT), derived from the SELENOT redox-active motif, to uncover the mechanisms through which PSELT could protect cardiomyocytes against lipotoxicity. To this aim, we modeled cardiac lipotoxicity by exposing H9c2 cardiomyocytes to palmitate (PA). The results showed that PSELT counteracted PA-induced cell death, lactate dehydrogenase release, and the accumulation of intracellular lipid droplets, while an inert form of the peptide (I-PSELT) lacking selenocysteine was not active against PA-induced cardiomyocyte death. Mechanistically, PSELT counteracted PA-induced cytosolic and mitochondrial oxidative stress and rescued SELENOT expression that was downregulated by PA through FAT/CD36 (cluster of differentiation 36/fatty acid translocase), the main transporter of fatty acids in the heart. Immunofluorescence analysis indicated that PSELT also relieved the PA-dependent increase in CD36 expression, while in SELENOT-deficient cardiomyocytes, PA exacerbated cell death, which was not mitigated by exogenous PSELT. On the other hand, PSELT improved mitochondrial respiration during PA treatment and regulated mitochondrial biogenesis and dynamics, preventing the PA-provoked decrease in PGC1-α and increase in DRP-1 and OPA-1. These findings were corroborated by transmission electron microscopy (TEM), revealing that PSELT improved the cardiomyocyte and mitochondrial ultrastructures and restored the ER network. Spectroscopic characterization indicated that PSELT significantly attenuated infrared spectral-related macromolecular changes (i.e., content of lipids, proteins, nucleic acids, and carbohydrates) and also prevented the decrease in membrane fluidity induced by PA. Our findings further delineate the biological significance of SELENOT in cardiomyocytes and indicate the potential of its mimetic PSELT as a protective agent for counteracting cardiac lipotoxicity.

Dystonia is thought to be a network disorder due to abnormalities in the basal ganglia-thalamo-cortical circuit. We aimed to investigate the white matter (WM) microstructural damage of bundles connecting pre-defined subcortical and cortical regions in cervical dystonia (CD) and blepharospasm (BSP). Thirty-five patients (17 with CD and 18 with BSP) and 17 healthy subjects underwent MRI, including diffusion tensor imaging (DTI). Probabilistic tractography (BedpostX) was performed to reconstruct WM tracts connecting the globus pallidus, putamen and thalamus with the primary motor, primary sensory and supplementary motor cortices. WM tract integrity was evaluated by deriving their DTI metrics. Significant differences in mean, radial and axial diffusivity between CD and HS and between BSP and HS were found in the majority of the reconstructed WM tracts, while no differences were found between the two groups of patients. The observation of abnormalities in DTI metrics of specific WM tracts suggests a diffuse and extensive loss of WM integrity as a common feature of CD and BSP, aligning with the increasing evidence of microstructural damage of several brain regions belonging to specific circuits, such as the basal ganglia-thalamo-cortical circuit, which likely reflects a common pathophysiological mechanism of focal dystonia.

Setting up physiologically relevant in vitro models requires realizing a proper hierarchical cellular structure, wherein the main tissue features are recapitulated [...]

This study aimed to validate a sensorized version of a perceptive surface that may be used for the early assessment of misperception of body midline representation in subjects with right stroke, even when they are not yet able to stand in an upright posture. This device, called SuPerSense, allows testing of the load distribution of the body weight on the back in a supine position. The device was tested in 15 patients with stroke, 15 age-matched healthy subjects, and 15 young healthy adults, assessing three parameters analogous to those conventionally extracted by a baropodometric platform in a standing posture. Subjects were hence tested on SuPerSense in a supine position and on a baropodometric platform in an upright posture in two different conditions: with open eyes and with closed eyes. Significant correlations were found between the lengths of the center of pressure path with the two devices in the open-eyes condition (R = 0.44, p = 0.002). The parameters extracted by SuPerSense were significantly different among groups only when patients were divided into those with right versus left brain damage. This last result is conceivably related to the role of the right hemisphere of the brain in the analysis of spatial information.

The interest in membranes and membrane bioreactors for health and life sciences is rapidly growing thanks to their wide applications in advanced therapies and biotechnologies [...]

The authors wish to make the following corrections to this paper [...]

Variants in the X-linked retinitis pigmentosa GTPase regulator gene (RPGR) and, specifically, in its retinal opening reading frame-15 isoform (RPGRORF15) may cause rod-cone (RCD), cone, and cone-rod dystrophies (CDs and CRDs). While RPGR-related RCDs have been frequently evaluated, the characteristics and progression of RPGR-related CD/CRDs are largely unknown. Therefore, the goal of our work was to perform genotype–phenotype correlations specifically in RPGRORF15-related CD/CRDs. This retrospective longitudinal study included 34 index patients and two affected relatives with a molecular diagnosis of RPGR-related CD/CRDs. Patients were recruited at the “Quinze-Vingts” Hospital, Paris, France and screened for mutations in RPGRORF15 at the Institut de la Vision, Paris, France. We identified 29 distinct variants, of which 27 were truncating. All were located in the 3′ half of the RPGRORF15 transcript. Twenty of them were novel. Fifteen subjects were affected by CD, the remaining had CRD. When analyzing the longitudinal data, a progressive decline in visual acuity (VA) was noted, with more than 60% of the patients reaching VA ≥ 1 LogMar in the best eye after the fifth decade of life. To our knowledge, this is the largest described study of a cohort of CD/CRD patients affected by RPGRORF15 variants. Longitudinal data showed a rapidly progressive disease, possibly locating an optimal window of intervention for future therapies in younger ages.

The characterization of river hydraulics is very important for the definition of many problems connected with flood and morphodynamical models, including the stability of banks, slopes and sediments transport [...]

Oxidative stress and endoplasmic reticulum stress (ERS) are strictly involved in myocardial ischemia/reperfusion (MI/R). Selenoprotein T (SELENOT), a vital thioredoxin-like selenoprotein, is crucial for ER homeostasis and cardiomyocyte differentiation and protection, likely acting as a redox-sensing protein during MI/R. Here, we designed a small peptide (PSELT), encompassing the redox site of SELENOT, and investigated whether its pre-conditioning cardioprotective effect resulted from modulating ERS during I/R. The Langendorff rat heart model was employed for hemodynamic analysis, while mechanistic studies were performed in perfused hearts and H9c2 cardiomyoblasts. PSELT improved the post-ischemic contractile recovery, reducing infarct size and LDH release with and without the ERS inducer tunicamycin (TM). Mechanistically, I/R and TM upregulated SELENOT expression, which was further enhanced by PSELT. PSELT also prevented the expression of the ERS markers CHOP and ATF6, reduced cardiac lipid peroxidation and protein oxidation, and increased SOD and catalase activities. An inert PSELT (I-PSELT) lacking selenocysteine was ineffective. In H9c2 cells, H2O2 decreased cell viability and SELENOT expression, while PSELT rescued protein levels protecting against cell death. In SELENOT-deficient H9c2 cells, H2O2 exacerbated cell death, that was partially mitigated by PSELT. Microscopy analysis revealed that a fluorescent form of PSELT was internalized into cardiomyocytes with a perinuclear distribution. Conclusions: The cell-permeable PSELT is able to induce pharmacological preconditioning cardioprotection by mitigating ERS and oxidative stress, and by regulating endogenous SELENOT.

Mitochondria are key organelles for the maintenance of myocardial tissue homeostasis, playing a pivotal role in adenosine triphosphate (ATP) production, calcium signaling, redox homeostasis, and thermogenesis, as well as in the regulation of crucial pathways involved in cell survival. On this basis, it is not surprising that structural and functional impairments of mitochondria can lead to contractile dysfunction, and have been widely implicated in the onset of diverse cardiovascular diseases, including ischemic cardiomyopathy, heart failure, and stroke. Several studies support mitochondrial targets as major determinants of the cardiotoxic effects triggered by an increasing number of chemotherapeutic agents used for both solid and hematological tumors. Mitochondrial toxicity induced by such anticancer therapeutics is due to different mechanisms, generally altering the mitochondrial respiratory chain, energy production, and mitochondrial dynamics, or inducing mitochondrial oxidative/nitrative stress, eventually culminating in cell death. The present review summarizes key mitochondrial processes mediating the cardiotoxic effects of anti-neoplastic drugs, with a specific focus on anthracyclines (ANTs), receptor tyrosine kinase inhibitors (RTKIs) and proteasome inhibitors (PIs).

The ability to walk without support usually develops in the first year of a typically developing toddler’s life and matures further in the following years. Mature walking is characterized by the correct timing of the different gait phases that make up a full gait cycle formed by stance, swing, and double support phases. The harmony of mature walking is given by a specific self-similar structure of the ratios between the durations of these phases (stride/stance, stance/swing, swing/double support), that in adults all converge to the golden ratio (phi, about 1.618). The aim of this longitudinal, prospective, experimental study was to investigate the evolution of this gait harmonic structure in the transition from supported to independent walking. In total, 27 children were recruited and recorded at various stages of locomotor development, ranging from neonatal stepping up to an independent walking experience of about six months. Differently from walking speed that progressively increased with age, the gait phase ratios started to converge to golden value only after the first independent steps, suggesting a relation to the maturation of the walking experience. The independent walking experience seems to represent a trigger for the evolution of a locomotor harmonic pattern in toddlers learning to walk.

Metabolic syndrome and its associated disorders such as obesity, insulin resistance, atherosclerosis and type 2 diabetes mellitus are globally prevalent. Different molecules showing therapeutic potential are currently available for the management of metabolic syndrome, although their efficacy has often been compromised by their poor bioavailability and side effects. Studies have been carried out on medicinal plant extracts for the treatment and prevention of metabolic syndrome. In this regard, isolated pure compounds have shown promising efficacy for the management of metabolic syndrome, both in preclinical and clinical settings. Apigenin, a natural bioactive flavonoid widely present in medicinal plants, functional foods, vegetables and fruits, exerts protective effects in models of neurological disorders and cardiovascular diseases and most of these effects are attributed to its antioxidant action. Various preclinical and clinical studies carried out so far show a protective effect of apigenin against metabolic syndrome. Herein, we provide a comprehensive review on both in vitro and in vivo evidence related to the promising antioxidant role of apigenin in cardioprotection, neuroprotection and renoprotection, and to its beneficial action in metabolic-syndrome-dependent organ dysfunction. We also provide evidence on the potential of apigenin in the prevention and/or treatment of metabolic syndrome, analysing the potential and limitation of its therapeutic use.

Membrane systems offer a broad range of applications in the field of tissue engineering [...]

Spinal cord injuries (SCIs) exert devastating effects on body awareness, leading to the disruption of the transmission of sensory and motor inputs. Researchers have attempted to improve perceived body awareness post-SCI by intervening at the multisensory level, with the integration of somatic sensory and motor signals. However, the contributions of interoceptive-visceral inputs, particularly the potential interaction of motor and interoceptive signals, remain largely unaddressed. The present perspective aims to shed light on the use of interoceptive signals as a significant resource for patients with SCI to experience a complete sense of body awareness. First, we describe interoceptive signals as a significant obstacle preventing such patients from experiencing body awareness. Second, we discuss the multi-level mechanisms associated with the homeostatic stability of the body, which creates a unified, coherent experience of one’s self and one’s body, including real-time updates. Body awareness can be enhanced by targeting the vagus nerve function by, for example, applying transcutaneous vagus nerve stimulation. This perspective offers a potentially useful insight for researchers and healthcare professionals, allowing them to be better equipped in SCI therapy. This will lead to improved sensory motor and interoceptive signals, a decreased likelihood of developing deafferentation pain, and the successful implementation of modern robotic technologies.

Dune recovery interventions that integrate natural, sustainable, and soft solutions have become increasingly popular in coastal communities. In the present study, the reliability of an innovative non-toxic colloidal silica-based solution for coastal sand dunes has been verified for the first time by means of laboratory experiments. An extensive experimental campaign aimed at studying the effectiveness of the use of nanosilica has been conducted in the 2D wave flume of the EUMER laboratory at the University of Salento (Italy). The study was first based on a horizontal seabed and then a cross-shore beach-dune profile was drawn similar to those generally observed in nature. Detailed measurements of wave characteristics and observed bed and cross-shore beach-dune profiles were analyzed for a wide range of wave conditions. In both cases, two sets of experiments were carried out. After the first set of experiments performed resembling the native conditions of the models composed with natural sand, the effects of the injection of the mineral colloidal silica-based grout were investigated. The observations show that mineral colloidal silica increases the mechanical strength of non-cohesive sediments reducing the volume of dune erosion, thus improving the resistance and longevity of the beach-dune system.

β-Adrenergic receptors (β-ARs) are G protein-coupled receptors involved in important physiological and pathological processes related to blood pressure and cardiac activity. The inhibition of cardiac β1-ARs could be beneficial in myocardial hypertrophy, ischemia and failure. Several carbazole-based compounds have been described as promising β-blockers. Herein, we investigate the capability of a carbazole derivative and three simplified indole analogs to interact with the active binding site of β1-AR by molecular docking studies. In the light of the obtained results, our compounds were tested by biological assays in H9c2 cardiomyocytes exposed to isoproterenol (ISO) to confirm their potential as β1-blockers agents, and two of them (8 and 10) showed interesting and promising properties. In particular, these compounds were effective against ISO-dependent in vitro cardiac hypertrophy, even at concentrations lower than the known β-AR antagonist propranolol. Overall, the data suggest that the indole derivatives 8 and 10 could act as potent β1-blockers and, active at low doses, could elicit limited side effects.

Patient’s active participation in therapy is a key component of successful rehabilitation. In fact, low participation has been shown to be a prognostic factor of poor outcome; however, participation is rarely assessed in clinical settings. The Pittsburgh Rehabilitation Participation Scale (PRPS) is a validated, quick, and accurate measure of participation, relying on clinicians’ observation, and not requiring any self-report by patients. The aim of this study was to validate an Italian version of the PRPS. Following forward and back-translation of PRPS into Italian, the translated version was validated in a total of 640 therapy sessions, related to a cohort of 32 patients admitted to an Italian hospital. It was tested for concurrent validity, finding significant correlations with Barthel Index (R > 0.58, p < 0.001) and SF-36 Physical and Mental Health (R > 0.4, p < 0.02), for predictive validity, finding significant correlation with the effectiveness of rehabilitation (R = 0.358, p = 0.045), and for inter-rater and intra-rater reliability, computing an Intra-class correlation coefficient (ICC = 0.926 and 0.756, respectively). These psychometric properties results were similar to those of the original version of this scale. The proposed PRPS can be helpful for Italian clinicians in the assessment of patient’s participation during rehabilitation.

The creation of partial or complete human epidermis represents a critical aspect and the major challenge of skin tissue engineering. This work was aimed at investigating the effect of nano- and micro-structured CHT membranes on human keratinocyte stratification and differentiation. To this end, nanoporous and microporous membranes of chitosan (CHT) were prepared by phase inversion technique tailoring the operational parameters in order to obtain nano- and micro-structured flat membranes with specific surface properties. Microporous structures with different mean pore diameters were created by adding and dissolving, in the polymeric solution, polyethylene glycol (PEG Mw 10,000 Da) as porogen, with a different CHT/PEG ratio. The developed membranes were characterized and assessed for epidermal construction by culturing human keratinocytes on them for up to 21 days. The overall results demonstrated that the membrane surface properties strongly affect the stratification and terminal differentiation of human keratinocytes. In particular, human keratinocytes adhered on nanoporous CHT membranes, developing the structure of the corneum epidermal top layer, characterized by low thickness and low cell proliferation. On the microporous CHT membrane, keratinocytes formed an epidermal basal lamina, with high proliferating cells that stratified and differentiated over time, migrating along the z axis and forming a multilayered epidermis. This strategy represents an attractive tissue engineering approach for the creation of specific human epidermal strata for testing the effects and toxicity of drugs, cosmetics and pollutants.

The problem of vortex shedding, which occurs when an obstacle is placed in a regular flow, is governed by Reynolds and Strouhal numbers, known by dimensional analysis. The present work aims to propose a thin films-based device, consisting of an elastic piezoelectric flapping flag clamped at one end, in order to determine the frequency of vortex shedding downstream an obstacle for a flow field at Reynolds number Re∼103 in the open channel. For these values, Strouhal number obtained in such way is in accordance with the results known in literature. Moreover, the development of the voltage over time, generated by the flapping flag under the load due to flow field, shows a highly fluctuating behavior and satisfies Taylor’s law, observed in several complex systems. This provided useful information about the flow field through the constitutive law of the device.

A proper validation of an engineered brain microenvironment requires a trade of between the complexity of a cellular construct within the in vitro platform and the simple implementation of the investigational tool. The present work aims to accomplish this challenging balance by setting up an innovative membrane platform that represents a good compromise between a proper mimicked brain tissue analogue combined with an easily accessible and implemented membrane system. Another key aspect of the in vitro modelling disease is the identification of a precise phenotypic onset as a definite hallmark of the pathology that needs to be recapitulated within the implemented membrane system. On the basis of these assumptions, we propose a multiplex membrane system in which the recapitulation of specific neuro-pathological onsets related to Alzheimer’s disease pathologies, namely oxidative stress and β-amyloid1–42 toxicity, allowed us to test the neuroprotective effects of trans-crocetin on damaged neurons. The proposed multiplex membrane platform is therefore quite a versatile tool that allows the integration of neuronal pathological events in combination with the testing of new molecules. The present paper explores the use of this alternative methodology, which, relying on membrane technology approach, allows us to study the basic physiological and pathological behaviour of differentiated neuronal cells, as well as their changing behaviour, in response to new potential therapeutic treatment.

Background: Childcare programs often include mandatory naptime during the day. Loss of daytime sleep could lead to a moderate-to-large decrease in self-regulation, emotion processing, and learning in early childhood. Nevertheless, daytime sleep has been less accurately studied than nighttime sleep. This study aims to explore the relationship between diurnal sleep habits in nursery settings, nocturnal sleep quality, and post-nap emotional intensity in infants and toddlers. Methods: Data of 92 children (52 girls, 40 boys) aged 6 to 36 months were obtained. Sleep habits as well as positive and negative emotions were monitored by educators during nursery times through a sleep and emotion diary for two weeks. Results: Explorative analyses showed that diurnal sleep hours decreased across age groups (except for females aged 25–36 months) and that all age groups had a lower amount of nocturnal sleep than is recommended by the National Sleep Foundation. Partial correlation analysis showed significant correlation between daytime sleep onset latency and positive emotions. Mediation analyses showed that daytime napping is relevant for emotional functioning independently of nocturnal sleep quality. Conclusions: Daytime sleep in early childhood seems to be linked to the management of positive and negative emotions and could play a role in healthy development of emotional processes.