Reversion of metabolic dysfunction-associated steatohepatitis by skeletal muscle-directed FGF21 gene therapy.

The highly prevalent metabolic dysfunction-associated steatohepatitis (MASH) is associated with liver steatosis, inflammation, and hepatocyte injury, which can lead to fibrosis and may progress to hepatocellular carcinoma and death. New treatment modalities such as gene therapy may be transformative for MASH patients. Here, we describe that one-time intramuscular administration of adeno-associated viral vectors of serotype 1 (AAV1) encoding native fibroblast growth factor 21 (FGF21), a key metabolic regulator, resulted in sustained increased circulating levels of the factor, which mediated long-term (>1 year) MASH and hepatic fibrosis reversion and halted development of liver tumors in obese male and female mouse models.

Improving well-being and enhancing awareness in patients undergoing hemodialysis through the person-centered IARA model: an exploratory study.

Chronic kidney disease (CKD) globally represents a significant health challenge, particularly among patients undergoing chronic hemodialysis. A careful nutritional and pharmacological prescription plays a key role in the effective management of these patients to optimize serum electrolytes, such as potassium, phosphorus, and protein intake. Furthermore, these patients can suffer psychological distress due to dietary restrictions and tight medication schedules.

A New Culture Medium Rich in Phenols Used for Screening Bitter Degrading Strains of Lactic Acid Bacteria to Employ in Table Olive Production.

The olive oil industry recently introduced a novel multi-phase decanter with the "Leopard DMF" series, which gives a by-product called pâté, made up of pulp and olive wastewater with a high content of phenolic substances and without pits. This study aims to create a new culture medium, the Olive Juice Broth (OJB), from DMF pâté, and apply it to select bacteria strains able to survive and degrade the bitter substances normally present in the olive fruit. Thirty-five different bacterial strains of from the CREA-IT.

Dialectical Behavioral Skills Group Therapy for Parents of Adolescents With Borderline Personality Disorder: A Pilot Study.

Research has indicated the effectiveness of Dialectical behavior therapy in adolescents (DBT-A) with severe emotion dysregulation and other symptoms of Borderline Personality Disorder (BPD). The objective was to determine if DBT skills group with caregivers only could influence in potential mediators of DBT outcomes including rearing styles, emotion regulation and mindfulness skills, evaluated in both parents and adolescents. We implemented a 12-week group intervention based on DBT-A addressed to seven parents of adolescents with features of BPD.

The Usefulness of In Vitro Percutaneous Absorption Experiments Applying the Infinite Dose Technique to Predict In Vivo Plasma Levels: Comparison of Model-Predicted and Observed Plasma Concentrations of Nortriptyline in Rats.

The aims of this study were to evaluate the feasibility of a nortriptyline (NT) formulation for transdermal administration and to assess the usefulness of an estimated kinetic parameter () using the in vitro infinite dose technique to predict in vivo plasma levels when used in combination with pharmacokinetic parameters. To do so, a simple one-compartment model was used to describe the transport of a permeant across a membrane (skin). This model provides relatively simple expressions for the amount of permeant in the skin, the cumulative amount of permeant that crosses the skin, and the flux of permeant, for both the infinite and the finite dose regimens.

AAV-mediated BMP7 gene therapy counteracts insulin resistance and obesity.

Type 2 diabetes, insulin resistance, and obesity are strongly associated and are a major health problem worldwide. Obesity largely results from a sustained imbalance between energy intake and expenditure. Therapeutic approaches targeting metabolic rate may counteract body weight gain and insulin resistance.

Seven-year follow-up of durability and safety of AAV CNS gene therapy for a lysosomal storage disorder in a large animal.

Delivery of adeno-associated viral vectors (AAVs) to cerebrospinal fluid (CSF) has emerged as a promising approach to achieve widespread transduction of the central nervous system (CNS) and peripheral nervous system (PNS), with direct applicability to the treatment of a wide range of neurological diseases, particularly lysosomal storage diseases. Although studies in small animal models have provided proof of concept and experiments in large animals demonstrated feasibility in bigger brains, there is not much information on long-term safety or durability of the effect. Here, we report a 7-year study in healthy beagle dogs after intra-CSF delivery of a single, clinically relevant dose (2 × 10 vg/dog) of AAV9 vectors carrying the canine sulfamidase, the enzyme deficient in mucopolysaccharidosis type IIIA.

Multisensory integration in cortical regions responding to locomotion-related visual and somatomotor signals.

During real-world locomotion, in order to be able to move along a path or avoid an obstacle, continuous changes in self-motion direction (i.e. heading) are needed.

Treatment of skeletal and non-skeletal alterations of Mucopolysaccharidosis type IVA by AAV-mediated gene therapy.

Mucopolysaccharidosis type IVA (MPSIVA) or Morquio A disease, a lysosomal storage disorder, is caused by N-acetylgalactosamine-6-sulfate sulfatase (GALNS) deficiency, resulting in keratan sulfate (KS) and chondroitin-6-sulfate accumulation. Patients develop severe skeletal dysplasia, early cartilage deterioration and life-threatening heart and tracheal complications. There is no cure and enzyme replacement therapy cannot correct skeletal abnormalities.

Lower visual field preference for the visuomotor control of limb movements in the human dorsomedial parietal cortex.

Visual cues coming from the lower visual field (VF) play an important role in the visual guidance of upper and lower limb movements. A recently described region situated in the dorsomedial parietal cortex, area hPEc (Pitzalis et al. in NeuroImage 202:116092, 2019), might have a role in integrating visually derived information with somatomotor signals to guide limb interaction with the environment.

Preference for locomotion-compatible curved paths and forward direction of self-motion in somatomotor and visual areas.

During locomotion, leg movements define the direction of walking (forward or backward) and the path one is taking (straight or curved). These aspects of locomotion produce characteristic visual motion patterns during movement. Here, we tested whether cortical regions responding to either egomotion-compatible visual motion, or leg movements, or both, are sensitive to these locomotion-relevant aspects of visual motion.

Olive Pâté by Multi-Phase Decanter as Potential Source of Bioactive Compounds of Both Nutraceutical and Anticancer Effects.

In the oil sector, a novelty in the centrifugal extraction system is represented by the multi-phase decanters (DMF) that work without adding process water and with the advantage of recovering a dried pomace and a by-product, called "pâté", consisting of the pulp and its vegetation water, without traces of stone. The pâté has a high content of phenolic compounds, mainly represented by secoiridoids and verbascoside. The present work investigated the efficacy of two different ways of debittering (by sequential filtrations and spontaneous fermentation) of DMF pâté from three olive cultivars ( L.

Table Olives Fermented in Iodized Sea Salt Brines: Nutraceutical/Sensory Properties and Microbial Biodiversity.

This research aimed to study the influence of different brining processes with iodized and noniodized salt on mineral content, microbial biodiversity, sensory evaluation and color change of natural fermented table olives. Fresh olives of Carolea and Leucocarpa cvs. were immersed in different brines prepared with two different types of salt: the PGI "Sale marino di Trapani", a typical sea salt, well known for its taste and specific microelement content, and the same salt enriched with 0.

The Comorbidities Coma Scale (CoCoS): Psychometric Properties and Clinical Usefulness in Patients With Disorders of Consciousness.

Although comorbidities have a well-known impact on the functional recovery of patients with disorders of consciousness, including coma, vegetative state (VS), and minimally conscious state (MCS), a specific tool for their assessment in this challenging group of patients is lacking. For this aim, a multistep process was used to develop and validate the Comorbidities Coma Scale (CoCoS) in a sample of 162 patients with a diagnosis of coma, VS or MCS admitted to four Acute Inpatient Rehabilitation Units. To establish the psychometric properties of the scale, content validity, and internal consistency were investigated through Exploratory Factor Analysis in the whole sample ( = 162).

Performance of F-fluciclovine PET/MR in the evaluation of osseous metastases from castration-resistant prostate cancer.

Purpose: F-Fluciclovine is indicated for evaluation of suspected prostate cancer (PCa) biochemical recurrence. There are few studies investigating fluciclovine with PET/MR and none evaluated osseous metastases. Our aim was to assess the performance of F-fluciclovine PET/MR (fluciclovine-PET/MR) for detecting osseous metastases in patients with castration-resistant prostate cancer (CRPC).

Gene Therapy for Mucopolysaccharidosis Type III (Sanfilippo Syndrome): A New Treatment Horizon.

For most lysosomal storage diseases (LSDs), there is no cure. Gene therapy is an attractive tool for treatment of LSDs caused by deficiencies in secretable lysosomal enzymes, in which neither full restoration of normal enzymatic activity nor transduction of all cells of the affected organ is necessary. However, some LSDs, such as mucopolysaccharidosis type III (MPSIII) diseases or Sanfilippo syndrome, represent a difficult challenge because patients suffer severe neurodegeneration with mild somatic alterations.

A putative human homologue of the macaque area PEc.

The cortical area PEc is anatomically and functionally well-defined in macaque, but it is unknown whether it has a counterpart in human. Since we know that macaque PEc, but not the nearby posterior regions, hosts a lower limb representation, in an attempt to recognize a possible human PEc we looked for the existence of leg representations in the human parietal cortex using individual cortical surface-based analysis, task-evoked paradigms and resting-state functional connectivity. fMRI images were acquired while thirty-one participants performed long-range leg movements through an in-house MRI-compatible set-up.

Walking-related locomotion is facilitated by the perception of distant targets in the extrapersonal space.

The Gibsonian notion of affordance has been massively employed in cognitive sciences to characterize the tight interdependence between hand-related actions, manipulable objects and peripersonal space. A behavioural facilitation effect, indeed, is observed for grasping actions directed to objects located in the 'reachable' peripersonal space. Relevantly, this relationship is supported by dedicated neural systems in the brain.

Egomotion-related visual areas respond to active leg movements.

Monkey neurophysiology and human neuroimaging studies have demonstrated that passive viewing of optic flow stimuli activates a cortical network of temporal, parietal, insular, and cingulate visual motion regions. Here, we tested whether the human visual motion areas involved in processing optic flow signals simulating self-motion are also activated by active lower limb movements, and hence are likely involved in guiding human locomotion. To this aim, we used a combined approach of task-evoked activity and resting-state functional connectivity by fMRI.

Cognitive and Emotional Empathy in Individuals with Spinal Cord Injury.

Background: Empathy has been conceptualized as comprising a cognitive and an emotional component, the latter being further divided into direct and indirect aspects, which refer, respectively, to the explicit evaluation of the observer's feelings while attending someone in an emotional situation and to the physiological response of the observer. Empathy has been previously investigated in several neurological disorders.

Objective: This study is aimed at investigating empathy in patients with spinal cord injury (SCI).

FGF21 gene therapy as treatment for obesity and insulin resistance.

Prevalence of type 2 diabetes (T2D) and obesity is increasing worldwide. Currently available therapies are not suited for all patients in the heterogeneous obese/T2D population, hence the need for novel treatments. Fibroblast growth factor 21 (FGF21) is considered a promising therapeutic agent for T2D/obesity.

Cortical Brain Changes in Patients With Locked-In Syndrome Experiencing Hallucinations and Delusions.

Previous evidence suggests that hallucinations and delusions may be detected in patients with the most severe forms of motor disability including locked-in syndrome (LIS). However, such phenomena are rarely described in LIS and their presence may be underestimated as a result of the severe communication impairment experienced by the patients. In this study, we retrospectively reviewed the clinical history and the neuroimaging data of a cohort of patients with LIS in order to recognize the presence of hallucinations and delusions and to correlate it with the pontine damage and the presence of any cortical volumetric changes.

Development of the Italian Version of the Near-Death Experience Scale.

Near-death experiences (NDEs) have been defined as any conscious perceptual experience occurring in individuals pronounced clinically dead or who came very close to physical death. They are frequently reported by patients surviving a critical injury and, intriguingly, they show common features across different populations. The tool traditionally used to assess NDEs is the NDE Scale, which is available in the original English version.