Publications by authors named "Gobbi L"

Purpose: The monoacylglycerol lipase (MAGL) plays a pivotal role in modulating the endocannabinoid system and is considered an attractive therapeutic target for diseases in both the central nervous system and periphery. The current study aimed to develop and evaluate a suitable carbon-11 labeled tracer for imaging MAGL in preclinical studies.

Methods: (R)-YH168 was synthesized via a multi-step pathway and its half-maximal inhibitory concentration (IC) values were measured using an enzymatic assay.

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Cell-free enzymatic assays are highly useful tools in early compound profiling due to their robustness and scalability. However, their inadequacy to reflect the complexity of target engagement in a cellular environment may lead to a significantly divergent pharmacology that is eventually observed in cells. The discrepancy that emerges from properties like permeability and unspecific protein binding may largely mislead lead compound selection to undergo further chemical optimization.

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: The advantage of a robotic-assisted (RARP) over a laparoscopic (LRP) approach in radical prostatectomy (RP) remains to be demonstrated. : The aim of the study is to use a homogeneous population in real life and single primary surgeon surgery to analyze the oncological and functional results based on the type of surgical approach and pathological features. : This is a prospective trial on non-metastatic prostate cancer (PCa) patients considered after a multidisciplinary decision to conduct a RP, using a RARP or LRP approach.

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Monoacylglycerol lipase (MAGL) is a key enzyme involved in the metabolism of the endogenous signaling ligand 2-arachidonoylglycerol, a neuroprotective endocannabinoid intimately linked to central nervous system (CNS) disorders associated with neuroinflammation. In the quest for novel MAGL inhibitors, a focused screening approach on a Roche library subset provided a reversible benzoxazinone hit exhibiting high ligand efficiency. The subsequent design of the three-dimensional -hexahydro-pyrido-oxazinone (-HHPO) moiety as benzoxazinone replacement enabled the combination of high MAGL potency with favorable ADME properties.

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The endocannabinoid system (ECS) is a critical regulatory network composed of endogenous cannabinoids (eCBs), their synthesizing and degrading enzymes, and associated receptors. It is integral to maintaining homeostasis and orchestrating key functions within the central nervous and immune systems. Given its therapeutic significance, we have launched a series of drug discovery endeavors aimed at ECS targets, including peroxisome proliferator-activated receptors (PPARs), cannabinoid receptors types 1 (CB1R) and 2 (CB2R), and monoacylglycerol lipase (MAGL), addressing a wide array of medical needs.

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Managing mineral bone disease (MBD) could reduce cardiovascular risk and improve the survival of dialysis patients. Our study focuses on the impact of calcium bath exposure in dialysis patients by comparing peritoneal dialysis patients (PD, intervention group) and hemodialysis patients (HD, control group). We assessed various factors, including calcium, phosphorus, magnesium, PTH, vitamin D 25-OH, C-terminal telopeptide (CTX), and FGF-23 levels, as well as the calcium bath six hours before the blood sample and the length of daily calcium exposure.

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Background: Impairments in postural responses to perturbation are common in people with Parkinson's disease (PwPD) and lack effective treatment. We recently showed that a single session of transcranial direct current stimulation (tDCS) promotes acute improvement of postural response to perturbation in PwPD. However, the effects of multiple tDCS sessions remain unclear.

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Background And Objective: Several minimally invasive treatments have been developed to treat benign prostatic obstruction (BPO) via a transurethral approach, with a non-negligible risk of complications such as urethral stricture and external sphincter damage. Our aim was to present the Gozzi surgical technique for suprapubic transvesical adenoma resection of the prostate (STAR-P) for BPO and to assess its safety, feasibility, and outcomes.

Methods: We conducted a retrospective analysis of 44 consecutive patients who underwent STAR-P for BPO.

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Gait impairments negatively affect the quality of life of people with Parkinson's disease (PwPD). Aerobic exercise (AE) is an alternative to alleviate these impairments and its combination with transcranial direct current stimulation (tDCS) has demonstrated synergistic effects. However, the effect of multitarget tDCS application (i.

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Monoacylglycerol lipase (MAGL) plays a crucial role in the degradation of 2-arachidonoylglycerol (2-AG), one of the major endocannabinoids in the brain. Inhibiting MAGL could lead to increased levels of 2-AG, which showed beneficial effects on pain management, anxiety, inflammation, and neuroprotection. In the current study, we report the characterization of an enantiomerically pure (R)-[C]YH132 as a novel MAGL PET tracer.

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This study aimed to evaluate ()-[F]YH134 as a novel PET tracer for imaging monoacylglycerol lipase (MAGL). Considering the ubiquitous expression of MAGL throughout the whole body, the impact of various MAGL inhibitors on ()-[F]YH134 brain uptake and its application in brain-periphery crosstalk were explored. MAGL knockout and wild-type mice were used to evaluate ()-[F]YH134 in in vitro autoradiography and PET experiments.

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Varicella Zoster Virus (VZV) infection is a common childhood exanthematous disease, which in adults and immunocompromised people may result in severe neurologic complications. Up to one-third of infected subjects may have VZV clinical reactivation particularly if immunocompromised. Patients affected by end-stage renal disease on hemodialysis present immunodepression that contributes to their higher incidence of VZV infections and reactivation.

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The cannabinoid type 2 receptor (CB2) has been implicated in a variety of central and peripheral inflammatory diseases, prompting significant interest in the development of CB2-targeted diagnostic and therapeutic agents. A validated positron emission tomography (PET) radioligand for imaging CB2 in the living human brain as well as in peripheral tissues is currently lacking. As part of our research program, we have recently identified the trisubstituted pyridine, [F]RoSMA-18-d, which proved to be highly suitable for and mapping of CB2 in rodents.

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Introduction: To analyze whether the use of an intermittent (IAD) versus continuous (CAD) androgen deprivation therapy for the treatment of biochemical progression after primary treatments in prostate cancer can influence the development of nonmetastatic castration resistant prostate cancer (CRPC-M0).

Patients: 170 male patients with an histologically confirmed diagnosis of PC, presenting a biochemical progression after primary treatments (82 after radical prostatectomy and 88 after external radiation therapy), nonmetastatic at imaging were considered for continuous (85 cases) or intermittent (85 cases) administration of androgen deprivation therapy.

Methods: we retrospectively collect all data regarding histological diagnosis, primary treatment, imaging for M0-M1 staging, PSA at progression, time to biochemical progression from primary therapy, ADT used, IAD cycles, so to compare in 2 groups (IAD vs.

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Purpose: Reinke's edema (RE) is a pathological condition involving increased volume of the vocal folds and resulting in significant impact on speech, fundamental frequency, and vocal range. Literature reports few studies which analyze vocal features according to the severity of RE. The aims of this study were to investigate the aerodynamics, acoustic characteristics, and sound spectrograms of a group of RE patients and to assess whether there was any correlation with their endoscopic grading.

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The pretargeting approach separates the biological half-life of an antibody from the physical half-life of the radioisotope label, providing a strategy for reducing the radiation burden. A widely explored pretargeting approach makes use of the bioorthogonal click reaction between tetrazines (Tzs) and -cyclooctenes (TCOs), combining the targeting specificity of monoclonal antibodies (mAbs) with the rapid clearance and precise reaction of Tzs and TCOs. Such a strategy can allow for the targeting and imaging (e.

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The introduction of pathways to enrol deceased donors after cardio-circulatory confirmation of death (donation after circulatory death, DCD) is expanding in many countries to face the shortage of organs for transplantation. The implementation of normothermic regional reperfusion (NRP) with warm oxygenated blood is a strategy to manage in-situ the organs of DCD donors. This approach, an alternative to in-situ cold preservation, and followed by prompt retrieval and cold static storage and/or ex-vivo machine perfusion (EVMP), could be limited to abdominal organs (A-NRP) or extended to the thorax (thoraco-abdominal, TA-NRP.

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Exosomes are extracellular nanovesicles (EV), that is, carriers of different biomolecules such as lipids, proteins, nucleic acids. Their composition and the fact that their release dramatically increases in cases of tumorigenesis open up different scenarios on their possible application to research into new biomarkers. The first purpose of the present review was to specifically analyze and compare different methodologies available for the use of exosomes in prostate cancer (PC).

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Background: Balance impairments in people with Parkinson's disease (PD) demonstrated mainly in challenging postural tasks, such as increased body oscillation may be attributed to the deficits in the brain structures functionality involved in postural control (e.g., motor cortex, midbrain, and brainstem).

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The neural correlates of locomotion impairments observed in people with Parkinson's disease (PD) are not fully understood. We investigated whether people with PD present distinct brain electrocortical activity during usual walking and the approach phase of obstacle avoidance when compared to healthy individuals. Fifteen people with PD and fourteen older adults walked overground in two conditions: usual walking and obstacle crossing.

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Background: Monitoring anesthesia depth in children is challenging. Pediatric anesthesiologists estimate general anesthesia depth using indirect methods such as pharmacokinetic models and neurovegetative reflexes. The application of processed electroencephalography may help to identify the correct anesthesia depth (i.

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Background: Erector spinae plane block is a locoregional anaesthetic technique widely used in several different surgeries due to its safety and efficacy. The aim of this study is to assess its utility in spinal degenerative and traumatic surgery in western countries and for patients of Caucasian ethnicity.

Methods: Patients undergoing elective lower-thoracic and lumbar spinal fusion were randomised into two groups: the case group (n = 15) who received erector spinae plane block (ropivacaine 0.

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The beta-site amyloid precursor protein cleaving enzyme (BACE1) is responsible for initiating the generation of beta-amyloid, the major constituent of amyloid plaques in Alzheimer's disease (AD). The purpose of this study was to develop a specific BACE1 radioligand for visualization of the distribution pattern and quantification of the BACE1 protein in the rodent and monkey brain both in vitro by autoradiography and in vivo by positron emission tomography (PET). The BACE1 inhibitor RO6807936 originating from an in-house chemical drug optimization program was selected based on its PET tracer-like physicochemical properties and a favorable pharmacokinetic profile.

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Objective: The main objective was to evaluate the anterior flexion force (AFF) and the lateral abduction force (LAF) of patients who underwent reverse shoulder arthroplasty (RSA) and to compare the measured force with that in a similar-age control group. The secondary objective was to identify prognostic factors for muscle strength recovery.

Methods: Forty-two shoulders that underwent primary RSA between September 2009 and April 2020 met the inclusion criteria and were called the arthroplasty group (AG).

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