Publications by authors named "Baldelli P"

Article Synopsis
  • Neurons rely on autophagy, a process that recycles damaged proteins and organelles, to maintain cellular health and function over their long lifespan, particularly in the face of challenges like starvation.
  • Research shows that a neuron-specific protein called APache plays a critical role in autophagy by helping transport autophagosomes back to the cell body, affecting synaptic health.
  • Silencing APache disrupts this transport, leading to an accumulation of autophagosomes at synapses which may contribute to early neurodegenerative issues linked to impaired autophagy.
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Introduction: While prior literature demonstrates gender-based differences in surgical residents' self-assessments, limited data exist examining these effects at the medical student level. This study aimed to understand how self-ratings of clinical performance differ across genders for clerkship students.

Methods: This was a retrospective study examining the results of an institutional Clinical Performance Examination administered at the end of the clerkship year.

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Light-driven modulation of neuronal activity at high spatial-temporal resolution is becoming of high interest in neuroscience. In addition to optogenetics, nongenetic membrane-targeted nanomachines that alter the electrical state of the neuronal membranes are in demand. Here, we engineered and characterized a photoswitchable conjugated compound (BV-1) that spontaneously partitions into the neuronal membrane and undergoes a charge transfer upon light stimulation.

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Article Synopsis
  • The study focuses on the role of endocannabinoids in epilepsy, particularly through the lens of SYN2 gene mutations associated with disorders like epilepsy and autism.
  • The researchers analyzed how these endocannabinoids affect excitatory (glutamatergic) and inhibitory (GABAergic) synapses in a specific type of brain cell in Synapsin II knockout mice at different developmental stages.
  • Findings indicate that endocannabinoids enhance excitatory synaptic suppression in young pre-symptomatic mice, but do not affect inhibitory transmission, highlighting a potential mechanism that helps stabilize the network in this genetic model of epilepsy.
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Dietary restriction, such as low glycemic index diet (LGID), have been successfully used to treat drug-resistant epilepsy. However, if such diet could also counteract antiepileptogenesis is still unclear. Here, we investigated whether the administration of LGID during the latent pre-epileptic period, prevents or delays the appearance of the overt epileptic phenotype.

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Introduction: High mammographic breast density (MBD) is an independent breast cancer risk factor. In organised breast screening settings, discussions are ongoing regarding the optimal clinical role of MBD to help guide screening decisions. The aim of this scoping review was to provide an overview of current practices incorporating MBD within population-based breast screening programmes and from professional organisations internationally.

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PRRT2 is a neuronal protein that controls neuronal excitability and network stability by modulating voltage-gated Na channel (Nav). PRRT2 pathogenic variants cause pleiotropic syndromes including epilepsy, paroxysmal kinesigenic dyskinesia and episodic ataxia attributable to loss-of-function pathogenetic mechanism. Based on the evidence that the transmembrane domain of PRRT2 interacts with Nav1.

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Proline-rich transmembrane protein 2 (PRRT2) is the single causative gene for pleiotropic paroxysmal syndromes, including epilepsy, kinesigenic dyskinesia, episodic ataxia, and migraine. PRRT2 is a neuron-specific type-2 membrane protein with a COOH-terminal intramembrane domain and a long proline-rich NH-terminal cytoplasmic region. A large array of experimental data indicates that PRRT2 is a neuron stability gene that negatively controls intrinsic excitability by regulating surface membrane localization and biophysical properties of voltage-dependent Na channels Nav1.

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Neuron-restrictive silencer factor/repressor element 1 (RE1)-silencing transcription factor (NRSF/REST) is a transcriptional repressor of a large cluster of neural genes containing RE1 motifs in their promoter region. NRSF/REST is ubiquitously expressed in non-neuronal cells, including astrocytes, while it is down-regulated during neuronal differentiation. While neuronal NRSF/REST homeostatically regulates intrinsic excitability and synaptic transmission, the role of the high NRSF/REST expression levels in the homeostatic functions of astrocytes is poorly understood.

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Proline-rich transmembrane protein 2 (PRRT2) is a neuron-specific protein implicated in the control of neurotransmitter release and neural network stability. Accordingly, PRRT2 loss-of-function mutations associate with pleiotropic paroxysmal neurological disorders, including paroxysmal kinesigenic dyskinesia, episodic ataxia, benign familial infantile seizures, and hemiplegic migraine. PRRT2 is a negative modulator of the membrane exposure and biophysical properties of Na channels Na1.

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Synapsin I (SynI) is a synaptic vesicle (SV)-associated phosphoprotein that modulates neurotransmission by controlling SV trafficking. The SynI C-domain contains a highly conserved ATP binding site mediating SynI oligomerization and SV clustering and an adjacent main Ca binding site, whose physiological role is unexplored. Molecular dynamics simulations revealed that the E373K point mutation irreversibly deletes Ca binding to SynI, still allowing ATP binding, but inducing a destabilization of the SynI oligomerization interface.

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Introduction: Efforts to improve pain education and knowledge about prescription opioid misuse and opioid/substance use disorder in undergraduate medical education continue to be inadequate. To advance educational practices and address training needs to counter the opioid epidemic, we created a longitudinal pain and addiction curriculum that includes three patient vignettes in which the patient requests an early refill of opioid medication. The goal was to introduce students to the potential impact of personal biases on health care delivery and medical decision-making with patients who have pain and/or substance use disorders.

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. Mammogram image quality in European breast screening systems is defined by threshold gold thickness () assessment of the CDMAM contrast-detail phantom. Previous studies have outlined several limitations of the phantom including expense, number of images required and inter-phantom manufacturing variability.

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The repressor-element 1-silencing transcription/neuron-restrictive silencer factor (REST/NRSF) controls hundreds of neuron-specific genes. We showed that REST/NRSF downregulates glutamatergic transmission in response to hyperactivity, thus contributing to neuronal homeostasis. However, whether GABAergic transmission is also implicated in the homeostatic action of REST/NRSF is unknown.

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Loss-of-function mutations in proline-rich transmembrane protein-2 (PRRT2) cause paroxysmal disorders associated with defective Ca dependence of glutamatergic transmission. We find that either acute or constitutive PRRT2 deletion induces a significant decrease in the amplitude of evoked excitatory postsynaptic currents (eEPSCs) that is insensitive to extracellular Ca and associated with a reduced contribution of P/Q-type Ca channels to the EPSC amplitude. This synaptic phenotype parallels a decrease in somatic P/Q-type Ca currents due to a decreased membrane targeting of the channel with unchanged total expression levels.

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Purpose: The aim of this work was to compare, in a clinical study, digital mammography and synthetic mammography imaging by evaluating the contrast in microcalcifications of different sizes.

Methods: A retrospective review of microcalcifications from 46 patients was undertaken. A Hologic 3-Dimensions mammography system and a HD Combo protocol was used for simultaneous acquisition of the digital and synthetic images.

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Mutations in PRoline Rich Transmembrane protein 2 (PRRT2) cause pleiotropic syndromes including benign infantile epilepsy, paroxysmal kinesigenic dyskinesia, episodic ataxia, that share the paroxysmal character of the clinical manifestations. PRRT2 is a neuronal protein that plays multiple roles in the regulation of neuronal development, excitability, and neurotransmitter release. To better understand the physiopathology of these clinical phenotypes, we investigated PRRT2 interactome in mouse brain by a pulldown-based proteomic approach and identified α1 and α3 Na/K ATPase (NKA) pumps as major PRRT2-binding proteins.

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PRoline-Rich Transmembrane protein-2 (PRRT2) is a recently described neuron-specific type-2 integral membrane protein with a large cytosolic N-terminal domain that distributes in presynaptic and axonal domains where it interacts with several presynaptic proteins and voltage-gated Na channels. Several PRRT2 mutations are the main cause of a wide and heterogeneous spectrum of paroxysmal disorders with a loss-of-function pathomechanism. The highest expression levels of PRRT2 in brain occurs in cerebellar granule cells (GCs) and cerebellar dysfunctions participate in the dyskinetic phenotype of PRRT2 knockout (KO) mice.

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Neuroinflammation is involved in the pathogenesis of several neurologic disorders, including epilepsy. Both changes in the input/output functions of synaptic circuits and cell Ca dysregulation participate in neuroinflammation, but their impact on neuron function in epilepsy is still poorly understood. Lipopolysaccharide (LPS), a toxic byproduct of bacterial lysis, has been extensively used to stimulate inflammatory responses both and LPS stimulates Toll-like receptor 4, an important mediator of the brain innate immune response that contributes to neuroinflammation processes.

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In the healthy brain, neuronal excitability and synaptic strength are homeostatically regulated to keep neuronal network activity within physiological boundaries. Epilepsy is characterized by episodes of highly synchronized firing across in widespread neuronal populations, due to a failure in regulation of network activity. Here we consider epilepsy as a failure of homeostatic plasticity or as a maladaptive response to perturbations in the activity.

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The ability to document a patient encounter is integral for any physician. Previous studies indicate that medical students' note writing skills are poor due to a lack of formal clinical documentation instruction. Barriers to formally teaching students how to write patient notes include the significant time burden and variability in faculty feedback.

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Optical technologies allowing modulation of neuronal activity at high spatio-temporal resolution are becoming paramount in neuroscience. In this respect, azobenzene-based photoswitches are promising nanoscale tools for neuronal photostimulation. Here we engineered a light-sensitive azobenzene compound (Ziapin2) that stably partitions into the plasma membrane and causes its thinning through trans-dimerization in the dark, resulting in an increased membrane capacitance at steady state.

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Purpose: Detector uniformity is an important parameter in digital mammography to guarantee a level of image quality adequate for early detection of breast cancer. Many problems with digital systems have been determined through the uniformity measurement, primarily as a result of incorrect flat-field calibration and artifacts caused by image receptor defects. The European guidelines suggest a method for the image uniformity assessment based on measurement of Signal-to-Noise ratio (SNR) and Pixel Value (PV) across a uniform image.

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Neurotransmitters can be released either synchronously or asynchronously with respect to action potential timing. Synapsins (Syns) are a family of synaptic vesicle (SV) phosphoproteins that assist gamma-aminobutyric acid (GABA) release and allow a physiological excitation/inhibition balance. Consistently, deletion of either or both Syn1 and Syn2 genes is epileptogenic.

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: The microbiota-gut brain (MGB) axis is the bidirectional communication between the intestinal microbiota and the brain. An increasing body of preclinical and clinical evidence has revealed that the gut microbial ecosystem can affect neuropsychiatric health. However, there is still a need of further studies to elucidate the complex gene-environment interactions and the role of the MGB axis in neuropsychiatric diseases, with the aim of identifying biomarkers and new therapeutic targets, to allow early diagnosis and improving treatments.

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