Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination.

During the development of the nervous system, there is an overproduction of neurons and synapses. Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or strengthening. We have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway, at the neuromuscular junction, in the axonal development and synapse elimination process versus the synapse consolidation.

Evaluating Person-Centred Integrated Care to People with Complex Chronic Conditions: Early Implementation Results of the ProPCC Programme.

Introduction: The evaluation of integrated care programmes for older people is a challenge. We aim to share the early implementation results of the ProPCC programme in the North-Barcelona metropolitan area, in Catalonia, Spain.

Methods: We analysed the intervention with retrospective data from May 2018 to December 2021 by describing the cohort complexity and by showing its 6-months pre-post impact on time spent at home and resources used: primary care visits, emergency department visits, hospital admissions and hospital stay.

Genotypic and phenotypic characterization of a Salmonella Typhimurium strain resistant to pulsed electric fields.

Pulsed Electric Fields (PEF) technology is regarded as one of the most interesting alternatives to current food preservation methods, due to its capability to inactivate vegetative microorganisms while leaving the product's organoleptic and nutritional properties mostly unchanged. However, many aspects regarding the mechanisms of bacterial inactivation by PEF are still not fully understood. The aim of this study was to obtain further insight into the mechanisms responsible for the increased resistance to PEF of a Salmonella Typhimurium SL1344 variant (SL1344-RS, Sagarzazu et al.

An Engineered IFNγ-Antibody Fusion Protein with Improved Tumor-Homing Properties.

Interferon-gamma (IFNγ) is one of the central cytokines produced by the innate and adaptive immune systems. IFNγ directly favors tumor growth control by enhancing the immunogenicity of tumor cells, induces IP-10 secretion facilitating (CXCR3+) immune cell infiltration, and can prime macrophages to an M1-like phenotype inducing proinflammatory cytokine release. We had previously reported that the targeted delivery of IFNγ to neoplastic lesions may be limited by the trapping of IFNγ-based products by cognate receptors found in different organs.

Muscarinic Receptors in Developmental Axonal Competition at the Neuromuscular Junction.

In recent years, we have studied by immunohistochemistry, intracellular recording, and western blotting the role of the muscarinic acetylcholine receptors (mAChRs; M, M, and M subtypes) in the mammalian neuromuscular junction (NMJ) during development and in the adult. Here, we evaluate our published data to emphasize the mAChRs' relevance in developmental synaptic elimination and their crosstalk with other metabotropic receptors, downstream kinases, and voltage-gated calcium channels (VGCCs). The presence of mAChRs in the presynaptic membrane of motor nerve terminals allows an autocrine mechanism in which the secreted acetylcholine influences the cell itself in feedback.

Glutamatergic synapse in autism: a complex story for a complex disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose pathophysiological mechanisms are still unclear. Hypotheses suggest a role for glutamate dysfunctions in ASD development, but clinical studies investigating brain and peripheral glutamate levels showed heterogenous results leading to hypo- and hyper-glutamatergic hypotheses of ASD. Recently, studies proposed the implication of elevated mGluR5 densities in brain areas in the pathophysiology of ASD.

Selection of a PD-1 blocking antibody from a novel fully human phage display library.

Programmed cell death protein 1 (PD-1) is an immunoregulatory target which is recognized by different monoclonal antibodies, approved for the therapy of multiple types of cancer. Different anti-PD-1 antibodies display different therapeutic properties and there is a pharmaceutical interest to generate and characterize novel anti-PD-1 antibodies. We screened multiple human antibody phage display libraries to target novel epitopes on the PD-1 surface and we discovered a unique and previously undescribed binding specificity (termed D12) from a new antibody library (termed AMG).

Fibroblast Activation Protein Triggers Release of Drug Payload from Non-internalizing Small Molecule Drug Conjugates in Solid Tumors.

Purpose: Small molecule drug conjugates (SMDC) are modular anticancer prodrugs that include a tumor-targeting small organic ligand, a cleavable linker, and a potent cytotoxic agent. Most of the SMDC products that have been developed for clinical applications target internalizing tumor-associated antigens on the surface of tumor cells. We have recently described a novel non-internalizing small organic ligand (named OncoFAP) of fibroblast activation protein (FAP), a tumor-associated antigen highly expressed in the stroma of most solid human malignancies.

Generation and validation of an IL-12 fusion protein based on a novel anti-human FAP monoclonal antibody.

Background: In this study, we describe the generation of a fully human monoclonal antibody (named '7NP2') targeting human fibroblast activation protein (FAP), an antigen expressed in the microenvironment of different types of solid neoplasms.

Methods: 7NP2 was isolated from a synthetic antibody phage display library and was improved by one round of mutagenesis-based affinity maturation. The tumor recognition properties of the antibody were validated by immunofluorescence procedures performed on cancer biopsies from human patients.

Interfacial Fracture Energy Between New Translucent Zirconias and a Resin Cement.

Purpose: To determine the interfacial fracture energy (IFE) and stress distribution of Brazil-nut-shaped specimens made of translucent zirconia and resin cement.

Materials And Methods: Three types of translucent zirconia were used: 3Y-TZP (high, Vita YZ HT), 4Y-TZP (super, Vita YZ ST), and 5Y-TZP (extra, Vita YZ XT). The adhesive surfaces were air abraded and 10-MDP-based resin cement was used.

An ultra-high-affinity small organic ligand of fibroblast activation protein for tumor-targeting applications.

We describe the development of OncoFAP, an ultra-high-affinity ligand of fibroblast activation protein (FAP) for targeting applications with pan-tumoral potential. OncoFAP binds to human FAP with affinity in the subnanomolar concentration range and cross-reacts with the murine isoform of the protein. We generated various fluorescent and radiolabeled derivatives of OncoFAP in order to study biodistribution properties and tumor-targeting performance in preclinical models.

Impact of the Resistance Responses to Stress Conditions Encountered in Food and Food Processing Environments on the Virulence and Growth Fitness of Non-Typhoidal .

The success of as a foodborne pathogen can probably be attributed to two major features: its remarkable genetic diversity and its extraordinary ability to adapt. cells can survive in harsh environments, successfully compete for nutrients, and cause disease once inside the host. Furthermore, they are capable of rapidly reprogramming their metabolism, evolving in a short time from a stress-resistance mode to a growth or virulent mode, or even to express stress resistance and virulence factors at the same time if needed, thanks to a complex and fine-tuned regulatory network.

The Role of Computed Tomography in Zygomatic Bone Fracture - A Case Report.

Introduction: The zygomatic complex is integral to the facial contour, protection of the eye and other facial structures, and dental occlusion. Its importance in facial function and aesthetics requires high quality outcomes of the treatment.

Case Presentation: This paper reports the case of a 46-year-old man who had an occupational accident resulting in extensive facial trauma and zygomatic fractures.

Distinct Hippocampal Subfields Atrophy in Older People With Vascular Brain Injuries.

Background And Purpose: Many neurological or psychiatric diseases affect the hippocampus during aging. The study of hippocampal regional vulnerability may provide important insights into the pathophysiological mechanisms underlying these processes; however, little is known about the specific impact of vascular brain damage on hippocampal subfields atrophy.

Methods: To analyze the effect of vascular injuries independently of other pathological conditions, we studied a population-based cohort of nondemented older adults, after the exclusion of people who were diagnosed with neurodegenerative diseases during the 14-year clinical follow-up period.

Novel human monoclonal antibodies specific to the alternatively spliced domain D of Tenascin C efficiently target tumors .

Antibody-based delivery of bioactive molecules represents a promising strategy for the improvement of cancer immunotherapy. Here, we describe the generation and characterization of R6N, a novel fully human antibody specific to the alternatively spliced domain D of Tenascin C, which is highly expressed in the stroma of primary tumors and metastasis. The R6N antibody recognized its cognate tumor-associated antigen with identical specificity in mouse and human specimens.

Outcomes of Type II Endoleak Treatment Using Ethylene Vinyl Alcohol Copolymer (Onyx).

Introduction: This study reports our experience with the use of an ethylene vinyl alcohol copolymer (Onyx™) for the treatment of type II endoleak after endovascular repair of abdominal aortic aneurysms (EVAR) in comparison to coils and cyanoacrylate glue.

Methods: Clinical data of all patients treated for type II endoleak following EVAR between 2009 and 2017 were retrospectively analyzed. Abdominal aortic aneurysm (AAA) diameter and AAA sac volume during follow-up were measured using computed tomography angiography (CTA).

Comparison between anal cytology, high-resolution anoscopy and HPV DNA genotyping by polymerase chain reaction in the post-treatment follow-up of condylomata acuminata.

Aim: to evaluate the presence of subclinical HPV-induced anal lesions with anal cytology, High-Resolution Anoscopy (HRA) and HPV genotyping by polymerase chain reaction (PCR) in the follow-up of treated condylomata acuminata (CA).

Methods: seventy-nine male patients were included. One month after anal CA eradication, the patients underwent brush samples collection for anal cytology and PCR, and HRA with biopsy of acetowhite lesions.

The immunocytokine L19-TNF eradicates sarcomas in combination with chemotherapy agents or with immune check-point inhibitors.

Antibody-cytokine fusion proteins (also called 'immunocytokines') represent an emerging class of biopharmaceutical products, which are being considered for cancer immunotherapy. When used as single agents, pro-inflammatory immunocytokines are rarely capable of inducing complete and durable cancer regression in mouse models and in patients. However, the combination treatment with conventional chemotherapy or with other immune-stimulatory agents typically increases the therapeutic efficacy of immunocytokines.

Differential annualized rates of hippocampal subfields atrophy in aging and future Alzheimer's clinical syndrome.

Several studies have investigated the differential vulnerability of hippocampal subfields during aging and Alzheimer's disease (AD). Results were often contradictory, mainly because these works were based on concatenations of cross-sectional measures in cohorts with different ages or stages of AD, in the absence of a longitudinal design. Here, we investigated 327 participants from a population-based cohort of nondemented older adults with a 14-year clinical follow-up.

Papilledema and Peripheral Neuropathies.

Introduction: Papilledema is a common sign in ophthalmology and is typically associated with increased intracranial pressure (ICP) in neurological diseases. Since the beginning of the 20th century, some cases of papilledema have been reported in association with acute or chronic inflammatory neuropathies.

Case Report: We describe a 42-year-old man with acute-onset inflammatory polyradiculoneuropathy and bilateral papilledema.

nPKCε Mediates SNAP-25 Phosphorylation of Ser-187 in Basal Conditions and After Synaptic Activity at the Neuromuscular Junction.

Protein kinase C (PKC) and substrates like SNAP-25 regulate neurotransmission. At the neuromuscular junction (NMJ), PKC promotes neurotransmitter release during synaptic activity. Thirty minutes of muscle contraction enhances presynaptic PKC isoform levels, specifically cPKCβI and nPKCε, through retrograde BDNF/TrkB signaling.