Bone cell differentiation and mineralization in wild-type and osteogenesis imperfecta zebrafish are compromised by per- and poly-fluoroalkyl substances (PFAS).

Perfluorinated compounds (PFAS) are well recognized toxic pollutants for humans, but if their effect is equally harmful for healthy and fragile people is unknown. Addressing this question represents a need for ensuring global health and wellbeing to all individuals in a world facing the progressive increase of aging and aging related diseases. This study aimed to evaluate the impact of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA) and perfluorohexanoic acid (PFHxA) exposure on development and skeletal phenotype using the osteogenesis imperfecta (OI) zebrafish model Chihuahua (Chi/+), carrying a dominant glycine substitution in the α1 chain of collagen I and their wild-type (WT) littermates.

Venoarterial extracorporeal membrane oxygenation using magnetic levitation centrifugal pumps for fulminant myocarditis in infants, children and young adults.

Background: Fulminant myocarditis (FM) is a potentially lethal disease with a wide spectrum of clinical presentation, thus making the diagnosis hard to depict. In cases where acute circulatory failure occurs venoarterial (VA) extracorporeal membrane oxygenation (ECMO) support is a valid management strategy, especially in the pediatric and adult patients. This study aims to report the results of VA ECMO for FM in our Institution.

Dual inhibition of MAPK/ERK and BMP signaling induces entorhinal-like identity in mouse ESC-derived pallial progenitors.

The mechanisms that determine distinct embryonic pallial identities remain elusive. The central role of Wnt signaling in directing dorsal telencephalic progenitors to the isocortex or hippocampus has been elucidated. Here, we show that timely inhibition of MAPK/ERK and BMP signaling in neuralized mouse embryonic stem cells (ESCs) specifies a cell identity characteristic of the allocortex.

Report on the 23rd FEBS Young Scientists' Forum 2024.

The 23rd FEBS YSF was held from 26th to 29th June 2024 in Pavia, Italy. Over 100 PhD students and early postdoctoral researchers from around 30 different countries came together at the inspiring rooms of the University of Pavia for a four-day event. This year's topic was 'Biochemistry for bridging the gap', meaning the opportunity to have a comprehensive perspective on all biochemistry applications.

Pathogenic mutations cause loss of primary cilia and Neurturin in striatal parvalbumin interneurons.

Parkinson's disease-associated, activating mutations in the LRRK2 kinase block primary cilium formation in cell culture and in specific cell types in the brain. In the striatum that is important for movement control, about half of astrocytes and cholinergic interneurons, but not the predominant medium spiny neurons, lose their primary cilia. Here, we show that mouse and human striatal parvalbumin interneurons that are inhibitory regulators of movement also lose primary cilia.

Minimally Invasive Mitral Valve Surgery in Elderly Patients: Results from a Multicenter Study.

Minimally invasive mitral valve surgery (MIMVS) has been increasingly adopted worldwide as an alternative to conventional sternotomy, especially for young patients. The remarkable results gained by MIMVS have encouraged its application in more complex and fragile patients, such as the elderly, though results in this subgroup remain controversial. It is the aim of this study to assess the postoperative outcomes of patients older than 75 years old undergoing MIMVS, and to compare these results to those of younger patients.

Zebrafish Models for Skeletal and Extraskeletal Osteogenesis Imperfecta Features: Unveiling Pathophysiology and Paving the Way for Drug Discovery.

In the last decades, the easy genetic manipulation, the external fertilization, the high percentage of homology with human genes and the reduced husbandry costs compared to rodents, made zebrafish a valid model for studying human diseases and for developing new therapeutical strategies. Since zebrafish shares with mammals the same bone cells and ossification types, it became widely used to dissect mechanisms and possible new therapeutic approaches in the field of common and rare bone diseases, such as osteoporosis and osteogenesis imperfecta (OI), respectively. OI is a heritable skeletal disorder caused by defects in gene encoding collagen I or proteins/enzymes necessary for collagen I synthesis and secretion.

Impact of size and fragmentation of the anteroinferior glenoid rim on clinical and functional outcomes of non-operatively treated Bony Bankart lesions in middle-aged population.

Introduction: The optimal treatment approach for Bony Bankart remains a subject of considerable debate among shoulder surgeons. Existing literature highlights low recurrence rates and high patient satisfaction with nonoperative treatment, particularly in the middle-aged population. This study aimed to evaluate the recurrence rate of dislocation, as well as the clinical and functional outcomes in middle-aged individuals treated nonoperatively following an acute bony Bankart fracture.

Loss of primary cilia and dopaminergic neuroprotection in pathogenic LRRK2-driven and idiopathic Parkinson's disease.

Activating leucine-rich repeat kinase 2 (LRRK2) mutations cause Parkinson's and phosphorylation of Rab10 by pathogenic LRRK2 blocks primary ciliogenesis in cultured cells. In the mouse brain, LRRK2 blockade of primary cilia is highly cell type specific: For example, cholinergic interneurons and astrocytes but not medium spiny neurons of the dorsal striatum lose primary cilia in LRRK2-pathway mutant mice. We show here that the cell type specificity of LRRK2-mediated cilia loss is also seen in human postmortem striatum from patients with LRRK2 pathway mutations and idiopathic Parkinson's.

Mechanisms of Action of Phytoestrogens and Their Role in Familial Adenomatous Polyposis.

Familial adenomatous polyposis (FAP) is a rare disease characterized by the development of adenomatous polyps in the colon and rectum already in adolescence. If left untreated, patients develop colorectal cancer (CRC) with a 100% probability. To date, the gold standard of FAP management is surgery, which is associated with morbidity and mortality.

Mental Disorders Among Healthcare Students Attending a Large University Hospital in Milan, Italy.

Background: The high incidence rates, treatment difficulties, and tendency to become chronic, which subsequently affects personal and occupational functioning, make mental health disorders among the most important public health concerns. In this context, healthcare university students (HS) appear to be more vulnerable to psychological distress than others.

Objective: Investigate the prevalence of diagnosed mental illness among different groups of HS to detect students who may be psychologically vulnerable and determine whether the implementation of support interventions is necessary.

RAB32 Ser71Arg in autosomal dominant Parkinson's disease: linkage, association, and functional analyses.

Background: Parkinson's disease is a progressive neurodegenerative disorder with multifactorial causes, among which genetic risk factors play a part. The RAB GTPases are regulators and substrates of LRRK2, and variants in the LRRK2 gene are important risk factors for Parkinson's disease. We aimed to explore genetic variability in RAB GTPases within cases of familial Parkinson's disease.

Nanoremediation and Antioxidant Potential of Biogenic Silver Nanoparticles Synthesized Using Leucena's Leaves, Stem, and Fruits.

Synthetic dyes are persistent organic environmental pollutants that can cause extensive damage to living beings and to the ecosystem as a whole. Cost-effective, sustainable, and efficient strategies to deal with this type of pollution are necessary as it commonly resists conventional water treatment methods. Silver nanoparticles (AgNPs) synthesized using the aqueous extract from the leaves, stem, and fruits of (Leucena) were produced and characterized through UV-vis, TEM, EDS, SDL, XPS, XRD, and zeta potential, and they proved to be able to promote adsorption to remediate methylene blue and tartrazine pollution in water.

Loss of primary cilia and dopaminergic neuroprotection in pathogenic LRRK2-driven and idiopathic Parkinson's disease.

Activating LRRK2 mutations cause Parkinson's disease. Previously, we showed that cholinergic interneurons and astrocytes but not medium spiny neurons of the dorsal striatum lose primary cilia in LRRK2 mutant mice. Single nucleus RNA sequencing shows that cilia loss in cholinergic interneurons correlates with higher LRRK2 expression and decreased glial derived neurotrophic factor transcription.

A pathogenic variant in RAB32 causes autosomal dominant Parkinson's disease and activates LRRK2 kinase.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder. Mendelian forms have revealed multiple genes, with a notable emphasis on membrane trafficking; RAB GTPases play an important role in PD as a subset are both regulators and substrates of LRRK2 protein kinase. To explore the role of RAB GTPases in PD, we undertook a comprehensive examination of their genetic variability in familial PD.

Rab29-dependent asymmetrical activation of leucine-rich repeat kinase 2.

Gain-of-function mutations in , which encodes the leucine-rich repeat kinase 2 (LRRK2), are the most common genetic cause of late-onset Parkinson's disease. LRRK2 is recruited to membrane organelles and activated by Rab29, a Rab guanosine triphosphatase encoded in the locus. We present cryo-electron microscopy structures of Rab29-LRRK2 complexes in three oligomeric states, providing key snapshots during LRRK2 recruitment and activation.

Parkinson's VPS35[D620N] mutation induces LRRK2-mediated lysosomal association of RILPL1 and TMEM55B.

We demonstrate that the Parkinson's VPS35[D620N] mutation alters the expression of ~220 lysosomal proteins and stimulates recruitment and phosphorylation of Rab proteins at the lysosome. This recruits the phospho-Rab effector protein RILPL1 to the lysosome where it binds to the lysosomal integral membrane protein TMEM55B. We identify highly conserved regions of RILPL1 and TMEM55B that interact and design mutations that block binding.

Pancreatic Neuroendocrine Tumors in MEN1 Patients: Difference in Post-Operative Complications and Tumor Progression between Major and Minimal Pancreatic Surgeries.

Pancreatic neuroendocrine neoplasms (PNENs) affect over 80% of patients with multiple endocrine neoplasia type 1 (MEN1). Surgery is usually the therapy of choice, but the real immediate and long-term therapeutic benefit of a partial extensive pancreatic resection remains controversial. We analyzed, in 43 PNEN MEN1 patients who underwent 19 pancreaticoduodenectomies (PD), 19 distal pancreatectomies (DP), and 5 minimal pancreatectomies, the prevalence of surgery-derived early complications and post-operative pancreatic sequelae, and the PNEN relapse-free survival time after surgery, comparing major (PD+DP) and minimal pancreatic surgeries.

Genome-wide screen reveals Rab12 GTPase as a critical activator of Parkinson's disease-linked LRRK2 kinase.

Activating mutations in the leucine-rich repeat kinase 2 (LRRK2) cause Parkinson's disease. LRRK2 phosphorylates a subset of Rab GTPases, particularly Rab10 and Rab8A, and we showed previously that these phosphoRabs play an important role in LRRK2 membrane recruitment and activation (Vides et al., 2022).

Low-molecular-weight heparin for the prevention of clinical worsening in severe non-critically ill COVID-19 patients: a joint analysis of two randomized controlled trials.

Coronavirus disease 2019 (COVID-19) carries a high risk of vascular thrombosis. However, whether a specific anticoagulation intensity strategy may prevent clinical worsening in severe COVID-19 patients is still debated. We conducted a joint analysis of two randomized controlled trials, COVID-19 HD (NCT044082359) and EMOS-COVID (NCT04646655), to assess the efficacy and safety of two anticoagulant regimens in hospitalized severe COVID-19 patients.

A blood-based marker of mitochondrial DNA damage in Parkinson's disease.

Parkinson's disease (PD) is the most common neurodegenerative movement disorder, and neuroprotective or disease-modifying interventions remain elusive. High-throughput markers aimed at stratifying patients on the basis of shared etiology are required to ensure the success of disease-modifying therapies in clinical trials. Mitochondrial dysfunction plays a prominent role in the pathogenesis of PD.

Development of a highly potent and selective degrader of LRRK2.

The discovery of disease-modifying therapies for Parkinson's Disease (PD) represents a critical need in neurodegenerative medicine. Genetic mutations in leucine-rich repeat kinase 2 (LRRK2) are risk factors for the development of PD, and some of these mutations have been linked to increased LRRK2 kinase activity and neuronal toxicity in cellular and animal models. Furthermore, LRRK2 function as a scaffolding protein in several pathways has been implicated as a plausible mechanism underlying neurodegeneration caused by LRRK2 mutations.