New findings about neuropathological outcomes in the PKU mouse throughout lifespan.

Phenylketonuria (PKU, OMIM 261600) is a genetic disorder caused by a deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH). If left untreated, PKU leads to systemic phenylalanine (Phe) accumulation, which can result in irreversible brain damage and intellectual disabilities. In the last 60 years, early and strict dietary restriction of phenylalanine (Phe) intake proved to prevent the severe clinical phenotype of untreated PKU.

The Role of POCUS to Face COVID-19: A Narrative Review.

COVID-19 has been a challenging outbreak to face, with millions of deaths among the globe. Acute respiratory failure due to interstitial pneumonia was the leading cause of death other than prothrombotic activation and complications. Lung ultrasound (LUS) and point-of-care ultrasound (POCUS) are widely used not only to triage, to identify, and to monitor lungs involvement but also to assess hemodynamic status and thrombotic and hemorrhagic complications, mainly in critically ill patients.

The Role of Pocus in Acute Respiratory Failure: A Narrative Review on Airway and Breathing Assessment.

Acute respiratory failure (ARF) is a challenging condition that clinicians, especially in emergency settings, have to face frequently. Especially in emergency settings, many underlying diseases can lead to ARF and life-threatening conditions have to be promptly assessed and correctly treated to avoid unfavorable outcomes. In recent years, point-of-care ultrasound (POCUS) gained growing consideration due to its bedside utilization, reliability and reproducibility even in emergency settings especially in unstable patients.

5HT1AR-FGFR1 Heteroreceptor Complexes Differently Modulate GIRK Currents in the Dorsal Hippocampus and the Dorsal Raphe Serotonin Nucleus of Control Rats and of a Genetic Rat Model of Depression.

The midbrain raphe serotonin (5HT) neurons provide the main ascending serotonergic projection to the forebrain, including hippocampus, which has a role in the pathophysiology of depressive disorder. Serotonin 5HT1A receptor (R) activation at the soma-dendritic level of serotonergic raphe neurons and glutamatergic hippocampal pyramidal neurons leads to a decrease in neuronal firing by activation of G protein-coupled inwardly-rectifying potassium (GIRK) channels. In this raphe-hippocampal serotonin neuron system, the existence of 5HT1AR-FGFR1 heteroreceptor complexes has been proven, but the functional receptor-receptor interactions in the heterocomplexes have only been investigated in CA1 pyramidal neurons of control (SD) rats.

Inhibition of ERK1/2 signaling prevents bone marrow fibrosis by reducing osteopontin plasma levels in a myelofibrosis mouse model.

Clonal myeloproliferation and development of bone marrow (BM) fibrosis are the major pathogenetic events in myelofibrosis (MF). The identification of novel antifibrotic strategies is of utmost importance since the effectiveness of current therapies in reverting BM fibrosis is debated. We previously demonstrated that osteopontin (OPN) has a profibrotic role in MF by promoting mesenchymal stromal cells proliferation and collagen production.

Does Antithrombotic Therapy Affect Outcomes in Major Trauma Patients? A Retrospective Cohort Study from a Tertiary Trauma Centre.

Antithrombotic therapy may affect outcomes in major trauma but its role is not fully understood. We aimed to investigate adverse outcomes among those with and without antithrombotic treatment in major trauma. This is a retrospective study conducted at the Emergency Department (ED) of the University Hospital of Genoa, a tertiary trauma center, including all major trauma between January 2019 and December 2020.

The impact of different exercise protocols on rat soleus muscle reinnervation and recovery following peripheral nerve lesion and regeneration.

Incomplete functional recovery following traumatic peripheral nerve injury is common, mainly because not all axons successfully regenerate and reinnervate target muscles. Exercise can improve functional outcomes increasing the terminal sprouting during the muscle reinnervation. However, exercise is not a panacea per se.

The Response to Oxidative Damage Correlates with Driver Mutations and Clinical Outcome in Patients with Myelofibrosis.

Myelofibrosis (MF) is the Philadelphia-negative myeloproliferative neoplasm characterized by the worst prognosis and no response to conventional therapy. Driver mutations in and impact on JAK-STAT pathway activation but also on the production of reactive oxygen species (ROS). ROS play a pivotal role in inflammation-induced oxidative damage to cellular components including DNA, therefore leading to greater genomic instability and promoting cell transformation.

Role of SatO2, PaO2/FiO2 Ratio and PaO2 to Predict Adverse Outcome in COVID-19: A Retrospective, Cohort Study.

COVID-19 respiratory failure is a life-threatening condition. Oxygenation targets were evaluated in a non-ICU setting. In this retrospective, observational study, we enrolled all patients admitted to the University Hospital of Genoa, Italy, between 1 February and 31 May 2020 with an RT-PCR positive for SARS-CoV-2.

Increased Plasma Levels of lncRNAs , and Correlate with Negative Prognostic Factors in Myelofibrosis.

Long non-coding RNAs (lncRNAs) have been recently described as key mediators in the development of hematological malignancies. In the last years, circulating lncRNAs have been proposed as a new class of non-invasive biomarkers for cancer diagnosis and prognosis and to predict treatment response. The present study is aimed to investigate the potential of circulating lncRNAs as non-invasive prognostic biomarkers in myelofibrosis (MF), the most severe among Philadelphia-negative myeloproliferative neoplasms.

Mutated clones driving leukemic transformation are already detectable at the single-cell level in CD34-positive cells in the chronic phase of primary myelofibrosis.

Disease progression of myeloproliferative neoplasms is the result of increased genomic complexity. Since the ability to predict disease evolution is crucial for clinical decisions, we studied single-cell genomics and transcriptomics of CD34-positive cells from a primary myelofibrosis (PMF) patient who progressed to acute myeloid leukemia (AML) while receiving Ruxolitinib. Single-cell genomics allowed the reconstruction of clonal hierarchy and demonstrated that TET2 was the first mutated gene while FLT3 was the last one.

Genomic Analysis of Hematopoietic Stem Cell at the Single-Cell Level: Optimization of Cell Fixation and Whole Genome Amplification (WGA) Protocol.

Single-cell genomics has become the method of choice for the study of heterogeneous cell populations and represents an elective application in defining the architecture and clonal evolution in hematological neoplasms. Reconstructing the clonal evolution of a neoplastic population therefore represents the main way to understand more deeply the pathogenesis of the neoplasm, but it is also a potential tool to understand the evolution of the tumor population with respect to its response to therapy. Pre-analytical phase for single-cell genomics analysis is crucial to obtain a cell population suitable for single-cell sorting, and whole genome amplification is required to obtain the necessary amount of DNA from a single cell in order to proceed with sequencing.

Evidence for the existence of A2AR-TrkB heteroreceptor complexes in the dorsal hippocampus of the rat brain: Potential implications of A2AR and TrkB interplay upon ageing.

Adenosine A2A receptors (A2AR) are crucial in facilitating the BDNF action on synaptic transmission in the rat hippocampus primarily upon ageing. Furthermore, it has been suggested that A2AR-Tropomyosin related kinase B receptor (TrkB) crosstalk has a pivotal role in adenosine A2AR-mediated modulation of the BDNF action on hippocampal plasticity. Considering the impact of the above receptors interplay on what concerns BDNF-induced enhancement of synaptic transmission, gaining a better insight into the mechanisms behind this powerful crosstalk becomes of primary interest.

Maternal Creatine Supplementation Positively Affects Male Rat Hippocampal Synaptic Plasticity in Adult Offspring.

Creatine plays a crucial role in developing the brain, so much that its genetic deficiency results in mental dysfunction and cognitive impairments. Moreover, creatine supplementation is currently under investigation as a preventive measure to protect the fetus against oxidative stress during difficult pregnancies. Although creatine use is considered safe, posing minimal risk to clinical health, we found an alteration in morpho-functional maturation of neurons when male rats were exposed to creatine loads during brain development.

Muscle activity prevents the uncoupling of mitochondria from Ca Release Units induced by ageing and disuse.

In fast-twitch fibers from adult mice Ca release units (CRUs, i.e. intracellular junctions of excitation-contraction coupling), and mitochondria are structurally linked to each other by small strands, named tethers.

Microcirculatory Impairment Is Associated With Multiple Organ Dysfunction Following Traumatic Hemorrhagic Shock: The MICROSHOCK Study.

Objectives: To assess the relationship between microcirculatory perfusion and multiple organ dysfunction syndrome in patients following traumatic hemorrhagic shock.

Design: Multicenter prospective longitudinal observational study.

Setting: Three U.

Which method is best for an early accurate diagnosis of acute heart failure? Comparison between lung ultrasound, chest X-ray and NT pro-BNP performance: a prospective study.

Acute heart failure is a common condition among adults presenting with dyspnea in the Emergency Department (ED), still the diagnosis is challenging as objective standardized criteria are lacking. First line work-up, other then clinical findings, is nowadays made with lung ultrasound imaging study, chest X-ray study and brain natriuretic peptide (BNP) level determination; however, it is not clear which is the best diagnostic test to be used and whether there is any real benefit for clinical judgement. We set up this study to compare the performances of these three diagnostic tools; furthermore, we combined them to find the best possible approach to dyspneic patients.

Effect of Different Exercise Intensities on the Myotendinous Junction Plasticity.

Myotendinous junctions (MTJs) are anatomical regions specialized in transmission of contractile strength from muscle to tendon and, for this reason, a common site where acute injuries occur during sport activities. In this work we investigated the influence of exercise intensity on MTJ plasticity, as well as on the expression of insulin-like growth factor 1 (IGF-1) and transforming growth factor beta (TGF-β) and their receptors in muscle and tendon. Three groups of rats were analyzed: control (CTRL), slow-runner (RUN-S) and fast-runner (RUN-F) trained using a treadmill.

Duplex ultrasound in the early diagnosis of acute mesenteric ischemia: a longitudinal cohort multicentric study.

Objective: Acute mesenteric ischemia (AMI) is a life-threatening condition requiring time-dependent treatment; thus, early recognition may improve outcomes. We hypothesized that clinician-performed mesenteric vessels duplex ultrasound (DUS) could facilitate early identification of patients with AMI in high-risk patients presenting with abdominal pain.

Methods: This was a single-operator, observational, prospective cohort study.

New insights into the trophic and cytoprotective effects of creatine in in vitro and in vivo models of cell maturation.

A growing body of scientific reports indicates that the role of creatine (Cr) in cellular biochemistry and physiology goes beyond its contribution to cell energy. Indeed Cr has been shown to exert multiple effects promoting a wide range of physiological responses in vitro as well as in vivo. Included in these, Cr promotes in vitro neuron and muscle cell differentiation, viability and survival under normal or adverse conditions; anabolic, protective and pro-differentiative effects have also been observed in vivo.

Motor activity affects adult skeletal muscle re-innervation acting via tyrosine kinase receptors.

Recently, muscle expression of brain-derived neurotrophic factor (BDNF) mRNA and protein under activity control has been reported. BDNF is a neurotrophin known to be involved in axon sprouting in the CNS. Hence, we set out to study the effect of chronic treadmill mid-intensity running on adult rat muscle re-innervation, and to explore the involvement of BDNF and tropomyosin-related kinase (Trk) receptors.