Diagnosis of pulmonary embolism in patients with haemoptysis: the POPEIHE study.

Aim: To determine the prevalence and characteristics of pulmonary embolism (PE) in patients presenting with haemoptysis. Additionally, we assessed the efficiency and failure rates of different clinical diagnostic algorithms for PE in this patient population.

Methods: We enrolled consecutive adult patients who presented to nine Italian emergency departments with haemoptysis as the primary complaint.

Brain-derived gangliosides prime human platelet aggregation and induce platelet-leukocyte aggregate formation.

Background: Platelet activation and interaction with leukocytes are crucial in inflammation. Gangliosides, sialic acid-containing glycosphingolipids, have been linked to different inflammatory conditions related to cardio- and neurodegenerative disorders. The role of gangliosides in platelet and leukocyte function, although reported, still needs further investigation.

Environmental effects on genetic variance are likely to constrain adaptation in novel environments.

Adaptive plasticity allows populations to cope with environmental variation but is expected to fail as conditions become unfamiliar. In novel conditions, populations may instead rely on rapid adaptation to increase fitness and avoid extinction. Adaptation should be fastest when both plasticity and selection occur in directions of the multivariate phenotype that contain abundant genetic variation.

Consensus paper on the management of acute isolated vertigo in the emergency department.

Acute vertigo is defined as the perception of movement of oneself or the surroundings in the absence of actual motion and it is a frequent cause for emergency department admissions. The utilization of medical resources and the duration of hospital stay for this kind of symptom is high. Furthermore, the efficiency of brain imaging in the acute phase is low, considering the limited sensitivity of both CT and MRI for diagnosing diseases that are the causes of central type of vertigo.

Reversal or Repletion Treatment Strategies and Outcomes of Patients With Major Bleeding Events Managed in the Emergency Department: Large Real-Life Investigation in the Northwestern Healthcare District of Tuscany.

Objective: To verify the incidence of bleeding events in patients on ongoing anticoagulant treatment in the real world and compare the results of different reversal or repletion strategies currently available for pharmacological treatment.

Methods: Patients managed in the emergency department (ED) with major bleeding events, on ongoing anticoagulation were stratified according to bleeding site and reversal or repletion therapy with andexanet alfa (ADX), idarucizumab (IDA), prothrombin complex concentrate (PCC), and vitamin K (Vit-K).

Endpoint: Death at 30 days was compared in the subgroups with cerebral hemorrhage (CH) and gastrointestinal (GI) bleeding.

Brain-Periphery Interactions in Huntington's Disease: Mediators and Lifestyle Interventions.

Prominent pathological features of Huntington's disease (HD) are aggregations of mutated Huntingtin protein (mHtt) in the brain and neurodegeneration, which causes characteristic motor (such as chorea and dystonia) and non-motor symptoms. However, the numerous systemic and peripheral deficits in HD have gained increasing attention recently, since those factors likely modulate disease progression, including brain pathology. While whole-body metabolic abnormalities and organ-specific pathologies in HD have been relatively well described, the potential mediators of compromised inter-organ communication in HD have been insufficiently characterized.

Autoimmune Hemolytic Anemia (AIHA) Secondary to (CMV) Infection in a 2-Month-Old Infant: A Case Report.

Autoimmune hemolytic anemia (AIHA) is a rare hematologic disorder in the pediatric population and most cases are associated with microbiological infection. The pathological process is not completely clear, but some evidence suggests immunological dysregulation triggered by bacterial or viral infections. Based on the thermal range of the pathogenic antibody, AIHA can be divided into warm (WAIHA) and cold (CAIHA) groups.

Abnormal expression of sphingolipid-metabolizing enzymes in the heart of spontaneously hypertensive rat models.

Sphingolipids exert important roles within the cardiovascular system and related diseases. Perturbed sphingolipid metabolism was previously reported in cerebral and renal tissues of spontaneously hypertensive rats (SHR). Specific defects related to the synthesis of sphingolipids and to the metabolism of Sphingosine-1-Phospahte (S1P) were exclusively identified in the stroke-prone (SHRSP) with the respect to the stroke-resistant (SHRSR) strain.

Genome-wide screening in pluripotent cells identifies Mtf1 as a suppressor of mutant huntingtin toxicity.

Huntington's disease (HD) is a neurodegenerative disorder caused by CAG-repeat expansions in the huntingtin (HTT) gene. The resulting mutant HTT (mHTT) protein induces toxicity and cell death via multiple mechanisms and no effective therapy is available. Here, we employ a genome-wide screening in pluripotent mouse embryonic stem cells (ESCs) to identify suppressors of mHTT toxicity.

Blood-Brain Barrier Integrity Is Perturbed in a -Null Mouse Model of Rett Syndrome.

Rett syndrome (RTT, online MIM 312750) is a devastating neurodevelopmental disorder characterized by motor and cognitive disabilities. It is mainly caused by pathogenetic variants in the X-linked gene, encoding an epigenetic factor crucial for brain functioning. Despite intensive studies, the RTT pathogenetic mechanism remains to be fully elucidated.

Treatment with the Glycosphingolipid Modulator THI Rescues Myelin Integrity in the Striatum of R6/2 HD Mice.

Huntington's disease is one of the most common dominantly inherited neurodegenerative disorders caused by an expansion of a polyglutamine (polyQ) stretch in the N-terminal region of huntingtin (Htt). Among all the molecular mechanisms, affected by the mutation, emerging evidence proposes glycosphingolipid dysfunction as one of the major determinants. High levels of sphingolipids have been found to localize in the myelin sheaths of oligodendrocytes, where they play an important role in myelination stability and functions.

Sphingolipids and impaired hypoxic stress responses in Huntington disease.

Huntington disease (HD) is a debilitating, currently incurable disease. Protein aggregation and metabolic deficits are pathological hallmarks but their link to neurodegeneration and symptoms remains debated. Here, we summarize alterations in the levels of different sphingolipids in an attempt to characterize sphingolipid patterns specific to HD, an additional molecular hallmark of the disease.

Contemporary Management and Clinical Course of Acute Pulmonary Embolism: The COPE Study.

Background:  New diagnosis, risk stratification, and treatment strategies became recently available for patients with acute pulmonary embolism (PE) leading to changes in clinical practice and potentially influencing short-term patients' outcomes.

Research Question:  The COntemporary management of PE (COPE) study is aimed at assessing the contemporary clinical management and outcomes in patients with acute symptomatic PE.

Study Design And Methods:  Prospective, noninterventional, multicenter study.

Common and Rare Variants in TMEM175 Gene Concur to the Pathogenesis of Parkinson's Disease in Italian Patients.

Parkinson's disease (PD) represents the most common neurodegenerative movement disorder. We recently identified 16 novel genes associated with PD. In this study, we focused the attention on the common and rare variants identified in the lysosomal K channel TMEM175.

Treatment with THI, an inhibitor of sphingosine-1-phosphate lyase, modulates glycosphingolipid metabolism and results therapeutically effective in experimental models of Huntington's disease.

Huntington's disease (HD) is a fatal neurodegenerative disorder with no effective cure currently available. Over the past few years our research has shown that alterations in sphingolipid metabolism represent a critical determinant in HD pathogenesis. In particular, aberrant metabolism of sphingosine-1-phosphate (S1P) has been reported in multiple disease settings, including human postmortem brains from HD patients.

Brain Region and Cell Compartment Dependent Regulation of Electron Transport System Components in Huntington's Disease Model Mice.

Huntington's disease (HD) is a rare hereditary neurodegenerative disorder characterized by multiple metabolic dysfunctions including defects in mitochondrial homeostasis and functions. Although we have recently reported age-related changes in the respiratory capacities in different brain areas in HD mice, the precise mechanisms of how mitochondria become compromised in HD are still poorly understood. In this study, we investigated mRNA and protein levels of selected subunits of electron transport system (ETS) complexes and ATP-synthase in the cortex and striatum of symptomatic R6/2 mice.

Curcumin-Loaded Nanoparticles Based on Amphiphilic Hyaluronan-Conjugate Explored as Targeting Delivery System for Neurodegenerative Disorders.

Identification of molecules able to promote neuroprotective mechanisms can represent a promising therapeutic approach to neurodegenerative disorders including Huntington's disease. Curcumin is an antioxidant and neuroprotective agent, even though its efficacy is limited by its poor absorption, rapid metabolism, systemic elimination, and limited blood-brain barrier (BBB) permeability. Herein, we report on novel biodegradable curcumin-containing nanoparticles to favor the compound delivery and potentially enhance its brain bioavailability.

The longevity-associated variant of BPIFB4 improves a CXCR4-mediated striatum-microglia crosstalk preventing disease progression in a mouse model of Huntington's disease.

The longevity-associated variant (LAV) of the bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) has been found significantly enriched in long-living individuals. Neuroinflammation is a key player in Huntington's disease (HD), a neurodegenerative disorder caused by neural death due to expanded CAG repeats encoding a long polyglutamine tract in the huntingtin protein (Htt). Herein, we showed that striatal-derived cell lines with expanded Htt (STHdh Q) expressed and secreted lower levels of BPIFB4, when compared with Htt expressing cells (STHdh Q), which correlated with a defective stress response to proteasome inhibition.

Stimulation of Sphingosine Kinase 1 (SPHK1) Is Beneficial in a Huntington's Disease Pre-clinical Model.

Although several agents have been identified to provide therapeutic benefits in Huntington disease (HD), the number of conventionally used treatments remains limited and only symptomatic. Thus, it is plausible that the need to identify new therapeutic targets for the development of alternative and more effective treatments is becoming increasingly urgent. Recently, the sphingosine-1-phosphate (S1P) axis has been reported to be a valid potential novel molecular target for therapy development in HD.

Author Correction: Defective Sphingosine-1-phosphate metabolism is a druggable target in Huntington's disease.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.