De Vries powers and proximity Specker algebras

By de Vries duality [9], the category ${\sf KHaus}$ of compact Hausdorff spaces is dually equivalent to the category ${\sf DeV}$ of de Vries algebras. In [5] an alternate duality for ${\sf KHaus}$ was developed, where de Vries algebras were replaced by proximity Baer-Specker algebras. The functor associating with each compact Hausdorff space a proximity Baer-Specker algebra was described by generalizing the notion of a boolean power of a totally ordered domain to that of a de Vries power. It follows that ${\sf DeV}$ is equivalent to the category ${\sf PBSp}$ of proximity Baer-Specker algebras. The equivalence is obtained by passing through ${\sf KHaus}$, and hence is not choice-free. In this paper we give a direct algebraic proof of this equivalence, which is choice-free. To do so, we give an alternate choice-free description of de Vries powers of a totally ordered domain.Comment: 23 page

Case report of sudden death after a gunshot wound to the C2 vertebral bone without direct spinal cord injury: Histopathological analysis of spinal-medullary junction

Gunshot wounds (GSW) are one of the most common causes of penetrating spinal injury, however few data are available regarding GSW causing an indirect fatal nervous tissue injury, such as that induced by the concussive force secondary to the bullet penetration. This report describes a rare case of a death following a GSW spine injury at the level of C2 vertebral body, without direct contact with the spinal cord, as seen with computed tomography scan performed soon after the death. At autopsy, vertebral canal and dura mater, as well as spinal cord and medulla oblongata, appeared devoid of pathologies and/or lesions, major viscera were unaltered. The cause of death was attributed to a cardiorespiratory arrest subsequent to the GSW injury of the C2 vertebral bone. Histopathological analysis of spinal cord and medulla oblongata was performed by means of conventional stainings, and glial fibrillary acidic protein (GFAP) and Neurofilaments 200 kD (NF) immunohistochemistry. Histological alterations stood out against a tissue with no other evident sign of neuropathology, and could be observed from the caudalmost part of the medulla oblongata to the level of the inferior olivary nucleus. Main structural changes were found in the white matter, involving often the adjacent gray matter, where they appeared as multiple scattered areas of degeneration, lacking the usual staining affinity, and showing a disrupted fibrillary pattern as evidenced by myelin staining, and GFAP- and NF-immunolabelling. The shock wave secondary to the impact on the C2 vertebral bone is likely to have been the cause of a widespread neuronal-axonal histopathological damage at the spinal-medullary junction and caudal medulla oblongata that is compatible with a severe fatal respiratory dysfunction and dysregulation of the autonomic pathways subserving the control of blood pressure and cardiac activity

Integration of multiple platforms for the analysis of multifluorescent marking technology applied to pediatric GBM and dipg

The intratumor heterogeneity represents one of the most difficult challenges for the development of effective therapies to treat pediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG). These brain tumors are composed of heterogeneous cell subpopulations that coexist and cooperate to build a functional network responsible for their aggressive phenotype. Understanding the cellular and molecular mechanisms sustaining such network will be crucial for the identification of new therapeutic strategies. To study more in-depth these mechanisms, we sought to apply the Multifluorescent Marking Technology. We generated multifluorescent pGBM and DIPG bulk cell lines randomly expressing six different fluorescent proteins and from which we derived stable optical barcoded single cell-derived clones. In this study, we focused on the application of the Multifluorescent Marking Technology in 2D and 3D in vitro/ex vivo culture systems. We discuss how we integrated different multimodal fluorescence analysis platforms, identifying their strengths and limitations, to establish the tools that will enable further studies on the intratumor heterogeneity and interclonal interactions in pGBM and DIPG

Resistance to retinopathy development in obese, diabetic and hypertensive ZSF1 rats: an exciting model to identify protective genes

Diabetic retinopathy (DR) is one of the major complications of diabetes, which eventually leads to blindness. Up to date, no animal model has yet shown all the co-morbidities often observed in DR patients. Here, we investigated whether obese 42 weeks old ZSF1 rat, which spontaneously develops diabetes, hypertension and obesity, would be a suitable model to study DR. Although arteriolar tortuosity increased in retinas from obese as compared to lean (hypertensive only) ZSF1 rats, vascular density pericyte coverage, microglia number, vascular morphology and retinal thickness were not affected by diabetes. These results show that, despite high glucose levels, obese ZSF1 rats did not develop DR. Such observations prompted us to investigate whether the expression of genes, possibly able to contain DR development, was affected. Accordingly, mRNA sequencing analysis showed that genes (i.e. Npy and crystallins), known to have a protective role, were upregulated in retinas from obese ZSF1 rats. Lack of retina damage, despite obesity, hypertension and diabetes, makes the 42 weeks of age ZSF1 rats a suitable animal model to identify genes with a protective function in DR. Further characterisation of the identified genes and downstream pathways could provide more therapeutic targets for the treat DR

Pediatric Moyamoya Disease and Syndrome in Italy: A Multicenter Cohort

Background: Moyamoya is a rare progressive cerebral arteriopathy, occurring as an isolated phenomenon (moyamoya disease, MMD) or associated with other conditions (moyamoya syndrome, MMS), responsible for 6–10% of all childhood strokes and transient ischemic attacks (TIAs). Methods: We conducted a retrospective multicenter study on pediatric-onset MMD/MMS in Italy in order to characterize disease presentation, course, management, neuroradiology, and outcome in a European country. Results: A total of 65 patients (34/65 women) with MMD (27/65) or MMS (38/65) were included. About 18% (12/65) of patients were asymptomatic and diagnosed incidentally during investigations performed for an underlying condition (incMMS), whereas 82% (53/65) of patients with MMD or MMS were diagnosed due to the presence of neurological symptoms (symptMMD/MMS). Of these latter, before diagnosis, 66% (43/65) of patients suffered from cerebrovascular events with or without other manifestations (ischemic stroke 42%, 27/65; TIA 32%, 21/65; and no hemorrhagic strokes), 18% (12/65) of them reported headache (in 4/12 headache was not associated with any other manifestation), and 26% (17/65) of them experienced multiple phenotypes (≥2 among: stroke/TIA/seizures/headache/others). Neuroradiology disclosed ≥1 ischemic lesion in 67% (39/58) of patients and posterior circulation involvement in 51% (30/58) of them. About 73% (47/64) of patients underwent surgery, and 69% (45/65) of them received aspirin, but after diagnosis, further stroke events occurred in 20% (12/61) of them, including operated patients (11%, 5/47). Between symptom onset and last follow-up, the overall patient/year incidence of stroke was 10.26% (IC 95% 7.58–13.88%). At last follow-up (median 4 years after diagnosis, range 0.5–15), 43% (26/61) of patients had motor deficits, 31% (19/61) of them had intellectual disability, 13% (8/61) of them had epilepsy, 11% (7/61) of them had behavioral problems, and 25% (13/52) of them had mRS > 2. The proportion of final mRS > 2 was significantly higher in patients with symptMMD/MMS than in patients with incMMS (p = 0.021). Onset age <4 years and stroke before diagnosis were significantly associated with increased risk of intellectual disability (p = 0.0010 and p = 0.0071, respectively) and mRS > 2 at follow-up (p = 0.0106 and p = 0.0009, respectively). Conclusions: Moyamoya is a severe condition that may affect young children and frequently cause cerebrovascular events throughout the disease course, but may also manifest with multiple and non-cerebrovascular clinical phenotypes including headache (isolated or associated with other manifestations), seizures, and movement disorder. Younger onset age and stroke before diagnosis may associate with increased risk of worse outcome (final mRS > 2)

The management of pediatric severe traumatic brain injury: Italian guidelines

Introduction: the aim of the work was to update the “guidelines for the Management of severe traumatic Brain Injury” published in 2012, to reflect the new available evidence, and develop the Italian national guideline for the management of severe pediatric head injuries to reduce variation in practice and ensure optimal care to patients. eViDeNce acQUisitioN: MeDliNe and eMBase were searched from January 2009 to october 2017. inclusion criteria were english language, pediatric populations (0-18 years) or mixed populations (pediatric/adult) with available age subgroup analyses. the guideline development process was started by the Promoting group that composed a multidisciplinary panel of experts, with the representatives of the Scientific Societies, the independent expert specialists and a representative of the Patient associations. the panel selected the clinical questions, discussed the evidence and formulated the text of the recommendations. the documentarists of the University of Florence oversaw the bibliographic research strategy. a group of literature reviewers evaluated the selected literature and compiled the table of evidence for each clinical question. EVIDENCE SYNTHESIS: The search strategies identified 4254 articles. We selected 3227 abstract (first screening) and, finally included 67 articles (second screening) to update the guideline. This Italian update includes 25 evidence-based recommendations and 5 research recommendations. coNclUsioNs: in recent years, progress has been made on the understanding of severe pediatric brain injury, as well as on that concerning all major traumatic pathology. this has led to a progressive improvement in the clinical outcome, although the quantity and quality of evidence remains particularly low

Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes.

Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histologic review, methylation profiling, and custom panel, genome, or exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an "intrinsic" spectrum of disease specific to the infant population. These included those with targetable MAPK alterations, and a large proportion of remaining cases harboring gene fusions targeting ALK (n = 31), NTRK1/2/3 (n = 21), ROS1 (n = 9), and MET (n = 4) as their driving alterations, with evidence of efficacy of targeted agents in the clinic. These data strongly support the concept that infant gliomas require a change in diagnostic practice and management. SIGNIFICANCE: Infant high-grade gliomas in the cerebral hemispheres comprise novel subgroups, with a prevalence of ALK, NTRK1/2/3, ROS1, or MET gene fusions. Kinase fusion-positive tumors have better outcome and respond to targeted therapy clinically. Other subgroups have poor outcome, with fusion-negative cases possibly representing an epigenetically driven pluripotent stem cell phenotype.See related commentary by Szulzewsky and Cimino, p. 904.This article is highlighted in the In This Issue feature, p. 890

A novel 72-kDa leukocyte-derived osteoglycin enhances the activation of toll-like receptor 4 and exacerbates cardiac inflammation during viral myocarditis

Background: Viral myocarditis can severely damage the myocardium through excessive infiltration of immune cells. Osteoglycin (OGN) is part of the small leucine-rich repeat proteoglycan (SLRP) family. SLRP’s may affect inflammatory and fibrotic processes, but the implication of OGN in cardiac inflammation and the resulting injury upon viral myocarditis is unknown. Methods and results: This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis. Its absence in mice significantly decreased cardiac inflammation and injury in Coxsackievirus-B3-induced myocarditis. It also delayed mortality in lipopolysaccharide-induced endotoxemia going along with a reduced systemic production of pro-inflammatory cytokines. This 72-kDa OGN is expressed in the cell membrane of circulating and resident cardiac macrophages and neutrophils. Co-immunoprecipitation and OGN siRNA experiments revealed that this 72-kDa variant activates the toll-like receptor-4 (TLR4) with a concomitant increase in IL-6, TNF-α, IL-1β, and IL-12 expression. This immune cell activation by OGN occurred via MyD88 and increased phosphorylation of c-jun. Finally, the 72-kDa chondroitin sulfate is the result of O-linked glycosylation of the 32-kDa protein core of OGN. In contrast, the 34-kDa dermatan sulfate-OGN, involved in collagen cross linking, was also the result of O-linked glycosylation. Conclusion: The current study discovered a novel 72-kDa chondroitin sulfate-OGN that is specific for innate immune cells. This variant is able to bind and activate TLR4. The absence of OGN decreases cytokine production by both circulating and cardiac leukocytes upon (systemic) LPS exposure, and reduces cardiac inflammation and injury in viral myocarditis