Exploring the mysteries of blast induced traumatic brain injury with a custom device

Introduction: Exposure from blast-pressure waves caused by explosive devices have resulted in traumatic brain injuries (TBI) with a variety of symptoms (e.g., tinnitus, depression, coordination, and impaired motor abilities). Blast exposure causes tearing, shredding, and rotational forces on brain structures. This pathology is more prominent in cells at the edge of structures with varying density or in neurons with extensive physical volume or dendritic processes. Understanding the unique pathophysiology of TBI may be critical for appropriate treatment of these injuries. Our lab developed a blast-pressure wave device to produce a supersonic energy wave at 20 psi. This wave is identical to a mild exposure to an explosive device without the secondary effects of shrapnel or heat. Objectives: Animals were tested with a novel blast-pressure wave device to determine whether the method would produce symptoms similar to other animal TBI experiments or human TBI patients. Methods: Animal behavior was tested for tinnitus with acoustic startle tests, depression with forced swim tests, and motor function with free-field tests before and after blast-pressure wave exposure. For each behavioral test, the behavior for each animal was compared to its own normal (pre-blast exposure) measures to determine if alterations in behavior (symptoms) developed due to the blast-exposure. Behavioral measures and the rate of symptom development were compared for the blast-exposed animal group versus a control group that were exposed to the sound but not the energy of the blast-pressure wave. Results: The results indicate that the blast-pressure wave device is able to provide consistent supersonic blast pressure-waves that can inflict TBI in a rodent model. Blast-exposed animals exhibited long-term symptoms of depression and tinnitus that were not expressed in control animals. These symptoms persisted for over 3 months. No motor impairments were observed in either the control or blast-exposed groups. Conclusions: The developed blast-pressure wave device is a reliable method for induction of a mild traumatic brain injury for TBI experiments. Induced TBI symptoms in our rodent populations were similar to human symptoms associated with mild blast-pressure wave exposure. Therefore, these methods provide a valid experimental model for examining both pathology and potential therapies for TBI

Infralittoral ostracoda and benthic foraminifera of the Gulf of Pozzuoli (Tyrrhenian Sea, Italy)

AbstractThe shallow water benthic foraminiferal and ostracod assemblages of the Gulf of Pozzuoli, located in the central Tyrrhenian Sea, were studied to investigate the relationship between calcareous meiofaunas and contaminant concentrations in bottom sediments exposed to prolonged industrial pollution. Both benthic foraminifers and ostracods displayed high-diversity and low-dominance, unusual features in highly contaminated environments. High-diversity values were possibly linked to the oligotrophic, well-oxygenated, and CaCO3-supersaturated coastal Mediterranean waters. The comparison with historical data suggested that assemblage composition changed in the last decades, with an increase in the relative abundance of benthic foraminiferal (Quinqueloculina seminulum, Bulimina elongata) and ostracod (Xestoleberis,Loxoconcha, Semicytherura rarecostata) taxa. They probably represent organisms tolerant to the environmental variations in the last decades. The relationships between granulometry and diversity indices, high correlation values betweenQuinqueloculina lataand heavy metal pollution, and the preference of the ostracod generaUrocythereisandParacytherideafor very shallow marine waters were highlighted

Propagators for p-forms in AdS_{2p+1} and correlation functions in the AdS_7/(2,0) CFT correspondence

In AdS_{2p+1} we construct propagators for p-forms whose lagrangians contain terms of the form A / d A. In particular we explore the case of forms satisfying ``self duality in odd dimensions'', and the case of forms with a topological mass term. We point out that the ``complete'' set of maximally symmetric bitensors previously used in all the other propagator papers is incomplete - there exists another bitensor which can and does appear in the formulas for the propagators in this particular case. Nevertheless, its presence does not affect the other propagators computed so far. On the AdS side of the correspondence we compute the 2 and 3 point functions involving the self-dual tensor of the maximal 7d gauged supergravity (sugra), S_{\mu\nu\rho}. Since the 7 dimensional antisymmetric self-dual tensor obeys first order field equations (S + * d S=0), to get a nonvanishing 2 point function we add a certain boundary term (to satisfy the variational principle on a manifold with boundary) to the 7d action. The 3 point functions we compute are of the type SSB and SBB, describing vertex interactions with the gauge fields B_{\mu}.Comment: 21 pages, Latex file, one reference adde

Biosafety in surgical pathology in the era of SARS-Cov2 pandemia. A statement of the Italian Society of Surgical Pathology and Cytology

Surgical pathology units face chemical and biological risks. While chemical risks have been intensely evaluated since the formalin ban, less attention has been drown to biological risks. The actual epidemiologic situation due to the SARS-CoV-2 pandemia has raised a series of questions, which need to be addressed as soon as possible. We have to pursue two lines of action: on one hand we must immediately adopt urgent measures to reduce the risk of SARS-CoV-2 infection of laboratory personnel, and on the other hand, we must address crucial technical and organizational aspects of biological risk reduction, preserving as much as possible the quality of tissue and cell samples. The evaluation of biological risk is an analytical process which involves different steps: a) characterization of the hazard (also known as risk assessment) and b) definition of a risk reduction strategy (also known as risk mitigation) 1. Risk assessment implies a) the identification of the intrinsic biologic characteristics of the infectious agent, and b) the identification of the laboratory procedures related to the agent. The intrinsic biologic characteristics of infectious agents are classified in 4 risk groups (RG) by the laboratory biosafety manual of the WHO 2. The RG range from level 1 (RG1) which includes microorganisms that are unlikely to cause human or animal disease, to level 4 (RG4) which includes pathogens which cause serious diseases, that can be readily transmitted from one individual to another, and for which effective treatment and preventive measures are not usually available. Risk mitigation includes the definition of the appropriate a) level of biosafety of the laboratory, b) type of personal protection equipment (PPE), c) type of infrastructure and equipment, and d) education of involved personnel. Laboratory biosafety is graded in 4 levels (BSL-1 to BSL-4) as exhaustively described in the laboratory biosafety manual of the WHO 2, and these levels are usually also defined by law (in Italy by the D. Lgs. 81/2008). BSL are a series of protections, which include individual safeguards designed to protect laboratory personnel, as well as the surrounding environment and community. The biosafety level required in laboratories derives from the characterization of the risk, and is not automatically derived from the risk group to which the pathogenic agent belongs. It is obvious that the biosafety level for a laboratory which cultivates a RG3 agent, will be higher than the level needed for a laboratory which performs diagnostic tests on inactivated biomaterials on the same agent. Specific checklists, derived from the WHO laboratory biosafety manual, which in Italy are also defined by the National Institute of Labor Safety Insurance (Istituto Nazionale Assicurazione Infortuni sul Lavoro) in its 6th Fascicle published in 2010 3 are necessary to verify the compliance of a given laboratory with the required biosafety level

Real-time analysis of the binding of fluorescent VEGF₁₆₅a to VEGFR2 in living cells: Effect of receptor tyrosine kinase inhibitors and fate of internalized agonist-receptor complexes

Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis. Here we have used a novel stoichiometric protein-labeling method to generate a fluorescent variant of VEGF (VEGF₁₆₅a-TMR) labeled on a single cysteine within each protomer of the antiparallel VEGF homodimer. VEGF₁₆₅a-TMR has then been used in conjunction with full length VEGFR2, tagged with the bioluminescent protein NanoLuc, to undertake a real time quantitative evaluation of VEGFR2 binding characteristics in living cells using bioluminescence resonance energy transfer (BRET). This provided quantitative information on VEGF-VEGFR2 interactions. At longer incubation times, VEGFR2 is internalized by VEGF₁₆₅a-TMR into intracellular endosomes. This internalization can be prevented by the receptor tyrosine kinase inhibitors (RTKIs) cediranib, sorafenib, pazopanib or vandetanib. In the absence of RTKIs, the BRET signal is decreased over time as a consequence of the dissociation of agonist from the receptor in intracellular endosomes and recycling of VEGFR2 back to the plasma membrane

Validity of the Maternal Antenatal Attachment Scale-Spanish Version for Mexican Pregnant Women

During pregnancy, parents experiment emotions, thoughts, and behaviors related to their unborn child as precursors of attachment in the caretaker-infant dyad. The Maternal Antenatal Attachment Scale (MAAS) is an instrument that has shown adequate psychometric properties to evaluate this construct in developed countries. The aim of this study was to assess the reliability and concurrent validity of the Maternal Antenatal Attachment Scale-Spanish version for Mexican women (MAAS-Spanish version). A sample of 142 women in their third trimester of pregnancy who received care in a tertiary hospital was selected. The full scale of the MAAS-Spanish version obtained a Cronbach alpha of .79. A significant negative correlation was found between the global MAAS-Spanish version score (r = -.23, p ≤ .01) and the Postpartum Depression Predictors Inventory-Revised and depressive symptoms (r = -.36 , p ≤ .01). The translated and adapted scale has adequate internal consistency and concurrent validity to measure this construct in this population

Vascular Wall-Resident CD44+ Multipotent Stem Cells Give Rise to Pericytes and Smooth Muscle Cells and Contribute to New Vessel Maturation

Here, we identify CD44(+)CD90(+)CD73(+)CD34(−)CD45(−) cells within the adult human arterial adventitia with properties of multipotency which were named vascular wall-resident multipotent stem cells (VW-MPSCs). VW-MPSCs exhibit typical mesenchymal stem cell characteristics including cell surface markers in immunostaining and flow cytometric analyses, and differentiation into adipocytes, chondrocytes and osteocytes under culture conditions. Particularly, TGFß1 stimulation up-regulates smooth muscle cell markers in VW-MPSCs. Using fluorescent cell labelling and co-localisation studies we show that VW-MPSCs differentiate to pericytes/smooth muscle cells which cover the wall of newly formed endothelial capillary-like structures in vitro. Co-implantation of EGFP-labelled VW-MPSCs and human umbilical vein endothelial cells into SCID mice subcutaneously via Matrigel results in new vessels formation which were covered by pericyte- or smooth muscle-like cells generated from implanted VW-MPSCs. Our results suggest that VW-MPSCs are of relevance for vascular morphogenesis, repair and self-renewal of vascular wall cells and for local capacity of neovascularization in disease processes

The burden of mental disorders, substance use disorders and self-harm among young people in Europe, 1990–2019: Findings from the Global Burden of Disease Study 2019

Summary Background Mental health is a public health issue for European young people, with great heterogeneity in resource allocation. Representative population-based studies are needed. The Global Burden of Disease (GBD) Study 2019 provides internationally comparable information on trends in the health status of populations and changes in the leading causes of disease burden over time. Methods Prevalence, incidence, Years Lived with Disability (YLDs) and Years of Life Lost (YLLs) from mental disorders (MDs), substance use disorders (SUDs) and self-harm were estimated for young people aged 10-24 years in 31 European countries. Rates per 100,000 population, percentage changes in 1990-2019, 95% Uncertainty Intervals (UIs), and correlations with Sociodemographic Index (SDI), were estimated. Findings In 2019, rates per 100,000 population were 16,983 (95% UI 12,823 – 21,630) for MDs, 3,891 (3,020 - 4,905) for SUDs, and 89·1 (63·8 - 123·1) for self-harm. In terms of disability, anxiety contributed to 647·3 (432–912·3) YLDs, while in terms of premature death, self-harm contributed to 319·6 (248·9–412·8) YLLs, per 100,000 population. Over the 30 years studied, YLDs increased in eating disorders (14·9%;9·4-20·1) and drug use disorders (16·9%;8·9-26·3), and decreased in idiopathic developmental intellectual disability (–29·1%;23·8-38·5). YLLs decreased in self-harm (–27·9%;38·3-18·7). Variations were found by sex, age-group and country. The burden of SUDs and self-harm was higher in countries with lower SDI, MDs were associated with SUDs. Interpretation Mental health conditions represent an important burden among young people living in Europe. National policies should strengthen mental health, with a specific focus on young people.publishedVersio

APOLLO 11 Project, Consortium in Advanced Lung Cancer Patients Treated With Innovative Therapies: Integration of Real-World Data and Translational Research

Introduction: Despite several therapeutic efforts, lung cancer remains a highly lethal disease. Novel therapeutic approaches encompass immune-checkpoint inhibitors, targeted therapeutics and antibody-drug conjugates, with different results. Several studies have been aimed at identifying biomarkers able to predict benefit from these therapies and create a prediction model of response, despite this there is a lack of information to help clinicians in the choice of therapy for lung cancer patients with advanced disease. This is primarily due to the complexity of lung cancer biology, where a single or few biomarkers are not sufficient to provide enough predictive capability to explain biologic differences; other reasons include the paucity of data collected by single studies performed in heterogeneous unmatched cohorts and the methodology of analysis. In fact, classical statistical methods are unable to analyze and integrate the magnitude of information from multiple biological and clinical sources (eg, genomics, transcriptomics, and radiomics). Methods and objectives: APOLLO11 is an Italian multicentre, observational study involving patients with a diagnosis of advanced lung cancer (NSCLC and SCLC) treated with innovative therapies. Retrospective and prospective collection of multiomic data, such as tissue- (eg, for genomic, transcriptomic analysis) and blood-based biologic material (eg, ctDNA, PBMC), in addition to clinical and radiological data (eg, for radiomic analysis) will be collected. The overall aim of the project is to build a consortium integrating different datasets and a virtual biobank from participating Italian lung cancer centers. To face with the large amount of data provided, AI and ML techniques will be applied will be applied to manage this large dataset in an effort to build an R-Model, integrating retrospective and prospective population-based data. The ultimate goal is to create a tool able to help physicians and patients to make treatment decisions. Conclusion: APOLLO11 aims to propose a breakthrough approach in lung cancer research, replacing the old, monocentric viewpoint towards a multicomprehensive, multiomic, multicenter model. Multicenter cancer datasets incorporating common virtual biobank and new methodologic approaches including artificial intelligence, machine learning up to deep learning is the road to the future in oncology launched by this project