Immortalized human keratinocytes: A model system to study the efficacy of therapeutic drugs in response to the chemical warfare agent sulfur mustard (HD)

Cytokines have been established as biomarkers to detect exposure of cells to chemical warfare agents such as sulfur mustard (2,2'-dichlorodiethyl sulfide, HD). In this study cultured normal and SV40 immortalized human epidermal keratinocyte (NHEK/IHEK) cells were compared as potential model systems to measure the efficacy of therapeutic drugs against HD. Immortalized human epidermal keratinocytes resemble their primary cell counterparts but have the advantage of being carried through long-term culture. Immortalized cells also provide consistency and durability and are less costly than primary keratinocytes. Immunoassay studies were performed to examine the response of these two cell lines to HD. We found that both normal and immortalized NHEKs secreted the pro-inflammatory mediator interleukin-8 (IL-8) when exposed to HD. However, a major difference was observed between the NHEK cell line 6207 and IHEK cell line 425. IHEK cell line 425 produced higher levels of Interleuken-8 then those of its normal counterpart cell line 6207. This observation is significant since therapeutic drugs such as ibuprofen, which depress cytokine production, may not allow these biomarkers to be detected efficiently in experimental analysis of certain NHEK cell lines. The fact that Il-8 production higher in cell line 425 cell makes this in vitro model a potential screening tool to study the efficacy of drugs that suppress production of cytokine markers

Automated Additive Construction (AAC) for Earth and Space Using In-situ Resources

Using Automated Additive Construction (AAC), low-fidelity large-scale compressive structures can be produced out of a wide variety of materials found in the environment. Compressionintensive structures need not utilize materials that have tight specifications for internal force management, meaning that the production of the building materials do not require costly methods for their preparation. Where a certain degree of surface roughness can be tolerated, lower-fidelity numerical control of deposited materials can provide a low-cost means for automating building processes, which can be utilized in remote or extreme environments on Earth or in Space. For space missions where every kilogram of mass must be lifted out of Earth’s gravity well, the promise of using in-situ materials for the construction of outposts, facilities, and installations could prove to be enabling if significant reduction of payload mass can be achieved. In a 2015 workshop sponsored by the Keck nstitute for Space Studies, on the topic of Three Dimensional (3D) Additive Construction For Space Using In-situ Resources, was conducted with additive construction experts from around the globe in attendance. The workshop explored disparate efforts, methods, and technologies and established a proposed framework for the field of Additive Construction Using In-situ Resources. This paper defines the field of Automated Additive Construction Using In-situ Resources, describes the state-of-the-art for various methods, establishes a vision for future efforts, identifies gaps in current technologies, explores investment opportunities, and proposes potential technology demonstration missions for terrestrial, International Space Station (ISS), lunar, deep space zero-gravity, and Mars environments

OTX015 (MK-8628), a novel BET inhibitor, exhibits antitumor activity in non-small cell and small cell lung cancer models harboring different oncogenic mutations.

Inhibitors targeting epigenetic control points of oncogenes offer a potential mean of blocking tumor progression in small cell and non-small cell lung carcinomas (SCLC, NSCLC). OTX015 (MK-8628) is a BET inhibitor selectively blocking BRD2/3/4. OTX015 was evaluated in a panel of NSCLC or SCLC models harboring different oncogenic mutations. Cell proliferation inhibition and cell cycle arrest were seen in sensitive NSCLC cells. MYC and MYCN were downregulated at both the mRNA and protein levels. In addition, OTX015-treatment significantly downregulated various stemness cell markers, including NANOG, Musashi-1, CD113 and EpCAM in H3122-tumors in vivo. Conversely, in SCLC models, weak antitumor activity was observed with OTX015, both in vitro and in vivo. No predictive biomarkers of OTX015 activity were identified in a large panel of candidate genes known to be affected by BET inhibition. In NSCLC models, OTX015 was equally active in both EML4-ALK positive and negative cell lines, whereas in SCLC models the presence of functional RB1 protein, which controls cell progression at G1, may be related to the final biological outcome of OTX015. Gene expression profiling in NSCLC and SCLC cell lines showed that OTX015 affects important genes and pathways with a very high overlapping between both sensitive and resistant cell lines. These data support the rationale for the OTX015 Phase Ib (NCT02259114) in solid tumors, where NSCLC patients with rearranged ALK gene or KRAS-positive mutations are currently being treated

Validating the efficacy of neurofeedback for optimising performance.

The field of neurofeedback training has largely proceeded without validation. Here we review our studies directed at validating SMR, beta and alpha–theta protocols for improving attention, memory, mood and music and dance performance in healthy participants. Important benefits were demonstrable with cognitive and neurophysiological measures which were predicted on the basis of regression models of learning. These are initial steps in providing a much needed scientific basis to neurofeedback, but much remains to be done

Potential Impact of Mediterranean Aquaculture on the Wild Predatory Bluefish

Aquaculture impacts on wild populations of fish have been considered principally due to farm escapes. The Bluefish Pomatomus saltatrix, which exhibits two distinct genetic units in the Mediterranean Sea, is a voracious predator and is attracted to aquaculture cages to prey on farmed fish, particularly Gilthead Seabream Sparus aurata and European Sea Bass Dicentrarchus labrax. We compared the genetic diversity of adult Bluefish caught inside one aquaculture farm located in Spanish waters of the western Mediterranean Sea with reference individuals of East and West Mediterranean stocks from the open sea. Bluefish were genetically assigned to their putative origin using seven microsatellite loci and mitochondrial cytochrome oxidase subunit I as molecular markers. As expected, most of the individuals caught from inside the fish farm cages were assigned to the local genetic population. However, between 7.14% and 11.9% of individuals were assigned to the distant and different genetic unit inhabiting Turkish waters, the East Mediterranean stock. The genetic membership of those individuals revealed some degree of interbreeding between the East and West Mediterranean Bluefish stocks. All results suggest that aquaculture acts as an attractor for Bluefish and could affect genetic diversity as well as phylogeography of this fish and maybe other similar species that aggregate around marine fish farms.We are very grateful to T. Ceyhan for providing the Bluefish samples from Turkey. The study was supported by the MICINN CGL-2009-08279 Grant (Spain) and the Asturian Grant GRUPIN2014-093. Laura Miralles held a PCTI Grant from the Asturias Regional Government, referenced BP 10-004. This is a contribution from the Marine Observatory of Asturias

Deep Learning-Based Dose Prediction for Automated, Individualized Quality Assurance of Head and Neck Radiation Therapy Plans

PURPOSE: This study aimed to use deep learning-based dose prediction to assess head and neck (HN) plan quality and identify suboptimal plans. METHODS AND MATERIALS: A total of 245 volumetric modulated arc therapy HN plans were created using RapidPlan knowledge-based planning (KBP). A subset of 112 high-quality plans was selected under the supervision of an HN radiation oncologist. We trained a 3D Dense Dilated U-Net architecture to predict 3-dimensional dose distributions using 3-fold cross-validation on 90 plans. Model inputs included computed tomography images, target prescriptions, and contours for targets and organs at risk (OARs). The model\u27s performance was assessed on the remaining 22 test plans. We then tested the application of the dose prediction model for automated review of plan quality. Dose distributions were predicted on 14 clinical plans. The predicted versus clinical OAR dose metrics were compared to flag OARs with suboptimal normal tissue sparing using a 2 Gy dose difference or 3% dose-volume threshold. OAR flags were compared with manual flags by 3 HN radiation oncologists. RESULTS: The predicted dose distributions were of comparable quality to the KBP plans. The differences between the predicted and KBP-planned D CONCLUSIONS: Deep learning can predict high-quality dose distributions, which can be used as comparative dose distributions for automated, individualized assessment of HN plan quality

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third- line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment-emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second- line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence-based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first-line treatments for acute mania. First-line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first-line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe

Colaboración entre dos facultades de veterinaria para la elaboración de material anatómico biblingüe en formato digital

[SPA]Se recopilan en este trabajo las actividades de colaboración entre la Facultad de Veterinaria de Murcia (área de Anatomía Veterinaria) y el Royal Veterinary College de Londres (E-media y Anatomy units) para la elaboración de diferentes recursos docentes on-line en formato bilingüe. Se trata de una experiencia de 4 años, en la que se han implicado tanto el profesorado como algunos alumnos. Durante este tiempo se han elaborado diversos programas interactivos basados en la identificación de estructuras sobre imágenes, así como contenidos en formato vídeo (podcasts). Otra vertiente del trabajo ha consistido en colaborar en el desarrollo de una Wiki específica de Veterinaria (WikiVet, http://en.wikivet.net/Veterinary_Education_Online). En este sentido, destaca la reciente creación de la versión de dicha Wiki en lengua española (http://es.wikivet.net/P%C3%A1gina_Principal). Todo el material se ha venido incluyendo en los entornos educativos virtuales de cada institución (SUMA y Blackboard), así como en la web del área de Anatomía Veterinaria http://www.um.es/anatvet/interactivo.php. La experiencia llevada a cabo se ha mostrado como un medio efectivo para la innovación docente en disciplinas de carácter morfológico como la Anatomía. Además, la producción de material en versión bilingüe ha supuesto una enriquecedora experiencia profesional, a la vez que un mayor número de potenciales usuarios. [ENG]This study summarizes the collaborative activities between the Faculty of Veterinary of Murcia (area of Veterinary Anatomy) and the Royal Veterinary College London (E-media and Anatomy units) for the development of different online teaching resources in a bilingual format. This 4 year experience involved faculty lecturers, students and technical staff. Interactive programs based on the identification of landmarks over images as well as podcast with practical demonstrations have been developed. The collaboration was also aimend at developing the Spanish version of the WikiVet (http://es.wikivet.net/P%C3%A1gina_Principal). All the materials were uploaded in virtual learning environments of each institution (SUMA and Blackboard), as well as on the web site of the Veterinary Anatomy (open http://www.um.es/anatvet/ingles/interactive.php. The experience has been proved to be an effective means for innovative teaching in morphology areas as Anatomy. Also, the production of bilingual versions of each resource has provided an enriching experience for teachers and given a greater number of potential users.Campus Mare Nostrum, Universidad Politécnica de Cartagena, Universidad de Murcia, Región de Murci