Epithelioid Malignant Mesothelioma Metastatic to the Skin: A Case Report and Review of the Literature

Malignant mesothelioma (MM) is an aggressive and invasive neoplasm primarily affecting the pleura, peritoneum and pericardium. While mesothelioma commonly metastasizes to visceral organs, it has rarely been documented to involve the skin and subcutaneous tissue. There is a paucity of reports of cutaneous metastatic mesothelioma, and histologic examination is often challenging because the tumor closely mimics other primary and metastatic neoplasms. We report a case of a 75-year-old man presenting with a firm, hard nodule on his upper back, which on initial histologic evaluation resembled metastatic adenocarcinoma. However, upon review of his medical history and immunohistochemical evaluation of the lesion, the diagnosis of epithelioid MM metastatic to the skin was rendered. The purpose of this case report and review of the literature is to summarize the most effective available immunostains to aid in the diagnosis of this challenging entity, highlight the histologic similarities between metastatic epithelioid MM and other primary and metastatic neoplasms of the skin, and provide prognostic information for these rare tumors

Delinquenz kultursensibel erklären – ein theoretisches Rahmenmodell

Die hohe kulturelle Diversität der Straffälligenpopulation bringt eine ganze Reihe an Herausforderungen für Forschung und Praxis mit sich. Diesen Herausforderungen ist mit gängigen Erklärungsmodellen von Delinquenz jedoch kaum zu begegnen. Einerseits bestehen erhebliche Zweifel an deren allgemeiner Gültigkeit im interkulturellen Kontext, weil sie fast ausschließlich für den euroamerikanischen Raum entwickelt wurden. Andererseits bauen viele der Theorien auf dem Konzept der dynamischen Risikofaktoren auf, welches vage definiert ist. Viele dieser Theorien können Delinquenz kaum erklären, weil sie die zugrunde liegenden psychologischen Mechanismen nur wenig spezifizieren. Mit dem Cultural Agency-Model of Criminal Behavior (CAMCB) schlagen die Autoren ein Rahmenmodell vor, das auf die zugrunde liegenden individuellen psychologischen Mechanismen zielgerichteten Handelns abhebt und dabei systematisch zwischen universellen Komponenten und deren kulturell und individuell gefärbten Ausprägungen differenziert. Im CAMCB wird der Einfluss der kulturellen Sozialisation nicht an eine geografische oder ethnische Herkunft gebunden, sondern an kulturelle „traits“ (z. B. interdependenter Verarbeitungsstil), welche die Verhaltensgenese allgemein beeinflussen. An einem Beispiel wird gezeigt, dass delinquentes Verhalten je nach angenommenem kulturellen Trait unterschiedlich erklärt werden kann, während sich die Situation und die Reaktion nicht unterscheiden müssen. Wesentlich sind: erstens die Identifikation der universellen Verhaltenskomponenten, zweitens die Beschreibung deren kulturell und individuell gefärbter Ausprägungen und drittens die Erklärung von Delinquenz auf der Grundlage dieses Wissens. Dieses stufenweise Vorgehen erscheint nicht nur für die kriminalpsychologische Theorieentwicklung von Bedeutung, sondern auch für die forensische Praxis, bei der für jeden Einzelfall kultursensibel eine individuelle Delinquenztheorie formuliert werden muss.Because offender populations are highly diverse research and practice face many challenges; however, meeting these challenges with common theories of crime is hardly possible. On the one hand, there is reasonable doubt about their cultural equivalence as these theories were mainly formulated for a Euro-American cultural context. On the other hand, most of the theories are based on the concept of dynamic risk factors, which is vaguely defined. Moreover, most theories do not explain criminal behavior as they do not specify the underlying psychological mechanisms. We propose a framework – the Cultural Agency-Model of Criminal Behavior (CAMCB), which depicts the general processes underpinning human beings’ goal-directed behavior. The CAMCB differentiates between universal components of behavior and the way cultural traits shape the content and operation of these components. The influence of cultural socialization on psychological processes is explained without referring to a person’s ethnic background or heritage but by referring to cultural traits (e.g. interdependency), which shape the agency processes in general. By means of example we show that criminal behavior can be explained differently depending on the cultural trait even though the situation and reaction might be the same. It is essential to first identify universal components of a behavioral process, second, describe how cultural traits influence this process and third, explain criminal behavior on the basis of this knowledge. This stepwise approach is not only central for theory development in criminal psychology but also for forensic practice, as practitioners have to formulate an individual theory of crime for every single person in a culture-sensitive manner

Methods for high-throughput analysis of RNA structure and dynamics

RNA sequences fold back on themselves to form secondary and tertiary structures that are difficult to predict. Knowledge of these structures and the time-resolved mechanism by which RNA molecules fold into these structures are necessary for a full understanding of structure-function relationships in RNA biology. A newly developed technology, called SHAPE, provides accurate and quantitative RNA structure information. SHAPE chemistry was developed using N-methylisatoic anhydride (NMIA), which is only moderately electrophilic and requires tens of minutes to form ribose 2'-O-adducts. In this work I design and evaluate several classes of significantly more useful reagents for SHAPE chemistry and create a new way to assess RNA tertiary structure in an experimentally straightforward way. First, I design and synthesize a faster reacting reagent for SHAPE chemistry, 1-methyl-7-nitroisatoic anhydride (1M7), based on the NMIA scaffold. With 1M7, single nucleotide resolution interrogation of RNA structure is complete in 70 seconds and appears to be the ideal reagent for equilibrium analysis of RNA structure. Second, I apply SHAPE reagents of varying electrophilicity to identify a class of nucleotides with slow conformational dynamics. The observation is that select C2´-endo nucleotides undergo extremely slow conformational changes on the order of ~10-4 sec-1. Third, I extend SHAPE chemistry to a benzoyl cyanide scaffold to make possible facile time-resolved kinetic studies of RNA in ~1 s snapshots. I then use SHAPE chemistry to follow the time-dependent folding of an RNase P specificity domain RNA and identify a slow folding region in the RNA. I am able to attribute this slow folding step to the conformational dynamics of a single nucleotide. Finally, I show that show that N,N-(dimethylamino)dimethylchlorosilane (DMAS-Cl) reacts selectively at the guanosine N2 position. Critically, DMAS-Cl reactivity yields a near-perfect measure (r greater than or equal to 0.82) of solvent accessibility for this position in a folded RNA. This silane-based chemistry represents a significant improvement over classical approaches that employ carbon electrophiles for probing solvent accessibility at the base pairing face of guanosine in RNA

A Systematic Review of Self-Reported Ethical Practices in Publications of Cluster Randomised Trials Conducted in Aboriginal and Torres Strait Islander Settings

Cluster randomised trials (CRTs) present unique ethical complexities for research ethics committees, participants, researchers and evidence users. In this design, whole social units (‘clusters’) such as hospitals, schools or entire communities are randomised to interventions. In addition, units of randomisation, intervention and outcome measurement differ within the one study. As a consequence, clearly determining research participants and establishing whose consent is required not only for randomisation and interventions but also data collection are correspondingly difficult. This systematic review describes self-reported ethical practices in research conducted in Australia in which social units comprising Aboriginal and Torres Strait Islander people, their communities or services upon which they rely were randomised as whole clusters to trial interventions. To undertake this systematic review, we developed a study protocol and registered it prospectively on a public database (PROSPERO1 protocol CRD42018106463). Applying this protocol meant we could methodically identify all CRTs conducted in Aboriginal and Torres Strait Islander settings in Australia by finding their peer-reviewed study protocols or articles with main results reporting primary outcomes.https://researchonline.nd.edu.au/nulungu_research/1006/thumbnail.jp

Pharmacist-generated electronic consults to improve hypertension management in a multisite health centre: pilot study

Background Utilisation of the electronic medical record (EMR) is believed to facilitate timely access to patient information, enhance communication between care team members and further promote clinical decision support.Objective To determine if pharmacist-generated electronic consults (e-consults) improve blood pressure control among patients with uncontrolled hypertension in a multisite health centre.Methods Pharmacists generated hypertension medication e-consults with review by primary care provider (PCP) during the patient appointment. We conducted a retrospective review of consults to determine types of pharmacist recommendations, PCP acceptance rates, and blood pressure changes.Results Pharmacists generated a total of 60 econsults, 41 patients with a systolic blood pressure above their respective goal; e-consults were accepted 46% (n = 19) of the time.Conclusion This pilot project demonstrates a unique way for pharmacists to proactively utilise the EMR when delivering coordinated care within a multisite health centre. In addition, pharmacists were successfully integrated into the planned care approach

The affects of genistein on the Bradyrhizobium japonicum bacterial transcriptome [abstract]

Abstract only availableFaculty Mentor: Gary Stacey, Plant Microbiology and PathologyBradyrhizobium japonicum forms a symbiotic relationship with the roots of the soybean plant (Glycine max). This bacterium is of great importance because of its ability to provide the soybean with a source of nitrogen by the conversion of atmospheric dinitrogen to ammonia. In order to establish this symbiosis, the bacteria must attach to the root hair surface and initiate development of a root nodule. The bacterium responds to plant flavonoids through production of nod factor, a product of the nod genes, which facilitates bacterial root entry and initiates nodule organogenesis. Therefore, we have investigated the expression of nod genes after treatment with a plant derived flavonoid inducer, genistein. Free-living cultures of Bradyrhizobium japonicum were treated and cells were harvested six hours after treatment and total RNA was extracted. Semi-quantitative and quantitative RT-PCR was performed to confirm induction of the nodY and nodC genes. The RT-PCR results confirmed that nodY and nodC are upregulated in the presence of genistein compared to an ethanol-treated control. To further define genistein regulation on the nod genes, a DNA microarray experiment was performed on the above extracted RNA to define the bacterial transcriptional response to genistein, the results of which will be presented.Bradyrhizobium japonicum forms a symbiotic relationship with the roots of the soybean plant (Glycine max).  This bacterium is of great importance because of its ability to provide the soybean with a source of nitrogen by the conversion of atmospheric dinitrogen to ammonia.   In order to establish this symbiosis, the bacteria must attach to the root hair surface and initiate development of a root nodule.  The bacterium responds to plant flavonoids through production of nod factor, a product of the nod genes, which facilitates bacterial root entry and initiates nodule organogenesis. Therefore, we have investigated the expression of nod genes after treatment with a plant derived flavonoid inducer, genistein. Free-living cultures of Bradyrhizobium japonicum were treated and cells were harvested six hours after treatment and total RNA was extracted.  Semi-quantitative and quantitative RT-PCR was performed to confirm induction of the nodY and nodC genes. The RT-PCR results confirmed that nodY and nodC are upregulated in the presence of genistein compared to an ethanol-treated control.  To further define genistein regulation on the nod genes, a DNA microarray experiment was performed on the above extracted RNA to define the bacterial transcriptional response to genistein, the results of which will be presented

Expression of lymphotoxin-αβ on antigen-specific T cells is required for DC function

During an immune response, activated antigen (Ag)-specific T cells condition dendritic cells (DCs) to enhance DC function and survival within the inflamed draining lymph node (LN). It has been difficult to ascertain the role of the tumor necrosis factor (TNF) superfamily member lymphotoxin-αβ (LTαβ) in this process because signaling through the LTβ-receptor (LTβR) controls multiple aspects of lymphoid tissue organization. To resolve this, we have used an in vivo system where the expression of TNF family ligands is manipulated only on the Ag-specific T cells that interact with and condition Ag-bearing DCs. We report that LTαβ is a critical participant required for optimal DC function, independent of its described role in maintaining lymphoid tissue organization. In the absence of LTαβ or CD40L on Ag-specific T cells, DC dysfunction could be rescued in vivo via CD40 or LTβR stimulation, respectively, suggesting that these two pathways cooperate for optimal DC conditioning

Electron Beam-Treated Enzymatically Mineralized Gelatin Hydrogels for Bone Tissue Engineering

Biological hydrogels are highly promising materials for bone tissue engineering (BTE) due to their high biocompatibility and biomimetic characteristics. However, for advanced and customized BTE, precise tools for material stabilization and tuning material properties are desired while optimal mineralisation must be ensured. Therefore, reagent-free crosslinking techniques such as high energy electron beam treatment promise effective material modifications without formation of cytotoxic by-products. In the case of the hydrogel gelatin, electron beam crosslinking further induces thermal stability enabling biomedical application at physiological temperatures. In the case of enzymatic mineralisation, induced by Alkaline Phosphatase (ALP) and mediated by Calcium Glycerophosphate (CaGP), it is necessary to investigate if electron beam treatment before mineralisation has an influence on the enzymatic activity and thus affects the mineralisation process. The presented study investigates electron beam-treated gelatin hydrogels with previously incorporated ALP and successive mineralisation via incubation in a medium containing CaGP. It could be shown that electron beam treatment optimally maintains enzymatic activity of ALP which allows mineralisation. Furthermore, the precise tuning of material properties such as increasing compressive modulus is possible. This study characterizes the mineralised hydrogels in terms of mineral formation and demonstrates the formation of CaP in dependence of ALP concentration and electron dose. Furthermore, investigations of uniaxial compression stability indicate increased compression moduli for mineralised electron beam-treated gelatin hydrogels. In summary, electron beam-treated mineralized gelatin hydrogels reveal good cytocompatibility for MG-63 osteoblast like cells indicating a high potential for BTE applications

SAGES consensus recommendations on surgical video data use, structure, and exploration (for research in artificial intelligence, clinical quality improvement, and surgical education)

BACKGROUND: Surgery generates a vast amount of data from each procedure. Particularly video data provides significant value for surgical research, clinical outcome assessment, quality control, and education. The data lifecycle is influenced by various factors, including data structure, acquisition, storage, and sharing; data use and exploration, and finally data governance, which encompasses all ethical and legal regulations associated with the data. There is a universal need among stakeholders in surgical data science to establish standardized frameworks that address all aspects of this lifecycle to ensure data quality and purpose. METHODS: Working groups were formed, among 48 representatives from academia and industry, including clinicians, computer scientists and industry representatives. These working groups focused on: Data Use, Data Structure, Data Exploration, and Data Governance. After working group and panel discussions, a modified Delphi process was conducted. RESULTS: The resulting Delphi consensus provides conceptualized and structured recommendations for each domain related to surgical video data. We identified the key stakeholders within the data lifecycle and formulated comprehensive, easily understandable, and widely applicable guidelines for data utilization. Standardization of data structure should encompass format and quality, data sources, documentation, metadata, and account for biases within the data. To foster scientific data exploration, datasets should reflect diversity and remain adaptable to future applications. Data governance must be transparent to all stakeholders, addressing legal and ethical considerations surrounding the data. CONCLUSION: This consensus presents essential recommendations around the generation of standardized and diverse surgical video databanks, accounting for multiple stakeholders involved in data generation and use throughout its lifecycle. Following the SAGES annotation framework, we lay the foundation for standardization of data use, structure, and exploration. A detailed exploration of requirements for adequate data governance will follow