Analysis of trauma symptomology, trauma-informed care, and student-teacher relationships in a residential treatment center for female adolescents.

Although there is a vast body of literature to support multiple positive outcomes related to positive student-teacher relationships, no prior study has investigated student-teacher relationships within the context of a residential treatment center for abused and neglected adolescents, students who theoretically could benefit from this relationship the most. The first goal of this study was to investigate the effects of student trauma symptomology, teacher beliefs about trauma-informed care, and teachers\u27 emotionally supportive behavior in the classroom on student-teacher relationship quality. Results revealed that teacher beliefs about trauma-informed care and student trauma symptomology, particularly as it is related to \u27Other-Control,\u27 are statistically significant predictor variables of student-teacher relationship quality (F7,45 = 3.002, p = .011, R2 =.318, /).R2 = .212). Additionally, teachers in on-campus schools within residential treatment centers are rarely trained to work with the traumatized students in their classrooms. Therefore, the second goal of this study was to examine the effects of a trauma-informed training intervention for teachers called Risking Connection. Changes in teachers\u27 knowledge about the training material, beliefs about trauma-informed care, and their emotionally supportive behavior in the classroom were evaluated before and after the teacher training as well as the subsequent changes in students\u27 reported trauma symptomology and their perceptions of the student-teacher relationship. Results revealed no statistically significant change in teacher scores; however, this was not expected due to the low sample size of teachers (n = 6). Descriptive statistics suggest that if teacher changes occurred initially, they did not sustain. There was no statistically significant difference in the amount of change in students before and after the teacher training; however, a trend of slightly higher student scores was noted at the third data collection time point directly following the teacher training. Overall, the findings indicate that characteristics of both the students and teachers impact the student-teacher relationship in the residential treatment center setting. Specifically, students\u27 trauma symptomology and teachers\u27 beliefs about the effectiveness of trauma-informed care are predictive of student perceptions of their relationship with their teachers. Implications for research, clinical practice, and effective training for teachers of this population are discussed

Molecular methods to investigate adhesion, transmigration, invasion and intracellular survival of the foodborne pathogen Campylobacter jejuni

AbstractCampylobacter jejuni is a spiral-shaped Gram-negative pathogen and major agent of gastrointestinal foodborne illness in humans worldwide. This pathogen encodes numerous described pathogenicity-associated factors involved in important processes including bacterial adhesion to, transmigration across, invasion into and intracellular survival within intestinal epithelial cells. This review article highlights various molecular techniques applied in the studies of each of these individual steps of C. jejuni host cell interactions in vitro including gentamicin protection assay, chemotaxis and motility assays, transwell and intracellular survival assays, G-Lisa, siRNA knockdown, immunohistochemistry, immunofluorescence, electron microscopy and luciferase reporter assays. We discuss the strengths and limitations of the methods as well as the different cell model systems applied. Future work should employ new technologies including modern microscopic, proteomics-based and cell signaling approaches to identify and characterise novel virulence mechanisms, which are crucial to provide fresh insights into the diversity of strategies employed by this important pathogen to cause disease

Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori

Helicobacter pylori is a highly successful pathogen uniquely adapted to colonize humans. Gastric infections with this bacterium can induce pathology ranging from chronic gastritis and peptic ulcers to gastric cancer. More virulent H. pylori isolates harbour numerous well-known adhesins (BabA/B, SabA, AlpA/B, OipA and HopZ) and the cag (cytotoxin-associated genes) pathogenicity island encoding a type IV secretion system (T4SS). The adhesins establish tight bacterial contact with host target cells and the T4SS represents a needle-like pilus device for the delivery of effector proteins into host target cells such as CagA. BabA and SabA bind to blood group antigen and sialylated proteins respectively, and a series of T4SS components including CagI, CagL, CagY and CagA have been shown to target the integrin β1 receptor followed by injection of CagA across the host cell membrane. The interaction of CagA with membrane-anchored phosphatidylserine may also play a role in the delivery process. While substantial progress has been made in our current understanding of many of the above factors, the host cell receptors for OipA, HopZ and AlpA/B during infection are still unknown. Here we review the recent progress in characterizing the interactions of the various adhesins and structural T4SS proteins with host cell factors. The contribution of these interactions to H. pylori colonization and pathogenesis is discussed

Immunopathological properties of the Campylobacter jejuni flagellins and the adhesin CadF as assessed in a clinical murine infection model

Background: Campylobacter jejuni infections constitute serious threats to human health with increasing prevalences worldwide. Our knowledge regarding the molecular mechanisms underlying host-pathogen interactions is still limited. Our group has established a clinical C. jejuni infection model based on abiotic IL-10-/- mice mimicking key features of human campylobacteriosis. In order to further validate this model for unraveling pathogen-host interactions mounting in acute disease, we here surveyed the immunopathological features of the important C. jejuni virulence factors FlaA and FlaB and the major adhesin CadF (Campylobacter adhesin to fibronectin), which play a role in bacterial motility, protein secretion and adhesion, respectively. Methods and results: Therefore, abiotic IL-10-/- mice were perorally infected with C. jejuni strain 81-176 (WT) or with its isogenic flaA/B (ΔflaA/B) or cadF (ΔcadF) deletion mutants. Cultural analyses revealed that WT and ΔcadF but not ΔflaA/B bacteria stably colonized the stomach, duodenum and ileum, whereas all three strains were present in the colon at comparably high loads on day 6 post-infection. Remarkably, despite high colonic colonization densities, murine infection with the ΔflaA/B strain did not result in overt campylobacteriosis, whereas mice infected with ΔcadF or WT were suffering from acute enterocolitis at day 6 post-infection. These symptoms coincided with pronounced pro-inflammatory immune responses, not only in the intestinal tract, but also in other organs such as the liver and kidneys and were accompanied with systemic inflammatory responses as indicated by increased serum MCP-1 concentrations following C. jejuni ΔcadF or WT, but not ΔflaA/B strain infection. Conclusion: For the first time, our observations revealed that the C. jejuni flagellins A/B, but not adhesion mediated by CadF, are essential for inducing murine campylobacteriosis. Furthermore, the secondary abiotic IL-10-/- infection model has been proven suitable not only for detailed investigations of immunological aspects of campylobacteriosis, but also for differential analyses of the roles of distinct C. jejuni virulence factors in induction and progression of disease

Oral history interview with Douglas R. Snow (SOH-078)

Dr. Douglas R. Snow, Professor Emeritus of the Institute of Public Services at Suffolk University, reflects on his personal and professional life before, during, and after his career at Suffolk University. Dr. Snow also talks about his role as a faculty member and chair of the Public Administration department, the growth of the various programs and degrees offered, as well as, the colleagues that inspired him during his career. Dr. Snow concludes with a reflection on what he hopes students gain from the MPA programs, their potential impact in the public sphere, and the future direction of Suffolk’s program.https://dc.suffolk.edu/soh/1052/thumbnail.jp

Four Chromosomal Type IV Secretion Systems in Helicobacter pylori: Composition, Structure and Function

The pathogenic bacterium Helicobacter pylori is genetically highly diverse and a major risk factor for the development of peptic ulcer disease and gastric adenocarcinoma in humans. During evolution, H. pylori has acquired multiple type IV secretion systems (T4SSs), and then adapted for various purposes. These T4SSs represent remarkable molecular transporter machines, often associated with an extracellular pilus structure present in many bacteria, which are commonly composed of multiple structural proteins spanning the inner and outer membranes. By definition, these T4SSs exhibit central functions mediated through the contact-dependent conjugative transfer of mobile DNA elements, the contact-independent release and uptake of DNA into and from the extracellular environment as well as the secretion of effector proteins in mammalian host target cells. In recent years, numerous features on the molecular functionality of these T4SSs were disclosed. H. pylori encodes up to four T4SSs on its chromosome, namely the Cag T4SS present in the cag pathogenicity island (cagPAI), the ComB system, as well as the Tfs3 and Tfs4 T4SSs, some of which exhibit unique T4SS functions. The Cag T4SS facilitates the delivery of the CagA effector protein and pro-inflammatory signal transduction through translocated ADP-heptose and chromosomal DNA, while various structural pilus proteins can target host cell receptors such as integrins or TLR5. The ComB apparatus mediates the import of free DNA from the extracellular milieu, whereas Tfs3 may accomplish the secretion or translocation of effector protein CtkA. Both Tfs3 and Tfs4 are furthermore presumed to act as conjugative DNA transfer machineries due to the presence of tyrosine recombinases with cognate recognition sequences, conjugational relaxases, and potential origins of transfer (oriT) found within the tfs3 and tfs4 genome islands. In addition, some extrachromosomal plasmids, transposons and phages have been discovered in multiple H. pylori isolates. The genetic exchange mediated by DNA mobilization events of chromosomal genes and plasmids combined with recombination events could account for much of the genetic diversity found in H. pylori. In this review, we highlight our current knowledge on the four T4SSs and the involved mechanisms with consequences for H. pylori adaptation to the hostile environment in the human stomach

Applied immunoinformatics: HLA peptidome analysis for cancer immunotherapy

Despite different therapeutic approaches, cancer is one of the leading causes of death worldwide. Therefore, new therapies, like immunotherapy, are being developed to cure cancer. All immunotherapies have in common that they need targets to recognize malignant cells. Both the malignant and the benign immunopeptidome have to be examined, to define these new targets. We herein present a large immunopeptidome dataset of benign tissues containing multiple tissue types from different individuals. Moreover, we introduce the HLA Ligand Atlas, a web-interface we developed to accompany the data. It provides user-friendly access to the data, a fast, interactive search option which can be used to search for tissue specific HLA-peptides, and provides common statistics to the user. Using the large dataset of benign samples, we were able to define general properties of the immunopeptidome. First, we showed that a short time storage of the samples at 8 °C does not alter the immunopeptidome in terms of the number of found peptides and their quality. Next, we performed quality control, in which we found an altered immunopeptidome in the samples of stomach tissue, which might be caused by pepsin in the samples. In addition, we analyzed both the inter- and the intra-individual variability of the immunopeptidome on protein and peptide level. This analysis revealed that sample variability was better explained by HLA type than by tissue-specific peptide presentation. Finally, the large dataset of benign samples allows us to describe properties like the length distribution of different HLA alleles and the nestedness of the peptides in the two HLA classes. In the last part of this thesis, we show how targets can be defined using immunopeptidome data. In this case, we investigated four different hematological malignancies. We describe entity-dividing lines by using a unsupervised hierarchical clustering of allotype-specific peptides, which showed that entity-specific analysis is recommended. Nevertheless, we found "panleukemia"- antigens shared across all four hematological malignancies, which were cancer exclusive.Trotz verschiedenster therapeutischen Behandlungsmethoden ist Krebs noch immer eine der häufigsten Todesursachen weltweit. Deshalb werden weiterhin neue Therapieansätze, wie zum Beispiel Immunotherapie, entwickelt, um Krebs zu heilen. Zur Entwicklung von Immunotherapien gegen Tumorzellen werden Angriffsziele benötigt, anhand derer Krebszellen erkannt werden können. Zur Bestimmung dieser ist es notwendig sowohl das Immunopeptidom von Krebszellen als auch das von gesundem Gewebe zu kennen. Wir präsentieren einen großen Immunopeptidomdatensatz von gesundem Gewebe, der sowohl verschiedene Organtypen eines Individuums, als auch verschiedene Individuen beinhaltet. Wir haben ein Webinterface - den HLA Ligand Atlas - entwickelt, um einen benutzerfreundlichen Zugriff auf die Daten zu ermöglichen. Dieses Webinterface erlaubt eine schnelle interaktive Suche im Datensatz, wie die Suche nach organspezifischen HLA Peptiden, und stellt zusätzliche Statisken bereit. Des Weiteren erlaubt es die Darstellung der Massenspektrometriespektren in einem interaktivem Spektrumviewer. Mit Hilfe des großen Datensatz an Normalgewebe konnten wir allgemeine Eigenschaften des Immunpeptidom bestimmen. Zuerst zeigen wir, dass das Immunopeptidom sich sowohl quantitativ als auch qualitativ nicht ändert, wenn die Probe kurzzeitig bei 8 °C gelagert wird. Als nächsten führten wir eine Qualitätskontrolle durch, die ein verändertes Immunopeptidom bei den Proben des Magengewebes aufzeigte, welches möglicherweise durch Pepsin in den Proben verursacht wurde. Zusätzlich untersuchten wir die inter- und intra-individuelle Variabilität des Immunopeptidom auf Protein- und Peptideebene. Die Analyse zeigte hier, dass der HLA-Typ einen größeren Einfluss auf die Variablität hat als die organspezifische Präsentation. Der große Datensatz von Normalgewebe erlaubte uns auch die Beschreibung weiterer Eigenschaften, wie die Peptidlängenverteilung für verschieden HLA Allele und die Beschreibung von Längenvarianten in den zwei HLA Klassen. Im letzten Teil dieser Doktorarbeit zeigen wir wie neue Angriffsziele mit Hilfe von Immunopeptidomdaten gefunden werden können. In unserem Fall untersuchten wir vier verschieden hämatologische Krebsarten. Durch eine unüberwachte hierarchische Clusteranalyse auf allotypspezifischen Peptide wurden hier klare, entitätsspezifische Cluster identifiziert. Dieser Befund spricht für die Notwendigkeit einer entitätsspezifischen Anaylse solcher Datenätze. Nichtsdestotrotz konnten wir auf allen vier hämatologischen Krebsarten „Pan-leukemia“ Antigene finden, die krebsexklusiv sind

Molecular Targets in Campylobacter Infections

Human campylobacteriosis results from foodborne infections with Campylobacter bacteria such as Campylobacter jejuni and Campylobacter coli, and represents a leading cause of bacterial gastroenteritis worldwide. After consumption of contaminated poultry meat, constituting the major source of pathogenic transfer to humans, infected patients develop abdominal pain and diarrhea. Post-infectious disorders following acute enteritis may occur and affect the nervous system, the joints or the intestines. Immunocompromising comorbidities in infected patients favor bacteremia, leading to vascular inflammation and septicemia. Prevention of human infection is achieved by hygiene measures focusing on the reduction of pathogenic food contamination. Molecular targets for the treatment and prevention of campylobacteriosis include bacterial pathogenicity and virulence factors involved in motility, adhesion, invasion, oxygen detoxification, acid resistance and biofilm formation. This repertoire of intervention measures has recently been completed by drugs dampening the pro-inflammatory immune responses induced by the Campylobacter endotoxin lipo-oligosaccharide. Novel pharmaceutical strategies will combine anti-pathogenic and anti-inflammatory effects to reduce the risk of both anti-microbial resistance and post-infectious sequelae of acute enteritis. Novel strategies and actual trends in the combat of Campylobacter infections are presented in this review, alongside molecular targets applied for prevention and treatment strategies