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Shiga toxin (Stx)-producing E. coli (STEC) cause food-borne outbreaks of hemorrhagic colitis. The main virulence factor expressed by STEC, Stx, is an AB5 toxin that has two antigenically distinct forms, Stx1a and Stx2a. Although Stx1a and Stx2a bind to the same receptor, globotriaosylceramide (Gb3), Stx2a is more potent than Stx1a in mice, whereas Stx1a is more cytotoxic than Stx2a in cell culture. In this study, we used chimeric toxins to ask what the relative contribution of individual Stx subunits is to the differential toxicity of Stx1a and Stx2a in vitro and in vivo. Chimeric stx1/stx2 operons were generated by PCR such that the coding regions for the A2 and B subunits of one toxin were combined with the coding region for the A1 subunit of the heterologous toxin. The toxicities of purified Stx1a, Stx2a, and the chimeric Stxs were determined on Vero and HCT-8 cell lines, while polarized HCT-8 cell monolayers grown on permeable supports were used to follow toxin translocation. In all in vitro assays, the activity of the chimeric toxin correlated with that of the parental toxin from which the B subunit originated. The origin of the native B subunit also dictated the 50% lethal dose of toxin after intraperitoneal intoxication of mice; however, the chimeric Stxs exhibited reduced oral toxicity and pH stability compared to Stx1a and Stx2a. Taken together, these data support the hypothesis that the differential toxicity of the chimeric toxins for cells and mice is determined by the origin of the B subunit.

Background. Shiga toxin (Stx) is the primary virulence factor of Stx-producing Escherichia coli (STEC). STEC can produce Stx1a and/or Stx2a, which are antigenically distinct. However, Stx2a-producing STEC are associated with more severe disease than strains producing both Stx1a and Stx2a. Methods and Results. To address the hypothesis that the reason for the association of Stx2a with more severe disease is because Stx2a crosses the intestinal barrier with greater efficiency that Stx1a, we covalently labeled Stx1a and Stx2a with Alexa Fluor 750 and determined the ex vivo fluorescent intensity of murine systemic organs after oral intoxication. Surprisingly, both Stxs exhibited similar dissemination patterns and accumulated in the kidneys. We next cointoxicated mice to determine whether Stx1a could impede Stx2a. Cointoxication resulted in increased survival and an extended mean time to death, compared with intoxication with Stx2a only. The survival benefit was dose dependent, with the greatest effect observed when 5 times more Stx1a than Stx2a was delivered, and was amplified when Stx1a was delivered 3 hours prior to Stx2a. Cointoxication with an Stx1a active site toxoid also reduced Stx2a toxicity. Conclusions. These studies suggest that Stx1a reduces Stx2a-mediated toxicity, a finding that may explain why STEC that produce only Stx2a are associated with more severe disease than strains producing Stx1a and Stx2a.

Acellular multivalent vaccines for pertussis (DTaP and Tdap) prevent symptomatic disease and infant mortality, but immunity to Bordetella pertussis infection wanes significantly over time resulting in cyclic epidemics of pertussis. The messenger RNA (mRNA) vaccine platform provides an opportunity to address complex bacterial infections with an adaptable approach providing Th1-biased responses. In this study, immunogenicity and challenge models were used to evaluate the mRNA platform with multivalent vaccine formulations targeting both B. pertussis antigens and diphtheria and tetanus toxoids. Immunization with mRNA formulations were immunogenetic, induced antigen specific antibodies, as well as Th1 T cell responses. Upon challenge with either historical or contemporary B. pertussis strains, 6 and 10 valent mRNA DTP vaccine provided protection equal to that of 1/20th human doses of either DTaP or whole cell pertussis vaccines. mRNA DTP immunized mice were also protected from pertussis toxin challenge as measured by prevention of lymphocytosis and leukocytosis. Collectively these pre-clinical mouse studies illustrate the potential of the mRNA platform for multivalent bacterial pathogen vaccines.

Background Shiga toxin (Stx)-producing E. coli (STEC) are responsible for foodborne outbreaks that can result in severe human disease. During an outbreak, differential disease outcomes are observed after infection with the same STEC strain. One question of particular interest is why some infected people resolve infection after hemorrhagic colitis whereas others progress to the hemolytic uremic syndrome (HUS). Host age and infection dose have been implicated; however, these parameters do not appear to fully account for all of the observed variation in disease severity. Therefore, we hypothesized that additional host genetic factors may play a role in progression to HUS. Methods and Results To mimic the genetic diversity in the human response to infection by STEC, we measured the capacity of an O157:H7 outbreak isolate to colonize mouse strains from the advanced recombinant inbred (ARI) BXD panel. We first infected the BXD parental strains C57BL/6 J (B6) and DBA/2 J (D2) with either 86–24 (Stx2a+) or TUV86-2, an Stx2a-negative isogenic mutant. Colonization levels were determined in an intact commensal flora (ICF) infection model. We found a significant difference in colonization levels between the parental B6 and D2 strains after infection with TUV86-2 but not with 86–24. This observation suggested that a host factor that may be masked by Stx2a affects O157:H7 colonization in some genetic backgrounds. We then determined the TUV86-2 colonization levels of 24 BXD strains in the ICF model. We identified several quantitative trait loci (QTL) associated with variation in colonization by correlation analyses. We found a highly significant QTL on proximal chromosome 9 (12.5–26.7 Mb) that strongly predicts variation in colonization levels and accounts for 15–20 % of variance. Linkage, polymorphism and co-citation analyses of the mapped region revealed 36 candidate genes within the QTL, and we identified five genes that are most likely responsible for the differential colonization. Conclusions The identification of the QTL on chromosome 9 supports our hypothesis that individual genetic makeup affects the level of colonization after infection with STEC O157:H7.

Shiga toxin (Stx)-producing E. coli (STEC) cause food-borne outbreaks of hemorrhagic colitis. The main virulence factor expressed by STEC, Stx, is an AB.sub.5 toxin that has two antigenically distinct forms, Stx1a and Stx2a. Although Stx1a and Stx2a bind to the same receptor, globotriaosylceramide (Gb3), Stx2a is more potent than Stx1a in mice, whereas Stx1a is more cytotoxic than Stx2a in cell culture. In this study, we used chimeric toxins to ask what the relative contribution of individual Stx subunits is to the differential toxicity of Stx1a and Stx2a in vitro and in vivo. Chimeric stx.sub.1 /stx.sub.2 operons were generated by PCR such that the coding regions for the A.sub.2 and B subunits of one toxin were combined with the coding region for the A.sub.1 subunit of the heterologous toxin. The toxicities of purified Stx1a, Stx2a, and the chimeric Stxs were determined on Vero and HCT-8 cell lines, while polarized HCT-8 cell monolayers grown on permeable supports were used to follow toxin translocation. In all in vitro assays, the activity of the chimeric toxin correlated with that of the parental toxin from which the B subunit originated. The origin of the native B subunit also dictated the 50% lethal dose of toxin after intraperitoneal intoxication of mice; however, the chimeric Stxs exhibited reduced oral toxicity and pH stability compared to Stx1a and Stx2a. Taken together, these data support the hypothesis that the differential toxicity of the chimeric toxins for cells and mice is determined by the origin of the B subunit.

Significance & Background: For patients with hematologic malignancies, stem cell transplantation may offer the best chance for achieving lasting remission. Lack of proximity to a transplant center can be a barrier to treatment. To improve access, one regional cancer institute set out to establish its own transplant program. The success of the program would be contingent in part on adequately preparing inexperienced nursing staffto care for this patient population. Purpose: Implement a multifaceted approach to educating inpatient oncology nurses in all aspects of stem cell transplantation to achieve optimal patient outcomes. Interventions: Staffeducation in stem cell transplantation was coordinated by an interdisciplinary team that included the director of the transplant program, the clinical nurse specialist for oncology, and the nurse educator for the transplant unit. A core group of registered nurses was selected for the initial phase of training, based on oncology experience and chemotherapy certification. These RNs were invited to attend a two-day in-person transplant course, along with a one-day on-site observation at an established transplant center. Weekly education sessions, each focusing on an aspect of the transplant process, were presented by the medical director of the transplant program and open to all unit staff. Nurses participated in simulations designed to provide hands-on experience in administering stem cells as well as specific drugs in the conditioning regimens. Validation of relevant skills was required prior to an RN assuming care of the transplant patient. In daily practice, the bedside nurse had on-demand access to resources including online practice guidelines, interdisciplinary team huddles, and transplant group texts. Results: As of May 2024, six inpatient oncology nurses had completed the necessary stem cell education and validations. In a post-discharge debrief, these RNs described feeling well-prepared and confident in their ability to provide care for transplant patients. Feedback from patients and providers has been positive as well, as the nursing staffhas demonstrated proficiency in implementing transplant protocols and modeling transplant nursing standards. Discussion: Education tailored to the inpatient oncology nurse has been central to the successful launch of a stem cell transplant program. The core group of transplant RNs now serve as mentors to their nursing colleagues who are preparing to assume the transplant nurse role. Their insights have helped to troubleshoot processes and identify improvements that collectively advance transplant policy and optimize patient care.

This study used a mixed methods research design to examine teachers’ perceptions of and knowledge about Universal Design for Learning (UDL). It specifically investigated whether participant teachers viewed the UDL instructional model as one that has the potential to improve student outcomes and whether the training in UDL was sufficient to allow them to use it effectively in their classrooms The survey was distributed with Survey Monkey and was completed anonymously. The study included the gathering of data from questions of both a quantitative and qualitative nature through an on-line survey. The online survey contained three sections: a section containing three demographic questions as well as 16 Likert Scale questions and two open-ended items regarding the teacher’s implementation of meeting the needs of all learners. Data was examined for themes to provide further insight into the impact, if any, of professional development and training in Universal Design for Learning and the components that teachers perceive to be important to implement UDL. It was expected that familiarity and training would influence the level of use of UDL by teachers and the relationship between teacher and administrator support toward the success of all students was also expected to influence the level of use of UDL.

Chiocca discusses a case of 14-year-old recently diagnosed with non-Hodgkin's lymphoma who is suffering from chest pain and shortness of breath. The patient's hypertension, poor perfusion, edema, and flushing indicate superior vena cava syndrome, or impeded venous blood flow through the superior vena cava to the right atrium.

\"The world is your classroom,\" according to the Global Education Office page on the Keene State College website.

Another thing I feel is overlooked when discussing Greek life is the fact that each fraternity and sorority have a philanthropy that they go by.