THE ROLE OF STREPTOCOCCUS GALLOLYTICUS SUBSPECIES GALLOLYTICUS IN COLON CANCER DEVELOPMENT

Colorectal cancer (CRC) is the third most common cancer in men and women and is also the third most common cause of cancer death. A large body of evidence points towards the possibility that bacteria can have a significant impact on the development of cancer. It has been suggested that Streptococcus gallolyticus subsp. gallolyticus, a group D streptococci, may play a role in the development of CRC. Sg, formerly S. bovis biotype I, has been shown to be highly associated with CRC. In observing patients with either Sg bacteremia or endocarditis it was found that 25-80% of patients with Sg bacteremia had tumors and 18-62% of patients with Sg endocarditis had colonic neoplasias. However, other closely related Streptococcal strains, such as S. pasterianus and S. infantarius, have not been shown to have this strong association with CRC. In fact, it has been shown that biotype I is more often associated with CRC (94%) as compared to biotype II (18%). This knowledge has important clinical implications, and yet little is known about the role of Sg on CRC and the underlying mechanisms. Here we show that mice treated with Sg had significantly more tumors, higher tumor burden and dysplasia grade, and increased cell proliferation and β-catenin level in colonic crypts compared to mice treated with control bacteria. Sg strains that promoted proliferation were also more efficient at adhering to CRC cell lines and colonizing a mouse model. Additionally, in human patients Sg was highly prevalent in CRC patients and tumor tissues had an increased Sg burden in comparison to normal adjacent tissues. These results provide exciting new information and establish a tumor-promoting role of Sg that involves specific bacterial and host factors

Illustrations and supporting texts for sound standing waves of air columns in pipes in introductory physics textbooks

In our pilot studies, we found that many introductory physics textbook illustrations with supporting text for sound standing waves of air columns in open-open, open-closed, and closed-closed pipes inhibit student understanding of sound standing wave phenomena due to student misunderstanding of how air molecules move within these pipes. Based on the construct of meaningful learning from cognitive psychology and semiotics, a quasiexperimental study was conducted to investigate the comparative effectiveness of two alternative approaches to student understanding: a traditional textbook illustration approach versus a newly designed air molecule motion illustration approach. Thirty volunteer students from introductory physics classes were randomly assigned to two groups of 15 each. Both groups were administered a presurvey. Then, group A read the air molecule motion illustration handout, and group B read a traditional textbook illustration handout; both groups were administered postsurveys. Subsequently, the procedure was reversed: group B read the air molecule motion illustration handout and group A read the traditional textbook illustration handout. This was followed by a second postsurvey along with an exit research questionnaire. The study found that the majority of students experienced meaningful learning and stated that they understood sound standing wave phenomena significantly better using the air molecule motion illustration approach. This finding provides a method for physics education researchers to design illustrations for abstract sound standing wave concepts, for publishers to improve their illustrations with supporting text, and for instructors to facilitate deeper learning in their students on sound standing waves

Exenatide extended release in patients with type 1 diabetes with and without residual insulin production

AimsTo test whether a long- acting GLP- 1 receptor agonist would improve glucose control in patients with type 1 diabetes (T1D) and to determine whether the presence of residual beta cell function would affect the response. In addition, we sought to determine whether the drug would affect beta cell function.MethodsWe performed a randomized placebo- controlled trial of exenatide extended release (ER) in participants with T1D with and without detectable levels of C- peptide. Seventy- nine participants were randomized to exenatide ER 2 mcg weekly, or placebo, stratified by the presence or absence of detectable C- peptide levels. The primary outcome was the difference in glycated haemoglobin (HbA1c) levels at 24- weeks. Participants were followed for another 6 months off study drug.ResultsAt week 24, the time of the primary outcome, the least squares (LS) mean HbA1c level was 7.76% (95% confidence interval [CI] 7.42, 8.10) in the exenatide ER group versus 8.0% (95% CI 7.64, 8.35) in the placebo group (P = 0.08). At week 12 the LS mean HbA1c levels were 7.71% (95% CI 7.37, 8.05) in the exenatide ER group versus 8.05% (95% CI 7.7, 8.4) in the placebo group (P = 0.01). The improvement at week 12 was driven mainly by those with detectable levels of C- peptide. Those treated with exenatide ER lost weight at 12 and 24- weeks compared to those treated with placebo (P- <0.001 and P = 0.007). The total insulin dose was lower, but not when corrected for body weight, and was not affected by residual insulin production. Adverse events were more frequent with exenatide ER, but hypoglycaemia was not increased.ConclusionTreatment with exenatide ER may have short- term benefits in some individuals with T1D who are overweight or who have detectable levels of C- peptide, but short- term improvements were not sustained.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163873/1/dom14121_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163873/2/dom14121.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163873/3/dom14121-sup-0001-Supinfo.pd

The impact of tumor metabolic activity assessed by 18^{18}F-FET amino acid PET imaging in particle radiotherapy of high-grade glioma patients

Selective uptake of (18)F-fluoro-ethyl-tyrosine ($^{18}$F-FET) is used in high-grade glioma (HGG) to assess tumor metabolic activity via positron emission tomography (PET). We aim to investigate its value for target volume definition, as a prognosticator, and associations with whole-blood transcriptome liquid biopsy (WBT lbx) for which we recently reported feasibility to mirror tumor characteristics and response to particle irradiation in recurrent HGG (rHGG)

The Lantern Vol. 56, No. 2, Spring 1990

• Brasil • Plastic Flowers • Be a Pepper • Grunge • Handling the Responsibility • Returning to the Forest • How Nice • Nooze • Emma • Restoration • Chestnuts • Frozen Moments • Once Upon A • Clipped Wings • Gerard Manley Hopkins • Roaches • In Grand Central • The Steelville Shark • Panama 1989 • Betrayal • Violations • Detourhttps://digitalcommons.ursinus.edu/lantern/1136/thumbnail.jp

Exploiting the glioblastoma peptidome to discover novel tumour-associated antigens for immunotherapy

Peptides presented at the cell surface reflect the protein content of the cell; those on HLA class I molecules comprise the critical peptidome elements interacting with CD8 T lymphocytes. We hypothesize that peptidomes from ex vivo tumour samples encompass immunogenic tumour antigens. Here, we uncover >6000 HLA-bound peptides from HLA-A*02+ glioblastoma, of which over 3000 were restricted by HLA-A*02. We prioritized in-depth investigation of 10 glioblastoma-associated antigens based on high expression in tumours, very low or absent expression in healthy tissues, implication in gliomagenesis and immunogenicity. Patients with glioblastoma showed no T cell tolerance to these peptides. Moreover, we demonstrated specific lysis of tumour cells by patients' CD8+ T cells in vitro. In vivo, glioblastoma-specific CD8+ T cells were present at the tumour site. Overall, our data show the physiological relevance of the peptidome approach and provide a critical advance for designing a rational glioblastoma immunotherapy. The peptides identified in our study are currently being tested as a multipeptide vaccine (IMA950) in patients with glioblastom

Human Impacts on Forest Biodiversity in Protected Walnut-Fruit Forests in Kyrgyzstan

We used a spatially explicit model of forest dynamics, supported by empirical field data and socioeconomic data, to examine the impacts of human disturbances on a protected forest landscape in Kyrgyzstan. Local use of 27 fruit and nut species was recorded and modeled. Results indicated that in the presence of fuelwood cutting with or without grazing, species of high socioeconomic impor- tance such as Juglans regia, Malus spp., and Armeniaca vulgaris were largely eliminated from the landscape after 50–150 yr. In the absence of disturbance or in the presence of grazing only, decline of these species occurred at a much lower rate, owing to competi- tive interactions between tree species. This suggests that the current intensity of fuelwood harvesting is not sustainable. Conversely, cur- rent grazing intensities were found to have relatively little impact on forest structure and composition, and could potentially play a positive role in supporting regeneration of tree species. These results indicate that both positive and negative impacts on biodiversity can arise from human populations living within a protected area. Potentially, these could be reconciled through the development of participatory approaches to conservation management within this reserve, to ensure the maintenance of its high conservation value while meeting human needs

Islet Harvest in Carbon Monoxide-Saturated Medium for Chronic Pancreatitis Patients Undergoing Islet Autotransplantation

Stresses encountered during human islet isolation lead to unavoidable beta-cell death after transplantation. This reduces the chance of insulin independence in chronic pancreatitis patients undergoing total pancreatectomy and islet autotransplantation. We tested whether harvesting islets in carbon monoxide-saturated solutions is safe and can enhance islet survival and insulin independence after total pancreatectomy and islet autotransplantation. Chronic pancreatitis patients who consented to the study were randomized into carbon monoxide (islets harvested in a carbon monoxide-saturated medium) or control (islets harvested in a normal medium) groups. Islet yield, viability, oxygen consumption rate, beta-cell death (measured by unmethylated insulin DNA), and serum cytokine levels were measured during the peri-transplantation period. Adverse events, metabolic phenotypes, and islet function were measured prior and at 6 months post-transplantation. No adverse events directly related to the infusion of carbon monoxide islets were observed. Carbon monoxide islets showed significantly higher viability before transplantation. Subjects receiving carbon monoxide islets had less beta-cell death, decreased CCL23, and increased CXCL12 levels at 1 or 3 days post transplantation compared with controls. Three in 10 (30%) of the carbon monoxide subjects and none of the control subjects were insulin independent. This pilot trial showed for the first time that harvesting human islets in carbon monoxide-saturated solutions is safe for total pancreatectomy and islet autotransplantation patients.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Testamente Bamberger Frauen des 16. und 17. Jahrhunderts

Testamente werden in der historischen Forschung bereits seit geraumer Zeit als wichtige Quellen für die Geschichte der sozialen Beziehungen, der materiellen Kultur, der Frömmigkeitspraktiken und der Einstellungen zum Tod betrachtet. Der vorliegende Band untersucht erstmals systematisch ein Korpus von 84 archivalisch überlieferten Testamenten, die Bamberger Frauen zwischen 1510 und 1700 diktierten. Die Erblasserinnen kamen aus unterschiedlichen sozialen Milieus – das Spektrum umfasst Adelige, Beamtenwitwen, Handwerkerfrauen und Klerikermägde –, und ihre letztwilligen Verfügungen gewähren aufschlussreiche Einblicke in Lebenssituationen, persönliche Erfahrungen und soziale Netzwerke in einer frühneuzeitlichen Bischofsstadt.Historical researchers have long realized the value of wills as sources for the history of social relations, material culture, practices of piety and attitudes towards death. The present volume provides the first systematic analysis of 84 archival wills which women in Bamberg dictated between 1510 and 1700. The testators came from different social strata – including noblewomen, widows of public officials, artisans‘ wives and maids of clergymen – and their last wills provide revealing insights into life situations, personal experiences and social networks in an early modern cathedral town

An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes.

BackgroundType 1 diabetes is a chronic autoimmune disease that leads to destruction of insulin-producing beta cells and dependence on exogenous insulin for survival. Some interventions have delayed the loss of insulin production in patients with type 1 diabetes, but interventions that might affect clinical progression before diagnosis are needed.MethodsWe conducted a phase 2, randomized, placebo-controlled, double-blind trial of teplizumab (an Fc receptor-nonbinding anti-CD3 monoclonal antibody) involving relatives of patients with type 1 diabetes who did not have diabetes but were at high risk for development of clinical disease. Patients were randomly assigned to a single 14-day course of teplizumab or placebo, and follow-up for progression to clinical type 1 diabetes was performed with the use of oral glucose-tolerance tests at 6-month intervals.ResultsA total of 76 participants (55 [72%] of whom were ≤18 years of age) underwent randomization - 44 to the teplizumab group and 32 to the placebo group. The median time to the diagnosis of type 1 diabetes was 48.4 months in the teplizumab group and 24.4 months in the placebo group; the disease was diagnosed in 19 (43%) of the participants who received teplizumab and in 23 (72%) of those who received placebo. The hazard ratio for the diagnosis of type 1 diabetes (teplizumab vs. placebo) was 0.41 (95% confidence interval, 0.22 to 0.78; P = 0.006 by adjusted Cox proportional-hazards model). The annualized rates of diagnosis of diabetes were 14.9% per year in the teplizumab group and 35.9% per year in the placebo group. There were expected adverse events of rash and transient lymphopenia. KLRG1+TIGIT+CD8+ T cells were more common in the teplizumab group than in the placebo group. Among the participants who were HLA-DR3-negative, HLA-DR4-positive, or anti-zinc transporter 8 antibody-negative, fewer participants in the teplizumab group than in the placebo group had diabetes diagnosed.ConclusionsTeplizumab delayed progression to clinical type 1 diabetes in high-risk participants. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01030861.)