POTENTIAL IMPACTS OF BST ON THE MINNESOTA MILK SUPPLY

Livestock Production/Industries,

Clinical characteristics and outcomes of clostridial bacteraemia in cancer patients

AbstractClostridial bacteraemia is usually associated with substantial morbidity and mortality in cancer patients. However, clinical characteristics and risk factors for early mortality in this population are poorly described. We retrospectively studied cancer patients with clostridial bacteraemia treated between January 1996 and December 2011. We compared clinical manifestations between patients with solid tumour and haematological malignancy and assessed risk factors for 7-day mortality. In all, 164 cancer patients developed clostridial bacteraemia during the study period—85 (52%) with solid tumour and 79 (48%) with haematological malignancy. Common isolates were Clostridium perfringens (27%), Clostridium septicum (19%) and Clostridium tertium (14%). Solid tumour malignancy patients were more likely to have a focal gastrointestinal source for bacteraemia and were more likely to undergo subsequent surgery. Haematological malignancy patients were more often neutropenic and more often had no focal source of bacteraemia. Seven-day mortality was 20% (33/164) and did not vary based on malignancy type. The adjusted odds ratio of dying within 7 days of clostridial bacteraemia among patients with hypotension (40/164) was 7.2 (95% CI, 2.9–18.1) and in patients with acute haemolysis (7/164) was 10.5 (95% CI, 1.3–85.2). Clostridial species also impacted mortality; no patient with C. tertium bacteraemia died within 7 days. In conclusion, clinical manifestations of clostridial bacteraemia differed between patients with solid tumour and haematological malignancy, but 7-day mortality was similar. Patients with hypotension and haemolysis at time of bacteraemia were at increased risk for early death

Acute phosphate depletion and in vitro rat proximal tubule injury: Protection by glycine and acidosis

Acute phosphate depletion and in vitro rat proximal tubule injury: Protection by glycine and acidosis.The effects of phosphate (PO4) removal from Krebs Henseleit buffer on freshly isolated rat proximal tubules (rPT) were assessed by measuring Ca2+ uptake (nmol/mg protein), cellular adenosine triphosphate (ATP) (nmol/mg), tissue K+ content (nmol/mg) and lactate dehydrogenase (LDH) as an index of cell integrity. Ca2+ uptake increased by 50% in rPT incubated in zero PO4 medium as compared to control (2.6 ±0.1 vs. 3.9 ±0.19, P < 0.001) and LDH release increased 2.5-fold from 14.2 ±0.6 to 31.6 ±1.6%, P < 0.001. Neither verapamil (200 µM) nor mepacrine (50 µM) reduced Ca2+ uptake or decreased LDH release suggesting that the increased Ca2+ uptake was not occurring through potential operated channels and that phospholipase-induced cell injury was not the cause of increased LDH release. Either glycine (2 mM) or extracellular fluid acidosis (pH 7.06), however, significantly diminished rPT injury and Ca2+ uptake. Specifically, as compared to the increased LDH released in untreated, PO4-depleted rPT, LDH release was diminished significantly by glycine treatment (31.0 ±0.9 vs. 15.5 ±1.6%, P < 0.001) or acidosis (30.3 ±0.04 vs. 19.2 ±0.9%, P < 0.01). Ca2+ uptake did not increase in glycine treated tubules (2.6 ±0.1 vs. 2.8 ±0.2 nmol/mg, NS) or in the presence of acidosis (2.6 ±0.1 vs. 2.97 ±0.17 nmol/mg, NS). ATP concentrations were markedly reduced by PO4 depletion (2.8±0.2 vs. 4.8±0.3 nmol/mg, P < 0.001) and remained at low levels during either acidosis or glycine-induced protection. ATP depletion was accompanied by loss of K+ from rPT and this was only modestly attenuated by either glycine or acidosis. Total cell PO4 was not significantly altered, however, perchloric acid (PCA) extractable free PO4 was reduced significantly (33.3 ±4.5 to 15.9 ±3.5 nmol/mg, P < 0.01). The rPT injury, associated with acute PO4 depletion, may be related to Ca2+ uptake since Ca2+ uptake and LDH release were both attenuated by glycine administration or acidosis

Hypoxia-induced SETX links replication stress with the unfolded protein response

YesTumour hypoxia is associated with poor patient prognosis and therapy resistance. A unique transcriptional response is initiated by hypoxia which includes the rapid activation of numerous transcription factors in a background of reduced global transcription. Here, we show that the biological response to hypoxia includes the accumulation of R-loops and the induction of the RNA/DNA helicase SETX. In the absence of hypoxia-induced SETX, R-loop levels increase, DNA damage accumulates, and DNA replication rates decrease. Therefore, suggesting that, SETX plays a role in protecting cells from DNA damage induced during transcription in hypoxia. Importantly, we propose that the mechanism of SETX induction in hypoxia is reliant on the PERK/ATF4 arm of the unfolded protein response. These data not only highlight the unique cellular response to hypoxia, which includes both a replication stress-dependent DNA damage response and an unfolded protein response but uncover a novel link between these two distinct pathways.SR, KBL, PV and MH were supported by a CRUK grant C5255/A23755 (awarded to E.M.H.). N.N. was supported by an MRC studentship (MC_ST_U16007). I. P.F. was supported by CRUK Oxford Centre Prize DPhil Studentship C38302/A12981. N.G. was supported by a Royal Society University Research fellowship. W.-C.C. was funded by CRUK grant 23969 (awarded to F.M.B.). S.F.E.-K. was supported by a Wellcome Trust Investigator Award (103844) and a Lister Institute of Preventative Medicine Fellowship (137661). J.G. was supported by a Jean Shanks Foundation/ Pathological Society of Great Britain and Ireland Clinical PhD Fellowship (JSPS CPhD 2018 01)

The Boundary-spanning Role of Democratic Learning Communities: Implementing the IDEALS

This multi-case study investigates characteristics and practices in schools that expand the traditional boundaries of school leadership and transform schools into democratic learning communities based on the level of implementation of the IDEALS framework. This investigation serves as a modus to illuminate democratic processes that change schools and address the needs of the students, not the needs of the adults in the system. A sample of five purposefully selected high schools, from the Midwest USA, was utilized. The schools serve Grade 9—12 students, but vary in size, residential area and socioeconomic status of the students. This study illuminates some of the challenges and strategies that facilitate or impede the process of creating more democratic schools that expand the boundaries of inquiry and discourse to include a broader range of community stakeholders and that respect and embrace issues of equity.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future

Purpose Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Design Meta-analysis of prevalence data. Participants A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. Methods AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Main Outcome Measures Prevalence of early and late AMD, BCVA, and number of AMD cases. Results Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%–5.0%) in those aged 55–59 years to 17.6% (95%