Bruceholden5978

BACKGROUND & AIMS Shiga toxin (Stx)-producing Escherichia coli (eg, O157H7) infection produces bloody diarrhea, while Stx inhibits protein synthesis and causes the life-threatening systemic complication of hemolytic uremic syndrome. The murine intestinal tract is resistant to O157H7 and Stx, and human cells in culture fail to model the complex tissue responses to intestinal injury. We used genetically identical, human stem cell-derived intestinal tissues of varying complexity to study Stx toxicity in vitro and in vivo. METHODS In vitro susceptibility to apical or basolateral exposure to Stx was assessed using human intestinal organoids (HIOs) derived from embryonic stem cells, or enteroids derived from multipotent intestinal stem cells. HIOs contain a lumen, with a single layer of differentiated epithelium surrounded by mesenchymal cells. Enteroids only contain epithelium. In vivo susceptibility was assessed using HIOs, with or without an enteric nervous system, transplanted into mice. RESULTS Stx induced necrosis and apoptotic death in both epithelial and mesenchymal cells. Responses that require protein synthesis (cellular proliferation and wound repair) also were observed. Epithelial barrier function was maintained even after epithelial cell death was seen, and apical to basolateral translocation of Stx was seen. Tissue cross-talk, in which mesenchymal cell damage caused epithelial cell damage, was observed. Stx induced mesenchymal expression of the epithelial marker E-cadherin, the initial step in mesenchymal-epithelial transition. In vivo responses of HIO transplants injected with Stx mirrored those seen in vitro. CONCLUSIONS Intestinal tissue responses to protein synthesis inhibition by Stx are complex. Organoid models allow for an unprecedented examination of human tissue responses to a deadly toxin. BACKGROUND & AIMS Recent evidence has suggested that the intact intestinal epithelial barrier protects our body from a range of immune-mediated diseases. The epithelial layer has an impressive ability to reconstitute and repair upon damage and this process of repair increasingly is seen as a therapeutic target. In vitro models to study this process in primary intestinal cells are lacking. METHODS We established and characterized an in vitro model of intestinal damage and repair by applying γ-radiation on small-intestinal organoids. We then used this model to identify novel regulators of intestinal regeneration. RESULTS We identified hepatocyte nuclear factor 4α (HNF4α) as a pivotal upstream regulator of the intestinal regenerative response. Organoids lacking Hnf4a were not able to propagate in vitro. Importantly, intestinal Hnf4a knock-out mice showed impaired regeneration after whole-body irradiation, confirming intestinal organoids as a valuable alternative to in vivo studies. CONCLUSIONS In conclusion, we established and validated an in vitro damage-repair model and identified HNF4α as a crucial regulator of intestinal regeneration. Transcript profiling GSE141515 and GSE141518. BACKGROUND Primary health care nurses can play an important role in assisting the diagnosis and management of dementia. This study describes the evaluation outcome of a training program developed on the 'Four Steps to Building Dementia Practice in Primary Care'. OBJECTIVE To evaluate a training program for primary health care nurses by assessing change in current practice and future intention; and their knowledge, confidence, and perceived importance about dementia diagnosis and management. DESIGN A longitudinal survey. Participants were surveyed at three time points pre-training, immediately post-training and six months (+/- 3 months) following their training. SETTING All states and territories in Australia. PARTICIPANTS Primary health care nurses (n = 1,290). METHODS A face-to-face and online training program on timely diagnosis and management of dementia was offered to primary health care nurses. A questionnaire was administered face-to-face and online to assess whether certain processes and services were core for perceived knowledge and confidence but not for perceived importance. Primary health care nurses who had 20 or more years of experience reported significantly more knowledge in attending patients with dementia than those with less than five years of experience (0.56, 95% CI 0.11-1.01). CONCLUSIONS With a growing ageing population, the demand for dementia care is rising. Primary health care nurses can lead practice change and promote the timely diagnosis and management of dementia in general practice. Training programs of this kind that build knowledge, confidence, awareness and skills should be made available to the primary care nursing workforce. Further research is recommended to examine the translation of this training outcome into practice. OBJECTIVE To estimate the serial interval of novel coronavirus (COVID-19) from information on 28 infector-infectee pairs. METHODS We collected dates of illness onset for primary cases (infectors) and secondary cases (infectees) from published research articles and case investigation reports. We subjectively ranked the credibility of the data and performed analyses on both the full dataset (n = 28) and a subset of pairs with highest certainty in reporting (n = 18). In addition, we adjust for right truncation of the data as the epidemic is still in its growth phase. RESULTS Accounting for right truncation and analyzing all pairs, we estimated the median serial interval at 4.0 days (95% credible interval [CrI] 3.1, 4.9). Limiting our data to only the most certain pairs, the median serial interval was estimated at 4.6 days (95% CrI 3.5, 5.9). CONCLUSIONS The serial interval of COVID-19 is close to or shorter than its median incubation period. This suggests that a substantial proportion of secondary transmission may occur prior to illness onset. The COVID-19 serial interval is also shorter than the serial interval of severe acute respiratory syndrome (SARS), indicating that calculations made using the SARS serial interval may introduce bias. The ongoing coronavirus disease 2019 (COVID-19) outbreak, emerged in Wuhan, China in the end of 2019, has claimed more than 2600 lives as of 24 February 2020 and posed a huge threat to global public health. The Chinese government has implemented control measures including setting up special hospitals and travel restriction to mitigate the spread. We propose conceptual models for the COVID-19 outbreak in Wuhan with the consideration of individual behavioural reaction and governmental actions, e.g., holiday extension, travel restriction, hospitalisation and quarantine. We employe the estimates of these two key components from the 1918 influenza pandemic in London, United Kingdom, incorporated zoonotic introductions and the emigration, and then compute future trends and the reporting ratio. The model is concise in structure, and it successfully captures the course of the COVID-19 outbreak, and thus sheds light on understanding the trends of the outbreak. The cognitive processing of spatial relations in Euclidean diagrams is central to the diagram-based geometric practice of Euclid's Elements. In this study, we investigate this processing through two dichotomies among spatial relations-metric vs topological and exact vs co-exact-introduced by Manders in his seminal epistemological analysis of Euclid's geometric practice. To this end, we carried out a two-part experiment where participants were asked to judge spatial relations in Euclidean diagrams in a visual half field task design. In the first part, we tested whether the processing of metric vs topological relations yielded the same hemispheric specialization as the processing of coordinate vs categorical relations. In the second part, we investigated the specific performance patterns for the processing of five pairs of exact/co-exact relations, where stimuli for the co-exact relations were divided into three categories depending on their distance from the exact case. Regarding the processing of metric vs topological relations, hemispheric differences were found for only a few of the stimuli used, which may indicate that other processing mechanisms might be at play. Regarding the processing of exact vs co-exact relations, results show that the level of agreement among participants in judging co-exact relations decreases with the distance from the exact case, and this for the five pairs of exact/co-exact relations tested. WAY316606 The philosophical implications of these empirical findings for the epistemological analysis of Euclid's diagram-based geometric practice are spelled out and discussed. V.Asymptomatic venous thrombosis is a common complication among hospitalised paediatric patients. Previous guidelines recommend the treatment of all asymptomatic venous thrombosis, even when the diagnosis is made incidentally or the risk factor is no longer present. Whether clinicians need to treat all asymptomatic thrombosis in children, given the likelihood of long-term sequelae, is unclear and there are significant risks associated with anticoagulation treatment. Asymptomatic thrombosis in children is most frequently associated with central venous catheters (CVCs). The incidence of asymptomatic CVC-related VTE is highest in cohorts of children with cancer, but also reported in neonates, children with congenital heart disease and critically ill children. There is significant variation in reported rates of CVC-related thrombosis among cohorts of children with different underlying diseases and of various ages. As asymptomatic thrombosis is often an incidental finding, rates of asymptomatic VTE in children are most likely underestimated. Evidence about the incidence, characteristics and long-term outcomes associated with asymptomatic thrombosis in children often lacks precision as data is presented collectively with symptomatic thrombosis. This review discusses the current evidence pertaining to the necessity for screening for asymptomatic thrombosis, the risk benefit ratio of treatment and the risk of long-term morbidity. To confidently determine the clinical significance of asymptomatic VTE in children, prospective studies with extended follow up are needed. Bright-field transmission electron microscope (TEM) images of ion milled or focused ion beam (FIB) sections of cortical bone sectioned parallel to the long axis of collagen fibrils display an electron-dense phase in the gap zones of the fibrils, as well as elongated plates (termed mineral lamellae) comprised of apatite crystals, which surround and lie between the fibrils. Energy dispersive X-ray spectroscopy (EDS) and electron energy loss spectroscopy (EELS) studies by others have shown that the material in the gap zones is calcium phosphate. Dark-field (DF) images are capable of revealing the projected position of crystals of apatite in a section of bone. We obtained bright field (BF) images of ion milled sections of bovine femoral cortical bone cut parallel to fibril axes (longitudinal view), and compared them with DF images obtained using the (002) apatite reflection to test a widely held theory that most of the mineral in bone resides in the gap zones. Most apatite crystals which were illuminated in DF images and which projected onto gap zones were extensions of crystals that also project onto adjacent overlap zones.