Trypanosome invasion of mammalian cells requires activation of the TGFβ signaling pathway

AbstractTrypanosoma cruzi invades most nucleated mammi lian cells by as yet unknown mechanisms. We repoi here that while T. cruzi attaches to epithelial cells lacl ing signaling transforming growth factor β (TGFβ) receptor I or II, the adherent parasites cannot penetrat and replicate inside the mutant cells, as they do i parental cells. Invasion of the mutants is restored by transfection with the TGFβ receptor genes, as are biological responses to TGFβ. Similar rescue of bot TGFβ antiproliferative response and T. cruzi invasio was demonstrated in a hybrid of TGFβ-resistant bladder and colon carcinoma cells. In addition, T. cruzi di not efficiently invade epithelial cells with dysfunctio of the intracellular signaling cascade caused by th constitutive expression of the cyclin-dependent kinas cdk4 or of the oncogene H-ras. Treatment with TGFβ, but not with other anti proliferative agents of nor phagocytic cells, greatly enhances T. cruzi invasior Moreover, infective, but not noninfective, trypanosome strongly induce a TGFβ-responsive reporter gene i TGFβ-sensitive, but not in TGFβ-insensitive, cell line: Thus, T. cruzi itself may directly trigger activation of the TGFβ signaling pathway required for parasite entr into the mammalian cells

In vivo validation of a miniaturized electrochemical oxygen sensor for measuring intestinal oxygen tension

Recent advances in the fields of electronics and microfabrication techniques have led to the development of implantable medical devices for use within the field of precision medicine. Monitoring visceral surface tissue O2 tension (ptO2) by means of an implantable sensor is potentially useful in many clinical situations including the peri-operative management of patients undergoing intestinal resection and anastomosis. This concept could provide a means by which treatment could be tailored to individual patients. This study describes the in vivo validation of a novel miniaturised electrochemical O2 sensor to provide real-time data on intestinal ptO2. A single O2 sensor was placed onto the serosal surface of the small intestine of anaesthetised rats that were exposed to ischaemic (superior mesenteric artery occlusion) and hypoxaemic (alterations in inspired fractional O2 concentrations) insults. Control experiments demonstrated that the sensors function and remain stable in an in vivo environment. Intestinal ptO2 decreased following superior mesenteric artery occlusion and with reductions in inspired O2 concentrations. These results were reversible after reinstating blood flow or increasing inspired O2 concentrations. We have successfully developed an anaesthetised rat intestinal ischaemic and hypoxic model for validation of a miniaturised O2 sensor to provide real-time measurement of intestinal ptO2. Our results support further validation of the sensors in physiological conditions using a large animal model to provide evidence of their use in clinical applications where monitoring visceral surface tissue O2 tension is important

Association between multimorbidity and mortality in a cohort of patients admitted to hospital with COVID-19 in Scotland

Funding: BREATHE - The Health Data Research Hub for Respiratory Health, which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK (MC_PC_19004); CSO Rapid Research in Covid-19 Programme (COV/SAN/20/06); HDR UK Measuring and Understanding Multi-morbidity using Routine Data in the UK (MurMuRUK) (HDR-9006-9006; CFC0110); Medical Research Council (MR/R008345/1).Objectives We investigated the association between multimorbidity among patients hospitalised with COVID-19 and their subsequent risk of mortality. We also explored the interaction between the presence of multimorbidity and the requirement for an individual to shield due to the presence of specific conditions and its association with mortality. Design We created a cohort of patients hospitalised in Scotland due to COVID-19 during the first wave (between 28 February 2020 and 22 September 2020) of the pandemic. We identified the level of multimorbidity for the patient on admission and used logistic regression to analyse the association between multimorbidity and risk of mortality among patients hospitalised with COVID-19. Setting Scotland, UK. Participants Patients hospitalised due to COVID-19. Main outcome measures Mortality as recorded on National Records of Scotland death certificate and being coded for COVID-19 on the death certificate or death within 28 days of a positive COVID-19 test. Results Almost 58% of patients admitted to the hospital due to COVID-19 had multimorbidity. Adjusting for confounding factors of age, sex, social class and presence in the shielding group, multimorbidity was significantly associated with mortality (adjusted odds ratio 1.48, 95%CI 1.26–1.75). The presence of multimorbidity and presence in the shielding patients list were independently associated with mortality but there was no multiplicative effect of having both (adjusted odds ratio 0.91, 95%CI 0.64–1.29). Conclusions Multimorbidity is an independent risk factor of mortality among individuals who were hospitalised due to COVID-19. Individuals with multimorbidity could be prioritised when making preventive policies, for example, by expanding shielding advice to this group and prioritising them for vaccination.Publisher PDFPeer reviewe

Wses Jerusalem Guidelines For Diagnosis And Treatment Of Acute Appendicitis

Acute appendicitis (AA) is among the most common cause of acute abdominal pain. Diagnosis of AA is challenging; a variable combination of clinical signs and symptoms has been used together with laboratory findings in several scoring systems proposed for suggesting the probability of AA and the possible subsequent management pathway. The role of imaging in the diagnosis of AA is still debated, with variable use of US, CT and MRI in different settings worldwide. Up to date, comprehensive clinical guidelines for diagnosis and management of AA have never been issued. In July 2015, during the 3rd World Congress of the WSES, held in Jerusalem (Israel), a panel of experts including an Organizational Committee and Scientific Committee and Scientific Secretariat, participated to a Consensus Conference where eight panelists presented a number of statements developed for each of the eight main questions about diagnosis and management of AA. The statements were then voted, eventually modified and finally approved by the participants to The Consensus Conference and lately by the board of co-authors. The current paper is reporting the definitive Guidelines Statements on each of the following topics: 1) Diagnostic efficiency of clinical scoring systems, 2) Role of Imaging, 3) Non-operative treatment for uncomplicated appendicitis, 4) Timing of appendectomy and in-hospital delay, 5) Surgical treatment 6) Scoring systems for intra-operative grading of appendicitis and their clinical usefulness 7) Non-surgical treatment for complicated appendicitis: abscess or phlegmon 8) Pre-operative and post-operative antibiotics.1

Measurement of proton, deuteron, triton, and α particle emission after nuclear muon capture on Al, Si, and Ti with the AlCap experiment

Heavy charged particles after nuclear muon capture are an important nuclear physics background to the muon-to-electron conversion experiments Mu2e and COMET, which will search for charged lepton flavor violation at an unprecedented level of sensitivity. The AlCap experiment measured the yield and energy spectra of protons, deuterons, tritons, and alpha particles emitted after the nuclear capture of muons stopped in Al, Si, and Ti in the low energy range relevant for the muon-to-electron conversion experiments. Individual charged particle types were identified in layered silicon detector packages and their initial energy distributions were unfolded from the observed energy spectra. Detailed information on yields and energy spectra for all observed nuclei are presented in the paper.Comment: 24 pages, 19 figure

Consequences Matter : Compassion in Conservation Means Caring for Individuals, Populations and Species

Funding This research received no external funding. Acknowledgments The manuscript benefitted from significant input from Dan Brockington, J.B. Callicott, Peter Coals, Tim Hodgetts, David Macdonald and Jeremy Wilson. Conflicts of Interest The authors declare no conflict of interest.Peer reviewedPublisher PD