Administration of drinking water supplement containing organic acids and medium chain fatty acids to sows significantly reduced incidence of Clostridium-associated diarrhoea in neonatal piglets: a case study

Neonatal diarrhoea in newborn piglets is an important problem in pig production that is frequently diagnosed as being the result of Clostridium perfringens infections. During parturition and in the first hours of life, the sow transmits the pathogen to its offspring. The objective of this study was to examine the possible prophylactic effect of a drinking water supplement containing organic acids and medium chain fatty acids (Selko-4-Health©), administered to sows on prevalence of neonatal diarrhoea in piglets during early lactation. The study was carried out at a farm with 1300 sows with a high incidence of neonatal diarrhoea. Gestating sows received the water supplement (0.1% per litre) daily from day 35 to end of gestation and during the lactation phase for 2 days a week

Timing of major fracture care in polytrauma patients – an update on principles, parameters and strategies for 2020

Objectives Sustained changes in resuscitation and transfusion management have been observed since the turn of the millennium, along with an ongoing discussion of surgical management strategies. The aims of this study are threefold: a) to evaluate the objective changes in resuscitation and mass transfusion protocols undertaken in major level I trauma centers; b) to summarize the improvements in diagnostic options for early risk profiling in multiply injured patients and c) to assess the improvements in surgical treatment for acute major fractures in the multiply injured patient. Methods I. A systematic review of the literature (comprehensive search of the MEDLINE, Embase, PubMed, and Cochrane Central Register of Controlled Trials databases) and a concomitant data base (from a single Level I center) analysis were performed. Two authors independently extracted data using a pre-designed form. A pooled analysis was performed to determine the changes in the management of polytraumatized patients after the change of the millennium. II. A data base from a level I trauma center was utilized to test any effects of treatment changes on outcome. Inclusion criteria: adult patients, ISS > 16, admission < less than 24 h post trauma. Exclusion: Oncological diseases, genetic disorders that affect the musculoskeletal system. Parameters evaluated were mortality, ICU stay, ICU complications (Sepsis, Pneumonia, Multiple organ failure). Results I. From the electronic databases, 5141 articles were deemed to be relevant. 169 articles met the inclusion criteria and a manual review of reference lists of key articles identified an additional 22 articles. II. Out of 3668 patients, 2694 (73.4%) were male, the mean ISS was 28.2 (SD 15.1), mean NISS was 37.2 points (SD 17.4 points) and the average length of stay was 17.0 days (SD 18.7 days) with a mean length of ICU stay of 8.2 days (SD 10.5 days), and a mean ventilation time of 5.1 days (SD 8.1 days). Both surgical management and nonsurgical strategies have changed over time. Damage control resuscitation, dynamic analyses of coagulopathy and lactate clearance proved to sharpen the view of the worsening trauma patient and facilitated the prevention of further complications. The subsequent surgical care has become safer and more balanced, avoiding overzealous initial surgeries, while performing early fixation, when patients are physiologically stable or rapidly improving. Severe chest trauma and soft tissue injuries require further evaluation. Conclusions Multiple changes in management (resuscitation, transfusion protocols and balanced surgical care) have taken place. Moreover, improvement in mortality rates and complications associated with several factors were also observed. These findings support the view that the management of polytrauma patients has been substantially improved over the past 3 decades

Ionospheric quasi-static electric field anomalies during seismic activity in August–September 1981

The paper proposes new results, analyses and information for the plate tectonic situation in the processing of INTERCOSMOS-BULGARIA-1300 satellite data about anomalies of the quasi-static electric field in the upper ionosphere over activated earthquake source regions at different latitudes. The earthquake catalogue is made on the basis of information from the United State Geological Survey (USGS) website. The disturbances in ionospheric quasi-static electric fields are recorded by IESP-1 instrument aboard the INTERCOSMOS-BULGARIA-1300 satellite and they are compared with significant seismic events from the period 14 August–20 September 1981 in magnetically very quiet, quiet and medium quiet days. The main tectonic characteristics of the seismically activated territories are also taken in account. The main goal of the above research work is to enlarge the research of possible connections between anomalous vertical electric field penetrations into the ionosphere and the earthquake manifestations, also to propose tectonic arguments for the observed phenomena. The studies are represented in four main blocks: (i) previous studies of similar problems, (ii) selection of satellite, seismic and plate tectonic data, (iii) data processing with new specialized software and observations of the quasi-static electric field and (iiii) summary, comparison of new with previous results in our studies and conclusion. We establish the high informativity of the vertical component &lt;i&gt;Ez&lt;/i&gt; of the quasi-static electric field in the upper ionosphere according observations by INTERCOSMOS-BULGARIA-1300 that are placed above considerably activated earthquake sources. This component shows an increase of about 2–10 mV/m above sources, situated on mobile structures of the plates. The paper discusses the observed effects. It is represented also a statistical study of ionospheric effects 5–15 days before and 5–15 days after the earthquakes with magnitude M 4.8–7.9

Atherosclerotic Plaque Stability Is Affected by the Chemokine CXCL10 in Both Mice and Humans.

Background. The chemokine CXCL10 is specifically upregulated during experimental development of plaque with an unstable phenotype. In this study we evaluated the functional consequences of these findings in mice and humans. Methods and Results. In ApoE(-/-) mice, we induced unstable plaque with using a flow-altering device around the carotid artery. From week 1 to 4, mice were injected with a neutralizing CXCL10 antibody. After 9 weeks, CXCL10 inhibition resulted in a more stable plaque phenotype: collagen increased by 58% (P = 0.002), smooth muscle cell content increased 2-fold (P = 0.03), while macrophage MHC class II expression decreased by 50% (P = 0.005). Also, the size of necrotic cores decreased by 41% (P = 0.01). In 106 human carotid endarterectomy specimens we found that increasing concentrations of CXCL10 strongly associate with an increase in atheromatous plaque phenotype (ANOVA, P = 0.003), with high macrophage, low smooth muscle cell, and low collagen content. Conclusions. In the present study we showed that CXCL10 is associated with the development of vulnerable plaque in human and mice. We conclude that CXCL10 might provide a new lead towards plaque-stabilizing therapy

CECR1-mediated cross talk between macrophages and vascular mural cells promotes neovascularization in malignant glioma

Glioblastomas (glioblastoma multiforme, GBM) are most malignant brain tumors characterized by profound vascularization. The activation of macrophages strongly contributes to tumor angiogenesis during GBM development. Previously, we showed that extracellular adenosine deaminase protein Cat Eye Syndrome Critical Region Protein 1 (CECR1) is highly expressed by M2-like macrophages in GBM where it defines macrophage M2 polarization and contributes to tumor expansion. In this study, the effect of CECR1 in macrophages on tumor angiogenesis was investigated. Immunohistochemical evaluation of GBM tissue samples showed that the expression of CECR1 correlates with microvascular density in the tumors, confirming data from the TCGA set. In a three-dimensional co-culture system consisting of human pericytes, human umbilical vein endothelial cells and THP1-derived macrophages, CECR1 knockdown by siRNA and CECR1 stimulation of macrophages inhibited and promoted new vessel formation, respectively. Loss and gain of function studies demonstrated that PDGFB mRNA and protein levels in macrophages are modulated by CECR1. The proangiogenic properties of CECR1 in macrophages were partially mediated via paracrine activation of pericytes by PDGFB–PDGFRβ signaling. CECR1–PDGFB–PDGFRβ cross-activation between macrophages and pericytes promoted pericyte migration, shown by transwell migration assay, and enhanced expression and deposition of periostin, a matrix component with proangiogenic properties. CECR1 function in (M2-like) macrophages mediates cross talk between macrophages and pericytes in GBM via paracrine PDGFB–PDGFRβ signaling, promoting pericyte recruitment and migration, and tumor angiogenesis. Therefore, CECR1 offers a new portent target for anti-angiogenic therapy in GBM via immune modulation.Oncogene advance online publication, 22 May 2017; doi:10.1038/onc.2017.145

Distinct mouse bone marrow macrophage precursors identified by differential expression of ER-MP12 and ER-MP20 antigens

The characterization of early branch points in the differentiation of leukocytes requires identification of precursor cells in the bone marrow. Recently, we produced two monoclonal antibodies, ER-MP12 and ER-MP20, which in two-color flow-cytometric analysis divide the murine bone marrow into six defined subsets. Here we show, using fluorescence-activated cell sorting followed by macrophage colony-stimulating factor-stimulated culture in soft agar, that precursors of the mononuclear phagocyte system reside only within the ER-MP12hi20−, ER-MP12+20+ and ER-MP12−20hi bone marrow subsets. Together, these subsets comprise 15% of nucleated bone marrow cells. Furthermore, we provide evidence that the macrophage precursors present in these subsets represent successive stages in a maturation sequence where the most immature ER-MP12hi20− cells develop via the ER-MP12+20+ stage into ER-MP12−20hi monocytes

Adopting Patient Portals in Hospitals: Qualitative Study

BACKGROUND: Theoretical models help to explain or predict the adoption of electronic health (eHealth) technology and illustrate the complexity of the adoption process. These models provide insights into general factors that influence the use of eHealth technology. However, they do not give hospitals much actionable knowledge on how to facilitate the adoption process. OBJECTIVE: Our study aims to provide insights into patient portal adoption processes among patients and hospital staff, including health care professionals (HCPs), managers, and administrative clerks. Studying the experiences and views of stakeholders answers the following question: How can hospitals encourage patients and HCPs to adopt a patient portal? METHODS: We conducted 22 semistructured individual and group interviews (n=69) in 12 hospitals and four focus groups with members of national and seminational organizations and patient portal suppliers (n=53). RESULTS: The effort hospitals put into adopting patient portals can be split into three themes. First, inform patients and HCPs about the portal. This communication strategy has four objectives: users should (1) know about the portal, (2) know how the portal works, (3) know that action on the portal is required, and (4) know where to find help with the portal. Second, embed the patient portal in the daily routine of HCPs and management. This involves three forms of support: (1) hospital policy, (2) management by monitoring the numbers, and (3) a structured implementation strategy that includes all staff of one department. Third, try to adjust the portal to meet patients' needs to optimize user-friendliness in two ways: (1) use patients' feedback and (2) focus on optimizing for patients with special needs (eg, low literacy and low digital skills). CONCLUSIONS: Asking stakeholders what they have learned from their efforts to stimulate patient portal use in hospitals elicited rich insights into the adoption process. These insights are missing in the theoretical models. Therefore, our findings help to translate the relatively abstract factors one finds in theoretical models to the everyday pragmatics of eHealth projects in hospitals

The deaminase APOBEC3B triggers the death of cells lacking uracil DNA glycosylase

Human cells express up to 9 active DNA cytosine deaminases with functions in adaptive and innate immunity. Many cancers manifest an APOBEC mutation signature and APOBEC3B (A3B) is likely the main enzyme responsible. Although significant numbers of APOBEC signature mutations accumulate in tumor genomes, the majority of APOBEC-catalyzed uracil lesions are probably counteracted in an error-free manner by the uracil base excision repair pathway. Here, we show that A3B-expressing cells can be selectively killed by inhibiting uracil DNA glycosylase 2 (UNG) and that this synthetic lethal phenotype requires functional mismatch repair (MMR) proteins and p53. UNG knockout human 293 and MCF10A cells elicit an A3B-dependent death. This synthetic lethal phenotype is dependent on A3B catalytic activity and reversible by UNG complementation. A3B expression in UNG-null cells causes a buildup of genomic uracil, and the ensuing lethality requires processing of uracil lesions (likely U/G mispairs) by MSH2 and MLH1 (likely noncanonical MMR). Cancer cells expressing high levels of endogenous A3B and functional p53 can also be killed by expressing an UNG inhibitor. Taken together, UNG-initiated base excision repair is a major mechanism counteracting genomic mutagenesis by A3B, and blocking UNG is a potential strategy for inducing the selective death of tumors.</p

Demographic patterns and outcomes of patients in level I trauma centers in three international trauma systems

Introduction: Trauma systems were developed to improve the care for the injured. The designation and elements comprising these systems vary across countries. In this study, we have compared the demographic patterns and patient outcomes of Level I trauma centers in three international trauma systems. Methods: International multicenter prospective trauma registry-based study, performed in the University Medical Center Utrecht (UMCU), Utrecht, the Netherlands, John Hunter Hospital (JHH), Newcastle, Australia, and Harborview Medical Center (HMC), Seattle, the United States. Inclusion: patients =18 years, admitted in 2012, registered in the institutional trauma registry. Results: In UMCU, JHH, and HMC, respectively, 955, 1146, and 4049 patients met the inclusion criteria of which 300, 412, and 1375 patients with Injury Severity Score (ISS) > 15. Mean ISS was higher in JHH (13.5; p < 0.001) and HMC (13.4; p < 0.001) compared to UMCU (11.7). Unadjusted mortality: UMCU = 6.5 %, JHH = 3.6 %, and HMC = 4.8 %. Adjusted odds of death: JHH = 0.498 [95 % confidence interval (CI) 0.303-0.818] and HMC = 0.473 (95 % CI 0.325-0.690) compared to UMCU. HMC compared to JHH was 1.002 (95 % CI 0.664-1.514). Odds of death patients ISS > 15: JHH = 0.507 (95 % CI 0.300-0.857) and HMC = 0.451 (95 % CI 0.297-0.683) compared to UMCU. HMC = 0.931 (95 % CI 0.608-1.425) compared to JHH. TRISS analysis: UMCU: Ws = 0.787, Z = 1.31, M = 0.87; JHH, Ws = 3.583, Z = 6.7, M = 0.89; HMC, Ws = 3.902, Z = 14.6, M = 0.84. Conclusion: This study demonstrated substantial differences across centers in patient characteristics and mortality, mainly of neurological cause. Future research must investigate whether the outcome differences remain with nonfatal and long-term outcomes. Furthermore, we must focus on the development of a more valid method to compare systems