Predictors of Mortality of Streptococcal Bacteremia and the Role of Infectious Diseases Consultation: A Retrospective Cohort Study.

Streptococcal bacteremia is associated with high mortality. Thia study aims to identify predictors of mortality among patients with streptococcal bacteremia. This retrospective study was conducted at the Lausanne University Hospital, Switzerland, and included episodes of streptococcal bacteremia among adult patients from 2015 to 2023. During the study period, 861 episodes of streptococcal bacteremia were included. The majority of episodes were categorized in the Mitis group (348 episodes; 40%), followed by the Pyogenic group (215; 25%). Endocarditis was the most common source of bacteremia (164; 19%). The overall 14-day mortality rate was 8% (65 episodes). The results from the Cox multivariable regression model showed that a Charlson comorbidity index >4 (P .001; hazard ratio [HR], 2.87; confidence interval [CI]: 1.58-5.22), Streptococcus pyogenes (P = .011; HR, 2.54;CI: 1.24-5.21), sepsis (P < .001; HR, 7.48; CI: 3.86-14.47), lower respiratory tract infection (P = .002; HR, 2.62; CI: 1.42-4.81), and absence of source control interventions within 48 hours despite being warranted (P = .002; HR, 2.62; CI: 1.43-4.80) were associated with 14-day mortality. Conversely, interventions performed within 48 hours of bacteremia onset, such as infectious diseases consultation (P < .001; HR, 0.29; CI: .17-.48) and appropriate antimicrobial treatment (P < .001; HR, .28; CI: .14-.57), were associated with improved outcome. Our findings underscore the pivotal role of infectious diseases consultation in guiding antimicrobial treatment and recommending source control interventions for patients with streptococcal bacteremia

Functional microvascularization of human myocardium in vitro

In this study, we report static and perfused models of human myocardial-microvascular interaction. In static culture, we observe distinct regulation of electrophysiology of human induced pluripotent stem cell derived-cardiomyocytes (hiPSC-CMs) in co-culture with human cardiac microvascular endothelial cells (hCMVECs) and human left ventricular fibroblasts (hLVFBs), including modification of beating rate, action potential, calcium handling, and pro-arrhythmic substrate. Within a heart-on-a-chip model, we subject this three-dimensional (3D) co-culture to microfluidic perfusion and vasculogenic growth factors to induce spontaneous assembly of perfusable myocardial microvasculature. Live imaging of red blood cells within myocardial microvasculature reveals pulsatile flow generated by beating hiPSC-CMs. This study therefore demonstrates a functionally vascularized in vitro model of human myocardium with widespread potential applications in basic and translational research

Does the Integration of Haptic and Visual Cues Reduce the Effect of a Biased Visual Reference Frame on the Subjective Head Orientation?

The selection of appropriate frames of reference (FOR) is a key factor in the elaboration of spatial perception and the production of robust interaction with our environment. The extent to which we perceive the head axis orientation (subjective head orientation, SHO) with both accuracy and precision likely contributes to the efficiency of these spatial interactions. A first goal of this study was to investigate the relative contribution of both the visual and egocentric FOR (centre-of-mass) in the SHO processing. A second goal was to investigate humans' ability to process SHO in various sensory response modalities (visual, haptic and visuo-haptic), and the way they modify the reliance to either the visual or egocentric FORs. A third goal was to question whether subjects combined visual and haptic cues optimally to increase SHO certainty and to decrease the FORs disruption effect.Thirteen subjects were asked to indicate their SHO while the visual and/or egocentric FORs were deviated. Four results emerged from our study. First, visual rod settings to SHO were altered by the tilted visual frame but not by the egocentric FOR alteration, whereas no haptic settings alteration was observed whether due to the egocentric FOR alteration or the tilted visual frame. These results are modulated by individual analysis. Second, visual and egocentric FOR dependency appear to be negatively correlated. Third, the response modality enrichment appears to improve SHO. Fourth, several combination rules of the visuo-haptic cues such as the Maximum Likelihood Estimation (MLE), Winner-Take-All (WTA) or Unweighted Mean (UWM) rule seem to account for SHO improvements. However, the UWM rule seems to best account for the improvement of visuo-haptic estimates, especially in situations with high FOR incongruence. Finally, the data also indicated that FOR reliance resulted from the application of UWM rule. This was observed more particularly, in the visual dependent subject. Conclusions: Taken together, these findings emphasize the importance of identifying individual spatial FOR preferences to assess the efficiency of our interaction with the environment whilst performing spatial tasks

Identification of Keratinocyte Growth Factor as a Target of microRNA-155 in Lung Fibroblasts: Implication in Epithelial-Mesenchymal Interactions

International audienceBACKGROUND: Epithelial-mesenchymal interactions are critical in regulating many aspects of vertebrate embryo development, and for the maintenance of homeostatic equilibrium in adult tissues. The interactions between epithelium and mesenchyme are believed to be mediated by paracrine signals such as cytokines and extracellular matrix components secreted from fibroblasts that affect adjacent epithelia. In this study, we sought to identify the repertoire of microRNAs (miRNAs) in normal lung human fibroblasts and their potential regulation by the cytokines TNF-alpha, IL-1beta and TGF-beta. METHODOLOGY/PRINCIPAL FINDINGS: MiR-155 was significantly induced by inflammatory cytokines TNF-alpha and IL-1beta while it was down-regulated by TGF-beta. Ectopic expression of miR-155 in human fibroblasts induced modulation of a large set of genes related to "cell to cell signalling", "cell morphology" and "cellular movement". This was consistent with an induction of caspase-3 activity and with an increase in cell migration in fibroblasts tranfected with miR-155. Using different miRNA bioinformatic target prediction tools, we found a specific enrichment for miR-155 predicted targets among the population of down-regulated transcripts. Among fibroblast-selective targets, one interesting hit was keratinocyte growth factor (KGF, FGF-7), a member of the fibroblast growth factor (FGF) family, which owns two potential binding sites for miR-155 in its 3'-UTR. Luciferase assays experimentally validated that miR-155 can efficiently target KGF 3'-UTR. Site-directed mutagenesis revealed that only one out of the 2 potential sites was truly functional. Functional in vitro assays experimentally validated that miR-155 can efficiently target KGF 3'-UTR. Furthermore, in vivo experiments using a mouse model of lung fibrosis showed that miR-155 expression level was correlated with the degree of lung fibrosis. CONCLUSIONS/SIGNIFICANCE: Our results strongly suggest a physiological function of miR-155 in lung fibroblasts. Altogether, this study implicates this miRNA in the regulation by mesenchymal cells of surrounding lung epithelium, making it a potential key player during tissue injury

Interglacial Antarctic–Southern Ocean climate decoupling due to moisture source area shifts

Succession of cold glacials and warm interglacials during the Quaternary results from large global climate responses to variable orbital configurations, accompanied by fluctuating greenhouse gas concentrations. Despite the influences of sea ice and atmospheric and ocean circulations in the Southern Ocean on atmospheric CO2 concentrations and climate, past changes in this region remain poorly documented. Here, we present the 800 ka deuterium excess record from the East Antarctica EPICA Dome C ice core, tracking sea surface temperature in evaporative regions of the Indian sector of the Southern Ocean from which moisture precipitated in East Antarctica is derived. We find that low obliquity leads to surface warming in evaporative moisture source regions during each glacial inception, although this relative temperature increase is counterbalanced by global cooling during glacial maxima. Links between the two regions during interglacials depends on the existence of a temperature maximum at the interglacial onset. In its absence, temperature maxima in the evaporative moisture source regions and in East Antarctica were synchronous. For the other interglacials, temperature maxima in the source areas lag early local temperature maxima by several thousand years, probably because of a change in the position of the evaporative source areas

Groundwater flowpaths and residence times inferred by 14 C, 36 Cl and 4 He isotopes in the Continental Intercalaire aquifer (North-Western Africa)

International audienc

Evaluation of the HANDOC score and the 2023 ISCVID and ESC Duke clinical criteria for the diagnosis of infective endocarditis among patients with streptococcal bacteremia.

Streptococci are a common cause of infective endocarditis (IE). We aimed to evaluate the performance of the HANDOC score to identify patients at high-risk for IE and the Duke clinical criteria of the European Society of Cardiology (ESC; 2015 and 2023 versions) and the 2023 version from the International Society of Cardiovascular Infectious Diseases (ISCVID) in diagnosing IE among patients with streptococcal bacteremia. This retrospective study included adult patients with streptococcal bacteremia hospitalized at Lausanne University Hospital. Episodes were classified as IE by the Endocarditis Team. A HANDOC score >2 classified patients as high-risk for IE. Among 851 episodes with streptococcal bacteremia, IE was diagnosed in 171 episodes (20%). Among 607 episodes with non-beta-hemolytic streptococci, 213 (35%) had HANDOC scores >2 points; 132 (22%) had IE. The sensitivity of the HANDOC score to identify episodes at high-risk for IE was 95% (90-98%), the specificity 82% (78-85%), and the NPV 98% (96-99%). 2015 Duke-ESC, 2023 Duke-ISCVID, and 2023 Duke-ESC clinical criteria classified 114 (13%), 145 (17%), and 126 (15%) episodes as definite IE, respectively. Sensitivity for the 2015 Duke-ESC, 2023 Duke-ISCVID, and 2023 Duke-ESC clinical criteria was calculated at 65% (57-72%), 81% (74-86%), and 73% (65-79%), respectively, with specificity at 100% (98-100%), 99% (98-100%), and 99% (98-100%), respectively. The HANDOC score showed an excellent NPV to identify episodes at high-risk for IE. Among the different versions of the Duke criteria, the 2023 Duke-ISCVID version fared better for the diagnosis of IE among streptococcal bacteremia