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Dyspnea is a frequent symptom in adults’ emergency departments (EDs). Misdiagnosis at initial clinical examination is common, leading to early inappropriate treatment and increased in-hospital mortality. Risk factors of inappropriate treatment assessable at early examination remain undescribed herein. The objective of this study was to identify clinical risk factors of dyspnea and inappropriate treatment in patients admitted to ED. This is an observational retrospective cohort study. Patients over the age of 15 who were admitted to adult EDs of the University Hospital of Toulouse (France) with dyspnea were included from 1 July to 31 December 2019. The primary end-point was dyspnea and inappropriate treatment was initiated at ED. Inappropriate treatment was defined by looking at the final diagnosis of dyspnea at hospital discharge and early treatment provided. Afterward, this early treatment at ED was compared to the recommended treatment defined by the International Guidelines for Acute Heart Failure, bacterial pneumonia, chronic obstructive pulmonary disease, asthma or pulmonary embolism. A total of 2123 patients were analyzed. Of these, 809 (38%) had inappropriate treatment in ED. Independent risk factors of inappropriate treatment were: age over 75 years (OR, 1.46; 95% CI, 1.18–1.81), history of heart disease (OR, 1.32; 95% CI, 1.07–1.62) and lung disease (OR, 1.47; 95% CI, 1.21–1.78), SpO2<90% (OR, 1.64; 95% CI, 1.37–2.02), bilateral rale (OR, 1.25; 95% CI, 1.01–1.66), focal cracklings (OR, 1.32; 95% CI, 1.05–1.66) and wheezing (OR, 1.62; 95% CI, 1.31–2.03). In multivariate analysis, under-treatment significantly increased in-hospital mortality (OR, 2.13; 95% CI, 1.29–3.52) compared to appropriate treatment. Over-treatment nonsignificantly increased in-hospital mortality (OR, 1.43; 95% CI, 0.99–2.06). Inappropriate treatment is frequent in patients admitted to ED for dyspnea. Patients older than 75 years, with comorbidities (heart or lung disease), hypoxemia (SpO2<90%) or abnormal pulmonary auscultation (especially wheezing) are at risk of inappropriate treatment.

Byline: Nicolas. Paleiron, Radj. Gervais, Gaelle. Rousseau-Bussac, Laurence. Game, Anne. Chiappa, Regine. Lamy, Florian. Guisier, Hervé. Le Caer, Gilles. Robinet, Acya. Bizieux, Christos. Chouaïd, . GFPC Purpose: Few data have [...]

Metabotropic glutamate (mGlu) receptors play a key role in modulating most synapses in the brain. The mGlu7 receptors inhibit presynaptic neurotransmitter release and offer therapeutic possibilities for post-traumatic stress disorders or epilepsy. Screening campaigns provided mGlu7-specific allosteric modulators as the inhibitor XAP044(Gee et al. J. Biol. Chem.2014). In contrast to other mGlu receptor allosteric modulators, XAP044does not bind in the transmembrane domain but to the extracellular domain of the mGlu7 receptor and not at the orthosteric site. Here, we identified the mode of action of XAP044, combining synthesis of derivatives, modeling and docking experiments, and mutagenesis. We propose a unique mode of action of these inhibitors, preventing the closure of the Venus flytrap agonist binding domain. While acting as a noncompetitive antagonist of L-AP4, XAP044and derivatives act as apparent competitive antagonists of LSP4-2022. These data revealed more potent XAP044analogues and new possibilities to target mGluRs.

What we have attended to in the past, as well as the stimulus context associated with past motor responses, have a strong impact on our current behavior. These influences have been investigated through inter-trial priming effects in visual search and sequence effects in action control, respectively. These two research fields are strongly complementary at the theoretical level and show striking similarities in their experimental-task structure, analyses, and results. Yet, they have developed largely separately. Here, we claim that such fragmentation impedes progress in these two research strands and highlight the potential benefits of intensifying crosstalk between visual search and action control in future research by exploiting the existing structural similarities with regard to sequence effects. We first discuss the main phenomena and theoretical explanations in each field, while emphasizing the similarities and differences between them. Then, we illustrate how the two fields could integrate each other’s insights—namely, how visual-search research could draw on the action-control literature to clarify the role of retrieval in selection and how action-control research could draw on the visual-search literature to explain response-related processes in more complex environments. We argue that combining the two research traditions is necessary for a coherent account of search-for-action behavior.

1 La recrudescence des infestations de punaises de lit decoule de I'augmentation des deplacements et de la resistance aux insecticides De nombreuses populations de punaises de lit sont maintenant resistantes [...]

Half of osteoporotic fractures occur in patients with normal/osteopenic bone density or at intermediate or low estimated risk. Muscle measures have been shown to contribute to fracture risk independently of bone mineral density. The objectives were to review the measurements of muscle health (muscle mass/quantity/quality, strength and function) and their association with incident fragility fractures and to summarize their use in clinical practice. This scoping review follows the PRISMA‐ScR guidelines for reporting. Our search strategy covered the three overreaching concepts of ‘fragility fractures’, ‘muscle health assessment’ and ‘risk’. We retrieved 14 745 references from Medline Ovid SP, EMBASE, Web of Science Core Collection and Google Scholar. We included original and prospective studies on community‐dwelling adults aged over 50 years that analysed an association between at least one muscle parameter and incident fragility fractures. We systematically extracted 17 items from each study, including methodology, general characteristics and results. Data were summarized in tables and graphically presented in adjusted forest plots. Sixty‐seven articles fulfilled the inclusion criteria. In total, we studied 60 muscle parameters or indexes and 322 fracture risk ratios over 2.8 million person‐years (MPY). The median (interquartile range) sample size was 1642 (921–5756), age 69.2 (63.5–73.6) years, follow‐up 10.0 (4.4–12.0) years and number of incident fragility fractures 166 (88–277). A lower muscle mass was positively/not/negatively associated with incident fragility fracture in 28 (2.0), 64 (2.5) and 10 (0.2 MPY) analyses. A lower muscle strength was positively/not/negatively associated with fractures in 53 (1.3), 57 (1.7 MPY) and 0 analyses. A lower muscle function was positively/not/negatively associated in 63 (1.9), 45 (1.0 MPY) and 0 analyses. An in‐depth analysis shows how each single muscle parameter was associated with each fragility fractures subtype. This review summarizes markers of muscle health and their association with fragility fractures. Measures of muscle strength and function appeared to perform better for fracture risk prediction. Of these, hand grip strength and gait speed are likely to be the most practical measures for inclusion in clinical practice, as in the evaluation of sarcopenia or in further fracture risk assessment scores. Measures of muscle mass did not appear to predict fragility fractures and might benefit from further research, on D3‐creatine dilution test, lean mass indexes and artificial intelligence methods.

The Antarctic Circumpolar Current (ACC) represents the world’s largest ocean-current system and affects global ocean circulation, climate and Antarctic ice-sheet stability1–3. Today, ACC dynamics are controlled by atmospheric forcing, oceanic density gradients and eddy activity4. Whereas palaeoceanographic reconstructions exhibit regional heterogeneity in ACC position and strength over Pleistocene glacial–interglacial cycles5–8, the long-term evolution of the ACC is poorly known. Here we document changes in ACC strength from sediment cores in the Pacific Southern Ocean. We find no linear long-term trend in ACC flow since 5.3 million years ago (Ma), in contrast to global cooling9and increasing global ice volume10. Instead, we observe a reversal on a million-year timescale, from increasing ACC strength during Pliocene global cooling to a subsequent decrease with further Early Pleistocene cooling. This shift in the ACC regime coincided with a Southern Ocean reconfiguration that altered the sensitivity of the ACC to atmospheric and oceanic forcings11–13. We find ACC strength changes to be closely linked to 400,000-year eccentricity cycles, probably originating from modulation of precessional changes in the South Pacific jet stream linked to tropical Pacific temperature variability14. A persistent link between weaker ACC flow, equatorward-shifted opal deposition and reduced atmospheric CO2during glacial periods first emerged during the Mid-Pleistocene Transition (MPT). The strongest ACC flow occurred during warmer-than-present intervals of the Plio-Pleistocene, providing evidence of potentially increasing ACC flow with future climate warming.

Inositol-requiring enzyme 1 (IRE1) is a transmembrane sensor that is part of a trio of sensors responsible for controlling the unfolded protein response within the endoplasmic reticulum (ER). Upon the accumulation of unfolded or misfolded proteins in the ER, IRE1 becomes activated and initiates the cleavage of a 26-nucleotide intron from human X-box-containing protein 1 (XBP1). The cleavage is mediated by the RtcB ligase enzyme, which splices together two exons, resulting in the formation of the spliced isoform XBP1s. The XBP1s isoform activates the transcription of genes involved in ER-associated degradation to maintain cellular homeostasis. The catalytic activity of RtcB is controlled by the phosphorylation and dephosphorylation of three tyrosine residues (Y306, Y316, and Y475), which are regulated by the ABL1 tyrosine kinase and PTP1B phosphatase, respectively. This study focuses on investigating the mechanism by which the PTP1B phosphatase activates the RtcB ligase using a range of advanced in silico methods. Protein–protein docking identified key interacting residues between RtcB and PTP1B. Notably, the phosphorylated Tyr306 formed hydrogen bonds and salt bridge interactions with the “gatekeeper” residues Arg47 and Lys120 of the inactive PTP1B. Classical molecular dynamics simulation emphasized the crucial role of Asp181 in the activation of PTP1B, driving the conformational change from an open to a closed state of the WPD-loop. Furthermore, QM/MM-MD simulations provided insights into the free energy landscape of the dephosphorylation reaction mechanism of RtcB, which is mediated by the PTP1B phosphatase.

Despite the high procedural success of transcatheter aortic valve replacement (TAVR), 2 out of 5 older adults report poor physical performance and health-related quality of life (HRQOL) in the ensuing months, particularly those with frailty. There has yet to be a trial examining the synergistic effects of exercise and protein supplementation to counteract frailty and improve patient-centred outcomes following TAVR. The PERFORM-TAVR trial is a multicentre parallel-group randomised clinical trial that is enrolling 200 frail older adults ≥ 70 years of age undergoing TAVR. Patients will be randomly allocated to 1 of 2 treatment groups: standard-of-care lifestyle education (control group) or protein-rich oral nutritional supplement for 4 weeks before TAVR with the addition of home-based supervised exercise sessions for 12 weeks after TAVR (intervention group). The primary outcome will be physical performance as measured by a blinded observer using the Short Physical Performance Battery at 3 months. Secondary outcomes at 3, 6, and 12 months will include HRQOL, as measured by the Short-Form 36 Physical and Mental Component summary scores, and a composite safety end point. The PERFORM-TAVR trial is testing a novel frailty intervention in older adults undergoing TAVR to optimise recovery and downstream HRQOL. This represents a potential paradigm shift that highlights the value of assessing and treating patients’ frailty in parallel with their underlying heart valve disease.

BACKGROUND: Perioperative corticosteroid use may reduce acute kidney injury. We sought to test whether methylprednisolone reduces the risk of acute kidney injury after cardiac surgery. METHODS: We conducted a prespecified substudy of a randomized controlled trial involving patients undergoing cardiac surgery with cardiopulmonary bypass (2007-2014); patients were recruited from 79 centres in 18 countries. Eligibility criteria included a moderate-to-high risk of perioperative death based on a preoperative score of 6 or greater on the European System for Cardiac Operative Risk Evaluation I. Patients (n = 7286) were randomly assigned (1:1) to receive intravenous methylprednisolone (250 mg at anesthetic induction and 250 mg at initiation of cardiopulmonary bypass) or placebo. Patients, caregivers, data collectors and outcome adjudicators were unaware of the assigned intervention. The primary outcome was postoperative acute kidney injury, defined as an increase in the serum creatinine concentration (from the preoperative value) of 0.3 mg/dL or greater ([greater than or equal to] 26.5 [micro]mol/L) or 50% or greater in the 14-day period after surgery, or use of dialysis within 30 days after surgery. RESULTS: Acute kidney injury occurred in 1479/3647 patients (40.6%) in the methylprednisolone group and in 1426/3639 patients (39.2%) in the placebo group (adjusted relative risk 1.04, 95% confidence interval 0.96 to 1.11). Results were consistent across several definitions of acute kidney injury and in patients with preoperative chronic kidney disease. INTERPRETATION: Intraoperative corticosteroid use did not reduce the risk of acute kidney injury in patients with a moderate-to-high risk of perioperative death who had cardiac surgery with cardiopulmonary bypass. Our results do not support the prophylactic use of steroids during cardiopulmonary bypass surgery. Trial registration: ClinicalTrials.gov, no. NCT00427388, About 20% of the 4 million cardiopulmonary bypass surgeries performed worldwide each year are complicated by acute kidney injury, defined as a sudden reduction in kidney function. (1) Acute kidney [...]

Avec ma tres mauvaise vue, mon insuffisance cardiaque chronique, mon diabete de type 2, mes problemes de poids et mon taux d'hemoglobine instable, il est difficile de ne pas avoir [...]

As a patient with very low vision, chronic heart failure, type 2 diabetes, weight management concerns and fluctuating hemoglobin levels, it is difficult to not have feelings of isolation, poor [...]

1 A resurgence in bedbugs is a result of increased travel and insecticide resistance Many bedbug populations are resistant to pyrethroid, a chemical contained in most currently used insecticides. (1) [...]

The necessity of epistemological theorisation for management science is questionable. However, epistemology can be useful if the following distinction between three kinds of epistemology, usually overlooked, is taken into account: epistemology as a structured academic discipline, epistemology as an intellectual exercise produced outside academic epistemology, and finally the epistemology specific to each researcher. When this distinction is not made, epistemology can become counterproductive and impede scientific work.

Assess how historical fragmentation in the form of perched culverts impacts Brook Trout Salvelinus fontinalisgenetic diversity and differentiation in the Beebe River watershed (central New Hampshire), the site of a major culvert removal project in 2017. We collected genetic samples from Brook Trout one year prior to (2016), and two years following (2018 and 2019) culvert removal from six tributaries in the watershed. We used two analytical approaches, STRUCTURE and discriminant analysis of principal components, to determine the degree to which admixture was occurring and the levels of genetic diversity in the sampled populations. We also compared pairwise FSTvalues to measure the genetic differentiation between tributaries. The analysis revealed that the tributaries with impassable culverts (GR1, GR3, and GR5) exhibited a distinct genetic cluster, indicating genetic homogeneity. In contrast, the tributaries without barriers (GR2, ECR1, and GR4) showed a mixture of individuals assigned to multiple genetic clusters, indicating genetic admixture and high diversity. Culvert outlet drop heights correlated with the level of genetic differentiation and diversity. Culvert replacement did not immediately result in significant changes in the genetic composition of the Brook Trout populations. Fish in tributaries with culverts remained genetically distinct from those in other tributaries even two years after culvert removal. The study demonstrates that historical fragmentation caused by culverts has influenced the population genetic structure of Brook Trout in the Beebe River watershed. Culvert replacement did not lead to immediate changes in genetic composition, suggesting that other factors, such as prespawning behavior and geomorphological disturbances, may have limited fish movement and spawning after culvert removal. The findings highlight the importance of considering the specific characteristics of culverts and their interactions with habitat conditions in assessing their impacts on genetic connectivity. Impact statementOur study took advantage of a unique opportunity to assess the popuation level response of Brook Trout to barrier removal. Our findings highlight the importance of monitoring postrestoration to gain insight into the timing and degree of response by different species. Our study took advantage of a unique opportunity to assess the popuation level response of Brook Trout to barrier removal. Our findings highlight the importance of monitoring postrestoration to gain insight into the timing and degree of response by different species.

Mieux prendre en charge les ALAM graves qui restent sous diagnostiquées, sous déclarées, et redéfinir les indications/contre-indications et le respect des posologies maximales de metformine, chez les patients âgés ou polypathologiques [1].

Currently, bladder cancer detection is based on cytology and cystoscopy. White light cystoscopy (WLC) is an invasive procedure and may under-detect flat lesions. Blue light cystoscopy (BLC) and narrow band imaging (NBI) cystoscopy are new modalities that could improve the detection of non-muscle invasive bladder cancer (NMIBC) and its recurrence or progression to muscle invasive bladder cancer. We present a systematic review on BLC and NBI cystoscopy for bladder cancer diagnosis and NMIBC follow-up.

Not sure you read your own letter? When only two to three pages an issue (out of 84) are devoted to 'drinkers' I'd say you pretty much got your wish! [...]

To evaluate the association between dose of skin-to-skin contact (SSC) per day and initiation time with the occurrence of deaths in newborns with weight up to 1800g.