Mitogen Activated Protein Kinase Activated Protein Kinase 2 Regulates Actin Polymerization and Vascular Leak in Ventilator Associated Lung Injury

Mechanical ventilation, a fundamental therapy for acute lung injury, worsens pulmonary vascular permeability by exacting mechanical stress on various components of the respiratory system causing ventilator associated lung injury. We postulated that MK2 activation via p38 MAP kinase induced HSP25 phosphorylation, in response to mechanical stress, leading to actin stress fiber formation and endothelial barrier dysfunction. We sought to determine the role of p38 MAP kinase and its downstream effector MK2 on HSP25 phosphorylation and actin stress fiber formation in ventilator associated lung injury. Wild type and MK2−/− mice received mechanical ventilation with high (20 ml/kg) or low (7 ml/kg) tidal volumes up to 4 hrs, after which lungs were harvested for immunohistochemistry, immunoblotting and lung permeability assays. High tidal volume mechanical ventilation resulted in significant phosphorylation of p38 MAP kinase, MK2, HSP25, actin polymerization, and an increase in pulmonary vascular permeability in wild type mice as compared to spontaneous breathing or low tidal volume mechanical ventilation. However, pretreatment of wild type mice with specific p38 MAP kinase or MK2 inhibitors abrogated HSP25 phosphorylation and actin polymerization, and protected against increased lung permeability. Finally, MK2−/− mice were unable to phosphorylate HSP25 or increase actin polymerization from baseline, and were resistant to increases in lung permeability in response to HVT MV. Our results suggest that p38 MAP kinase and its downstream effector MK2 mediate lung permeability in ventilator associated lung injury by regulating HSP25 phosphorylation and actin cytoskeletal remodeling

Simultaneous occurrence of cerebellar medulloblastoma and pituitary adenoma: A case report

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Antimicrobial de-escalation in the critically ill patient and assessment of clinical cure: the DIANA study

Purpose: The DIANA study aimed to evaluate how often antimicrobial de-escalation (ADE) of empirical treatment is performed in the intensive care unit (ICU) and to estimate the effect of ADE on clinical cure on day 7 following treatment initiation. Methods: Adult ICU patients receiving empirical antimicrobial therapy for bacterial infection were studied in a prospective observational study from October 2016 until May 2018. ADE was defined as (1) discontinuation of an antimicrobial in case of empirical combination therapy or (2) replacement of an antimicrobial with the intention to narrow the antimicrobial spectrum, within the first 3 days of therapy. Inverse probability (IP) weighting was used to account for time-varying confounding when estimating the effect of ADE on clinical cure. Results: Overall, 1495 patients from 152 ICUs in 28 countries were studied. Combination therapy was prescribed in 50%, and carbapenems were prescribed in 26% of patients. Empirical therapy underwent ADE, no change and change other than ADE within the first 3 days in 16%, 63% and 22%, respectively. Unadjusted mortality at day 28 was 15.8% in the ADE cohort and 19.4% in patients with no change [p = 0.27; RR 0.83 (95% CI 0.60\u20131.14)]. The IP-weighted relative risk estimate for clinical cure comparing ADE with no-ADE patients (no change or change other than ADE) was 1.37 (95% CI 1.14\u20131.64). Conclusion: ADE was infrequently applied in critically ill-infected patients. The observational effect estimate on clinical cure suggested no deleterious impact of ADE compared to no-ADE. However, residual confounding is likely

Evolution d’un bassin laitier français à l’heure de l’annonce d’une nouvelle PAC : Le cas d’une zone à enjeu environnemental dans le pays de Caux

Dans les régions de polyculture-élevage laitier de plaine, situées en zone tempérée, comme en Haute-Normandie (France), les prairies présentent un intérêt pour l'environnement. Dans l'aire d’alimentation de captage d'Héricourt-en-caux que nous avons étudiée, le maintient des prairies contribuerait à la qualité de la ressource en eau. Notre objectif est de comprendre les stratégies des acteurs, au moment de la transition des quotas laitiers vers des contacts liant agriculteurs et collecteurs. Des analyses de statistique agricoles et du Référentiel Parcellaire Graphique et des entretiens avec les principaux acteurs impliqués localement nous permettent de dresser un état des lieux de l'évolution des assolements et des stratégies des collecteurs, et d'esquisser des perspectives d'évolution des élevages. Depuis 2006, sur ces terres à haut potentiel agronomique, la tendance est à l'augmentation du blé tendre et du colza, à la stabilité du maïs ensilage, et à une diminution globale des prairies. Cette évolution est favorisée par des cessations laitières (retraite ou surcharge de travail) et par l'intensification de la production laitière (souvent en diminuant la place de l'herbe dans l'alimentation des vaches, surtout quand les prairies sont éloignées et retournables). Quatre opérateurs, une coopérative et trois industriels, se différencient par la valorisation du lait, produits de grande consommation ou produits industriels. Les contrats proposés aux éleveurs se distinguent notamment par des modalités de calcul du prix du lait, qui pourraient à terme accroitre les différences de rémunération. Le maintient de la production laitière reste souvent lié au nombre de personnes devant vivre de l'exploitation. On voit se développer des exploitations à plusieurs associés, de 150 ha environ, avec 60 à 80 vaches laitières, utilisant des sous-produits des cultures. Quelques-unes misent sur l'autonomie alimentaire, avec une surface en herbe importante. Beaucoup cependant basent la ration des vaches sur le maïs, l'herbe ne venant qu'en appoint

Immunocytological and Preliminary Immunohistochemical Studies of Prothymosin α, a Human Cancer–associated Polypeptide, With a Well-characterized Polyclonal Antibody

Prothymosin α (ProTα) is a nuclear polypeptide of great biological and, possibly clinical, importance, because its expression levels have been associated with early diagnosis/prognosis of human cancer. It is therefore interesting to raise easily available and cost-effective antibodies that would be applied to develop reliable ProTα immunodiagnostics. In this study, New Zealand white rabbits and laying hens were parallel immunized against intact ProTα or the synthetic fragments ProTα[1-28], ProTα[87-109], and ProTα[101-109], all conjugated to keyhole limpet hemocyanin (KLH). The corresponding antibodies G and Y were immunochemically evaluated in parallel with ELISA and Western blot systems and applied to fluorescence immunocytology experiments using various cancer cell lines and normal cells. The antibody G raised against ProTα[101-109]/KLH had excellent functional characteristics in the Western blot and immunocytology experiments, where the fluorescent signal was almost exclusively shown in the cell nucleus independently of the cells assayed. The above antibody has been applied to preliminary IHC staining of human cancer prostate tissues, leading to a high percentage of clearly and intensively stained nuclei in the adenocarcinoma tissue; this antibody can be further used in cancer tissue immunostaining and in research concerning the role of ProTα in tumorigenesis. (J Histochem Cytochem 56:1023–1031, 2008

The gut microbiomes of Channel Island foxes and island spotted skunks exhibit fine‐scale differentiation across host species and island populations

Abstract California's Channel Islands are home to two endemic mammalian carnivores: island foxes (Urocyon littoralis) and island spotted skunks (Spilogale gracilis amphiala). Although it is rare for two insular terrestrial carnivores to coexist, these known competitors persist on both Santa Cruz Island and Santa Rosa Island. We hypothesized that examination of their gut microbial communities would provide insight into the factors that enable this coexistence, as microbial symbionts often reflect host evolutionary history and contemporary ecology. Using rectal swabs collected from island foxes and island spotted skunks sampled across both islands, we generated 16S rRNA amplicon sequencing data to characterize their gut microbiomes. While island foxes and island spotted skunks both harbored the core mammalian microbiome, host species explained the largest proportion of variation in the dataset. We further identified intraspecific variation between island populations, with greater differentiation observed between more specialist island spotted skunk populations compared to more generalist island fox populations. This pattern may reflect differences in resource utilization following fine‐scale niche differentiation. It may further reflect evolutionary differences regarding the timing of intraspecific separation. Considered together, this study contributes to the growing catalog of wildlife microbiome studies, with important implications for understanding how eco‐evolutionary processes enable the coexistence of terrestrial carnivores–and their microbiomes–in island environments

CD36 Is Significantly Correlated with Adipophilin in Human Carotid Lesions and Inversely Correlated with Plasma ApoAI

OxLDL uptake and cholesterol efflux inhibition in macrophages play a key role in atherosclerotic plaque formation, rupture, and thrombotic ischemia. This study investigates genes implicated in OxLDL uptake (CD36, SRA), cholesterol efflux inhibition (adipophilin, ADFP), and inflammatory recruitments of leukocytes (IL-8) in plaque lesion areas (PLAs) compared to nonplaque lesion areas (NPLAs) in human carotid endarterectomy specimens. Gene and protein expressions were assayed using quantitative PCR and quantitative immunohistochemistry. Pearson tests were used to investigate potential correlation between (a) different gene expressions and (b) gene expression and patient's plasma constituents. CD36, SRA, ADFP, and IL-8 were shown to be significantly more expressed in PLA compared to NPLA. In PLA, a significant correlation was observed between CD36, SRA, ADFP, and IL-8 mRNA levels. Moreover, CD36 expression level was significantly inversely correlated to plasma marker ApoAI. The above investigated genes/proteins may play a key role in the maturation of atherosclerotic lesions. Copyright (C) 2008 Sophie Collot-Teixeira et al