The apicomplexan parasite Eimeria arloingi induces caprine neutrophil extracellular traps

As a novel effector mechanism polymorphonuclear neutrophils (PMN) release neutrophil extracellular traps (NETs), which represent protein-labeled DNA matrices capable of extracellular trapping and killing of invasive pathogens. Here, we demonstrate for the first time NET formation performed by caprine PMN exposed to different stages (sporozoites and oocysts) of the goat apicomplexan protozoan parasite Eimeria arloingi. Scanning electron microscopy as well as fluorescence microscopy of sporozoites- and oocysts-PMN co-cultures revealed a fine network of DNA fibrils partially covering the parasites. Immunofluorescence analyses confirmed the co-localization of histones (H3), neutrophil elastase (NE), and myeloperoxidase (MPO) in extracellular traps released from caprine PMN. In addition, the enzymatic activity of NE was found significantly enhanced in sporozoite-exposed caprine PMN. The treatment of caprine NET structures with deoxyribonuclease (DNase) and the NADPH oxidase inhibitor diphenylene iodondium (DPI) significantly reduced NETosis confirming the classical characteristics of NETs. Caprine NETs efficiently trapped vital sporozoites of E. arloingi since 72 % of these stages were immobilized—but not killed—in NET structures. As a consequence, early infection rates were significantly reduced when PMN-pre-exposed sporozoites were allowed to infect adequate host cells. These findings suggest that NETs may play an important role in the early innate host response to E. arloingi infection in goats.     

Investigation of the mechanical properties of the human crural fascia and their possible clinical implications

The mechanical properties of deep fasciae strongly affect muscular actions, development of pathologies, such as acute and chronic compartment syndromes, and the choice of the various fascial flaps. Actually, a clear knowledge of the mechanical characterization of these tissues still lacks. This study focuses attention on experimental tests of different regions of human crural fascia taken from an adult frozen donor. Tensile tests along proximal–distal and medial–lateral direction at a strain rate of 120 %/s were performed at the purpose of evaluating elastic properties. Viscous phenomena were investigated by applying incremental relaxation tests at total strain of 7, 9 and 11 % and observing stress decay for a time interval of 240 s. The elastic response showed that the fascia in the anterior compartment is stiffer than in the posterior compartment, both along the proximal–distal and medial–lateral directions. This result can explain why the compartment syndromes are more frequent in this compartment with respect to posterior one. Furthermore, the fascia is stiffer along the proximal–distal than along medial–lateral direction. This means that the crural fascia can adapt to the muscular variation of volume in a transversal direction, while along the main axis it could be considered as a structure that contributes to transmitting the muscular forces at a distance and connecting the different segments of the limb. The stress relaxation tests showed that the crural fascia needs 120 s to decrease stress of 40 %, suggesting a similar time also in the living so that the static stretching could have an effect on the fascia.     

L-citrulline Prevents Alveolar and Vascular Derangement in a Rat Model of Moderate Hyperoxia-induced Lung Injury

Background

Moderate normobaric hyperoxia causes alveolar and vascular lung derangement in the newborn rat. Endogenous nitric oxide (NO), which promotes lung growth, is produced from the metabolism of l-arginine to l-citrulline in endothelial cells. We investigated whether administering l-citrulline by raising the serum levels of l-arginine and enhancing NO endogenous synthesis attenuates moderate hyperoxia-induced lung injury.

Methods

Newborn rats were exposed to FiO₂?=?0.6 or room air for 14?days to induce lung derangement and then were administered l-citrulline or a vehicle (sham). Lung histopathology was studied with morphometric features. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected for analysis. Lung vascular endothelial growth factor (VEGF), nitric oxide synthase (eNOS), and matrix metalloproteinase 2 (MMP2) gene and protein expressions were assessed.

Results

Serum l-arginine rose in the L-citr?+?hyperoxia group (p?=?0.05), as well as the Von Willebrand factor stained vessels count (p?=?0.0008). Lung VEGF immune staining, localized on endothelial cells, was weaker in the sections under hyperoxia than the l-citr?+?hyperoxia and room air groups. This pattern was comparable with the VEGF gene and protein expression profiles. Mean alveolar size increased in the untreated hyperoxia and sham-treated groups compared with the groups reared in room air or treated with l-citrulline under exposure to hyperoxia (p?=?0.0001). Lung VEGF and eNOS increased in the l-citrulline-treated rats, though this treatment did not change MMP2 gene expression but regulated the MMP2 active protein, which rose in BALF (p?=?0.003).

Conclusions

We conclude that administering l-citrulline proved effective in improving alveolar and vascular growth in a model of oxygen-induced pulmonary damage, suggesting better lung growth and matrix regulation than in untreated groups.     

B1a lymphocytes in the rectal mucosa of ulcerative colitis patients

AIM:To assess B1a cell expression in the rectal mucosa of ulcerative colitis (UC) patients in comparison with healthy controls.METHODS:Rectal mucosa biopsies were collected from 15 UC patients and 17 healthy controls.CD5 + B cells were analysed by three colour flow cytometry from rectal mucosal samples after mechanical disaggregation by Medimachine.Immunohistochemical analysis of B and T lymphocytes was also performed.Correlations between,on the one hand,rectal B1a cell concentrations and,on the other,erythrocyte sedimentation rate and C-reactive protein levels and clinical,endoscopic and histological disease activity indices were evaluated.RESULTS:Rectal B-lymphocyte (CD19 + /CD45 +) rate and concentration were higher in UC patients compared with those in healthy controls (47.85% ± 3.12% vs 26.10% ± 3.40%,P=0.001 and 501 ± 91 cells/mm 2 vs 117 ± 18 cells/mm 2,P 0.001);Rectal B1a cell density (CD5 + CD19 +) was higher in UC patients than in healthy controls (85 ± 15 cells/mm 2 vs 31 ± 6.7 cells/mm 2,P=0.009).Rectal B1a cell (CD5/CD19 +) rate correlated inversely with endoscopic classification (Rs=-0.637,P 0.05).CONCLUSION:B1a lymphocytes seem to be involved in the pathogenesis of UC,however,the role they play in its early phases and in disease activity,have yet to be defined.     

The assimilation of problematic experiences in linguistic therapy of evaluation: How did maría assimilate the experience of dizziness?

Abstract

The assimilation model proposes eight stages through which patients with problematic experiences pass during assimilation, ranging from suppression or dissociation to mastery. These are summarized in the Assimilation of Problematic Experiences Scale (APES). The assimilation model and the APES have been developed through intensive qualitative study of significant therapeutic events. This article describes the process of assimilation of the problematic experiences of dizziness in a patient, María, treated with linguistic therapy of evaluation. All treatment sessions were analyzed with the goals of describing the process of assimilation and connecting this process with the therapeutic change. The results showed that the assimilation process includes setbacks within a general pattern of progress through the APES stages. The process of assimilation was associated with the changes in María's life.

Zusammenfassung

Die Assimilation problematischer Erfahrungen in linguistischer Bewertungstherapie: Wie hat Maria ihre Erfahrungen von Schwindel assimiliert?

Das Assimilationsmodell geht von acht Stadien aus, die Patienten mit problematischen Erfahrungen durchlaufen, angefangen bei der Unterdrückung oder Dissoziation bis hin zur Problembewältigung. Diese Stadien sind in den Skalen für problematische Erfahrungen (Assimilation of Problematic Experiences Scales, APES) zusammengefasst. Das Assimilationsmodell und APES wurden mithilfe von intensiven qualitativen Studien zu signifikanten therapeutischen Geschehnissen entwickelt. Dieser Artikel beschreibt den Assimilationsprozess der problematischen Erfahrungen von Schwindel einer Patientin, Maria, die mit linguistischer Bewertungstherapie behandelt wurde. Alle Behandlungssitzungen wurden analysiert mit dem Ziel, den Prozess den Assimilationsprozess zu beschreiben und diesen Prozess mit durch die Therapie bewirkten Veränderungen in Verbindung zu bringen. Die Ergebnisse zeigten, dass der Assimilationsprozess bei einem allgemeinen Fortschritt durch die APES-Stadien auch Rückschritte einschließt. Der Assimilationsprozess war mit Veränderungen im Leben von Maria verbunden.

Résumé

L'assimilation d'expériences problématiques en thérapie linguistique d’évaluation: comment Maria a-t-elle assimilé son expérience de vertige??

Le modèle d'assimilation propose 8 phases par lesquelles des patients avec des expériences problématiques passent en cours d'assimilation, allant de la suppression ou de la dissociation à la maîtrise. Celles-ci sont résumées dans l'Echelle d'Assimilation d'Expériences Problématiques (APES). Le modèle d'assimilation et l'APES ont été développés par l’étude qualitative intense d’événements thérapeutiques significatifs. Cet article décrit le processus d'assimilation des expériences problématiques avec le vertige chez la patiente Maria qui a été traitée par la thérapie linguistique d’évaluation. Toutes les séances du traitement étaient analysées dans le but de décrire le processus d'assimilation et de connecter ce processus avec le changement thérapeutique. Les résultats montrent que le processus d'assimilation inclut des reculs qui font partie d'un pattern général de progrès à travers les phases APES. Le processus d'assimilation était associé avec les changements dans la vie de Maria.

Resumen

Asimilación de experiencias problemÁticas en la terapia de evaluación lingüística: ¿cómo maría asimiló la experiencia de vértigo?

El modelo de asimilación propone 8 etapas por las que transitan los pacientes con experiencias problemáticas a fin de asimilarlas, las que van desde la supresión o disociación hasta su dominación. Estas están resumidas en la Escala de Asimilación de Experiencias Problemáticas (APES). El modelo de asimilación y el APES han sido desarrollados a lo largo de un estudio cualitativo intensivo de acontecimientos significativos terapéuticos. Este artículo describe el proceso de asimilación de las experiencias problemáticas de vértigo de una paciente, María, tratada con una terapia de evaluación lingüística. Todas las sesiones se analizaron con el objeto de describir el proceso de asimilación y de conectarlo con el cambio terapéutico. Los resultados muestran que, a través de las etapas de APES, el proceso de asimilación incluye retrocesos dentro de una pauta general de progreso. El proceso de asimilación se asoció con los cambios en la vida de María.

Resumo

A Assimiliação de Experiências Problemáticas em Terapia Linguística de Avaliação: Como é que a Maria assimilou a experiência de tonturas

O modelo de assimilação propõe 8 estádios através dos quais o paciente com experiências problemáticas tem que passar durante a assimilação, desde da supressão ou dissociação até à mestria. Estes são sumariados na Escala de Assimilação de Experiências Problemáticas (EAEP). O modelo de assimilação e a EAEP têm sido desenvolvidos através do estudo qualitativo intensivo de acontecimentos terapêuticos significativos. Este artigo descreve o processo de assimilação de experiências problemáticas de tonturas numa paciente, a Maria, tratada com terapia linguística de avaliação. Analisaram-se todas as sessões de tratamento com o objectivo de descrever os processos de assimilação e relacionar estes processos com a mudança terapêutica. Os resultados demonstraram que o processo de assimilação inclui retrocessos dentro de um padrão geral de progresso através dos estádios da EAEP. O processo de assimilação foi associado com as mudanças na vida da Maria.

Sommario

L'assimilazione delle esperienze problematiche nella Terapia Linguistica della Valutazione: come Maria ha assimilato l'esperienza delle vertigini?

Il modello dell'assimilazione propone 8 stadi attraverso i quali i pazienti con esperienze problematiche passano durante l'assimilazione, estendendosi dalla soppressione o dissociazione al padroneggiamento.

Questi sono riassunti nell'Assimilation of Problematic Experiences Scale (APES).

Il modello dell'assimilazione e l'APES sono stati sviluppati attraverso uno studio qualitativo intensivo di eventi terapeutici significativi.

Questo articolo descrive il processo dell'assimilazione delle esperienze problematiche delle vertigini in un paziente, Maria, trattata con la terapia linguistica della valutazione.

Tute le sedute di trattamento sono state analizzate con gli obiettivi di descrivere il processo dell'assimilazione e connettere questo processo con il cambiamento terapeutico.

I risultati hanno mostrato che il processo dell'assimilazione include battute di arresto all'interno di un modello generale di progresso attraverso gli stadi APES. Il processo dell'assimilazione è stato associato con i cambiamenti nella vita di Maria.

     

Prediction of successful dose reduction or discontinuation of adalimumab,etanercept, or infliximab in rheumatoid arthritis patients using serum drug levels and antidrug antibody measurement

Background: To evaluate if TNF inhibitor serum drug levels (DL) or anti-drug antibodies (ADAb) can predict successful dose reduction (in patients with high DL) or discontinuation (in patients with no/low DL or ADAb) in rheumatoid arthritis (RA) patients.

Research design and methods: RA patients that were using adalimumab (n = 42), etanercept (n = 76) or infliximab (n = 51) and were doing well, were tapered until discontinuation or flare (1–1.5 year follow up). Random timed DL for adalimumab and etanercept and trough DL for infliximab were measured before dose reduction: Receiver-Operator-Curves (ROC) analyses with optimal cut-off DL were determined.

Results: No predictive value of adalimumab and infliximab DL for all outcomes were found, except for an inverse association of lower etanercept DL and higher chance for successful dose reduction (Area Under the Curve (AUC) 0.36, 95% CI 0.23–0.49; cut-off <2.6 mg/l). In sub analyses, higher adalimumab trough DL predicted successful dose reduction (AUC 0.86, 0.58–1.00; cut-off >7.8). ADAb were infrequent and not predictive of successful discontinuation.

Conclusions: No predictive value of baseline adalimumab, etanercept and infliximab DL or ADAb for successful dose reduction or discontinuation in RA was found in this context, with the possible exception of high adalimumab trough levels for successful dose reduction.