Patient Quality of Life and Symptoms after Surgical Treatment for Endometriosis

Study Objective

To assess the impact of surgical treatment of endometriosis on quality of life and pain over a 3-year period of postoperative follow-up.

Airway neutrophil inflammation in nonasthmatic patients with food allergy

BACKGROUND: Patients with food allergy (FA) have been recently shown to develop bronchial hyperresponsiveness (BHR), despite the absence of any concomitant asthmatic manifestation. In order to explain this observation, we sought to examine the presence of a bronchial inflammation in induced sputum of nonasthmatic patients with FA. METHODS: Twelve nonasthmatic patients with FA (urticaria, digestive symptoms, anaphylaxis) were included in the study. Results were compared to these obtained from eight asthmatic patients without food allergy and eight healthy controls. Diagnosis of FA was based on double-blind placebo-controlled challenge. Sputum cells and fluid-phase eosinophil cationic protein (ECP), myeloperoxidase (MPO) and interleukin-8 (IL-8) were measured in induced sputum. BHR was evaluated using methacholine inhalation. RESULTS: Sputum from asthmatics, in comparison with the sputum of healthy subjects and patients with FA contained a higher proportion of eosinophils and higher levels of ECP (< 0.001). In marked contrast, patients with FA exhibited an increased proportion of neutrophils and IL-8 in comparison with asthmatics and controls (P < 0.05 for neutrophils and P < 0.001 for IL-8). There was a significant correlation between sputum neutrophils and IL-8 (r = 0.68, P < 0.001). MPO levels were not different between the groups. There was a trend toward higher levels of IL-8 and ECP in food allergic patients with BHR in comparison with patients with FA without BHR. CONCLUSION: Our results demonstrate that a subclinical neutrophil airway inflammation is present in patients with food allergy free of clinical respiratory symptoms and that IL-8 may be an important mediator of this neutrophilia.     

Haptic discrimination of object shape in humans: two-dimensional angle discrimination

The human ability to recognize objects on the basis of their shape, as defined by active exploratory movements, is dependent on sensory feedback from mechanoreceptors located both in the skin and in deep structures ( haptic feedback). Surprisingly, we have little information about the mechanisms for integrating these different signals into a single sensory percept. With the eventual aim of studying the underlying central neural mechanisms, we developed a shape discrimination test that required active exploration of objects, but was restricted to one component of shape, two-dimensional (2D) angles. The angles were machined from 1-cm-thick Plexiglas, and consisted of two 8-cm-long arms that met to form an angle of 90 degrees (standard) or 91 degrees to 103 degrees (comparison angles). Subjects scanned pairs of angles with the index finger of the outstretched arm and identified the larger angle of each pair explored. Discrimination threshold (75% correct) was 4.7 degrees (range 0.7 degrees to 12.1 degrees), giving a precision of 5.2% (0.8-13.4%: difference/standard). Repeated blocks of trials, either in the same session or on different days, had no effect on discrimination threshold. In contrast, the motor strategy was partly modified: scanning speed increased but dwell-time at the intersection did not change. Finally, 2D angle discrimination was not significantly modified by rotating the orientation of one of the angles in the pair (0 degrees, 4 degrees or 8 degrees rotation towards the midline, in the vertical plane), providing evidence that subjects evaluated each angle independently in each trial. Subject reports indicated that they relied on cutaneous feedback from the exploring digit (amount of compression of the finger at the angle) and mental images of the angles, most likely arising from proprioceptive information (from the shoulder) generated during the to-and-fro scans over the angle. In terms of shoulder angles, the mean discrimination threshold here was 0.54 degrees (range 0.08 degrees to 1.36 degrees). These values are lower than previous estimates of position sense at the shoulder. In light of the subjects' strategies, it therefore seems likely that both cutaneous and proprioceptive (including both dynamic and static position-related signals) feedback contributed to the haptic discrimination of 2D angles.     

The MSHA pilus of Vibrio parahaemolyticus has lectin functionality and enables TTSS-mediated pathogenicity

Vibrio parahaemolyticus is a seafood-borne pathogen which causes acute inflammatory gastroenteritis – a process which is mediated by the translocation of type three secretion system effector proteins. The molecular interactions governing colonization of the intestinal epithelium by this pathogen remain poorly understood. The mannose-sensitive haemagglutinin (MSHA) pilus was identified in this study as a significant factor in bacterial-host cell adherence and subsequent pathogenesis towards Caco-2 human intestinal epithelial cells. Deletion of essential components of the MSHA pilus resulted in a 60% decrease in adherence and a similar reduction in bacterial uptake by human intestinal cells. The diminished adherence of MSHA mutants correlated with significant decreases in V. parahaemolyticus-induced Caco-2 cell lysis, cell rounding and IL-8 secretion. Glycan array comparison between the V. parahaemolyticus wild type and MSHA deficient mutants identified lectin functionality for the MSHA pilus with specificity towards the fucosylated blood group oligosaccharide antigens Lewis A and X and blood groups A and B. The MSHA pilus also exhibited high affinity for the structurally related asialo-GM1 ganglioside, lacto-N-fucopentaose I and lacto-N-difucohexaose I. We hypothesize that these glycans act as receptors for the MSHA pilus in the gastrointestinal tract, thereby facilitating efficient colonization of the intestinal epithelium by V. parahaemolyticus.     

Inhibition of AMP-Activated Protein Kinase Accentuates Lipopolysaccharide-Induced Lung Endothelial Barrier Dysfunction and Lung Injury in Vivo

The aim of this study was to determine the role of AMP-activated protein kinase (AMPK) in lipopolysaccharide (LPS)-induced lung endothelial barrier dysfunction and lung injury in vivo. Both cultured human pulmonary artery endothelial cells (HPAECs) and experimental animals [AMPK subunit α–deficient mice and wild-type (WT) control mice (C57BL/6J)] were used. In cultured HPAECs, LPS increased endothelial permeability in parallel with a decrease in AMPK activity. Consistent with this observation, AMPK activation with the potent AMPK activator 5-aminoimidazole-4-carboxamide-1-d-ribofuranoside (AICAR) attenuated LPS-induced endothelial hyperpermeability in vitro. Intratracheal administration of LPS (1 mg/kg) in WT mice reduced AMPK phosphorylation at Thr172 in lung tissue extracts, increased protein content and cell count in bronchial alveolar lavage fluid, and increased Evans Blue dye infiltration into the lung. These same attributes were similarly enhanced in AMPKα-knockout mice, compared with WT mice. Pretreatment with AICAR reduced these lung injury indicators in LPS-treated WT mice. AMPK activation with AICAR attenuated LPS-induced endothelial hyperpermeability by activating the Rac/Cdc42/PAK pathway, with concomitant inhibition of the Rho pathway, and decreased VE-cadherin phosphorylation at Tyr658. We conclude that AMPK activity supports normal endothelial barrier function and that LPS exposure inhibits AMPK, thereby contributing to endothelial barrier dysfunction and lung injury.Vascular endothelial permeability plays a pivotal role in regulating many physiological and pathological processes, including angiogenesis, immunity, and inflammation.¹ In lungs, endothelial cells form a semipermeable barrier between the vessel lumen and underlying alveoli, thereby mediating the transmigration of blood cells and maintaining fluid homeostasis. The integrity of the endothelial cell (EC) monolayer therefore directly determines lung vascular permeability. For example, EC barrier dysfunction can lead to an increase in permeation of fluid and macromolecules into the interstitium and alveolar space, resulting in pulmonary edema, a major characteristic of acute lung injury.RhoA, Rac1, and Cdc42 are key members of the Rho GTPase family and are activated on binding GTP at the membrane.² These proteins are intimately involved in regulating cell adhesion and cytoskeletal dynamics, both of which play an important role in endothelial barrier function.^3–5 For example, Rac1 and Cdc42 are important in maintaining, stabilizing, and restoring the endothelial barrier.³ More specifically, Baumer et al⁶ demonstrated that Rac1 is involved in mitigating endothelial hyperpermeability by a subset of agonists, including thrombin and lipopolysaccharide (LPS). In addition, activation of the Rho GTPases Cdc42 and Rac1 restores endothelium integrity after lung injury.⁷ Although the contributions of Rho GTPases in maintaining endothelial barrier function are well established, how Rho GTPase is regulated in endothelial cells is largely unknown.AMP-activated protein kinase (AMPK) is a heterotrimeric serine/threonine kinase; a catalytic α subunit and regulatory β and γ subunits are important in maintaining the stability of the complex. AMPK belongs to a family of energy-sensing enzymes that function as fuel gauges, monitoring changes in the energy status of the cell.⁸ AMPK is activated in response to a variety of stressors that increase the intracellular ratio of AMP to ATP. On activation, AMPK phosphorylates a number of downstream targets, thereby affecting glucose metabolism, fatty acid oxidation, hepatic lipogenesis, and cholesterol synthesis.⁹ In addition to its regulatory role in metabolism, recent studies have demonstrated a role for AMPK in maintaining normal endothelial function.¹⁰ For example, AMPK subunit α2 exerts protective effects against atherosclerosis by inhibiting the endoplasmic reticulum stress response in ECs.¹¹ Thus, agents that enhance EC barrier function are of potential therapeutic value in a variety of pathological settings, including inflammatory disease, atherosclerosis, and tumor angiogenesis. The effects of AMPK on endothelial barrier function and vascular permeability have not been investigated previously. Thus, the aim of the present study was to investigate whether AMPK protects lung endothelial barrier function and mitigates acute lung injury in response to LPS.     

Lagooning of wastewaters favors dissemination of clinically relevant Pseudomonas aeruginosa

The significance of wastewater treatment lagoons (WWTLs) as point sources of clinically relevant Pseudomonas aeruginosa that can disseminate through rural and peri-urban catchments was investigated. A panel of P. aeruginosa strains collected over three years from WWTLs and community-acquired infections was compared by pulsed field gel electrophoresis (PFGE) DNA fingerprinting and multilocus sequence typing (MLST). Forty-four distantly related PFGE profiles and four clonal complexes were found among the WWTL strains analyzed. Some genotypes were repeatedly detected from different parts of WWTLs, including the influent, suggesting an ability to migrate and persist over time. MLST showed all investigated lineages to match sequence types described in other countries and strains from major clinical clones such as PA14 of ST253 and “C” of ST17 were observed. Some of these genotypes matched isolates from community-acquired infections recorded in the WWTL geographic area. Most WWTL strains harbored the main P. aeruginosa virulence genes; 13% harbored exoU-encoded cytoxins, but on at least six different genomic islands, with some of these showing signs of genomic instability. P. aeruginosa appeared to be highly successful opportunistic colonizers of WWTLs. Lagooning of wastewaters was found to favor dissemination of clinically relevant P. aeruginosa among peri-urban watersheds.     

Failure of ticks to transmit Scopulariopsis brevicaulis (Deuteromycota), a common filamentous fungal commensal of ticks

The capacity of ticks to transmit a fungus was examined by analyzing tick saliva, host tissue from feeding sites, and host blood for presence of Scopulariopsis brevicaulis (Sacc.) Bainier, an internal mycosymbiont of the American dog tick, Dermacentor variabilis (Say), and lone star tick, Amnblyomma americanum (L.). Although >85% of ticks were infected with S. brevicaulis, conidia presence was low (0-5% of samples) in microscopic observations and mycological culturing of saliva expressed from larvae, nymphs, and adults. Additionally, the recovery of S. brevicaulis from blood and tissue feeding sites from a rabbit where S. brevicaulis-positive adult ticks had attached and fed was not increased compared with control tissue where no feeding occurred, indicating that transmission does not occur by the blood-feeding route. Tick mouthparts were found to contain S. brevicaulis in addition to Penicillium glabrum (Wehmer) Westling, but these agents were sparse in isolations from the feeding sites, which makes it unlikely that ticks act frequently as a mechanical fungal vector.