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L’objectif de cette étude anatomique est d’évaluer la faisabilité d’un lambeau libre ostéocutané prélevé à partir de l’ulna proximal pouvant être proposé lors de reconstructions des traumatismes complexes de la main.

Even if adoptive cell transfer (ACT) has already shown great clinical efficiency in different types of disease, such as cancer, some adverse events consistently occur, and suicide genes are an interesting system to manage these events. Our team developed a new medical drug candidate, a chimeric antigen receptor (CAR) targeting interleukin-1 receptor accessory protein (IL-1RAP), which needs to be evaluated in clinical trials with a clinically applicable suicide gene system. To prevent side effects and ensure the safety of our candidate, we devised two constructs carrying an inducible suicide gene, RapaCasp9-G or RapaCasp9-A, containing a single-nucleotide polymorphism (rs1052576) affecting the efficiency of endogenous caspase 9. These suicide genes are activated by rapamycin and based on the fusion of human caspase 9 with a modified human FK-binding protein, allowing conditional dimerization. RapaCasp9-G- and RapaCasp9-A-expressing gene-modified T cells (GMTCs) were produced from healthy donors (HDs) and acute myeloid leukemia (AML) donors. The RapaCasp9-G suicide gene demonstrated better efficiency, and we showed its in vitro functionality in different clinically relevant culture conditions. Moreover, as rapamycin is not pharmacologically inert, we also demonstrated its safe use as part of our therapy.

Protein complexes constitute the primary functional modules of cellular activity. To respond to perturbations, complexes undergo changes in their abundance, subunit composition, or state of modification. Understanding the function of biological systems requires global strategies to capture this contextual state information. Methods based on cofractionation paired with mass spectrometry have demonstrated the capability for deep biological insight, but the scope of studies using this approach has been limited by the large measurement time per biological sample and challenges with data analysis. There has been little uptake of this strategy into the broader life science community despite its rich biological information content. We present a rapid integrated experimental and computational workflow to assess the reorganization of protein complexes across multiple cellular states. The workflow combines short gradient chromatography and DIA/SWATH mass spectrometry with a data analysis toolset to quantify changes in a complex organization. We applied the workflow to study the global protein complex rearrangements of THP-1 cells undergoing monocyte to macrophage differentiation and subsequent stimulation of macrophage cells with lipopolysaccharide. We observed substantial proteome reorganization on differentiation and less pronounced changes in macrophage stimulation. We establish our integrated differential pipeline for rapid and state-specific profiling of protein complex organization.

Lung cancer is the leading cause of cancer-associated mortality worldwide1. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFRmutations and for RET, ROS1, ALKand METoncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource.

Introduction: Renal scintigraphy (RS) is occasionally performed to assess the risk of persistent renal failure (PRF) in patients with acute kidney disease (AKD). However, its diagnostic performance has never been assessed. Methods: We identified all patients with AKD for whom RS was performed in our institution between 2010 and 2017. PRF was defined as persistently low (< 33% of baseline) estimated glomerular filtration rates (eGFR), 1 year after RS. Nuclear medicine specialists reviewed RS data and rated, for each patient, the likelihood of PRF (“PRF score”). We evaluated the performance to predict PRF (area under the ROC curve (AUC)) of RS-derived parameters such as renal accumulation index, accumulation slope, and new parameters derived from serial kidney activity counts. We tested the ability of those parameters to improve a clinical model including hypertension, diabetes, AKI severity and baseline eGFR. Finally, we conducted sensitivity analyses using alternate PRF definitions. Results: Among 97 patients included, 57 (59%) fulfilled the criteria for PRF. The PRF score was able to predict PRF with an AUC of 0.63. Similarly, the accumulation index and accumulation slope respective AUCs were 0.64 and 0.63. None of these parameters were able to improve the performance of the clinical model. Among new parameters, the 3rd/2nd minute activity ratio and 3rd/2nd minute activity slope had fair diagnostic performance (AUC 0.72 and 0.74, respectively) and improved the performance of the clinical model. Results were confirmed in sensitivity analyses. Conclusion: Conventional renal scintigraphy can identify patients at high risk of PRF with a high specificity but a low sensitivity. New parameters, with comparable diagnostic abilities can be obtained within three minutes of injection. Graphical abstract:

Persistent airflow limitation (PAL) occurs in a subset of patients with asthma. Previous studies on PAL in asthma have included relatively small populations, mostly restricted to severe asthma, or have no included longitudinal data. The aim of this post-hoc analysis was to investigate the determinants, clinical implications, and outcome of PAL in patients with asthma who were included in the ATLANTIS study.

Barrier integrity is central to the maintenance of healthy immunological homeostasis. Impaired skin barrier function is linked with enhanced allergen sensitization and the development of diseases such as atopic dermatitis (AD), which can precede the development of other allergic disorders, for example, food allergies and asthma. Epidemiological evidence indicates that children suffering from allergies have lower levels of dietary fibre-derived short-chain fatty acids (SCFA). Using an experimental model of AD-like skin inflammation, we report that a fermentable fibre-rich diet alleviates systemic allergen sensitization and disease severity. The gut-skin axis underpins this phenomenon through SCFA production, particularly butyrate, which strengthens skin barrier function by altering mitochondrial metabolism of epidermal keratinocytes and the production of key structural components. Our results demonstrate that dietary fibre and SCFA improve epidermal barrier integrity, ultimately limiting early allergen sensitization and disease development.

Barrier integrity is central to the maintenance of healthy immunological homeostasis. Impaired skin barrier function is linked with enhanced allergen sensitization and the development of diseases such as atopic dermatitis (AD), which can precede the development of other allergic disorders, for example, food allergies and asthma. Epidemiological evidence indicates that children suffering from allergies have lower levels of dietary fibre-derived short-chain fatty acids (SCFA). Using an experimental model of AD-like skin inflammation, we report that a fermentable fibre-rich diet alleviates systemic allergen sensitization and disease severity. The gut-skin axis underpins this phenomenon through SCFA production, particularly butyrate, which strengthens skin barrier function by altering mitochondrial metabolism of epidermal keratinocytes and the production of key structural components. Our results demonstrate that dietary fibre and SCFA improve epidermal barrier integrity, ultimately limiting early allergen sensitization and disease development.

Les amputations digitales distales pulpaires et unguéales constituent un motif fréquent de consultation des services d’urgences de la main.

Background: Physiological focal radiopharmaceutical uptake in the head and uncinate process of the pancreas may be seen on somatostatin receptor-based PET/CT and might lead to false-positive results for neuroendocrine tumours (NETs). We aimed to perform a systematic review and a meta-analysis about the prevalence of this finding. Methods: We performed a comprehensive computer literature search across several databases until July 2020. Pooled prevalence of physiological focal uptake on somatostatin receptor-based PET/CT in the pancreas was calculated on a per-examination-based analysis and 95% confidence interval values (95% CI) were reported. Results: Six studies (684 patients and 829 PET/CT scans) were included. The pooled prevalence of physiological uptake in the head and uncinate process of the pancreas on somatostatin receptor-based PET/CT imaging was 34% (95% CI 19.5–48.7%) with average SUVmax values ranging from 5 to 12.6. Heterogeneity was seen across the selected studies. Conclusions: High radiopharmaceutical uptake in the head and uncinate process of the pancreas is frequent at somatostatin receptor-based PET/CT and it should be recognized by nuclear medicine physicians to prevent unnecessary additional investigations. In addition, next generation PET/CT tomographs might increase the prevalence of this finding.

Although chimeric antigen receptor CAR) T cell immunotherapies are an undeniable and unequivocal success, knowledge obtained from the monitoring of the first clinical trials targeting the CD19 antigen in B malignancies, either refractory/relapsed acute lymphoid leukemia (ALL) or lymphomas, contributed to the identification of tumor cell escape in about 30–50% of B-ALL. Resistance occurred due to loss of surface expression of the antigen (rCD19−) or to the early disappearance or inactivation of CAR T cells (rCD19+). In a recently reported clinical case, rCD19− relapse resulted from masking of the antigen by the CAR at the surface of B-ALL leukemia cells following the unexpected viral transduction of a leukemic cell present in the cytapheresis sample. The objective of this work was to reproduce this epitope-masking resistance model, in the context of acute myeloid leukemia (AML), based on our immunotherapeutic CAR T cell model targeting the accessory protein of the interleukin-1 receptor (IL-1RAP) expressed by leukemic stem cells. As AML primary blasts express different levels of IL-1RAP, we modeled transduction of different AML tumor cell lines screened for density of antigenic sites with our lentiviral vectors carrying a third-generation IL-1RAP CAR, an iCASP9 suicide gene, and a truncated CD19 surface gene. We demonstrated that primary AML blasts can be easily transduced (74.55 ± 21.29%, n= 4) and that CAR T cytotoxicity to IL-1RAP is inversely correlated with epitope masking in relation to the number of antigenic sites expressed on the surface of IL-1RAP+ lines. Importantly, we showed that, in vitro, a 24-h exposure of IL-1RAP+/CAR+ leukemia lines to Rimiducid eliminated >85% of the cells. We confirmed that the expression of IL-1RAP CAR by an IL-1RAP+ leukemic cell, by decreasing the membrane availability of the targeted antigen, can induce resistance while a high epitope density maintains sensitivity to CAR T cells. Moreover, the presence of the iCASP9/Rimiducid suicide system safety switch makes this immunotherapy approach safe for application in a future phase 1 clinical trial.

Abstract:Jean Nicod, born in 1893, died far too young in 1924. He is remembered today as one of the foreign disciples (among them Ludwig Wittgenstein and Norbert Wiener) attracted to Cambridge by Russell after the publication of the Principia. We publish here a translation of “Les tendances philosophiques de M. Bertrand Russell”, which appeared in the Revue de Métaphysique et de Morale in 1922. The article is testimony not only to Nicod’s philosophical talents, but also of how Russell’s philosophy could be received in France at the beginning of the twentieth century.

Dupuytren's disease is a hereditary condition leading to progressive fibrosis in the palm of the hand, causing gradual contracture of the digits and significant functional impairment.

[68Ga]Ga-NODAGA-RGDyk PET/CT and [18F]FDG PET/CT were performed in a 65-year-old woman during the work-up of a squamous cell carcinoma of the tongue within a clinical study protocol. Images revealed both tracers’ uptake in the primary tumor and cervical lymph nodes, but also bilaterally in the shoulders, elbows, wrists, metacarpophalangeal, interphalangeal, and hip joints. The patient had been diagnosed with rheumatoid arthritis 8 years prior to the examination. Images showed a significantly higher [18F]FDG than [68Ga]Ga-NODAGA-RGDyk uptake in primary tumor and cervical lymph nodes. However, the patient with moderately active rheumatoid arthritis had similar levels of [68Ga]Ga-NODAGA-RGDyk and [18F]FDG uptake in the involved joints, but with no [68Ga]Ga-NODAGA-RGDyk uptake in the surrounding muscles, unlike with [18F]FDG. Our case suggests that [68Ga]Ga-NODAGA-RGDyk PET/CT allows imaging of integrins expression in rheumatoid arthritis, including integrins expressed in synovial angiogenesis, with potentially a better signal-to-noise ratio than on [18F]FDG PET/CT.

Bronchiolitis obliterans syndrome is the main limitation for long‐term survival after lung transplantation. Some specific B cell populations are associated with long‐term graft acceptance. We aimed to monitor the B cell profile during early development of bronchiolitis obliterans syndrome after lung transplantation. The B cell longitudinal profile was analyzed in peripheral blood mononuclear cells from patients with bronchiolitis obliterans syndrome and patients who remained stable over 3 years of follow‐up. CD24hiCD38hitransitional B cells were increased in stable patients only, and reached a peak 24 months after transplantation, whereas they remained unchanged in patients who developed a bronchiolitis obliterans syndrome. These CD24hiCD38hitransitional B cells specifically secrete IL‐10 and express CD9. Thus, patients with a total CD9+B cell frequency below 6.6% displayed significantly higher incidence of bronchiolitis obliterans syndrome (AUC = 0.836, PPV = 0.75, NPV = 1). These data are the first to associate IL‐10‐secreting CD24hiCD38hitransitional B cells expressing CD9 with better allograft outcome in lung transplant recipients. CD9‐expressing B cells appear as a contributor to a favorable environment essential for the maintenance of long‐term stable graft function and as a new predictive biomarker of bronchiolitis obliterans syndrome–free survival. In lung transplant patients with bronchiolitis obliterans syndrome and patients who remained stable over 3 years of follow‐up, IL‐10–secreting CD24hiCD38hi transitional B cells expressing CD9 are associated with better allograft outcome, suggesting CD9‐expressing B cells as a new predictive biomarker of bronchiolitis obliterans syndrome–free survival.

Different imaging methods have been used to detect hepatocellular carcinoma (HCC). As there are increasing literature data about the role of radiolabelled choline PET/CT in this setting, we aimed to perform an updated meta-analysis about the detection rate (DR) of this imaging method in HCC. A comprehensive computer literature search of studies published through December 2018 in PubMed/MEDLINE, Embase and Cochrane library databases regarding the DR of radiolabelled choline PET or PET/CT in patients with HCC was carried out. Pooled DR were calculated on a per patient- and on a per lesion-based analysis. Subgroup analyses taking into account the radiopharmaceutical used were performed. Nine studies (283 HCC patients) were included in the pooled analysis. The pooled DR of radiolabelled choline PET or PET/CT on a per patient- and on a per lesion-based analysis was 83% [95% confidence interval (95% CI) 75–89%] and 79% (95% CI 72–86%), respectively. A significant heterogeneity among the studies was found on a per lesion-based analysis only. No significant publication bias was found. The subgroup analysis demonstrated a trend towards a higher DR when using 18F-choline compared to 11C-choline, without a statistically significant difference. Pooled DR of HCC using dual-tracer PET/CT (radiolabelled choline and 18F-FDG) on a per patient- and a per lesion-based analysis was 91% (95% CI 87–95%) and 89% (95% CI 80–95%), respectively, without significant heterogeneity. Radiolabelled choline PET/CT demonstrated good ability in detecting HCC. The DR increased when dual-tracer PET/CT was performed. Large multicenter studies and cost-effectiveness analyses are warranted.

This research examines the effect of customer training on the customer’s role during service encounters. We examine its influence on coproduction outcomes from the standpoint of both the company (productivity) and the customer (customer satisfaction). The analysis of the influence of customer training is implemented in two stages. First, we establish that customer training improves the company’s productivity without decreasing customer satisfaction. With this verified, we consider the content of training (cognitive vs cognitive and affective) and the medium deployed (employees vs digital). We then establish that training increases productivity more when its content is both cognitive and affective, whereas the medium has no effect. Conversely, when employees deliver training, customer satisfaction is higher, while training content has no effect on this variable. Results provide guidelines for enhancing the benefits for both companies and customers.

Cette recherche étudie l’impact de la formation du client à son rôle lors d’une rencontre de service. Elle examine l’influence de celle-ci sur les bénéfices de la coproduction en adoptant un regard croisé : celui de l’entreprise, à travers la productivité du personnel en contact, et celui du client, via sa satisfaction. La recherche se décompose en deux phases. Elle montre d’abord que globalement la formation accroît la productivité du personnel sans nuire à la satisfaction. Une fois l’intérêt de former le client avéré, elle s’intéresse à deux caractéristiques de la formation : son contenu (cognitif seul ou cognitif et affectif) et le moyen par lequel elle est délivrée (en personne ou numérique). La formation du client augmente la productivité particulièrement quand son contenu est à la fois cognitif et affectif alors que son moyen ne l’influence pas. Inversement, concernant la satisfaction, la formation donnée par du personnel a un impact plus important qu’une formation numérique tandis que son contenu ne l’affecte pas. Ces résultats donnent des pistes d’actions aux entreprises pour améliorer leurs bénéfices et ceux du client.

Die zystischen Lungenerkrankungen sind eine distinkte Gruppe seltener Lungenkrankheiten. Zwei von ihnen sind die Folge monogener Defekte von Tumorsuppressorgenen: Die Lymphangioleiomyomatose - entweder sporadisch oder im Rahmen des Tuberöse-Sklerose-Komplexes - und das Birt-Hogg-Dubé-Syndrom. Diese Krankheiten weisen Gemeinsamkeiten im klinischen Erscheinungsbild auf, vom Auftreten im jungen Erwachsenenalter über multiple pulmonale Zysten, rezidivierenden Pneumothorax und Hamartome der Haut bis hin zu Nierentumoren. Sie unterscheiden sich jedoch deutlich im Hinblick auf die Verteilung auf die Geschlechter, die Pathogenese, den Krankheitsverlauf und die Prognose. In der Erforschung beider seltenen Krankheiten werden derzeit rapide Fortschritte gemacht. Beim Management der Lymphangioleiomyomatose sind in den letzten zehn Jahren wesentliche Verbesserungen erzielt worden, nachdem die pathogenen Mechanismen erforscht, eine wirksame Therapie entdeckt und große Kohortenstudien sowie internationale Leitlinien erstellt wurden. Das Birt-Hogg-Dubé-Syndrom wurde erst vor kürzerer Zeit erstmals beschrieben; die Klärung der pathophysiologischen Hintergründe steht noch aus. Übersetzung aus Respiration 2017;94:467-485 (DOI: 10.1159/000485106)

Supplemental Digital Content is Available in the Text.A meta-analysis of vitrectomy for diabetic macular edema found no significant difference in visual outcome compared with laser or observation. Retinal thickness was better than with laser/observation at 6 months, but this benefit had reversed by 12 months. Intraoperative retinal breaks occurred in 7.1%, and postoperative retinal detachment in 1.2%.

Chez les patients atteints d’hyperparathyroïdie, la scintigraphie planaire par soustraction à double isotope est un examen efficace pour localiser les parathyroïdes. Tout d’abord, la région d’intérêt (ROI) dans l’image technétium et l’image d’iode est déterminée par le médecin après normalisation. Ensuite, l’image de soustraction est obtenue entre les images ROI technétium et l’image iode. La soustraction n’est pas entièrement automatique et le résultat n’est pas toujours optimal.

Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. Chronic lung allograft dysfunction manifests as bronchiolitis obliterans syndrome or the recently described restrictive allograft syndrome. Although numerous risk factors have been identified so far, the physiopathological mechanisms of CLAD remain poorly understood. We investigate here the immune mechanisms involved in the development of CLAD after lung transplantation. We explore the innate or adaptive immune reactions induced by the allograft itself or by the environment and how they lead to allograft dysfunction. Because current literature suggests bronchiolitis obliterans syndrome and restrictive allograft syndrome as 2 distinct entities, we focus on the specific factors behind one or the other syndromes. Chronic lung allograft dysfunction is a multifactorial disease that remains irreversible and unpredictable so far. We thus finally discuss the potential of systems-biology approach to predict its occurrence and to better understand its underlying mechanisms.Royer et al review the immune mechanisms involved in the development chronic lung allograft dysfunction (CLAD), which manifests as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS), concluding that CLAD is a multifactorial disease that remains irreversible and unpredictable.

Two bottlenecks impeding the genetic analysis of complex traits in rodents are access to mapping populations able to deliver gene-level mapping resolution and the need for population-specific genotyping arrays and haplotype reference panels. Here we combine low-coverage (0.15×) sequencing with a new method to impute the ancestral haplotype space in 1,887 commercially available outbred mice. We mapped 156 unique quantitative trait loci for 92 phenotypes at a 5% false discovery rate. Gene-level mapping resolution was achieved at about one-fifth of the loci, implicating Unc13c and Pgc1a at loci for the quality of sleep, Adarb2 for home cage activity, Rtkn2 for intensity of reaction to startle, Bmp2 for wound healing, Il15 and Id2 for several T cell measures and Prkca for bone mineral content. These findings have implications for diverse areas of mammalian biology and demonstrate how genome-wide association studies can be extended via low-coverage sequencing to species with highly recombinant outbred populations.

Fragile X syndrome (FraX) is caused by the expansion of an unstable CGG repeat located in the Fragile X mental retardation 1 gene (FMR1) gene. Preimplantation genetic diagnosis (PGD) can be proposed to couples at risk of transmitting the disease, that is, when the female carries a premutation or a full mutation. We describe two new single-cell, single-round multiplex PCR for indirect and direct diagnosis of FraX on biopsied embryos. These tests include five unpublished, highly heterozygous simple sequence repeats, and the co-amplification of non-expanded CGG repeats for the direct test. Heterozygosity of the new markers ranged from 69 to 81%. The mean rate of non-informative marker included in the tests was low (26% and 23% for the new indirect and direct tests, respectively). This strategy allows offering a PGD for FraX to 96% of couples requesting it in our centre. A conclusive genotype was obtained in all cells with a rate of cells presenting an allele dropout ranging from 17% for the indirect test to 26% for the direct test. The new indirect test was applied for eight PGD cycles: 32 embryos were analysed, 9 were transferred and 3 healthy babies were born. By multiplexing these highly informative markers, robustness of the diagnosis is improved and the loss of potentially healthy embryos (because they are non-diagnosed or misdiagnosed) is limited. This may increase the chances of success of couples requesting a PGD for FraX, in particular, when premature ovarian insufficiency in premutated women leads to a reduced number of embryos available for analysis.

In a post-prognostics decision context, this paper addresses the problem of maximizing the useful life of a platform composed of several parallel machines under service constraint. Application on multi-stack fuel cell systems is considered. In order to propose a solution to the insufficient durability of fuel cells, the purpose is to define a commitment strategy by determining at each time the contribution of each fuel cell stack to the global output so as to reach the demand as long as possible. Two algorithms making use of convex optimization are proposed to cope with the assignment problem. First one is based on the Mirror-prox for Saddle Points method and second one uses the Lasso (Least Absolute Shrinkage and Selection Operator) principle. Results based on computational experiments assess the efficiency of these two approaches in comparison with an intuitive resolution performing successive basic convex projections onto the sets of constraints associated to the optimization problem.

Supplemental Digital Content is available in the text.Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are operative endoscopies that have been performed since a long time. Recently, an evolution of laparoscopy called transanal minimally invasive surgery began to be popularized, and it can be adopted in the face of difficult cases for EMR/ESD. In this video, a 36-year-old woman was submitted to transanal minimally invasive surgery resection, after unsuccessful ESD, for a 2-cm polyp located anteriorly in the anal canal, just beyond the pectineal line. Preoperative workup showed a uT1m versus T1sm N0 M0 lesion. The procedure was performed with a new reusable transanal platform and a monocurved coagulating hook and grasping forceps. The operative time was 90 minutes. No perioperative complications were registered, and the patient was discharged on postoperative day 1. The pathologic report showed a villotubular adenoma with high-grade dysplasia and distant-free margins. After 1 year, the patient was going well, without any recurrent disease. Transanal minimally invasive surgery resection is a good alternative to conventional endoscopic therapies, allowing a meticulous dissection under the magnified operative field's exposure, and a mucosal-submucosal flap closure under satisfactory surgeon's ergonomics.

A specific proliferation of the peripheral blood mononuclear cells (PBMC) stimulated by antigens of Echinococcussp. has been shown in patients with cystic as well as alveolar echinococcosis. However, the development of a major granulomatous reaction around the parasitic larvae is a characteristic feature of the local immune response to E. multiloculariswhile humoral immune responses seem to predominate in E. granulosusinfection. The aim of this study was to analyse the specific proliferation of the PBMC from 36 patients with alveolar echinococcosis, and 23 controls, induced by a crude preparation of E. rnultilocularis(EmcAg) as well as by two E. multilocularisspecific antigen preparations, the Em2 antigen and the protoscolex (ESAg) antigen. The significant correlation observed between the proliferation index either by Em2 and ES or by Emc suggests that both antigens account for an important part of the lymphocyte proliferative response. The strong effect of these species specific antigens on lymphocyte proliferation is confirmed by the comparison of the results obtained in this study to those obtained in a previous study of specific cellular immunity to E. granulosusantigens in patients with cystic echinococcosis. The proliferation indices were significantly elevated in all those 7 patients with a proven AE who were sero-negative using the Emc ELISA, as well as in the 12 patients also seronegative, but using the Em2 ELISA. In 5 seronegative patients who had had a complete resection of the parasitic lesions two years before the lymphocyte proliferation evaluation, the PI was above the threshold value for two dilutions of EmcAg. PI under the threshold values were obtained only in patients with residual lesions. These results suggest that E. multilocularisspecific antigens promote the proliferation of lymphocytes which could be TH1 cells, responsible for the intense periparasitic granulomatous reaction characteristic of alveolar echinococcosis.

Traditionally, sleep studies in mammals are performed using electroencephalogram/electromyogram (EEG/EMG) recordings to determine sleep-wake state. In laboratory animals, this requires surgery and recovery time and causes discomfort to the animal. In this study, we evaluated the performance of an alternative, noninvasive approach utilizing piezoelectric films to determine sleep and wakefulness in mice by simultaneous EEG/EMG recordings. The piezoelectric films detect the animal's movements with high sensitivity and the regularity of the piezo output signal, related to the regular breathing movements characteristic of sleep, serves to automatically determine sleep. Although the system is commercially available (Signal Solutions LLC, Lexington, KY), this is the first statistical validation of various aspects of sleep.

Although traditionally thought to be sterile, accumulating evidence now supports the concept that our airways harbor a microbiome. Thus far, studies have focused upon characterizing the bacterial constituents of the airway microbiome in both healthy and diseased lungs, but what perhaps provides the greatest impetus for the exploration of the airway microbiome is that different bacterial phyla appear to dominate diseased as compared with healthy lungs. As yet, there is very limited evidence supporting a functional role for the airway microbiome, but continued research in this direction is likely to provide such evidence, particularly considering the progress that has been made in understanding host-microbe mutualism in the intestinal tract. In this review, we highlight the major advances that have been made discovering and describing the airway microbiome, discuss the experimental evidence that supports a functional role for the microbiome in health and disease, and propose how this emerging field is going to impact clinical practice.

Acute exposure to high altitude stimulates free radical formation in lowlanders, yet whether this persists during chronic exposure in healthy, well-adapted and maladapted highlanders suffering from chronic mountain sickness (CMS) remains to be established.