The Metacognitions about Binge Eating Questionnaire: Investigation of the association between specific metacognitions and Binge Eating Disorder.

Literature suggested that metacognitions are involved in eating problems and may be relevant to the understanding of Binge Eating Disorder (BED). The goal of the current studies was to develop the first self-report instrument on metacognitions about binge eating. In Study 1, a community sample completed the Metacognitions about Binge Eating Questionnaire (MBEQ); an Exploratory Factor Analysis (EFA) was performed. In study 2, a community sample completed the MBEQ and measures assessing severity of binge eating, irrational food beliefs, anxiety, depression, impulsiveness. A Confirmatory Factor Analysis (CFA) was performed. Concurrent and incremental validity were assessed. In study 3, a clinical sample of participants with a diagnosis of BED completed the MBEQ and other measures. Bivariate correlational analysis and hierarchical linear regression were performed. Participants from the general population and participants with a diagnosis of BED were compared. EFA and CFA supported a two-factor solution consisting of positive and negative metacognitions about binge eating. Concurrent and incremental validity were acceptable. The metacognitions factors correlated positively with anxiety, depression, irrational food beliefs, impulsiveness in the community sample, and anxiety, irrational food beliefs, impulsiveness in clinical sample. The metacognitions factors contributed to the prediction of BEDs symptoms, in community and clinical samples, over and above age, gender, impulsiveness, anxiety, depression, irrational food beliefs. The MBEQ possesses good psychometric properties and appears a reliable and valid measure of positive and negative metacognitions about binge eating. Metacognitions about binge eating could be a therapeutic target to reduce the severity of binge eating episodes.

Prevalence and 6-month recovery of olfactory dysfunction: a multicentre study of 1363 COVID-19 patients.

OBJECTIVE: To investigate prevalence and recovery of olfactory dysfunction (OD) in COVID-19 patients according to the disease severity. METHODS: From 22 March to 3 June 2020, 2581 COVID-19 patients were identified from 18 European hospitals. Epidemiological and clinical data were extracted at baseline and within the 2-month post-infection. RESULTS: The prevalence of OD was significantly higher in mild form (85.9%) compared with moderate-to-critical forms (4.5-6.9%; P = 0.001). Of the 1916 patients with OD, 1363 completed the evaluations (71.1%). A total of 328 patients (24.1%) did not subjectively recover olfaction 60 days after the onset of the dysfunction. The mean duration of self-reported OD was 21.6 ± 17.9 days. Objective olfactory evaluations identified hyposmia/anosmia in 54.7% and 36.6% of mild and moderate-to-critical forms, respectively (P = 0.001). At 60 days and 6 months, 15.3% and 4.7% of anosmic/hyposmic patients did not objectively recover olfaction, respectively. The higher baseline severity of objective olfactory evaluations was strongly predictive of persistent OD (P < 0.001). CONCLUSION: OD is more prevalent in mild COVID-19 forms than in moderate-to-critical forms. OD disappeared in 95% of patients regarding objective olfactory evaluations at 6 months.

Recent trends in primary-care antidepressant prescribing to children and young people: an e-cohort study.

BACKGROUND: Concerns relating to increased use of psychotropic medication contrast with those of under-treatment and under-recognition of common mental disorders in children and young people (CYP) across developed countries. Little is known about the indications recorded for antidepressant prescribing in primary care in CYP. METHOD: This was an electronic cohort study of routinely collected primary-care data from a population of 1.9 million, Wales, UK. Poisson regression was undertaken to model adjusted counts of recorded depression symptoms, diagnoses and antidepressant prescriptions. Associated indications were explored. RESULTS: 3 58 383 registered patients aged 6-18 years between 1 January 2003 and 31 December 2013 provided a total of 19 20 338 person-years of follow-up. The adjusted incidence of antidepressant prescribing increased significantly [incidence rate ratio (IRR) for 2013 = 1.28], mainly in older adolescents. The majority of new antidepressant prescriptions were for citalopram. Recorded depression diagnoses showed a steady decline (IRR = 0.72) while depression symptoms (IRR = 2.41) increased. Just over half of new antidepressant prescriptions were associated with depression (diagnosis or symptoms). Other antidepressant prescribing, largely unlicensed, was associated with diagnoses such as anxiety and pain. CONCLUSION: Antidepressant prescribing is increasing in CYP while recorded depression diagnoses decline. Unlicensed citalopram prescribing occurs outside current guidelines, despite its known toxicity in overdose. Unlicensed antidepressant prescribing is associated with a wide range of diagnoses, and while accepted practice, is often not supported by safety and efficacy studies. New strategies to implement current guidance for the management of depression in CYP are required.

Comparing de novo and reference-based transcriptome assembly strategies by applying them to the blood-sucking bug Rhodnius prolixus.

High Throughput Sequencing capabilities have made the process of assembling a transcriptome easier, whether or not there is a reference genome. But the quality of a transcriptome assembly must be good enough to capture the most comprehensive catalog of transcripts and their variations, and to carry out further experiments on transcriptomics. There is currently no consensus on which of the many sequencing technologies and assembly tools are the most effective. Many non-model organisms lack a reference genome to guide the transcriptome assembly. One question, therefore, is whether or not a reference-based genome assembly gives better results than de novo assembly. The blood-sucking insect Rhodnius prolixus-a vector for Chagas disease-has a reference genome. It is therefore a good model on which to compare reference-based and de novo transcriptome assemblies. In this study, we compared de novo and reference-based genome assembly strategies using three datasets (454, Illumina, 454 combined with Illumina) and various assembly software. We developed criteria to compare the resulting assemblies: the size distribution and number of transcripts, the proportion of potentially chimeric transcripts, how complete the assembly was (completeness evaluated both through CEGMA software and R. prolixus proteome fraction retrieved). Moreover, we looked for the presence of two chemosensory gene families (Odorant-Binding Proteins and Chemosensory Proteins) to validate the assembly quality. The reference-based assemblies after genome annotation were clearly better than those generated using de novo strategies alone. Reference-based strategies revealed new transcripts, including new isoforms unpredicted by automatic genome annotation. However, a combination of both de novo and reference-based strategies gave the best result, and allowed us to assemble fragmented transcripts.

Recent trends in the incidence of anxiety and prescription of anxiolytics and hypnotics in children and young people: An e-cohort study.

BACKGROUND: Little is known regarding the recognition of anxiety in children and young people (CYP) in primary care. This study examined trends in the presentation, recognition and recording of anxiety and of anxiolytic and hypnotic prescriptions for CYP in primary care. METHOD: A population-based retrospective electronic cohort of individuals aged 6-18 years between 2003 and 2011 within the Secure Anonymised Information Linkage (SAIL) Databank primary care database was created. Incidence rates were calculated using person years at risk (PYAR) as a denominator accounting for deprivation, age and gender. RESULTS: We identified a cohort of 311,343 registered individuals providing a total of 1,546,489 person years of follow up. The incidence of anxiety symptoms more than tripled over the study period (Incidence Rate Ratio (IRR)=3.55, 95% CI 2.65-4.77) whilst that of diagnosis has remained stable. Anxiolytic/hypnotic prescriptions for the cohort as a whole did not change significantly over time; however there was a significant increase in anxiolytic prescriptions for the 15-18 year age group (IRR 1.62, 95% CI 1.30-2.02). LIMITATIONS: There was a lack of reliable information regarding other interventions available or received at a primary, secondary or tertiary level such as psychological treatments. CONCLUSIONS: There appears to be a preference over time for the recording of general symptoms over diagnosis for anxiety in CYP. The increase in anxiolytic prescriptions for 15-18 year olds is discrepant with current prescribing guidelines. Specific guidance is required for the assessment and management of CYP presenting with anxiety to primary care, particularly older adolescents.

De novo transcriptome assembly for a non-model species, the blood-sucking bug Triatoma brasiliensis, a vector of Chagas disease.

High throughput sequencing (HTS) provides new research opportunities for work on non-model organisms, such as differential expression studies between populations exposed to different environmental conditions. However, such transcriptomic studies first require the production of a reference assembly. The choice of sampling procedure, sequencing strategy and assembly workflow is crucial. To develop a reliable reference transcriptome for Triatoma brasiliensis, the major Chagas disease vector in Northeastern Brazil, different de novo assembly protocols were generated using various datasets and software. Both 454 and Illumina sequencing technologies were applied on RNA extracted from antennae and mouthparts from single or pooled individuals. The 454 library yielded 278 Mb. Fifteen Illumina libraries were constructed and yielded nearly 360 million RNA-seq single reads and 46 million RNA-seq paired-end reads for nearly 45 Gb. For the 454 reads, we used three assemblers, Newbler, CAP3 and/or MIRA and for the Illumina reads, the Trinity assembler. Ten assembly workflows were compared using these programs separately or in combination. To compare the assemblies obtained, quantitative and qualitative criteria were used, including contig length, N50, contig number and the percentage of chimeric contigs. Completeness of the assemblies was estimated using the CEGMA pipeline. The best assembly (57,657 contigs, completeness of 80 %, <1 % chimeric contigs) was a hybrid assembly leading to recommend the use of (1) a single individual with large representation of biological tissues, (2) merging both long reads and short paired-end Illumina reads, (3) several assemblers in order to combine the specific advantages of each.

Controlled formation and reflection of a bright solitary matter-wave.

Bright solitons are non-dispersive wave solutions, arising in a diverse range of nonlinear, one-dimensional systems, including atomic Bose-Einstein condensates with attractive interactions. In reality, cold-atom experiments can only approach the idealized one-dimensional limit necessary for the realization of true solitons. Nevertheless, it remains possible to create bright solitary waves, the three-dimensional analogue of solitons, which maintain many of the key properties of their one-dimensional counterparts. Such solitary waves offer many potential applications and provide a rich testing ground for theoretical treatments of many-body quantum systems. Here we report the controlled formation of a bright solitary matter-wave from a Bose-Einstein condensate of (85)Rb, which is observed to propagate over a distance of ∼1.1 mm in 150 ms with no observable dispersion. We demonstrate the reflection of a solitary wave from a repulsive Gaussian barrier and contrast this to the case of a repulsive condensate, in both cases finding excellent agreement with theoretical simulations using the three-dimensional Gross-Pitaevskii equation.

γδT cells elicited by CMV reactivation after allo-SCT cross-recognize CMV and leukemia.

Human cytomegalovirus (CMV) infections and relapse of disease remain major problems after allogeneic stem cell transplantation (allo-SCT), in particular in combination with CMV-negative donors or cordblood transplantations. Recent data suggest a paradoxical association between CMV reactivation after allo-SCT and reduced leukemic relapse. Given the potential of Vδ2-negative γδT cells to recognize CMV-infected cells and tumor cells, the molecular biology of distinct γδT-cell subsets expanding during CMV reactivation after allo-SCT was investigated. Vδ2(neg) γδT-cell expansions after CMV reactivation were observed not only with conventional but also cordblood donors. Expanded γδT cells were capable of recognizing both CMV-infected cells and primary leukemic blasts. CMV and leukemia reactivity were restricted to the same clonal population, whereas other Vδ2(neg) T cells interact with dendritic cells (DCs). Cloned Vδ1 T-cell receptors (TCRs) mediated leukemia reactivity and DC interactions, but surprisingly not CMV reactivity. Interestingly, CD8αα expression appeared to be a signature of γδT cells after CMV exposure. However, functionally, CD8αα was primarily important in combination with selected leukemia-reactive Vδ1 TCRs, demonstrating for the first time a co-stimulatory role of CD8αα for distinct γδTCRs. Based on these observations, we advocate the exploration of adoptive transfer of unmodified Vδ2(neg) γδT cells after allo-SCT to tackle CMV reactivation and residual leukemic blasts, as well as application of leukemia-reactive Vδ1 TCR-engineered T cells as alternative therapeutic tools.

Magnetic transport apparatus for the production of ultracold atomic gases in the vicinity of a dielectric surface.

We present an apparatus designed for studies of atom-surface interactions using quantum degenerate gases of (85)Rb and (87)Rb in the vicinity of a room temperature dielectric surface. The surface to be investigated is a super-polished face of a glass Dove prism mounted in a glass cell under ultra-high vacuum. To maintain excellent optical access to the region surrounding the surface, magnetic transport is used to deliver ultracold atoms from a separate vacuum chamber housing the magneto-optical trap (MOT). We present a detailed description of the vacuum apparatus highlighting the novel design features; a low profile MOT chamber and the inclusion of an obstacle in the transport path. We report the characterization and optimization of the magnetic transport around the obstacle, achieving transport efficiencies of 70% with negligible heating. Finally, we demonstrate the loading of a hybrid optical-magnetic trap with (87)Rb and the creation of Bose-Einstein condensates via forced evaporative cooling close to the dielectric surface.

[A clinical case of spontaneous involution of systemic cat scratch disease]. / Involution spontanée d'une forme systémique de maladie par griffade de chat: à propos d'un cas.

Typical Cat-scratch disease (CSD) manifests as regional lymphadenopathy following cat scratch and sometimes associated with mild fever. There is a lot of atypical manifestations and some of those have systemic involvement. Hepatosplenic CSD is a systemic presentation associating fever of unknown origin with nodules in the liver and/or the spleen. Ultrasound abdominal examination shows nodules (3-30 mm) in the spleen and/or in the liver. Diagnostic is based on serology for B henselae (always IgG + and sometimes IgM +), or polymerase chain reaction (PCR) on the liver to test for the presence of B henselae. Hepatosplenic CSD is rare and therefore underdiagnosed. There is no consensus about the treatment but most of the authors suggest to treat with rifampicine. We report a case of a 4-years-old girl presenting with fever of unknown origin (FUO), high inflammatory markers with normal leukocytosis and hepatosplenic nodules. The diagnosis of CSD was made retrospectively. Evolution was favourable even though no specific antibiotic treatment for Bartonella henselae was administrated.

Sedación, seguridad y utilidad de la endoscopia digestiva alta en pediatría / Sedation, safety and usefulness of upper gastrointestinal endoscopy in pediatrics

Introduction: Upper gastrointestinal studies are routine diagnostic and therapeutic procedures. In pediatrics, however, they are limited by the need for sedation and monitoring. Objectives: Po evaluate sedation, indication, and parent perception of these exams. Patients and Methods: A prospective study of 190 pediatric upper gastrointestinal endoscopies was undertaken. Demographic data, as well as information regarding the exam was obtained. Results: Patients' average age was 8.5 +/- 4.2, mostly referred by pediatricians (60 percent) Main reason for referral was recurrent abdominal pain (29.8 percent). Patients were classified according to ASA criteria (93 percent ASA I and II). Most patients required two or more medications for optimal sedation, with satisfactory procedure in over 90 percent. Over 75.5 percent had complete amnesia, 42.7 percent presented minor discomfort after the procedure. Findings of these procedures included 61 percent of normal exams, 13.9 percent esophagitis. More findings were there result of analyses according to children's weight (over or under 14 kg), age, ASA, reason for referral, nurse's evaluation of sedation. Conclusion: Ambulatory endoscopio procedures can be performed safely in children, with moderate sedation. Requirements are adequate monitoring, and deep knowledge of resuscitation techniques.

Introducción: El estudio endoscópico alto es un procedimiento diagnóstico y terapéutico considerado de rutina, pero su realización en pediatría se encuentra limitada dada la necesidad de sedación y monitoreo adecuados. Objetivos: Evaluar la sedación, indicación y percepción de los padres del examen. Materiales y Métodos: Estudio prospectivo de 190 niños sometidos a endoscopia digestiva alta. Se obtuvieron datos bio-demográficos, tipo de sedación y resultados del examen. Resultados: La edad fue 8,5 + 4,2 años, la mayoría referidos por pediatra (60 por ciento). La principal indicación del estudio fue el dolor abdominal recurrente (29,8 por ciento). Los pacientes fueron clasificados de acuerdo al ASA (93 por ciento ASA I y II). En la mayoría se requirió de 2 ó más drogas para lograr sedación óptima. La calidad del procedimiento fue satisfactoria en más del 90 por ciento. Un 75,5 por ciento presentaron amnesia completa y un 42,7 por ciento molestias leves posterior al procedimiento. Entre los hallazgos destacaron signos de esofagitis en el 13,9 por ciento, observándose un 61 por ciento de los exámenes normales. Al analizar los pacientes por peso (mayores y menores de 14 kg), se encontraron diferencias en edad (p < 0,00001), ASA (p = 0,001), indicación de endoscopia (p = 0,001) y evaluación de la sedación por enfermera (p = 0,038). Conclusión: Procedimientos endoscópicos en niños pueden realizarse de manera segura en forma ambulatoria mediante sedación moderada. Una adecuada monitorización y conocimiento de técnicas de reanimación son básicos al momento de realizar dichos procedimientos.

A dynamic model of nutrient uptake by root hairs.

Root hairs are known to be important in the uptake of sparingly soluble nutrients by plants, but quantitative understanding of their role in this is weak. This limits, for example, the breeding of more nutrient-efficient crop genotypes. We developed a mathematical model of nutrient transport and uptake in the root hair zone of single roots growing in soil or solution culture. Accounting for root hair geometry explicitly, we derived effective equations for the cumulative effect of root hair surfaces on uptake using the method of homogenization. Analysis of the model shows that, depending on the morphological and physiological properties of the root hairs, one of three different effective models applies. They describe situations where: (1) a concentration gradient dynamically develops within the root hair zone; (2) the effect of root hair uptake is negligibly small; or (3) phosphate in the root hair zone is taken up instantaneously. Furthermore, we show that the influence of root hairs on rates of phosphate uptake is one order of magnitude greater in soil than solution culture. The model provides a basis for quantifying the importance of root hair morphological and physiological properties in overall uptake, in order to design and interpret experiments in different circumstances.

[Prospective evaluation of the safety and tolerance of colonoscopy in children]. / Evaluación prospectiva de la seguridad y tolerancia de los procedimientos colonoscópicos en pacientes pediátricos.

BACKGROUND: Colonoscopy is a well established diagnostic and therapeutic procedure in pediatrics. AIM: To evaluate colon preparation alternatives for colonoscopy or sigmoidoscopy, type of sedation, clinical indications and findings. PATIENTS AND METHODS: Prospective study of 123 children referred for colonoscopy. Demographic data, type of colon preparation, sedation, type of endoscope and endoscopic results were obtained. The following day, a phone interview was carried out inquiring about duration, quality and adverse effects of the sedation and procedure. RESULTS: Seventy one boys (58%) and 52 girls (42%) with a mean age of 6.7+/-4.4 years, were recruited. The main indication was lower gastrointestinal bleeding (71%). The different colon preparations produced elimination of clear liquid stools in 50%, non transparent liquid in 23%, semi liquid in 22% and solid in 6% of the patients. Most common side effects were abdominal distension (20%) and nausea (16.8%). The most commonly used drugs were midazolam (76%) and demerol (43%). The average duration of the procedure was 18.3 minutes (range: 4-50). The most common findings were rectal polyps (18.7%) and hemorrhagic colitis (14.6%). In 77% of cases, the sedation was considered very good or good. Colon visualization was described as very good (51%) or good (36%). Seventy three percent of children had complete amnesia. The most common adverse effect was vomiting (7.5%). CONCLUSION: Lower endoscopies are feasible procedures to carry out in children, in an ambulatory basis, with intravenous sedation and minimum adverse effects.

Influence of genetic and environmental factors on the immunogenicity of Hib vaccine in Gambian twins.

The differences in incidence rates of Haemophilus influenzae type b disease and the variation in Hib conjugate vaccine efficacy achieved among different ethnic groups suggest genetic influences on the immune response to Hib vaccine. The serum anti-PRP antibody concentration of 43 monozygotic (MZ) and 147 dizygotic (DZ) twin pairs in the Gambia was measured using a standardised Hib ELISA. Intrapair correlations for MZ and DZ twin pairs were compared and heritability in antibody responses to Hib conjugate vaccine was estimated to be 51% (95% CI: 32-66%), indicating a significant genetic contribution in the response. We conclude that genetic factors may be involved in the variation in immune response to Hib vaccine observed in different populations and may contribute to cases of vaccine failure.

AXR4 is required for localization of the auxin influx facilitator AUX1.

The AUX1 and PIN auxin influx and efflux facilitators are key regulators of root growth and development. For root gravitropism to occur, AUX1 and PIN2 must transport auxin via the lateral root cap to elongating epidermal cells. Genetic studies suggest that AXR4 functions in the same pathway as AUX1. Here we show that AXR4 is a previously unidentified accessory protein of the endoplasmic reticulum (ER) that regulates localization of AUX1 but not of PIN proteins. Loss of AXR4 resulted in abnormal accumulation of AUX1 in the ER of epidermal cells, indicating that the axr4 agravitropic phenotype is caused by defective AUX1 trafficking in the root epidermis.

Evaluación prospectiva de la seguridad y tolerancia de los procedimientos colonoscópicos en pacientes pediátricos / Prospective evaluation of safety and tolerance of colonoscopy in children

Background: Colonoscopy is a well established diagnostic and therapeutic procedure in pediatrics. Aim: To evaluate colon preparation alternatives for colonoscopy or sigmoidoscopy, type of sedation, clinical indications and findings. Patients and methods: Prospective study of 123 children referred for colonoscopy. Demographic data, type of colon preparation, sedation, type of endoscope and endoscopic results were obtained. The following day, a phone interview was carried out inquiring about duration, quality and adverse effects of the sedation and procedure. Results: Seventy one boys (58%) and 52 girls (42%) with a mean age of 6.7±4.4 years, were recruited. The main indication was lower gastrointestinal bleeding (71%). The different colon preparations produced elimination of clear liquid stools in 50%, non transparent liquid in 23%, semi liquid in 22% and solid in 6% of the patients. Most common side effects were abdominal distension (20%) and nausea (16.8%). The most commonly used drugs were midazolam (76%) and demerol (43%). The average duration of the procedure was 18.3 minutes (range: 4-50). The most common findings were rectal polyps (18.7%) and hemorrhagic colitis (14.6%). In 77% of cases, the sedation was considered very good or good. Colon visualization was described as very good (51%) or good (36%). Seventy three percent of children had complete amnesia. The most common adverse effect was vomiting (7.5%). Conclusion: Lower endoscopies are feasible procedures to carry out in children, in an ambulatory basis, with intravenous sedation and minimum adverse effects.

Implementation of a tight glycaemic control protocol using a web-based insulin dose calculator.

We describe the implementation of a glucose control protocol supported by a web-based insulin dose calculator in a 16-bedded intensive care unit. The protocol was introduced and then modified after 15 months' use. Glucose concentrations were retrospectively reviewed and compared for the 9-month period before introduction of the protocol (288 patients), for 15 months after its introduction (502 patients) and for a further 5 months after its modification to increase insulin dose (101 patients). The mean (SD) blood glucose concentrations decreased from 7.3 (1.8) mmol.l(-1) to 6.6 (1.6) mmol.l(-1) and then to 6.2 (1.3) mmol.l(-1). The proportion of values < 8.0 mmol.l(-1) increased from 69% to 81% and then to 89%. Blood glucose concentrations were increased by the use of intravenous nutrition and by vasoactive drugs but not by the administration of propofol. The odds ratio [95% CI] for death for glucose values > 8.0 mmol.l(-1) was 2.10 [1.19-3.73] compared to values < 6.1 mmol.l(-1). However, patient mortality remained constant during the study. Glycaemic control was improved outside a research setting using a protocol supported by a web-based insulin dose calculator.

T cell-mediated immune responses in human newborns: ready to learn?

Infections with intracellular pathogens are often more severe or more prolonged in young infants suggesting that T cell-mediated immune responses are different in early life. Whereas neonatal immune responses have been quite extensively studied in murine models, studies of T cell-mediated immunity in human newborns and infants are scarce. Qualitative and quantitative differences when compared with adult immune responses have been observed but on the other hand mature responses to certain vaccines and infectious pathogens were demonstrated during the postnatal period and even during foetal life. Herein, we review the evidence suggesting that under appropriate conditions of stimulation, protective T cell-mediated immune responses could be induced by vaccines in early life.

Mature dendritic cells differentiated in the presence of interferon-beta and interleukin-3 prime functional antigen-specific CD8 T cells.

Dendritic cell (DC)-based immunization represents a promising approach for the immunotherapy of cancer. The optimal conditions required to prepare DCs remain to be defined. Monocytes incubated in the presence of interferon (IFN)-beta and interleukin (IL)-3 give rise to a distinct type of DCs (IFN-beta/IL-3 DCs) that are particularly efficient at eliciting IFN-gamma and IL-5 production by allogeneic helper T cells. We assessed the capacity of this new type of DCs to prime antigen-specific naive CD8(+) T cells and compared them to the conventional DCs differentiated in the presence of granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-4 (GM-CSF/IL-4 DCs). We demonstrate that IFN-beta/IL-3 DCs matured by TLR3 or CD40 ligation efficiently prime Melan-A(26-35)-specific CD8(+) T cells in vitro, at a similar level as GM-CSF/IL-4 DCs. Activated antigen-specific CD8(+) T cells produced IFN-gamma and displayed potent cytotoxic activity against peptide-pulsed target cells. Expansion of CD8(+) T cell numbers was generally higher following priming with CD40-L than with polyinosinic-polycytidylic acid (poly I:C) matured DCs. Cytolytic activity was induced by both maturing agents. These data indicate that IFN-beta/IL-3 DCs represent a promising cell population for the immunotherapy of cancer.

The toll-like receptor 4 Asp299Gly variant: no influence on LPS responsiveness or susceptibility to pulmonary tuberculosis in The Gambia.

SETTING: Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide. Studies in a murine model of pulmonary TB have identified a role for Toll-like receptor 4 (TLR4) in the development of chronic lung infection with Mycobacterium tuberculosis. The Asp299Gly polymorphism in the human TLR4 gene is associated with in vivo hyporesponsiveness to lipopolysaccharide (LPS) in Caucasians. OBJECTIVE: To determine whether TLR4 Asp299Gly influences LPS responses or susceptibility to pulmonary TB in humans in a Gambian population sample. DESIGN: We compared whole blood monokine responses to LPS in 245 healthy blood donors stratified by TLR4 Asp299Gly genotype to assess whether this polymorphism was functional in this population. A case-control study of 640 subjects was conducted to investigate whether TLR4 Asp299Gly was associated with TB. RESULTS: LPS-induced tumour necrosis factor, interleukin-1 beta and interleukin-10 production was not influenced by TLR4 Asp299Gly genotype. There was no association between TLR4 Asp299Gly and TB. CONCLUSION: Our data suggest that TLR4 Asp299Gly has no influence on monocyte LPS responses or susceptibility to TB in Gambians and could be an ancient neutral polymorphism.