Lymphoid progenitors in normal mouse lymph nodes develop into NK cells and T cells in vitro and in vivo

We have identified a population of normal mouse LN cells, termed LN lymphoid progenitor (LNLP), resembling common lymphoid progenitor (CLP) in the bone marrow. LNLPs lack lineage markers and express CD127, low levels of CD117 (c-Kit), and Sca-1, but lack fms-related tyrosine kinase 3. They efficiently differentiate in vitro into natural killer (NK) cells and T cells, but not mature B cells. LNLPs injected into nonirradiated lymphopenic mice that have no LN develop into mostly splenic T cells with low numbers of NK cells and B cells. When injected into irradiated mice, they generate NK cells and T cells, but not B cells, in the LN. By contrast, bone marrow CLPs develop into mostly B cells with very small numbers of T and NK cells in recipients' spleen and LN. LNLPs have NK and T-cell potentials, but little B-cell potential, and they can develop into NK cells within the LN of normal mice, but their contribution to the T-cell lineage is unknown.     

Outcome of Poor-Grade Subarachnoid Hemorrhage as Determined by Biomarkers of Glucose Cerebral Metabolism

Purpose

The aim of this study was to determine if the measurement of blood biomarkers of glucose cerebral metabolism, performed with retrograde jugular catheter, could predict the outcome of poor-grade aneurysmal subarachnoid hemorrhage (aSAH) patients.

Methods

This study was conducted in 68 poor-grade aSAH patients. A total of 4,024 blood samples obtained from jugular and radial catheters were analyzed for glucose, lactate, and oxygen content every 8 h for 10 ± 0.5 days. Metabolic ratio (MR) and lactate–oxygen index (LOI) were obtained by ratios using arterio-jugular differences. Functional outcome was evaluated at 12 months with the Glasgow Outcome Scale.

Results

Outcome was unfavorable in 40 patients. In this group of patients, the MR was significantly lower (p < 0.0001) and the LOI was significantly higher (p = 0.0001) than in the group with favorable outcome. The MR cutoff value, below which the patients are likely to have an unfavorable outcome, was determined to be 3.35. More interestingly, the data obtained in this study demonstrated that the patients achieving an unfavorable outcome were distinguished from those with a favorable outcome by having at least three events of MR inferior to 3.35 (sensitivity = 90 %, specificity = 82.1 %). Moreover, in patients who developed cerebral vasospasm, we observed a significant decrease in the MR.

Conclusion

Our data provide additional support to the view that the MR is a reliable marker for predicting the outcome of poor-grade aSAH patients. Prospective studies are needed to confirm its value in multimodal monitoring.     

Age-related differences in the prevalence and correlates of anxiety in youth with autism spectrum disorders

Age-related differences in the prevalence and correlates of anxiety were cross-sectionally examined in 1316 children and adolescents with autism spectrum disorder (ASD) who presented for initial evaluation at 14 outpatient autism centers around the country and in Canada. The prevalence of clinical and subclinical anxiety as well as the correlates of anxiety were examined in three age groups of children: preschool, school age and adolescents. Findings showed that the prevalence of anxiety in each age group exceeded the prevalence of anxiety in the general population. Adolescents and school age children had the highest prevalence of clinical (40%) and subclinical anxiety (26%), respectively. Higher IQ and less ASD severity were each weakly correlated with more anxiety in preschool and school age children. Affective symptoms were strongly associated with anxiety in each age group. Age specific psychiatric comorbidities were also present. Anxiety was associated with attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms in the preschool group, ODD and somatic symptoms in the school age children, and ADHD symptoms in adolescents. These data underscore the need for prevention and treatment of anxiety as well as research examining the characteristics of anxiety in children with ASD using a developmental framework.     

Cell micropatterning on superhydrophobic diamond nanowires

Cell micropatterning was achieved in a spatially controlled manner based on heterogeneously wetted superhydrophilic/superhydrophobic diamond nanowire (NW) surfaces. Diamond NWs were synthesized on boron-doped diamond substrates using reactive ion etching and functionalized with octadecyltrichlorosilane to achieve superhydrophobicity. Superhydrophilic motifs of 400 × 400 μm² and 10 × 10 μm² single cell-sized motifs, surrounded by superhydrophobic regions, were then generated by selectively exposing the substrates to UV light. This design allowed successful patterning of single HeLa and MCF-10A cells within the superhydrophilic regions without additional surface modification. To add a further level of complexity, micropatterned co-cultures were obtained using bovine serum albumin to promote cell adhesion. This method is simple and does not require any complicated processing steps such as mask deposition or template removal. Potential applications are in the development of cell-based biological assays in well-controlled and biologically relevant environments.     

Systemic sclerosis at the crossroad of polyautoimmunity

Objectives

Several epidemiological studies have revealed the co-occurrence of other autoimmune diseases (AIDs) within patients with systemic sclerosis (SSc). However, some of these studies were based on small cohorts and wide ranges of prevalence have been reported. Therefore to overcome these limitations of individual studies, we sought to perform a meta-analysis to determine the accurate prevalence of polyautoimmunity in SSc.

Methods

We performed a systematic review and a meta-analysis of literature in MEDLINE and Embase databases from January 1960 to March 2013. All cohort studies reporting on prevalence of other AIDs known to be associated with SSc were analyzed. Prevalence of polyautoimmunity and of each AID were then calculated.

Results

Ten studies reporting polyautoimmunity were identified corresponding to a total of 6102 SSc patients. Overall 1432 patients with at least one AID were identified corresponding to a weighted prevalence of polyautoimmunity equal to 25.7% CI 95% [20.1%–31.6%]. Overall 208/5139 SSc-patients had at least two additional AIDs resulting in a weighted prevalence of 3.9% [3.3%–4.4%]. The most prevalent associated AIDs were autoimmune thyroid disease (10.4%) followed by Sjögren's syndrome (7.7%) and dermatopolymyositis/polymyositis (5.6%).

Conclusion

Our results confirm that SSc polyautoimmunity is a frequent condition in SSc affecting a quarter of SSc-patients. The impact on the phenotype and also on the management and therapy will need to be addressed now in further works.     

Rating data are underrated: Validity of US expectancy in human fear conditioning

Background and objectivesHuman fear conditioning is widely regarded as one of the prime paradigms for the study of fear and anxiety disorders. We provide an evaluation of a commonly used subjective measure in the human fear conditioning paradigm, namely the US-expectancy measurement.MethodsWe assess the validity of US-expectancy with respect to conditions of pathological fear and anxiety using four established criteria for scrutiny of a laboratory test or model (i.e., face validity, diagnostic validity, predictive validity, construct validity).ResultsArguably, there is sufficient evidence for the face validity, diagnostic validity, predictive validity and construct validity of the US-expectancy measure.LimitationsPresumed limitations of the US-expectancy measure, including its susceptibility to experimental demand and memory bias, are discussed.ConclusionsThe US-expectancy measure is a valuable measurement method that can be effectively used in research that aims to enhance our understanding of fear and anxiety disorders.     

Incomplete thymic involution in systemic sclerosis and rheumatoid arthritis

ObjectiveThe thymus plays a crucial role in immune system homeostasis. Thymic abnormalities have been reported in many autoimmune diseases, but data for systemic sclerosis (SSc) and rheumatoid arthritis (RA) are sparse. The aim of this study was to evaluate the prevalence and correlates of radiological incomplete involution of the thymus in SSc and RA patients, and in a non-autoimmune group of controls.MethodsAll patients were at least 40 years old: 96 SSc patients (median age 59 years, 80% women) and 65 RA patients (median age 57 years, 88% women) were compared with 32 control individuals (median age 63 years, 62% women). Pulmonary CT-scans performed for lung assessment were available for all individuals. For the purpose of our study, complete involution of the thymus was defined as the absence of a residual thymus or a gland thickness, corresponding to the short axis on the axial slice, of less than 7 mm. We defined incomplete involution of the thymus as a residual thymic tissue more than 7 mm thick.ResultsThe frequency of incomplete thymus involution was significantly higher in SSc and RA patients (respectively 15 and 14%) than in the control group (0%; P < 0.05). Incomplete thymus involution was associated with pulmonary restrictive syndrome in SSc patients, and with biotherapy and an absence of antinuclear antibodies in RA patients.ConclusionOur findings show that two autoimmune diseases, SSc and RA, are associated with incomplete thymus involution.