Protection against renal ischemia reperfusion injury by CD44 disruption

Inflammation contributes to renal ischemia reperfusion (I/R) injury, potentially causing renal dysfunction. The inflammatory infiltrate mainly consists of neutrophils, which are deleterious for the renal tissue. Because CD44 is expressed by neutrophils and is rapidly upregulated by capillary endothelial cells after I/R injury, it was hypothesized that CD44 might play an important role in the development of I/R injury. This study showed that rapid CD44 upregulation on renal capillary endothelial cells mediates neutrophil recruitment to the postischemic tissue. Hence, CD44 deficiency led to decreased influx of neutrophils regardless of comparable levels in chemotactic factors expressed in the kidney. The reduced influx of neutrophils was associated with preserved renal function and morphology. Adoptive transfer experiments of labeled neutrophils revealed that endothelial CD44 rather than neutrophil CD44 mediates neutrophil migration. Activation of neutrophils increased cell-surface expression of hyaluronic acid (HA). Altogether, a novel mechanism in the recruitment of neutrophils that involves interaction of endothelial CD44 and neutrophil HA was found. Either blocking endothelial CD44 or removal of neutrophil HA decreased rolling and adhesion of neutrophils. Administration of anti-CD44 to mice reduced the influx of neutrophils into the postischemic tissue, associated with renal function preservation. Therefore, anti-CD44-based therapies may contribute to prevent or reduce renal I/R injury.     

Echocardiographic and physiological performance characteristics of triathletes

BACKGROUND: Endurance sports require a variety of physiological adaptations. OBJECTIVE: To examine the structural and functional heart adaptations and their hemodynamic implications in triathletes. PATIENTS AND METHODS: A group of 52 male triathletes was compared with a control group of 22 healthy male nonathletes. All of the subjects were given a bidimensional cardiac Doppler echocardiography examination and administered maximal exercise tests with lactic acid determinations, on a bicycle ergometer and a treadmill. Results: The triathletes showed clear structural and functional heart adaptations with concentric and eccentric hypertrophy with evidence of a supernormal diastolic left ventricular function. The performance capacity of the triathlete differed significantly from that of the control subject. The maximal oxygen consumption and the maximal oxygen consumption per kilogram on the bicycle and on the treadmill were significantly higher in the triathletes. The same results and conclusions were obtained concerning aerobic capacities and power outputs on a bicycle ergometer at blood lactate concentrations of 2, 3 and 4 mmol/L. The heart rate 6 min after the start of exercise is a significant parameter for the evaluation of the physical condition of a subject. The lactic acid determinations during the recovery phase enabled important conclusions to be drawn about the physical condition of the subjects. CONCLUSIONS: The triathletes showed evidence of important structural and functional heart adaptations with hemodynamic implications. The maximal performing capacities, on the bicycle as well as on the treadmill, were distinctly higher in the triathlete group. Furthermore, the aerobic and anaerobic capacities were significantly different between the groups. In this context, the heart rate 6 min after the start of exercise and the blood lactate concentrations 20 min after the maximal exercise test were significant parameters. It was not always the best triathletes who had the most significant structural cardiac adaptations. Thus, the 'athletic heart' syndrome as a physiological entity is questioned.     

The information score as a measure of oral discourse comprehension in the early school years

Abstract

Purpose: Oral discourse comprehension is a fundamental skill that is predictive of future reading comprehension. The ability to identify important semantic propositions, in a narrative text, and their attachment to a mental model is an essential component of discourse comprehension. This study aimed to pilot a measure of free-recall in a narrative retell across three age groups to explore development. A secondary aim compared measures of free-recall and cued-recall.

Method: One hundred and thirty-two (132) typically developing children aged 4–7 years provided a retell of the Squirrel Story narrative and completed the Narrative Comprehension Assessment (NCA). The Squirrel Story Information Score (SSIS) was used as a novel measure of free-recall calculated from the narrative retells. The NCA, which involves literal and inferential comprehension questions, was used as a measure of cued-recall. Scoring reliability was calculated to ensure test–retest validity.

Result: Correlation analysis found excellent reliability of the SSIS measure. The difference between 4 and 5 year olds, and 5 and 6 year olds, was significant, with a large effect size. The difference between the 5 and 6 year olds was not significant. A large positive correlation was found between the measures of SSIS and NCA.

Conclusion: The measure of SSIS proved sensitive to developmental progression, with a positive relationship found between the measures of free-recall and cued-recall. Variability between the measures highlights the need to consider both measures to ensure an accurate representation of discourse comprehension skills.     

Use of risk stratification to target therapies in patients with recent onset arthritis; design of a prospective randomized multicenter controlled trial

Background  

Early and intensive treatment is important to inducing remission and preventing joint damage in patients with rheumatoid arthritis. While intensive combination therapy (Disease Modifying Anti-rheumatic Drugs and/or biologicals) is the most effective, rheumatologists in daily clinical practice prefer to start with monotherapy methotrexate and bridging corticosteroids. Intensive treatment should be started as soon as the first symptoms manifest, but at this early stage, ACR criteria may not be fulfilled, and there is a danger of over-treatment. We will therefore determine which induction therapy is most effective in the very early stage of persistent arthritis. To overcome over-treatment and under-treatment, the intensity of induction therapy will be based on a prediction model that predicts patients' propensity for persistent arthritis.     

Oral literal and inferential narrative comprehension in young typically developing children and children with developmental language disorder

Abstract

Purpose: The Squirrel Story Narrative Comprehension Assessment (NCA) was used to investigate the literal and inferential comprehension skills of young typically developing (TD) children aged between 4 and 6 years and to compare the performance of 5-year-old TD children and those with developmental language disorder (DLD).

Method: A total of 132 typically developing children across three age groups between 4 to 6 years (4;0–4;11, 5;0–5;11, 6;0–6;11, years;months), and 94 children with DLD aged 5 years, were assessed using the NCA.

Result: There was a significant increase in both literal and inferential scores for TD children from 4 to 6 years. The TD children aged 4;0 to 4;11 scored significantly lower than the two older age groups for both literal and inferential comprehension, while there was no significant difference between the 5;0 to 5;11 and 6;0 to 6;11 TD groups. The 5;0 to 5;11 TD group scored significantly higher than the age-matched DLD group for literal and inferential comprehension.

Conclusion: The findings indicate that the Squirrel Story NCA is a clinically useful task which is sensitive to developmental improvement in literal and inferential comprehension in young typically developing children and confirm previous research findings of poor narrative comprehension in children with DLD.     

Renal-associated TLR2 mediates ischemia/reperfusion injury in the kidney

TLRs are conserved pattern recognition receptors that detect motifs of pathogens and host material released during injury. For unknown reasons, renal TLR2 mRNA is mainly expressed by tubular cells and is enhanced upon renal ischemia/reperfusion (I/R) injury. We evaluated the role of TLR2 in I/R injury using TLR2-/- and TLR2+/+ mice, TLR2 antisense oligonucleotides, and chimeric mice deficient in leukocyte or renal TLR2. Tubular cells needed TLR2 to produce significant cytokine and chemokine amounts upon ischemia in vitro. TLR2 played a proinflammatory and detrimental role in vivo after I/R injury, as reflected by a reduction in the amount of local cytokines and chemokines, leukocytes, and the level of renal injury and dysfunction in TLR2-/- mice compared with controls. Analysis of chimeric mice suggested that TLR2 expressed on renal parenchyma plays a crucial role in the induction of inflammation and injury. TLR2-antisense treatment protected mice from renal dysfunction, neutrophil influx, and tubular apoptosis after I/R injury compared with nonsense treatment. In summary, we identified renal-associated TLR2 as an important initiator of inflammatory responses leading to renal injury and dysfunction in I/R injury. These data imply that TLR2 blockade could provide a basis for therapeutic strategies to treat or prevent renal ischemic injury.