Concurrent validity of a touchscreen application to detect early cognitive delay.

OBJECTIVE: To explore the ability of an interactive screening tool to identify cognitive delay in children aged 18 to 24 months. DESIGN: Children were assessed using the Bayley Scale of Infant and Toddler Development-third edition (BSID-III) and a touchscreen measure of problem-solving (Babyscreen V.1.5). We examined the internal consistency and concurrent validity between the two measures. A BSID-III cognitive composite score (BSID-IIIcc) ≤1 SD below population mean was used to indicate a low average cognitive ability. RESULTS: 87 children with a mean (SD) age of 20.4 (1.3) months who experienced complications at delivery (n=53) and healthy age-matched controls (n=34) were included in the study. A moderate positive correlation between the BSID-IIIcc and the total number of tasks completed on the Babyscreen suggested reasonable concurrent validity (r=0.414, p<0.001). Children with a BSID-IIIcc ≤90 had lower median (IQR) Babyscreen score (7 (6, 8.5) vs 11 (8.5, 13); p=0.003) and a lower median (IQR) age-adjusted z-score (BST z-score) for number of items completed compared with those >90 (-1.08 (-1.5 to -0.46) vs 0.31 (-0.46 to 0.76); p=0.001). The area under the receiver operating characteristic curve for the prediction of a low normal BSID-IIIcc was 0.787 (CI 0.64 to 0.93). A BST z-score of <-0.44 yielded 82.4% sensitivity and 71.4% specificity in identifying children with cognitive delay. CONCLUSIONS: A touchscreen-based application has concurrent validity with the BSID-IIIcc and could be used to screen for cognitive delay at 18-24 months of age.

The flagellin of candidate live biotherapeutic Enterococcus gallinarum MRx0518 is a potent immunostimulant.

Many links between gut microbiota and disease development have been established in recent years, with particular bacterial strains emerging as potential therapeutics rather than causative agents. In this study we describe the immunostimulatory properties of Enterococcus gallinarum MRx0518, a candidate live biotherapeutic with proven anti-tumorigenic efficacy. Here we demonstrate that strain MRx0518 elicits a strong pro-inflammatory response in key components of the innate immune system but also in intestinal epithelial cells. Using a flagellin knock-out derivative and purified recombinant protein, MRx0518 flagellin was shown to be a TLR5 and NF-κB activator in reporter cells and an inducer of IL-8 production by HT29-MTX cells. E. gallinarum flagellin proteins display a high level of sequence diversity and the flagellin produced by MRx0518 was shown to be more potent than flagellin from E. gallinarum DSM100110. Collectively, these data infer that flagellin may play a role in the therapeutic properties of E. gallinarum MRx0518.

Motor dexterity and strength depend upon integrity of the attention-control system.

Attention control (or executive control) is a higher cognitive function involved in response selection and inhibition, through close interactions with the motor system. Here, we tested whether influences of attention control are also seen on lower level motor functions of dexterity and strength-by examining relationships between attention control and motor performance in healthy-aged and hemiparetic-stroke subjects (n = 93 and 167, respectively). Subjects undertook simple-tracking, precision-hold, and maximum force-generation tasks, with each hand. Performance across all tasks correlated strongly with attention control (measured as distractor resistance), independently of factors such as baseline performance, hand use, lesion size, mood, fatigue, or whether distraction was tested during motor or nonmotor cognitive tasks. Critically, asymmetric dissociations occurred in all tasks, in that severe motor impairment coexisted with normal (or impaired) attention control whereas normal motor performance was never associated with impaired attention control (below a task-dependent threshold). This implies that dexterity and force generation require intact attention control. Subsequently, we examined how motor and attention-control performance mapped to lesion location and cerebral functional connectivity. One component of motor performance (common to both arms), as well as attention control, correlated with the anatomical and functional integrity of a cingulo-opercular "salience" network. Independently of this, motor performance difference between arms correlated negatively with the integrity of the primary sensorimotor network and corticospinal tract. These results suggest that the salience network, and its attention-control function, are necessary for virtually all volitional motor acts while its damage contributes significantly to the cardinal motor deficits of stroke.

Is There Potential for Repurposing Statins as Novel Antimicrobials?

Statins are members of a class of pharmaceutical widely used to reduce high levels of serum cholesterol. In addition, statins have so-called "pleiotropic effects," which include inflammation reduction, immunomodulation, and antimicrobial effects. An increasing number of studies are emerging which detail the attenuation of bacterial growth and in vitro and in vivo virulence by statin treatment. In this review, we describe the current information available concerning the effects of statins on bacterial infections and provide insight regarding the potential use of these compounds as antimicrobial therapeutic agents.

The impact of simvastatin on pulmonary effectors of Pseudomonas aeruginosa infection.

The statin family of cholesterol-lowering drugs is known to have pleiotropic properties which include anti-inflammatory and immunomodulatory effects. Statins exert their pleiotropic effects by altering expression of human immune regulators including pro-inflammatory cytokines. Previously we found that statins modulate virulence phenotypes of the human pathogen Pseudomonas aeruginosa, and sought to investigate if simvastatin could alter the host response to this organism in lung epithelial cells. Simvastatin increased the expression of the P. aeruginosa target genes KLF2, KLF6, IL-8 and CCL20. Furthermore, both simvastatin and P. aeruginosa induced alternative splicing of KLF6. The novel effect of simvastatin on wtKLF6 expression was found to be responsible for induction of the KLF6 regulated genes CCL20 and iNOS. Simvastatin also increased the adhesion of P. aeruginosa to host cells, without altering invasion or cytotoxicity. This study demonstrated that simvastatin had several novel effects on the pulmonary cellular immune response.