Functional neurological disorder in children and young people: Incidence, clinical features, and prognosis.

AIM: To report incidence, demographic and clinical characteristics, and symptom outcome of functional neurological disorder (FND) in children. METHOD: Children diagnosed with FND at a regional children's hospital were prospectively recruited by weekly active surveillance for 36 months. Demographic, clinical, and follow-up data were retrospectively extracted by review of electronic records. Descriptive statistical analyses were used. RESULTS: Ninety-seven children (age range 5-15 years) met the case definition of FND (annual incidence 18.3 per 100 000 children). Children with FND were likely to be female (n = 68 [70%]) and older (median 13 years) with no difference in the Scottish Index of Multiple Deprivation (marker of socioeconomic status) compared with the general childhood population. Functional motor (41%) and sensory (41%) symptoms were most common; other somatic symptoms such as headache (31%) and pain (27%) were frequent. Self-reported psychiatric symptoms and infection/inflammation were the most common predisposing and precipitating factors respectively. At a median of 15 months follow-up, 49% of 75 children reported improvement or resolution of FND symptoms with no prognostic factors found. INTERPRETATION: At this regional centre, FND in children had a higher incidence than previously reported and a less optimistic outcome than in some other studies.

Area under the curve analysis of blood pressure reveals increased spontaneous locomotor activity in SPAK knock-in mice: relevance for hypotension induced by SPAK inhibition?

SPAK (Ste20/SPS1-related proline/alanine-rich kinase) has been recently identified as a protein kinase which targets the electroneutral cation-coupled chloride cotransporters and it stands out as a target for inhibition in novel anti-hypertensive agents. From this prospective, any information about physiological consequences of SPAK inhibition would be useful to better understand the efficacy and potential adverse effects of the SPAK-based anti-hypertensive therapy. Radiotelemetry was employed to continuously measure the parameters of blood pressure (mean arterial blood pressure, systolic blood pressure, and diastolic blood pressure), heart rate, and physical activity in SPAK knock-in (KI) mice and littermate controls for 24 h. For each parameter, the area under the curve (AUC) was calculated and compared between the SPAK KI mice and wild type mice. There was no statistically significant difference in the AUC of blood pressure parameters between SPAK KI and littermate mice. When mice were physically inactive, the AUCs for blood pressures were significantly lower in SPAK KI than in littermates. When physically active, blood pressures were significantly higher in SPAK KI than in littermates. The heart rate followed a similar pattern. The AUC of physical activity was significantly increased in SPAK KI mice when compared to littermates and the SPAK KI mice spent significantly less time in an inactive state and significantly more time in active states. Comparison between SPAK KI mice and unrelated wild type mice yielded similar results to the comparison between SPAK KI mice and littermates. We conclude that SPAK inhibition increases spontaneous locomotor activity, which has a significant effect on blood pressure.

The Effect of Molecular Properties on Active Ingredient Release from Electrospun Eudragit Fibers.

The formation of nanoscale fibers from pH-sensitive polymers is a route which has been widely explored for targeted drug delivery. In particular, the Eudragit L100 and S100 families of polymers have received significant attention for this purpose. However, while in some cases it is shown that making drug-loaded Eudragit polymers effectively prevents drug release in low-pH media where the polymer is insoluble, this is not always the case, and other studies have reported significant amounts of drug release at acidic pHs. In this study, we sought to gain insight into the factors influencing the release of active ingredients from Eudragit S100 (ES100) fibers. A family of materials was prepared loaded with the model active ingredients (AIs) benzoic acid, 1-naphthoic acid, 1-naphthylamine, and 9-anthracene carboxylic acid. Analogous systems were prepared with an AI-loaded core and an ES100 sheath. The resultant fibers were smooth and cylindrical in the majority of cases, and X-ray diffraction and differential scanning calorimetry showed them to comprise amorphous solid dispersions. When AI release from the monolithic fibers was probed, it was found that there was significant release at pH 1 in all cases except with 9-anthracene carboxylic acid. Analysis of the results indicated that both the molecular weight of the AI and its acidity/basicity are important in controlling release, with lower molecular weight AIs and basic species released more quickly. The same release trends are seen with the core/shell fibers, but AI release at pH 1 is attenuated. The most significant change between the monolithic and core/shell systems was observed in the case of 1-naphthylamine. Mathematical equations were devised to connect molecular properties and AI release under acidic conditions.