Sun-protection factor of zinc-oxide sunscreens: SPFin vitro too low compared to SPFin vivo-a brief review.

Sunscreens are mainly characterized by their sun-protection factor (SPF), which is measured according to the in vivo gold standard ISO 24444. Although the SPF concept is simple, SPF values are difficult to measure, due to the rather high variability caused by the complex interaction of light and skin. For half a century, there have been attempts to correlate the costly and ethically controversial in vivo procedure with a non-invasive (in vitro) method. After decades of development, alternative non-invasive SPF methods are expected to become available as ISO standards in early 2025. In particular, sunscreen manufacturers who use zinc oxide (ZnO) in higher concentrations (conc.) (10-25%) in their formulations, are concerned that these new in vitro methods would not confirm the SPF-values on their labels that have been determined in vivo, according to ISO 24444. This brief review reveals that sunscreen formulations with high conc. of ZnO often yield SPFin vitro values that are lower than the SPFin vivo values. This can be explained by the fact that in vitro methods have been developed for conventional emulsions products with organic UV filters, but not for highly concentrated ZnO-alone sunscreens. Fortunately, there seems to be a fix for this problem. There is a difference in density between ordinary emulsions with organic filters (density of the residual oil phase ~ 1.0 g/ml) and highly concentrated ZnO-alone formulations (~ 1.3-1.7 g/ml). As the application of current standards is weight-based, this makes the film on the PMMA plate much thinner, which is likely to lead to lower SPFin vitro values. Preliminary experiments show that using the same volume on the PMMA plates instead of the same weight as organic UV filters gives a much better correlation between in vitro and in vivo SPF results. A recent evaluation of three samples of highly concentrated ZnO sunscreens by the Dutch NVWA seems to confirm these findings. Further experimental evidence is required to fully understand this phenomenon and to adapt the in vitro method for higher conc. ZnO formulations accordingly.

The Feasibility of a Parent Group Treatment for Youth with Anxiety Disorders and Obsessive Compulsive Disorder.

Cognitive behavioral therapy (CBT) is an effective treatment for children and adolescents with anxiety disorders and obsessive-compulsive disorder (OCD). Yet CBT is insufficiently effective in approximately half of cases in clinical trials and in a substantial number of cases children refuse to participate in CBT sessions altogether. Parent training offers a promising alternative to direct child therapy. The present study examined the feasibility of a group implementation of SPACE (Supportive Parenting for Anxious Childhood Emotions), a novel parent training approach aimed at reducing parent's accommodation of children's anxiety symptoms. Based on parent reports (N = 25), following treatment there was a significant decrease in parental accommodation, in family power struggles and in parental sense of helplessness, as well as a significant reduction in anxiety and OCD symptom severity. Results support the promise of group SPACE treatment and underscore the need for additional clinical trial research.

Genetic investigation confirmed the clinical phenotype of congenital chloride diarrhea in a Hungarian patient: a case report.

BACKGROUND: Congenital chloride diarrhea (CCD, OMIM 214700) is a rare autosomal recessively inherited condition characterized by watery diarrhea, hypochloremia and metabolic alkalosis. Mutations of the solute carrier family 26, member 3 (SLC26A3, OMIM 126650) gene are responsible for the disease. The gene encodes a transmembrane protein, which is essential for intestinal chloride absorption. CASE PRESENTATION: Here we report a Hungarian boy, presenting the clinical phenotype of CCD. The patient born at 32 weeks of gestation and underwent surgery for abdominal distension and intestinal obstruction related to malrotation. After recovery, electrolyte replacement therapy was necessary due to several periods of diarrhea. After exclusion of other possible causes, increased chloride concentration in the feces supported the diagnosis of CCD. The diagnosis was confirmed by molecular genetic testing. Direct sequencing revealed compound-heterozygosity for a frameshift mutation c.1295delT (p.Leu432Argfs*11) and the known Polish founder mutation c.2024_2026dupTCA (p.Ile675_Arg676insLeu). CONCLUSIONS: Here we present the clinical symptoms of the first patient in Hungary diagnosed with CCD. Based on the clinical symptoms, stool analysis and genetic testing, the diagnosis of CCD was established. Our study provides expansion for the mutation spectrum of the SLC26A3 gene and the genetic background of CCD.

Adult neurogenesis is associated with the maintenance of a stereotyped, learned motor behavior.

Adult neurogenesis is thought to provide neural plasticity used in forming and storing new memories. Here we show a novel relationship between numbers of new neurons and the stability of a previously learned motor pattern. In the adult zebra finch, new projection neurons are added to the nucleus HVC and become part of the motor pathway for producing learned song. However, new song learning occurs only in juveniles and the behavioral impact of adding new neurons to HVC throughout life is unclear. We report that song changes after deafening are inversely correlated with the number of new neurons added to HVC, suggesting that adult neurogenesis in this context may contribute to behavioral stability. More broadly, we propose that new neuron function may depend on the site of integration and can vary as widely as promoting, or restricting, behavioral plasticity.

Identification and Validation of ERK5 as a DNA Damage Modulating Drug Target in Glioblastoma.

Brain tumours kill more children and adults under 40 than any other cancer, with approximately half of primary brain tumours being diagnosed as high-grade malignancies known as glioblastomas. Despite de-bulking surgery combined with chemo-/radiotherapy regimens, the mean survival for these patients is only around 15 months, with less than 10% surviving over 5 years. This dismal prognosis highlights the urgent need to develop novel agents to improve the treatment of these tumours. To address this need, we carried out a human kinome siRNA screen to identify potential drug targets that augment the effectiveness of temozolomide (TMZ)-the standard-of-care chemotherapeutic agent used to treat glioblastoma. From this we identified ERK5/MAPK7, which we subsequently validated using a range of siRNA and small molecule inhibitors within a panel of glioma cells. Mechanistically, we find that ERK5 promotes efficient repair of TMZ-induced DNA lesions to confer cell survival and clonogenic capacity. Finally, using several glioblastoma patient cohorts we provide target validation data for ERK5 as a novel drug target, revealing that heightened ERK5 expression at both the mRNA and protein level is associated with increased tumour grade and poorer patient survival. Collectively, these findings provide a foundation to develop clinically effective ERK5 targeting strategies in glioblastomas and establish much-needed enhancement of the therapeutic repertoire used to treat this currently incurable disease.