Pediatric Burns Unique Characteristics Among Ultra-Orthodox Jewish Minority-Retrospective Study.

Burn injuries are a significant cause of morbidity among children. Ultra-Orthodox Jewish children are at higher risk for burn injuries. The goal of this study was to examine the clinical characteristics of moderate to severe burns in this population in comparison to the general population in Israel. This retrospective cohort study included all pediatric patients 0 to 18 years of age admitted with burn injuries from January 1, 2015 through December 31, 2018. Data were collected regarding demography, etiology, and clinical characteristics. Of 778 burns injuries presented to our tertiary center, 385 (49.5%) were hospitalized. Of those 212 (55%) were non-ultra-Orthodox Jews, 135 (35%) were ultra-Orthodox Jews, and 38 (10%) were non-Jewish patients. The total body surface area percentage (TBSA%) of scald-type burns was larger in ultra-Orthodox compared to non-ultra-Orthodox children (median TBSA% of 7% vs 5%, respectively, P < .05). Among the ultra-Orthodox group, the median TBSA% during weekdays was 6%, and for weekends, the TBSA% was 7.5% (P < .05). Females demonstrated the greatest diversity between subgroups. On weekends, ultra-Orthodox female's median TBSA% was 10%, and non-ultra-Orthodox female's TBSA% was 4.5% (P < .05). Ultra-Orthodox children and especially girls had a significantly higher median TBSA% than non-ultra-Orthodox children for burns occurring during weekends. This may be the result of the unique cultural norms of the ultra-Orthodox Jewish community, in particular, their lifestyle and observation of the Sabbath. These findings provide a focus for better intervention and prevention of pediatric burns among this unique population.

Use dependence of presynaptic tenacity.

Recent studies indicate that synaptic vesicles (SVs) are continuously interchanged among nearby synapses at very significant rates. These dynamics and the lack of obvious barriers confining synaptic vesicles to specific synapses would seem to challenge the ability of synapses to maintain a constant amount of synaptic vesicles over prolonged time scales. Moreover, the extensive mobilization of synaptic vesicles associated with presynaptic activity might be expected to intensify this challenge. Here we examined the ability of individual presynaptic boutons of rat hippocampal neurons to maintain their synaptic vesicle content, and the degree to which this ability is affected by continuous activity. We found that the synaptic vesicle content of individual boutons belonging to the same axons gradually changed over several hours, and that these changes occurred independently of activity. Intermittent stimulation for 1 h accelerated rates of vesicle pool size change. Interestingly, however, following stimulation cessation, vesicle pool size change rates gradually converged with basal change rates. Over similar time scales, active zones (AZs) exhibited substantial remodeling; yet, unlike synaptic vesicles, AZ remodeling was not affected by the stimulation paradigms used here. These findings indicate that enhanced activity levels can increase synaptic vesicle redistribution among nearby synapses, but also highlight the presence of forces that act to restore particular set points in terms of SV contents, and support a role for active zones in preserving such set points. These findings also indicate, however, that neither AZ size nor SV content set points are particularly stable, questioning the long-term tenacity of presynaptic specializations.

Molecular dynamics of a presynaptic active zone protein studied in Munc13-1-enhanced yellow fluorescent protein knock-in mutant mice.

GFP (green fluorescent protein) fusion proteins have revolutionized research on protein dynamics at synapses. However, corresponding analyses usually involve protein expression methods that override endogenous regulatory mechanisms, and therefore cause overexpression and temporal or spatial misexpression of exogenous fusion proteins, which may seriously compromise the physiological validity of such experiments. These problems can be circumvented by using knock-in mutagenesis of the endogenous genomic locus to tag the protein of interest with a fluorescent protein. We generated knock-in mice expressing a fusion protein of the presynaptic active zone protein Munc13-1 and enhanced yellow fluorescent protein (EYFP) from the Munc13-1 locus. Munc13-1-EYFP-containing nerve cells and synapses are functionally identical to those of wild-type mice. However, their presynaptic active zones are distinctly fluorescent and readily amenable for imaging. We demonstrated the usefulness of these mice by studying the molecular dynamics of Munc13-1-EYFP at individual presynaptic sites. Fluorescence recovery after photobleaching (FRAP) experiments revealed that Munc13-1-EYFP is rapidly and continuously lost from and incorporated into active zones (tau1 approximately 3 min; tau2 approximately 80 min). Munc13-1-EYFP steady-state levels and exchange kinetics were not affected by proteasome inhibitors or acute synaptic stimulation, but exchange kinetics were reduced by chronic suppression of spontaneous activity. These experiments, performed in a minimally perturbed system, provide evidence that presynaptic active zones of mammalian CNS synapses are highly dynamic structures. They demonstrate the usefulness of the knock-in approach in general and of Munc13-1-EYFP knock-in mice in particular for imaging synaptic protein dynamics.