Pediatric snow sport injuries differ by age

BackgroundUnintentional injury is the leading cause of death among pediatric patients. There were 13,436 injuries related to snow sports in those younger than 15 in 2015, with 4.8% requiring admission. These sports are high-risk given the potential for injury even when using protective equipment. We hypothesized that snow sport injury patterns would differ based on patient age.MethodsA cross-sectional analysis of the 2009 and 2012 Kids' Inpatient Database was performed.Cases of injuries were identified and analyzed using ICD-9 codes. National estimates were obtained using case weighting. Multivariable logistic regression was used to assess for confounders.ResultsWithin 745 admissions, there was a statistically significant decrease in skull/facial fractures with increasing age and a statistically significant increase in abdominal injuries with increasing age. Children in early and middle childhood were at increased odds of being hospitalized with skull/facial fractures, while older children were more likely hospitalized with abdominal injuries.ConclusionsWithin the pediatric snow sport population, younger children are more likely to experience head injuries, while older children are more likely to experience abdominal injuries.Further research is needed to determine the origin of this difference, and continued legislation on helmets is also necessary in reducing intracranial injuries.Level of EvidenceIII     

Effect of age and care organization on sources of variation in kidney transplant waiting list registration

Despite national guidelines, medical practices and kidney transplant waiting list registration policies may differ from one dialysis/transplant unit to another. Benefit risk assessment variations, especially for elderly patients, have also been described. The aim of this study was to identify sources of variation in early kidney transplant waiting list registration in France. Among 16 842 incident patients during the period 2016–2017, 4386 were registered on the kidney transplant waiting list at the start of, or during the first year after starting, dialysis (26%). We developed various log-linear mixed effect regression models on three levels: patients, dialysis networks, and transplant centers. Variability was expressed as variance from the random intercepts (± standard error). Although patient characteristics have an important impact on the likelihood of registration, the overall magnitude of variability in registration was low and shared by dialysis networks and transplant centers. Between-transplant center variability (0.23 ± 0.08) was 1.8 higher than between-dialysis network variability (0.13 ± 0.004). Older age was associated with a lower probability of registration and greater variability between networks (0.04, 0.20, & 0.93 in the 18–64, 65–74, and 75–84 age groups). Targeted interventions should focus on elderly patients and/or certain regions with greater variability in waiting list access.     

Wagner vitreoretinal degeneration with genetic linkage refinement on chromosome 5q13-q14

· Background: It has been previously described that Wagner disease is linked to chromosome 5q13-q14. This study was carried out to describe the ophthalmological aspects and report the results of genetic linkage analysis in a large pedigree affected by Wagner disease. · Methods: Fourty members of one same family agreed to be examined. · Results: Twenty patients presented vitreoretinal degeneration in both eyes without any extra-ocular abnormalities. In young patients, visual acuity was usually normal after correction of frequent mild myopia. Presenile cataracts progressed by the third decade and required removal for visual rehabilitation. The primary disorder involved an abnormal vitreous. A few avascular vitreous bands were usually the only optical feature in the mostly empty vitreous cavity. A circumferential vitreous condensation formed in contact with the retina on many spots. Less common retinal findings included retinal detachment, abnormal retinal pigmentation, progressive atrophy of the RPE simulating choroideremia and lattice degeneration. Genetic analysis revealed a highly significant linkage (lod score >5.0) between the disease and 10 markers of the chromosome 5q13-q14 region. Two recombination events allowed us to refine the linked interval to 20 cM between the D5S650 and D5S618 markers. · Conclusion: Ophthalmological aspects of Wagner’s disease appear to progress with age. Regular ophthalmological examination is important for detecting retinal abnormalities. The gene involved in Wagner’s disease lies in a 20 cM interval on chromosome 5q13-q14. Received: 30 June 1998 Revised version received: 5 October 1998 Accepted: 6 October 1998     

Multiple myeloma regression mediated by bruceantin.

PURPOSE: Bruceantin has been shown to induce cell differentiation in a number of leukemia and lymphoma cell lines. It also down-regulated c-MYC, suggesting a correlation of down-regulation with induction of cell differentiation or cell death. In the present study, we focused on multiple myeloma, using the RPMI 8226 cell line as a model. EXPERIMENTAL DESIGN: The effects of bruceantin on c-MYC levels and apoptosis were examined by immunoblotting, 4',6-diamidino-2-phenylindole staining, evaluation of caspase-like activity, and 3,3'-dihexyloxacarbocyanine iodide staining. The potential of bruceantin to inhibit primary tumor growth was assessed with RPMI 8226 xenografts in SCID mice, and apoptosis in the tumors was evaluated by the terminal deoxynucleotidyl transferase-mediated nick end labeling assay. RESULTS: c-MYC was strongly down-regulated in cultured RPMI 8226 cells by treatment with bruceantin for 24 h. With U266 and H929 cells, bruceantin did not regulate c-MYC in this manner. Apoptosis was induced in the three cell lines. In RPMI 8226 cells, apoptosis occurred through proteolytic processing of procaspases and degradation of poly(ADP-ribose) polymerase. The mitochondrial pathway was also involved. Because RPMI 8226 cells were the most sensitive, they were used in a xenograft model. Bruceantin treatment (2.5-5 mg/kg) resulted in a significant regression of tumors without overt toxicity. Apoptosis was significantly elevated in tumors derived from animals treated with bruceantin (37%) as compared with the control tumors (14%). CONCLUSIONS: Bruceantin interferes with the growth of RPMI 8226 cells in cell culture and xenograft models. These results suggest that bruceantin should be reinvestigated for clinical efficacy against multiple myeloma and other hematological malignancies.     

Mitochondrial free calcium levels (Rhod-2 fluorescence) and ultrastructural alterations in neuronally differentiated PC12 cells during ceramide-dependent cell death

Mitochondrial free calcium levels measured by Rhod-2 fluorescence and ultrastructure were examined during cell death in nerve growth factor (NGF)-differentiated PC12 cells that were 1) exposed to C2-ceramide, 2) deprived of serum to induce endogenous ceramide production, or 3) treated with calcium ionophore A23187. Rhod-2 fluorescence in mitochondria and also in the nucleolus increased to a maximum within 3 hours after C2-ceramide treatment or serum withdrawal. In A23187-treated cells, Rhod-2 fluorescence remained at baseline levels. In all three models, enlargement of the endoplasmic reticulum was the first ultrastructural alteration, followed by mitochondrial shrinkage in ionophore-treated cells, but by mitochondrial swelling in the ceramide-dependent models, in which rupture of the outer mitochondrial membrane and unfolding of the inner membrane were frequently seen. Dihydro-C2-ceramide, which did not cause cell death, had no effect on cellular ultrastructure. NGF, which inhibits ceramide-dependent cell death, prevented the effects of serum deprivation on mitochondrial ultrastructure but not on endoplasmic reticulum morphology or Rhod-2 fluorescence. Nuclear shrinkage with loss of nuclear membrane integrity, characterized by nuclear pores, free or surrounded by electron-dense filaments, was a late event in ceramide-dependent cell death. Chromatin condensation and other morphological features associated with apoptosis were seen in only a few atypical cells. Ceramide-mediated cell death, therefore, did not involve classical apoptosis but was mediated by a reproducible series of events beginning in the endoplasmic reticulum, followed by the mitochondria, and then the nucleus. NGF-dependent cell death inhibition intervenes at the mitochondrial level, not by blocking the increase in Rhod-2 fluorescence but by preventing the ultrastructural changes that follow.     

First report in a river in France of the benthic cyanobacterium Phormidium favosum producing anatoxin-a associated with dog neurotoxicosis.

The first identification of anatoxin-a in a French lotic system is reported. Rapid deaths of dogs occurred in 2003 after the animals drank water from the shoreline of the La Loue River in eastern France. Sediments, stones and macrophytes surfaces at the margin of the river were covered by a thick biofilm containing large quantities of several benthic species of filamentous, non-heterocystous cyanobacteria. Known cyanotoxins, such as microcystins, saxitoxins and anatoxins were screened from biofilm samples by biochemical and analytical assays. A compound with similar UV spectra to the anatoxin-a standard was detected by high-performance liquid chromatography (HPLC) coupled with photo-diode array detector. This toxin was further identified by HPLC coupled with a UV detector and by electrospray ionisation-Quadrupole-Time-Of-Flight mass spectrometer, and confirmed by tandem mass spectrometry. These two techniques were necessary to discriminate anatoxin-a in phenylalanine-containing matrices such as liver samples of poisoned dogs. The toxin and the aromatic amino acid, phenylalanine, present the same pseudomolecular ion at m/z 166, but have differing fragmentation patterns, retention times and UV spectra. Finally, several cyanobacterial strains were isolated from the green biofilm and tested for anatoxin-a production. Phormidium favosum was identified as a new anatoxin-a producing species.     

Organ slice viability extended for pathway characterization: an in vitro model to investigate fibrosis.

Liver slice viability is extended to 96 h for rat, expanding the use of this in vitro model for studying mechanisms of injury and repair, including pathways of fibrosis. The contributing factors to increased organ slice survival consist of the use of a preservation solution for liver perfusion and slice preparation, obtaining rats that are within the weight range of 250-325 g, placing a cellulose filter atop the titanium mesh roller-insert to support the slice, and maintaining the slices in an optimized culture medium which is replaced daily. The liver slices remain metabolically active, synthesizing adenosine triphosphate (ATP), glutathione, and glycogen, and exhibit preserved organelle integrity and slice morphology. Slice preparation results in 2-cut surfaces which likely triggers a repair and regenerative response. The fibrogenic pathways are evident by the activation of stellate cells, the proliferation of myofibroblast-like cells, and an increased collagen deposition by 48 h. Markers indicative of activated stellate cells, alpha-smooth muscle actin, collagen 1a1, desmin, and HSP47 are substantiated by real time-PCR. Increased staining of alpha-smooth muscle actin initially around the vessels and by 72-96 h in the tissue is accompanied by increased collagen staining. Microarray gene expression revealed extracellular matrix changes with the up-regulation of cytoskeleton, filaments, collagens, and actin genes; and the down-regulation of genes linked with lipid metabolism. The improvements in extending liver slice survival, in conjunction with its three-dimensional multi-cellular complexity, increases the application of this in vitro model for investigating pathways of injury and repair, and fibrosis.     

Development and pretesting of “Becoming Breastfeeding Friendly”: Empowering governments for global scaling up of breastfeeding programmes

Scaling up breastfeeding programmes has not been highly prioritized despite overwhelming evidence that breastfeeding benefits the health of mothers and children. Lack of evidence‐based tools for scaling up may deter countries from prioritizing breastfeeding. To fill this gap, Becoming Breastfeeding Friendly (BBF) was developed to guide countries in effectively scaling up programmes to protect, promote, and support breastfeeding. BBF includes an evidence‐based toolbox that consists of a BBF Index, case studies, and a 5‐meeting process. These three interrelated components enable countries to assess their breastfeeding scaling up environment, identify gaps, propose policy recommendations, develop a scaling up plan, and track progress. The toolbox was developed based on current evidence and expert guidance from a Technical Advisory Group, which was composed of global breastfeeding and metric experts with experience in the scaling up of health and nutrition programmes in low‐, middle‐, and high‐income countries. The BBF toolbox required a step‐by‐step iterative approach to describe and systematize each component, thus an operational manual was developed. The BBF toolbox and BBF operational manual underwent intensive pretesting in two countries, Ghana and Mexico, resulting in the modification of each component plus the operational manual. Pretesting continues in six additional countries demonstrating that BBF is a robust and dynamic multi‐sectoral process that, with relatively minor adaptations, can be successfully implemented in countries across world regions.     

Dietary Administration of Asimina triloba. (Paw Paw) Extract Increases Tumor Latency in N.-Methyl-N.-nitrosourea–Treated Rats

Abstract

The paw paw tree, Asimina triloba. (L.) Dunal (Annonaceae), contains more than 50 bioactive components, primarily annonaceous acetogenins. Some therapeutic activities have been associated with this material, but the potential to mediate a cancer chemopreventive effect has not been reported. In this study, a standardized extract from the twigs, in which bullatacin, asimicin, and trilobacin represent the most potent and major bioactive acetogenins, was tested in the N.-methyl-N.-nitrosourea–induced mammary carcinogenesis model. With Sprague-Dawley rats given a diet containing paw paw extract (1250 and 2500 mg/kg diet; based on maximum tolerated dose studies), mammary tumor latency was increased from 55 to 66 days. However, mammary tumor incidence and multiplicity were not affected by extract consumption.