Pediatric Emergency Medicine ECHO (Extension for Community Health Care Outcomes): Cultivating Connections to Improve Pediatric Emergency Care.

BACKGROUND: An Extension for Community Health Care Outcomes (ECHO) provides the opportunity for specialists at academic medical centers (AMCs) and frontline community generalists to engage in bidirectional learning. Specialists provide generalists with the current best evidence, and generalists share the local challenges applying this evidence to their practice. All ECHO participants strategize how to navigate these challenges together. Pediatric emergency medicine (PEM) may benefit from this knowledge translation strategy because most children seek emergency care from generalists in community emergency departments (CEDs) where variations in care between the AMC and the CED have been reported. METHODS: Our objective was to use ECHO to cultivate a PEM community of practice that facilitated knowledge translation and generated future CED pediatric improvement initiatives. As such, we developed, implemented, and evaluated a PEM ECHO. We conducted general and targeted needs assessments to inform our curriculum and formatted the sessions to generate bidirectional learning. A postparticipation evaluation collected self-reported perceptions about knowledge translation, planned provider practice changes, and perceptions of the formation of a community of practice. Additionally, we solicited information on the implementation of any pediatric improvement activities attributed to the PEM ECHO. RESULTS: Thirteen 1-hour sessions covered the chosen PEM topics. Participants represented diverse CEDs, with varied experience and roles in caring for children. All respondents (13/13) appreciated the ECHO learning format, reported improved PEM knowledge, and perceived the cultivation of a community of practice. Nine (85%) individuals attributed implementation of new pediatric improvement activities to the PEM ECHO. CONCLUSIONS: Our PEM ECHO was associated with improved perceptions of PEM knowledge, cultivated a community of practice, and facilitated the implementation of CED pediatric improvement activities. The PEM ECHO's bidirectional learning format generated new initiatives and partnerships aiming to improve the emergency care of children.

Different cell death mechanisms are induced by a hydrophobic flavin in human tumor cells after visible light irradiation.

Riboflavin (RF) is an endogenous cell component and an efficient photosensitizer that can act by both types I and II photochemical mechanisms. Human tumor cells lines cultured in vitro, were used as model to study the effect of a photosensitizer synthesized from riboflavin, the 2',3',4',5'-riboflavin-tetrabutyrate (RTB), to increase the flavin concentration in the human promyelocytic leukemia cell line HL-60 and the human epithelial cervical cancer cell line HeLa. We demonstrate that this compound, alone or with Trp, has a toxic dose-response effect evidenced by abnormal cell morphology and a decrease in the cell proliferation rate. The mechanism of cell death was investigated and the experimental evidence indicates that it proceeds primarily via apoptosis; however, autophagy cannot be discarded. Nuclear fluorescent staining with Hoechst 33258 and transmission electron microscopy of the cells showed condensed chromatin margination at the nuclear periphery and the formation of apoptotic bodies. Furthermore, Caspase-3 activity was demonstrated in both cell lines. In addition, the characteristic apoptotic DNA ladder was observed in HL-60 cells. On the other hand, a high cytoplasmic vacuolization was observed by electron transmission and confocal microscopy. LysoTraker-red localization in the vacuoles was observed by fluorescence microscopy, and a significant decrease in the number of vacuoles and in the cell proliferation rate diminution was observed when irradiation was performed in the presence of the autophagy inhibitor 3-methyladenine. Considering that both cell death mechanisms have a dual role in the killing of tumor cells in vivo, a harmful effect that does not cause inflammation leading to tumor prophylaxis, we conclude that RTB could have potential clinical applications.

Photophysical behaviour and photodynamic activity of zinc phthalocyanines associated to liposomes.

Phthalocyanines are macrocyclic compounds that can be employed as photosensitizers in the treatment of various infections and diseases, as well as in photodynamic therapy. Nevertheless, a disadvantage for the clinical application of these compounds is their strong tendency to form oligomers (especially dimers), a phenomenon that reduces their efficiency as photosensitizers. In the present contribution, we have studied the photophysical and photochemical properties of ZnPc and ZnF(16)Pc in an organic solvent (THF) and liposomal formulations (DMPC, DPPC and DSPC). Our results show that dye incorporation into liposomes decreases its aggregation degree, as revealed by absorption spectra, triplet quantum yield, and singlet oxygen quantum yield measurements. Additionally, we studied the photodynamic activity of both phthalocyanines in liposomal formulation on human cervical carcinoma (HeLa) cells. For ZnF(16)Pc the photophysical behavior and phototoxicity in vitro correlate with the aggregation degree. The dimers are not photoactive and the photochemistry of ZnF(16)Pc depends of the fraction present as monomer. On the other hand, ZnPc aggregation is minimal and its photophysical and photochemical properties are similar in the three liposomes studied. Nevertheless, its phototoxicity in vitro is liposome dependent.

Photophysics and photochemistry of zinc phthalocyanine/bovine serum albumin adducts.

Zinc phthalocyanine (ZnPc) is a well known Type II (singlet oxygen mediated) hydrophobic photosensitizer with potential use in PDT. We have found that the presence of bovine serum albumin diminishes the aggregation degree of ZnPc in aqueous solution, indicating that albumins could be potentially useful carriers for this type of photosensitizer in PDT. In order to explore the photochemical and photophysical behavior of ZnPc associated to the protein, we have evaluated triplet excited state lifetime and yield, dye bleaching, oxygen consumption, formation of carbonyls and peroxides, and the spontaneous chemiluminescence emitted after photolysis. The results show that dye association to BSA modifies the photophysics and photochemistry of ZnPC. In particular the decreased yield of long lived triplets suggests singlet state and/or static triplet quenching of the bound dye by the host protein.