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1.
BMC Public Health ; 24(1): 1221, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38698393

RESUMO

BACKGROUND: Firearm violence is an intensifying public health problem in the United States. News reports shape the way the public and policy makers understand and respond to health threats, including firearm violence. To better understand how firearm violence is communicated to the public, we aimed to determine the extent to which firearm violence is framed as a public health problem on television news and to measure harmful news content as identified by firearm-injured people. METHODS: This is a quantitative content analysis of Philadelphia local television news stories about firearm violence using a database of 7,497 clips. We compiled a stratified sample of clips aired on two randomly selected days/month from January-June 2021 from the database (n = 192 clips). We created a codebook to measure public health frame elements and to assign a harmful content score for each story and then coded the clips. Characteristics of stories containing episodic frames that focus on single shooting events were compared to clips with thematic frames that include broader social context for violence. RESULTS: Most clips employed episodic frames (79.2%), presented law enforcement officials as primary narrators (50.5%), and included police imagery (79.2%). A total of 433 firearm-injured people were mentioned, with a mean of 2.8 individuals shot included in each story. Most of the firearm-injured people featured in the clips (67.4%) had no personal information presented apart from age and/or gender. The majority of clips (84.4%) contained at least one harmful content element. The mean harmful content score/clip was 2.6. Public health frame elements, including epidemiologic context, root causes, public health narrators and visuals, and solutions were missing from most clips. Thematic stories contained significantly more public health frame elements and less harmful content compared to episodic stories. CONCLUSIONS: Local television news produces limited public health coverage of firearm violence, and harmful content is common. This reporting likely compounds trauma experienced by firearm-injured people and could impede support for effective public health responses to firearm violence. Journalists should work to minimize harmful news content and adopt a public health approach to reporting on firearm violence.


Assuntos
Armas de Fogo , Saúde Pública , Televisão , Violência , Humanos , Philadelphia , Televisão/estatística & dados numéricos , Armas de Fogo/estatística & dados numéricos , Violência/estatística & dados numéricos , Violência/prevenção & controle , Ferimentos por Arma de Fogo/prevenção & controle , Ferimentos por Arma de Fogo/epidemiologia , Violência com Arma de Fogo/prevenção & controle , Violência com Arma de Fogo/estatística & dados numéricos
2.
Anesthesiology ; 139(4): 393-404, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37440275

RESUMO

BACKGROUND: Children undergoing complex cardiac surgery are exposed to substantial cumulative doses of sedative medications and volatile anesthetics and are more frequently anesthetized with ketamine, compared with healthy children. This study hypothesized that greater exposure to sedation and anesthesia in this population is associated with lower neurodevelopmental scores at 18 months of age. METHODS: A secondary analysis was conducted of infants with congenital heart disease who participated in a prospective observational study of environmental exposures and neurodevelopmental outcomes to assess the impact of cumulative volatile anesthetic agents and sedative medications. Cumulative minimum alveolar concentration hours of exposure to volatile anesthetic agents and all operating room and intensive care unit exposures to sedative and anesthesia medications were collected before administration of Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley III), at 18 months of age. RESULTS: The study cohort included 41 (37%) single-ventricle and 69 (63%) two-ventricle patients. Exposures to volatile anesthetic agents, opioids, benzodiazepines, and dexmedetomidine were not associated with abnormal Bayley III scores. At 18-month follow-up, after adjusting for confounders, each mg/kg increase in ketamine exposure was associated with a 0.34 (95% CI, -0.64 to -0.05) point decrease in Bayley III motor scores (P = 0.024). CONCLUSIONS: Total cumulative exposures to volatile anesthetic agents were not associated with neurodevelopmental impairment in infants with congenital heart disease undergoing various imaging studies and procedures, whereas higher ketamine doses were associated with poorer motor performance.


Assuntos
Anestesia , Anestésicos , Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas , Ketamina , Humanos , Lactente , Estudos Retrospectivos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cardiopatias Congênitas/cirurgia , Hipnóticos e Sedativos/efeitos adversos
3.
J Org Chem ; 84(17): 11091-11102, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31454235

RESUMO

Synthesis of 1,11-dithia-4,8-diazacyclotetradecane (L1), a constitutional isomer of the macrocyclic [14]aneN2S2 series, is accompanied with reaction and method optimization. Chelation of L1 with copper(II) provided assessment of lattice packing, ring contortion, and evidence of conformational fluxionality in solution through two unique crystal structures: L1Cu(ClO4)2 and [(L1Cu)2µ-Cl](ClO4)3. Multiple synthetic approaches are presented, supplemented with reaction methodology and reagent screening to access [14]aneN2S2 L1. Reductive alkylation of bis-tosyl-cystamine was integrated into the synthetic route, eliminating the use and isolation of volatile thiols and streamlining the synthetic scale-up. Late-stage cleavage of protecting sulfonamides was addressed using reductive N-S cleavage to furnish macrocyclic freebase L1.


Assuntos
Quelantes/química , Quelantes/síntese química , Cobre/química , Compostos Macrocíclicos/química , Compostos Macrocíclicos/síntese química , Técnicas de Química Sintética , Modelos Moleculares , Conformação Molecular
4.
J Org Chem ; 83(17): 10025-10036, 2018 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-30067366

RESUMO

The synthesis of a rigid macrobicyclic N,S lactam L1 and a topologically favored in/in N,S cryptand L2 are reported with X-ray structure analysis, dynamic correlation NMR spectroscopy, and computational analysis. Lactam L1 exhibits two distinct rotameric conformations (plus their enantiomeric counterparts) at 25 °C, as confirmed via NMR spectroscopy and computational analysis. Coalescence of the resonances of L1 was observed at 115 °C, allowing for complete nuclei to frequency correlation. Combining computational investigations with experimental data, topological equilibria and relative energies/strain relating to the perturbation of the pore were determined. Due to the increased conformational strain of the N2S2 template, the nitrogen lone pairs in L2 elicit a unique transannular interaction, resulting in a thermodynamically favored in/in nephroidal racemate. The combination of preferred topology, steric relief, and electronic localization of L2 induces a chiral environment imparted through the amine with a computed inversion barrier of 10.3 kcal mol-1.

5.
Biochemistry ; 56(10): 1518-1528, 2017 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-28186720

RESUMO

Cuprizone intoxication is a common animal model used to test myelin regenerative therapies for the treatment of diseases such as multiple sclerosis. Mice fed this copper chelator develop reversible, region-specific oligodendrocyte loss and demyelination. While the cellular changes influencing the demyelinating process have been explored in this model, there is no consensus about the biochemical mechanisms of toxicity in oligodendrocytes and about whether this damage arises from the chelation of copper in vivo. Here we have identified an oligodendroglial cell line that displays sensitivity to cuprizone toxicity and performed global metabolomic profiling to determine biochemical pathways altered by this treatment. We link these changes with alterations in brain metabolism in mice fed cuprizone for 2 and 6 weeks. We find that cuprizone induces widespread changes in one-carbon and amino acid metabolism as well as alterations in small molecules that are important for energy generation. We used mass spectrometry to examine chemical interactions that are important for copper chelation and toxicity. Our results indicate that cuprizone induces global perturbations in cellular metabolism that may be independent of its copper chelating ability and potentially related to its interactions with pyridoxal 5'-phosphate, a coenzyme essential for amino acid metabolism.


Assuntos
Encéfalo/efeitos dos fármacos , Quelantes/toxicidade , Cuprizona/toxicidade , Doenças Desmielinizantes/metabolismo , Esclerose Múltipla/metabolismo , Oligodendroglia/efeitos dos fármacos , Aminoácidos/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Química Encefálica , Linhagem Celular , Quelantes/metabolismo , Cobre/metabolismo , Cuprizona/metabolismo , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/patologia , Modelos Animais de Doenças , Metabolismo Energético , Masculino , Metaboloma , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/induzido quimicamente , Esclerose Múltipla/patologia , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Fosfato de Piridoxal/metabolismo
6.
Prev Med Rep ; 42: 102739, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38699078

RESUMO

Objective: To better understand how community firearm violence (CFV) is communicated to the public, we aimed to identify systematic differences between the characteristics of shooting victims and events covered on television news and all shootings in Philadelphia, PA, a city with escalating CFV incidence. Methods: We compiled a stratified sample of local television news clips covering shootings that occurred in Philadelphia aired on two randomly selected days per month from January-June 2021 (n = 154 clips). We coded the clips to determine demographic and geographic information about the shooting victims and events and then matched coded shootings with corresponding shootings in the Philadelphia police database. We compared characteristics of shooting victims and shooting event locations depicted in television clips (n = 62) with overall characteristics of shootings in Philadelphia during the study period (n = 1082). Results: Compared to all individuals shot, victims whose shootings were covered on local television news more likely to be children and more likely to be shot in a mass shooting. The average median household income of shooting locations featured on television was significantly higher than the median household income across all shooting locations ($60,302 for television shootings vs. $41,233 for all shootings; p = 0.002). Shootings featured on television occurred in areas with lower rates of income inequality and racialized economic segregation compared to all shooting locations. Conclusions: Television news outlets in Philadelphia systematically over-reported shootings of children, mass shootings, and shootings that occurred in neighborhoods with higher median household income, less socioeconomic inequality, and lower rates of racialized economic segregation.

7.
Dalton Trans ; 49(40): 14088-14098, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32970072

RESUMO

Synthesis and characterisation of a dithiadiaza chelator NSNS2A, as well as copper complexes thereof are reported in this paper. Solution structures of copper(i/ii) complexes were calculated using density functional theory (DFT) and validated by both NMR and EPR spectroscopy. DFT calculations revealed a switch in the orientation of tetragonal distortion upon protonation, which might be responsible for poor stability of the Cu(II)NSNS2A complex in aqueous media, whilst the same switch in tetragonal distortion was experimentally observed by changing the solvent. The chelator was radiolabeled with 64Cu and evaluated using PET/MRI in rats. Despite a favorable redox potential to stabilize the cuprous state in vivo, the 64Cu(II)NSNS2A complex showed suboptimal stability compared to its tetraazamacrocyclic analogue, 64Cu(TE2A), with a significant 64Cu uptake in the liver.


Assuntos
Compostos Aza/química , Quelantes/síntese química , Complexos de Coordenação/síntese química , Radioisótopos de Cobre/química , Compostos Macrocíclicos/síntese química , Compostos Radiofarmacêuticos/síntese química , Animais , Azurina/química , Complexos de Coordenação/sangue , Complexos de Coordenação/farmacocinética , Teoria da Densidade Funcional , Técnicas Eletroquímicas , Rim , Fígado , Imageamento por Ressonância Magnética/métodos , Masculino , Conformação Molecular , Oxirredução , Tomografia por Emissão de Pósitrons/métodos , Ligação Proteica , Compostos Radiofarmacêuticos/sangue , Compostos Radiofarmacêuticos/farmacologia , Ratos Wistar , Solventes/química , Coloração e Rotulagem , Relação Estrutura-Atividade
8.
Dalton Trans ; 44(46): 20200-6, 2015 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-26536355

RESUMO

To improve understanding of copper at the active site of Type 1 copper proteins, Cu(I) and Cu(II) complexes of 1,8-dithia-4,11-diazacyclotetradecane, shown in , have been successfully isolated and structurally characterized by X-ray crystallography. In these compounds, both Cu(I) and Cu(II) are centered in the plane of the macrocycle containing two sulphur and two nitrogen heteroatoms comprising the distorted tetrahedral/square planar coordination geometry. The UV/VIS spectra, electrochemistry and EPR properties have been obtained for the Cu(II) complex 2. Three absorption bands at 295 nm, 354 nm, and 545 nm are observed in aqueous solution at a pH of 5. These bands have been assigned to the N → Cu(II) and S → Cu(II) charge transfer bands and the d-d transitions respectively. The Cu(I/II) redox midpoint potential of complex 2 in CH3CN is +403 mV versus NHE.


Assuntos
Complexos de Coordenação/química , Cobre/química , Compostos Heterocíclicos com 1 Anel/química , Metaloproteínas/química , Domínio Catalítico , Cristalografia por Raios X , Modelos Moleculares
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