A Study of Households with Children and Firearms in Baltimore, Maryland.

Firearm injuries are the leading cause of death among children and adolescents in the US. Safe storage of firearms in the home is one of the most effective ways of preventing firearm injuries in children. This feasibility study was conducted in both the pediatric and general Emergency Departments of a large urban academic medical center in a community with high rates of firearm injuries in children. The objective was to pilot a survey seeking to describe sociodemographic characteristics, firearm specific risk factors, and firearm storage practices of households with children in the community. One hundred participants completed a survey containing items regarding participant demographics, household features, firearm ownership, firearm characteristics, and storage practices. Descriptive statistics were used to define sociodemographic characteristics of the enrolled population, comparing those with firearms to those without, and to describe firearms and storage practices of firearm owners in households with children. Of 100 participants, 30 lived in households with firearms and children. Most firearms in homes with children were stored locked and unloaded most of the time; however, 30% of participants with firearms and children in the home reported not consistently storing a firearm locked and unloaded. The most common reason given for not storing a firearm in the safest manner possible was that storing a firearm locked and unloaded would make it difficult to access quickly. Engaging families with children in discussions around firearm prevention during Emergency Department visits is feasible and may have implications for future efforts to promote safe firearm storage practices.

Differentiation of the Aziridine Functionality from Related Functional Groups in Protonated Analytes by Using Selective Ion-Molecule Reactions Followed by Collision-Activated Dissociation in a Linear Quadrupole Ion Trap Mass Spectrometer.

Aziridines are commonly used as reagents for the synthesis of drug substances although they are potentially mutagenic and genotoxic. Therefore, their unambiguous detection is critically important. Unfortunately, tandem mass spectrometry (MS2) based on collision-activated dissociation (CAD), a powerful method used for the identification of many unknown compounds in complex mixtures, does not provide diagnostic fragmentation patterns for ionized aziridines. Therefore, a different mass spectrometry approach based on MS3 experiments is presented here for the identification of the aziridine functionalities. This approach is based on selective gas-phase ion-molecule reactions of protonated analytes with tris(dimethylamino)borane (TDMAB) followed by diagnostic CAD reactions in a modified linear quadrupole ion trap (LQIT) mass spectrometer. TDMAB reacts with protonated aziridines by forming adduct ions that have lost a dimethylamine (DMA) molecule ([M + H + TDMAB - HN(CH3)2]+). CAD on these product ions generated diagnostic fragment ions with m/z-values 25- and 43-units lower than those of the ion-molecule reaction product ions. None of the ion-molecule reaction product ions formed from other, structurally related, protonated analytes produced related fragment ions. Quantum chemical calculations were employed to explore the mechanisms of the observed reactions.

Proton Affinities of Alkanes.

Chemical characterization of complex mixtures of large alkanes is critically important for many fields, including petroleomics and the development of renewable transportation fuels. Tandem mass spectrometry is the only analytical method that can be used to characterize such mixtures at the molecular level. Many ionization methods used in mass spectrometry involve proton transfer to the analyte. Unfortunately, very few proton affinity (PA) values are available for alkanes. Indeed, previous research has shown that most protonated alkanes (MH+) are not stable but fragment spontaneously via the elimination of a hydrogen molecule to form [M - H]+ ions. Here, the PAs of several n-alkanes and alkylcyclohexanes containing 5-8 carbon atoms, n-pentane, n-hexane, n-heptane, n-octane, cyclohexane, methylcyclohexane, and ethylcyclohexane, were determined via bracketing experiments by using a linear quadrupole ion trap mass spectrometer. Monitoring the formation of the [M - H]+ ions in reactions between the alkanes and protonated reference bases with known PAs revealed that the PAs of all the alkanes fell into the range 721 ± 20 kJ mol-1. In order to obtain a more accurate estimate of the relative PAs of different alkanes, two alkanes were introduced simultaneously into the ion trap and allowed to react with the same protonated reference base. Based on these experiments, the longer the alkyl chain in an n-alkane or alkylcyclohexane the greater the PA. Further, when considering alkanes with the same number of carbon atoms, the PAs of those with a cyclohexane ring were found to be greater than those with no such ring.

Study on the Gas-Phase Reactivity of Charged Pyridynes.

The reactivities of three isomeric, charged ortho-pyridynes, the 1,2-, 2,3-, and 3,4-didehydropyridinium cations, were examined in the gas phase using Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometry. The structures of selected product ions were probed using collision-activated dissociation (CAD) experiments in a linear quadrupole ion trap (LQIT) mass spectrometer. Mechanisms based on quantum chemical calculations are proposed for the formation of all major products. The products of the reactions of the charged ortho-pyridynes in the gas phase were found to closely resemble those formed upon reactions of neutral ortho-arynes in solution, but the mechanisms of these reactions exhibit striking differences. Additionally, no radical reactions were observed for any of the charged ortho-pyridynes examined, in contrast to previous proposals that ortho-benzyne can occasionally react via radical mechanisms. Finally, the relative reactivities of those charged gaseous ortho-pyridynes that yielded similar product distributions were found to be affected mainly by the (calculated) vertical electron affinities of the dehydrocarbon sites, which suggests that the reactivity of these species is controlled by polar effects.

Studies of the Fragmentation Mechanisms of Deprotonated Lignin Model Compounds in Tandem Mass Spectrometry.

Unlabeled and deuterium-labeled dimeric lignin model compounds with ß-O-4 linkages were evaporated and ionized using negative ion mode electrospray ionization, transferred into a linear quadrupole ion trap, isolated, and subjected to collision-activated dissociation (CAD; MS2 experiments). The elemental compositions of the fragment ions were determined by using a high-resolution Orbitrap mass analyzer, and their structures were examined using further CAD experiments (MSn experiments wherein n = 2-5). Data analysis was facilitated by determining the fragmentation pathways for several deprotonated model compounds. The structures of the key fragment ions of several pathways were determined by comparison of the CAD mass spectra measured for undeuterated and deuterated analogues and for deprotonated authentic compounds. Some of the proposed reaction mechanisms were tested by examining additional deprotonated synthetic model compounds. Quantum chemical calculations were used to delineate the most likely reaction pathways and reaction mechanisms. This work provides basic information needed for the design of tandem mass spectrometry-based CAD sequencing strategies for mixtures of lignin degradation products.

Fragmentation of Saturated Hydrocarbons upon Atmospheric Pressure Chemical Ionization Is Caused by Proton-Transfer Reactions.

Chemical characterization of complex mixtures of large saturated hydrocarbons is critically important for numerous fields, including petroleomics and renewable transportation fuels, but difficult to achieve. Atmospheric pressure chemical ionization (APCI) mass spectrometry has shown some promise in the analysis of saturated hydrocarbons. However, APCI causes extensive fragmentation to these compounds, which impedes its effectiveness. To prevent this fragmentation, its causes were examined via gas-phase ion-molecule reactions in vacuum in a linear quadrupole ion trap mass spectrometer. The results demonstrate that the mechanism proposed previously for ionization of saturated hydrocarbons upon APCI, hydride abstraction by carbocation reagent ions, is not correct. Instead, the fragmentation is caused by ionization of saturated hydrocarbons via exothermic proton-transfer reactions involving highly acidic, protonated atmospheric molecules, such as nitrogen and water. Accordingly, the extent of fragmentation was found to correlate with the proton affinities of the atmospheric molecules studied. Remarkably, controlled experiments involving isolated atmospheric ions and neat saturated hydrocarbons in vacuum yielded almost identical mass spectra as APCI involving atmospheric pressure conditions, the presence of many different chemicals, and an electrical discharge. In order to prevent or reduce the extent of fragmentation of saturated hydrocarbons upon APCI, and therefore enable accurate mass spectrometric characterization of complex mixtures of saturated hydrocarbons, the ion source should be purged of air to remove nitrogen and water and fill it with an inert gas with a substantially lower proton affinity.

Measurement of the Proton Affinities of a Series of Mono- and Biradicals of Pyridine.

The proton affinity (PA) of a neutral molecule is defined as the negative of the enthalpy change for the gas-phase reaction between a proton and the neutral molecule to produce the (charged) conjugate acid of the molecule. PA is a fundamental property that is related to the structure of a molecule and affects its reactivity. Very few PA values are available for basic organic monoradicals and none for biradicals. Here, the PA values for several σ-type carbon-centered pyridine-based monoradicals and biradicals have been experimentally determined by monitoring proton transfer from the protonated mono- and biradicals to reference bases with known proton affinities as a function of time in Fourier-transform ion cyclotron resonance (FT-ICR) and linear quadrupole ion trap (LQIT) mass spectrometers. A procedure was developed for both instruments that permits differentiation between exo- and endothermic proton transfer reactions. The PA values of all the (bi)radicals studied were found to be lower than that of pyridine. This is rationalized based on the electron-withdrawing nature of the radical site(s). Thus, the PA values decrease in the order: pyridine > monoradicals > biradicals. The PA values of the monoradicals were also found to increase (making the protonated radicals less acidic) as the distance between the basic nitrogen atom and the radical site increases. Similar behavior was found for the biradicals, with one exception: 3,5-didehydropyridine has a larger PA (215.3 ± 3.3 kcal mol-1) than 3,4-didehydropyridine (PA = 213.4 ± 3.3 kcal mol-1) even though the latter biradical has one radical site farther away from the basic nitrogen atom. Quantum chemical calculations of the PAs of the (bi)radicals are in reasonably good agreement with the experimentally determined values. At the DFT (B3LYP), CCSD(T), and CASPT2 levels of theory, the mean unsigned errors are 2.3, 1.7, and 2.1 kcal mol-1.

Differentiation of Deprotonated Acyl-, N-, and O-Glucuronide Drug Metabolites by Using Tandem Mass Spectrometry Based on Gas-Phase Ion-Molecule Reactions Followed by Collision-Activated Dissociation.

Glucuronidation, a common phase II biotransformation reaction, is one of the major in vitro and in vivo metabolism pathways of xenobiotics. In this process, glucuronic acid is conjugated to a drug or a drug metabolite via a carboxylic acid, a hydroxy, or an amino group to form acyl-, O-, and/or N-glucuronide metabolites, respectively. This process is traditionally thought to be a detoxification pathway. However, some acyl-glucuronides react with biomolecules in vivo, which may result in immune-mediated idiosyncratic drug toxicity (IDT). In order to avoid this, one may attempt in early drug discovery to modify the lead compounds in such a manner that they then have a lower probability of forming reactive acyl-glucuronide metabolites. Because most drugs or drug candidates bear multiple functionalities, e.g., hydroxy, amino, and carboxylic acid groups, glucuronidation can occur at any of those. However, differentiation of isomeric acyl-, N-, and O-glucuronide derivatives of drugs is challenging. In this study, gas-phase ion-molecule reactions between deprotonated glucuronide metabolites and BF3 followed by collision-activated dissociation (CAD) in a linear quadrupole ion trap mass spectrometer were demonstrated to enable the differentiation of acyl-, N-, and O-glucuronides. Only deprotonated N-glucuronides and deprotonated, migrated acyl-glucuronides form the two diagnostic product ions: a BF3 adduct that has lost two HF molecules, [M - H + BF3 - 2HF]-, and an adduct formed with two BF3 molecules that has lost three HF molecules, [M - H + 2BF3 - 3HF]-. These product ions were not observed for deprotonated O-glucuronides and unmigrated, deprotonated acyl-glucuronides. Upon CAD of the [M - H + 2BF3 - 3HF]- product ion, a diagnostic fragment ion is formed via the loss of 2-fluoro-1,3,2-dioxaborale (MW of 88 Da) only in the case of deprotonated, migrated acyl-glucuronides. Therefore, this method can be used to unambiguously differentiate acyl-, N-, and O-glucuronides. Further, coupling this methodology with HPLC enables the differentiation of unmigrated 1-ß-acyl-glucuronides from the isomeric acyl-glucuronides formed upon acyl migration. Quantum chemical calculations at the M06-2X/6-311++G(d,p) level of theory were employed to probe the mechanisms of the reactions of interest.

Polar Effects Control the Gas-Phase Reactivity of para-Benzyne Analogs.

We report herein a gas-phase reactivity study on a para-benzyne cation and its three cyano-substituted, isomeric derivatives performed using a dual-linear quadrupole ion trap mass spectrometer. All four biradicals were found to undergo primary and secondary radical reactions analogous to those observed for the related monoradicals, indicating the presence of two reactive radical sites. The reactivity of all biradicals is substantially lower than that of the related monoradicals, as expected based on the singlet ground states of the biradicals. The cyano-substituted biradicals show substantially greater reactivity than the analogous unsubstituted biradical. The greater reactivity is rationalized by the substantially greater (calculated) electron affinity of the radical sites of the cyano-substituted biradicals, which results in stabilization of their transition states through polar effects. This finding is in contrast to the long-standing thinking that the magnitude of the singlet-triplet splitting controls the reactivity of para-benzynes.

Selective increase in subtelomeric DNA methylation: an epigenetic biomarker for malignant glioma.

BACKGROUND: Subtelomeric regions dynamically change their epigenetic pattern during development and progression of several malignancies and degenerative disorders. However, DNA methylation of human subtelomeres and their correlation to telomere length (TL) remain undetermined in glioma. RESULTS: Herein, we report on the selective changes in subtelomeric DNA methylation at the end of five chromosomes (Chr.) (7q, 8q. 18p, 21q, and XpYp) and ascertain their correlation with TL in patients with glioma. Subtelomeric methylation level was invariably higher in glioma patients compared to the control group, irrespective of their age and tumor grade. In particular, a significant increase in methylation was observed at the subtelomeric CpG sites of Chr. 8q, 21q, and XpYp in tissues, obtained from the brain tumor of glioma patients. In contrast, no significant change in methylation was observed at the subtelomere of Chr. 7q and 18p. Selective changes in the subtelomeric methylation level, however, did not show any significant correlation to the global TL. This observed phenomenon was validated in vitro by inducing demethylation in a glioblastoma cell line (SF-767) using 5-azacytidine (AZA) treatment. AZA treatment caused significant changes in the subtelomeric methylation pattern but did not alter the TL, which supports our hypothesis. CONCLUSIONS: DNA methylation level dramatically increased at the subtelomere of Chr.8q, 21q, and XpYp in malignant glioma, which could be used as an early epigenetic diagnostic biomarker of the disease. Alterations in subtelomeric methylation, however, have no effects on the TL.

Outras freqüentes arteriopatias do idoso / Aged's other frequent arterial oclusive

Inclui artigos que abordam várias formas de arteriopatias do idoso

Teste de compressao das arterias femorais: metodo nao invasivo para deteccao de lesao obstrutiva de arteria iliaca interna / Femoral arteries compression test: a non invasive method for detection of obstructive injury of internal iliac artery

Para deteccao nao invasiva da presenca de doenca obstrutiva em arteria iliaca interna criou-se o teste de compressao das femorais. Este teste consiste na compressao da arcada inguinal com o polegar do examinador ate desaparecimento dos batimentos arteriais na regiao e distalmente no membro inferior correspondente, enquanto se ausculta o som na arteria dorsal peniana com estetoscopio ultra-sonico e se mede a pressao peniana. O teste foi considerado positivo quando houve abolicao do som na arteria peniana, ou reducao superior a 15 por cento na pressao peniana e, negativo, quando nao houve abolicao do som nem reducao da PP. Em 15 individuos normais, os 30 testes feitos, um para cada regiao inguinal, foram negativos. Em 23 pacientes com isquemia de membros inferiores selecionados pela analise de angiografias a que foram submetidos, foram realizados 39 testes, um em cada regiao inguinal em que havia batimento femoral. Houve abolicao do som na arteria dorsal peniana em 20 dos 22 testes em que a arteriografia mostrava obstrucao da arteria iliaca interna homolateral. Em 15 testes em que houve reducao da pressao peniana a arteriografia mostrava presenca de estenoses unica ou multiplas na arteria iliaca interna homolateral. Em dois casos com arteria iliaca interna homolateral pervia o teste foi negativo.

Arterites dependentes de processo infeccioso: a conveniencia do uso de heparina / Arteritis dependent of infectious process: the convenience of heparin use

Em 20 pacientes com arterite periferica foram investigadas 1) a presenca do agente etiologico nos vasos pertencentes as areas isquemicas, 2) a relacao entre o tempo de instalacao e de evolucao das lesoes cutaneas e de extremidades e o processo infeccioso, e 3) a conveniencia da anticoagulacao terapeutica. Dez pacientes eram portadores de doenca meningococica com hemocultura positiva para Neisseria meningitidis. Indetificou-se a presenca de meningococo em vasos das areas isquemico-necroticas, atraves de microscopia eletronica. As lesoes cutaneas tiveram instalacao e evolucao rapidas e no momento do diagnostico clinico da infeccao meningococia, elas ja eram irreversiveis. Por isso, considerou-se que a anticoagulacao terapeutica nao seria eficiente. Cinco pacientes tinham infeccao pulmonar ou gastrointestinal. Nao se encontrou microrganismos nos vasos das areas lesadas. As lesoes cutaneas tiveram instalacao e evolucao ao longo de dois a seis dias apos o momento do diagnostico clinico do quadro infeccioso. Por isso, considerou-se conveniente a heparinizacao visando bloquear o alastramento de coagulacao intravascular secundaria a vasculite disseminada. Cinco pacientes tiveram possivel arterite de sensibilizacao pos-estreptococica (tres) e arterite de sensibilizacao pos-sarampo (dois). Nao se identificou microrganismo nos vasos das areas lesadas. As lesoes cutaneas e de extremidades instalaram-se cinco a 21 dias apos resolucao clinica da infeccao pregressa e evoluiram ate a forma definitiva por um periodo de um a quatro dias. considerou-se conveniente iniciar a heparinizacao no periodo de evolucao das lesoes perifericas, pretendendo-se assim, reduzir a intensidade da isquemia por bloqueio da coagulacao intravascular secundaria a vasculite...

Levantamento epidemiológico sobre o vício de fumar entre estudantes de medicina no Estado de Säo Paulo / Epidemiological survey of smoking habits among medical studants in the State of Säo Paulo

Os autores analisam o resultado de um inquérito sobre o vício tabágico em uma populaçäo de 1.113 estudantes de Medicina em duas cidades do Estado de Säo Paulo, tendo verificado tabagismo atual ou recente em cerca de 28% dos universitários.Concluem que o exemplo da classe médica e dos pais é muito importante, sendo primordial a instituiçäo de programas eductivos e de orientaçäo sobre os ricos do tabagismo junto a criança, adolescentes, estudantes e profissionais da área de saúde