Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 231
Filtrar
1.
Molecules ; 26(17)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34500777

RESUMO

Human neutrophil elastase (HNE) is a uniquely destructive serine protease with the ability to unleash a wave of proteolytic activity by destroying the inhibitors of other proteases. Although this phenomenon forms an important part of the innate immune response to invading pathogens, it is responsible for the collateral host tissue damage observed in chronic conditions such as chronic obstructive pulmonary disease (COPD), and in more acute disorders such as the lung injuries associated with COVID-19 infection. Previously, a combinatorially selected activity-based probe revealed an unexpected substrate preference for oxidised methionine, which suggests a link to oxidative pathogen clearance by neutrophils. Here we use oxidised model substrates and inhibitors to confirm this observation and to show that neutrophil elastase is specifically selective for the di-oxygenated methionine sulfone rather than the mono-oxygenated methionine sulfoxide. We also posit a critical role for ordered solvent in the mechanism of HNE discrimination between the two oxidised forms methionine residue. Preference for the sulfone form of oxidised methionine is especially significant. While both host and pathogens have the ability to reduce methionine sulfoxide back to methionine, a biological pathway to reduce methionine sulfone is not known. Taken together, these data suggest that the oxidative activity of neutrophils may create rapidly cleaved elastase "super substrates" that directly damage tissue, while initiating a cycle of neutrophil oxidation that increases elastase tissue damage and further neutrophil recruitment.


Assuntos
Imunidade Inata , Elastase de Leucócito/metabolismo , Metionina/análogos & derivados , Neutrófilos/imunologia , Biocatálise , COVID-19/imunologia , COVID-19/patologia , COVID-19/virologia , Domínio Catalítico/genética , Ensaios Enzimáticos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Elastase de Leucócito/antagonistas & inibidores , Elastase de Leucócito/genética , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Metionina/metabolismo , Simulação de Dinâmica Molecular , Infiltração de Neutrófilos , Neutrófilos/enzimologia , Oxirredução/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/patologia , SARS-CoV-2/imunologia , Especificidade por Substrato/imunologia
2.
J Clin Gastroenterol ; 55(9): 733-739, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34334765

RESUMO

Leaving no significant polyp behind while avoiding risks due to unnecessary resections is a commonsense strategy to safely and effectively prevent colorectal cancer (CRC) with colonoscopy. It also alludes to polyps worth removing and, therefore, worth finding. The majority of "worthy" precancerous polyps are adenomas, which for over 2 decades, have received the most attention in performance research and metrics. Consequently, the detection rate of adenomas is currently the only validated, outcome-based measure of colonoscopy demonstrated to correlate with reduced risk of postcolonoscopy CRC. However, a third or more of postcolonoscopy CRCs originate from sessile serrated polyps (SSPs), which are notoriously difficult to find, diagnose and completely resect. Among serrated polyps, the agreement among pathologists differentiating SSPs from non-neoplastic hyperplastic polyps is moderate at best. This lack of ground truth precludes SSPs from consideration in primary metrics of colonoscopy quality or performance of novel polyp detection technologies. By instead leveraging the distinct endoscopic and clinical features of serrated polyps, including those considered important due to proximal location and larger size, clinically significant serrated polyps represent serrated polyps worth removing, enriched with subtle precancerous SSPs. With the explosion of technologies to assist polyp detection, now is the time to broaden benchmarks to include clinically significant serrated polypss alongside adenomas, a measure that is relevant both for assessing the performance of endoscopists, and for assessing new polyp detection technologies.

3.
PLoS One ; 16(7): e0248324, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34319978

RESUMO

Wearing a facial mask can limit COVID-19 transmission. Measurements of communities' mask use behavior have mostly relied on self-report. This study's objective was to devise a method to measure the prevalence of improper mask use and no mask use in indoor public areas without relying on self-report. A stratified random sample of retail trade stores (public areas) in Louisville, Kentucky, USA, was selected and targeted for observation by trained surveyors during December 14-20, 2020. The stratification allowed for investigating mask use behavior by city district, retail trade group, and public area size. The total number of visited public areas was 382 where mask use behavior of 2,080 visitors and 1,510 staff were observed. The average prevalence of mask use among observed visitors was 96%, while the average prevalence of proper use was 86%. In 48% of the public areas, at least one improperly masked visitor was observed and in 17% at least one unmasked visitor was observed. The average prevalence of proper mask use among staff was 87%, similar to the average among visitors. However, the percentage of public areas where at least one improperly masked staff was observed was 33. Significant disparities in mask use and its proper use were observed among both visitors and staff by public area size, retail trade type, and geographical area. Observing unmasked and improperly masked visitors was more common in small (less than 1500 square feet) public areas than larger ones, specifically in food and grocery stores as compared to other retail stores. Also, the majority of the observed unmasked persons were male and middle-aged.


Assuntos
COVID-19/prevenção & controle , Máscaras/estatística & dados numéricos , COVID-19/epidemiologia , COVID-19/transmissão , Transmissão de Doença Infecciosa/prevenção & controle , Transmissão de Doença Infecciosa/estatística & dados numéricos , Humanos , Kentucky/epidemiologia , Pandemias , Prevalência , Logradouros Públicos , Saúde Pública/métodos , SARS-CoV-2/isolamento & purificação
4.
Am J Gastroenterol ; 116(10): 1970-1971, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34101669
5.
World J Gastroenterol ; 27(18): 2054-2072, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34025064

RESUMO

Genomic sequencing, bioinformatics, and initial speciation (e.g., relative abundance) of the commensal microbiome have revolutionized the way we think about the "human" body in health and disease. The interactions between the gut bacteria and the immune system of the host play a key role in the pathogenesis of gastrointestinal diseases, including those impacting the esophagus. Although relatively stable, there are a number of factors that may disrupt the delicate balance between the luminal esophageal microbiome (EM) and the host. These changes are thought to be a product of age, diet, antibiotic and other medication use, oral hygiene, smoking, and/or expression of antibiotic products (bacteriocins) by other flora. These effects may lead to persistent dysbiosis which in turn increases the risk of local inflammation, systemic inflammation, and ultimately disease progression. Research has suggested that the etiology of gastroesophageal reflux disease-related esophagitis includes a cytokine-mediated inflammatory component and is, therefore, not merely the result of esophageal mucosal exposure to corrosives (i.e., acid). Emerging evidence also suggests that the EM plays a major role in the pathogenesis of disease by inciting an immunogenic response which ultimately propagates the inflammatory cascade. Here, we discuss the potential role for manipulating the EM as a therapeutic option for treating the root cause of various esophageal disease rather than just providing symptomatic relief (i.e., acid suppression).


Assuntos
Esôfago de Barrett , Doenças do Esôfago , Bactérias , Disbiose , Humanos
6.
Circulation ; 142(13): 1261-1278, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32686471

RESUMO

BACKGROUND: Atrial fibrillation (AF) is the most common heart rhythm disorder in adults and a major cause of stroke. Unfortunately, current treatments of AF are suboptimal because they are not targeted to the molecular mechanisms underlying AF. Using a highly novel gene therapy approach in a canine, rapid atrial pacing model of AF, we demonstrate that NADPH oxidase 2 (NOX2) generated oxidative injury causes upregulation of a constitutively active form of acetylcholine-dependent K+ current (IKACh), called IKH; this is an important mechanism underlying not only the genesis, but also the perpetuation of electric remodeling in the intact, fibrillating atrium. METHODS: To understand the mechanism by which oxidative injury promotes the genesis and maintenance of AF, we performed targeted injection of NOX2 short hairpin RNA (followed by electroporation to facilitate gene delivery) in atria of healthy dogs followed by rapid atrial pacing. We used in vivo high-density electric mapping, isolation of atrial myocytes, whole-cell patch clamping, in vitro tachypacing of atrial myocytes, lucigenin chemiluminescence assay, immunoblotting, real-time polymerase chain reaction, immunohistochemistry, and Masson trichrome staining. RESULTS: First, we demonstrate that generation of oxidative injury in atrial myocytes is a frequency-dependent process, with rapid pacing in canine atrial myocytes inducing oxidative injury through the induction of NOX2 and the generation of mitochondrial reactive oxygen species. We show that oxidative injury likely contributes to electric remodeling in AF by upregulating IKACh by a mechanism involving frequency-dependent activation of PKCε (protein kinase C epsilon). The time to onset of nonsustained AF increased by >5-fold in NOX2 short hairpin RNA-treated dogs. Furthermore, animals treated with NOX2 short hairpin RNA did not develop sustained AF for up to 12 weeks. The electrophysiological mechanism underlying AF prevention was prolongation of atrial effective refractory periods, at least in part attributable to the attenuation of IKACh. Attenuated membrane translocation of PKCε appeared to be a likely molecular mechanism underlying this beneficial electrophysiological remodeling. CONCLUSIONS: NOX2 oxidative injury (1) underlies the onset, and the maintenance of electric remodeling in AF, as well, and (2) can be successfully prevented with a novel, gene-based approach. Future optimization of this approach may lead to a novel, mechanism-guided therapy for AF.

7.
Inorg Chem ; 59(15): 10756-10767, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32687342

RESUMO

Previous published entropies of solid lanthanide trichloride hydrates are reviewed and revised by taking account of the Kramers degeneracy of ground states with half-integral values of J. The revised values necessitate corrections to the standard entropies of the aqueous tripositive lanthanide ions which display an irregular variation with both atomic number and ionic radius. These irregularities can be smoothed out by taking account of contributions from the electronic or magnetic entropy, from structural changes in the coordination that have been revealed by EXAFS and XANES measurements and X-ray crystallography, and from an increasing intrusion of eight coordination across the series. When these contributions are removed, the entropies of the aqueous ions refer to a hypothetical nine-coordinate state in trigonal triprismatic coordination. Within experimental error, they then vary uniformly across the lanthanide series and there is a good linear correlation with the reciprocal of the metal-oxygen distance in the nine-coordinate aqua complexes.

8.
Endosc Int Open ; 8(5): E673-E683, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32355887

RESUMO

Background and study aims Colonoscopy for colorectal cancer (CRC) screening has reduced CRC incidence and mortality and improved prognosis. Optimal bowel preparation and high-quality endoscopic technique facilitate early CRC detection. This review provides a narrative on the clinical importance of bowel preparation for colonoscopy and highlights available bowel preparations. Methods A PubMed search was conducted through June 2019 to identify studies evaluating clinical outcomes, efficacy, safety, and tolerability associated with bowel preparation for CRC screening-related colonoscopy. Results Selecting the optimal bowel preparation regimen is based on considerations of efficacy, safety, and tolerability, in conjunction with individual patient characteristics and preferences. Available bowel preparations include high-volume (4 L) and low-volume (2 L and 1 L), polyethylene glycol (PEG) solutions, sodium sulfate, sodium picosulfate/magnesium oxide plus anhydrous citric acid, sodium phosphate tablets, and the over-the-counter preparations magnesium citrate and PEG-3350. These preparations may be administered as a single dose on the same day or evening before, or as two doses administered the same day or evening before/morning of colonoscopy. Ingesting at least half the bowel preparation on the day of colonoscopy (split-dosing) is associated with higher adequate bowel preparation quality versus evening-before dosing (odds ratio [OR], 2.5; 95 % confidence interval [CI], 1.9-3.4). Conclusions High-quality bowel preparation is integral for optimal CRC screening/surveillance by colonoscopy. Over the last 30 years, patients and providers have gained more options for bowel preparation, including low-volume agents with enhanced tolerability and cleansing quality that are equivalent to 4 L preparations. Split-dosing is preferred for achieving a high-quality preparation.

9.
Nat Plants ; 6(4): 349-354, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32203292

RESUMO

How species coexist despite competing for the same resources that are in limited supply is central to our understanding of the controls on biodiversity1,2. Resource partitioning may facilitate coexistence, as co-occurring species use different sources of the same limiting resource3,4. In plant communities, however, direct evidence for partitioning of the commonly limiting nutrient, phosphorus (P), has remained scarce due to the challenges of quantifying P acquisition from its different chemical forms present in soil5. To address this, we used 33P to directly trace P uptake from DNA, orthophosphate and calcium phosphate into monocultures and mixed communities of plants growing in grassland soil. We show that co-occurring plants acquire P from these important organic and mineral sources in different proportions, and that differences in P source use are consistent with the species' root adaptations for P acquisition. Furthermore, the net benefit arising from niche plasticity (the gain in P uptake for a species in a mixed community compared to monoculture) correlates with species abundance in the wild, suggesting that niche plasticity for P is a driver of community structure. This evidence for P resource partitioning and niche plasticity may explain the high levels of biodiversity frequently found in P-limited ecosystems worldwide6,7.


Assuntos
Fósforo/metabolismo , Plantas/metabolismo , Solo/química , Biodiversidade , DNA de Plantas/metabolismo , Ecossistema , Compostos de Fósforo/metabolismo
10.
Bioorg Med Chem Lett ; 30(6): 126984, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-32001135

RESUMO

Toll-like receptors 7 and 8 (TLR7/8) agonists are potent immunostimulants that are attracting considerable interest as vaccine adjuvants. We recently reported the synthesis of a new series of 2-O-butyl-8-oxoadenines substituted at the 9-position with various linkers and N-heterocycles, and showed that TLR7/8 selectivity, potency and cytokine induction could be modulated by varying the alkyl linker length and the N-heterocyclic ring. In the present study, we further optimized the oxoadenine scaffold by investigating the effect of different substituents at the 2-position of the oxoadenine on TLR7/8 potency/selectivity, cytokine induction and DC maturation in human PBMCs. The results show that introducing a 1-(S)-methylbutoxy group at the 2-position of the oxoadenine significantly increased potency for TLR7/8 activity, cytokine induction and DC maturation.


Assuntos
Adenina/análogos & derivados , Adjuvantes Imunológicos/química , Receptor 7 Toll-Like/agonistas , Receptor 8 Toll-Like/agonistas , Adenina/química , Adenina/imunologia , Adjuvantes Imunológicos/metabolismo , Citocinas/metabolismo , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Quinolinas/química , Relação Estrutura-Atividade
11.
Emerg Radiol ; 27(1): 41-44, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31617107

RESUMO

PURPOSE: To determine the effect on time to diagnosis of making MRI imaging for hip fractures available directly in the emergency department (ED). METHODS: We conducted a retrospective observational study of patients with MRI imaging of the hip for suspected occult fracture, comparing time to diagnosis and time to disposition of populations imaged in the year preceding and the year following installation of an MRI scanner in the ED. RESULTS: Time to diagnosis of hip fractures was 709 min before installation of a dedicated ED MRI scanner and 280 min after, a 60% reduction. Including the MRI in the diagnostic workup did not increase ED throughput time, and we were able to save 48% of the patients who had an ED-based MRI from an admission to the hospital. CONCLUSION: Implementation of an MRI scanner for dedicated emergency department use enables faster hip fracture diagnosis and surgical consultation, or definitive disposition without increasing ED throughput time.


Assuntos
Serviço Hospitalar de Emergência , Fraturas do Quadril/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Idoso , Diagnóstico Diferencial , Fraturas do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
ACS Omega ; 4(13): 15665-15677, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31572869

RESUMO

Toll-like receptors 7 and 8 (TLR7/8) are broadly expressed on antigen-presenting cells, making TLR7/8 agonists likely candidates for the development of new vaccine adjuvants. We previously reported the synthesis of a new series of 8-oxoadenines substituted at the 9-position with a 4-piperidinylalkyl moiety and demonstrated that TLR7/8 selectivity and potency could be modulated by varying the length of the alkyl linker. In the present study, we broadened our initial structure-activity relationship study to further evaluate the effects of N-heterocycle ring size, chirality, and substitution on TLR7/8 potency, receptor selectivity, and cytokine (IFNα and TNFα) induction from human peripheral blood mononuclear cells (PBMCs). TLR7/8 activity correlated primarily to linker length and to a lesser extent to ring size, while ring chirality had little effect on TLR7/8 potency or selectivity. Substitution of the heterocyclic ring with an aminoalkyl or hydroxyalkyl group for subsequent conjugation to phospholipids or antigens was well tolerated with the retention of both TLR7/8 activity and cytokine induction from human PBMCs.

13.
JCI Insight ; 4(20)2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31503549

RESUMO

Atrial fibrillation (AF) is the most common heart rhythm disorder and a major cause of stroke. Unfortunately, current therapies for AF are suboptimal, largely because the molecular mechanisms underlying AF are poorly understood. Since the autonomic nervous system is thought to increase vulnerability to AF, we used a rapid atrial pacing (RAP) canine model to investigate the anatomic and electrophysiological characteristics of autonomic remodeling in different regions of the left atrium. RAP led to marked hypertrophy of parent nerve bundles in the posterior left atrium (PLA), resulting in a global increase in parasympathetic and sympathetic innervation throughout the left atrium. Parasympathetic fibers were more heterogeneously distributed in the PLA when compared with other left atrial regions; this led to greater fractionation and disorganization of AF electrograms in the PLA. Computational modeling revealed that heterogeneously distributed parasympathetic activity exacerbates sympathetic substrate for wave break and reentry. We further discovered that levels of nerve growth factor (NGF) were greatest in the left atrial appendage (LAA), where AF was most organized. Preferential NGF release by the LAA - likely a direct function of frequency and regularity of atrial stimulation - may have important implications for creation of a vulnerable AF substrate.


Assuntos
Apêndice Atrial/inervação , Fibrilação Atrial/fisiopatologia , Remodelamento Atrial , Fator de Crescimento Neural/metabolismo , Sistema Nervoso Parassimpático/fisiopatologia , Animais , Apêndice Atrial/citologia , Apêndice Atrial/patologia , Apêndice Atrial/fisiopatologia , Fibrilação Atrial/patologia , Modelos Animais de Doenças , Cães , Humanos , Miócitos Cardíacos/metabolismo
14.
Proc Natl Acad Sci U S A ; 116(26): 12974-12979, 2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31182601

RESUMO

Pulsatile shear (PS) and oscillatory shear (OS) elicit distinct mechanotransduction signals that maintain endothelial homeostasis or induce endothelial dysfunction, respectively. A subset of microRNAs (miRs) in vascular endothelial cells (ECs) are differentially regulated by PS and OS, but the regulation of the miR processing and its implications in EC biology by shear stress are poorly understood. From a systematic in silico analysis for RNA binding proteins that regulate miR processing, we found that nucleolin (NCL) is a major regulator of miR processing in response to OS and essential for the maturation of miR-93 and miR-484 that target mRNAs encoding Krüppel-like factor 2 (KLF2) and endothelial nitric oxide synthase (eNOS). Additionally, anti-miR-93 and anti-miR-484 restore KLF2 and eNOS expression and NO bioavailability in ECs under OS. Analysis of posttranslational modifications of NCL identified that serine 328 (S328) phosphorylation by AMP-activated protein kinase (AMPK) was a major PS-activated event. AMPK phosphorylation of NCL sequesters it in the nucleus, thereby inhibiting miR-93 and miR-484 processing and their subsequent targeting of KLF2 and eNOS mRNA. Elevated levels of miR-93 and miR-484 were found in sera collected from individuals afflicted with coronary artery disease in two cohorts. These findings provide translational relevance of the AMPK-NCL-miR-93/miR-484 axis in miRNA processing in EC health and coronary artery disease.


Assuntos
Doença da Artéria Coronariana/genética , Mecanotransdução Celular/genética , MicroRNAs/metabolismo , Fosfoproteínas/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Adulto , Idoso , Animais , Estudos de Casos e Controles , Células Cultivadas , Biologia Computacional , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Células Endoteliais/patologia , Endotélio Vascular/citologia , Endotélio Vascular/patologia , Feminino , Técnicas de Silenciamento de Genes , Humanos , Fatores de Transcrição Kruppel-Like/genética , Masculino , Camundongos , MicroRNAs/antagonistas & inibidores , MicroRNAs/sangue , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo III/genética , Fosforilação , Processamento de Proteína Pós-Traducional , Processamento Pós-Transcricional do RNA , Serina/metabolismo , Estresse Mecânico
16.
Ann Bot ; 124(1): 77-90, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-31008510

RESUMO

BACKGROUND AND AIMS: By the year 2100, atmospheric CO2 concentration ([CO2]a) could reach 800 ppm, having risen from ~200 ppm since the Neogene, beginning ~24 Myr ago. Changing [CO2]a affects plant carbon-water balance, with implications for growth, drought tolerance and vegetation shifts. The evolution of C4 photosynthesis improved plant hydraulic function under low [CO2]a and preluded the establishment of savannahs, characterized by rapid transitions between open C4-dominated grassland with scattered trees and closed forest. Understanding directional vegetation trends in response to environmental change will require modelling. But models are often parameterized with characteristics observed in plants under current climatic conditions, necessitating experimental quantification of the mechanistic underpinnings of plant acclimation to [CO2]a. METHODS: We measured growth, photosynthesis and plant-water relations, within wetting-drying cycles, of a C3 tree (Vachellia karroo, an acacia) and a C4 grass (Eragrostis curvula) grown at 200, 400 or 800 ppm [CO2]a. We investigated the mechanistic linkages between trait responses to [CO2]a under moderate soil drying, and photosynthetic characteristics. KEY RESULTS: For V. karroo, higher [CO2]a increased assimilation, foliar carbon:nitrogen, biomass and leaf starch, but decreased stomatal conductance and root starch. For Eragrostis, higher [CO2]a decreased C:N, did not affect assimilation, biomass or starch, and markedly decreased stomatal conductance. Together, this meant that C4 advantages in efficient water-use over the tree were maintained with rising [CO2]a. CONCLUSIONS: Acacia and Eragrostis acclimated differently to [CO2]a, with implications for their respective responses to water limitation and environmental change. Our findings question the carbon-centric focus on factors limiting assimilation with changing [CO2]a, how they are predicted and their role in determining productivity. We emphasize the continuing importance of water-conserving strategies in the assimilation response of savannah plants to rising [CO2]a.


Assuntos
Fotossíntese , Poaceae , Dióxido de Carbono , Folhas de Planta , Árvores , Água
17.
Chimia (Aarau) ; 73(3): 144-151, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30890209

RESUMO

The development of ideas of chemical periodicity from Lavoisier to Mendeleyev's first periodic table of 1869 is surveyed. Although his first periodic table contained a number of errors and weaknesses, his remarkable predictions of the properties of several then unknown elements, together with his capacity to adapt the table to new discoveries, slowly led to its general acceptance. The theory of atomic structure slowly developed to a point where it could rationalise the structure of the table which had, however, been established solely on the basis of experimental observations. Chemistry has played the central role, up to and including the final modification of Seaborg to introduce the actinides - although this had been foreseen by Alfred Werner! Finally we discuss the many physical forms in which the table has been presented.

18.
Org Lett ; 21(5): 1379-1383, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30785292

RESUMO

A stereoselective reaction process including a one-pot deconjugation, aldol, and stabilized Peterson olefination of α-trialkylsilyl-ß-alkyl-α,ß-unsaturated esters coupled with aliphatic aldehydes is described. This sequential procedure afforded tri-and disubstituted conjugated diene ester products with dr values of 12-20:1 for the newly established alkene moieties in modest to good isolated yields.

19.
Acad Med ; 94(2): 182-186, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30303814

RESUMO

American medicine has progressively embraced transparency and accountability in professional self-regulation. While public members serving on health care regulatory boards involved with the accreditation, assessment, certification, education, and licensing of physicians provide formal opportunities for voicing public interests, their presence has not been deeply explored. Using 2016 survey and interview data from health care organizations and public members, the authors explore the value and challenges of public members. Public members were often defined as individuals who did not have a background in health care and provided a patient perspective, but in some instances prior health care experience did not automatically exclude these individuals from serving as public members. Public members served on the majority of national health care regulatory boards and constituted an average 9% to 15% of board composition, depending on how rigidly the organizations defined "public member." Public members were valued for their commitment to the priorities and interests of the public, ability to help boards maintain that public focus, and various professional skills they offer to boards. A main challenge that public members faced was their lack of familiarity with and knowledge of the health care field. The authors suggest several considerations for improved public member integration into health care regulatory organizations: clearly defined roles of public members, including evaluating whether or not previous health care experience either contributes or hinders their role within the organization; greater visibility of opportunities for the public to serve on these boards; and potentially a more intensive orientation for public members.


Assuntos
Participação da Comunidade , Atenção à Saúde/legislação & jurisprudência , Regulamentação Governamental , Humanos , Estados Unidos
20.
Curr Opin Gastroenterol ; 35(1): 51-57, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30489414

RESUMO

PURPOSE OF REVIEW: Colonoscopy is recognizably, the best colon cancer prevention test, provided the quality of the preparation is adequate for detection of precancerous polyps but also allowing for accurate identification of margins, thereby facilitating complete endoscopic resection. As there are many aspects effecting colon prep outcomes, it is timely to review new standards for optimizing outcomes, including product selection based on patient demographics. RECENT FINDINGS: New national guidelines have set a minimum quality threshold for adequacy and also defined a split day delivery for oral options as the "standard of care". Several new prep options have been recently released and these data are discussed. SUMMARY: Optimizing the quality of colon preps has major implications for clinical practice. Clinicians must recognize new targets for standard of care, providing the best approach for each individual patient, considering variable factors which may otherwise compromise success.


Assuntos
Catárticos/normas , Pólipos do Colo/cirurgia , Colonoscopia/métodos , Neoplasias Colorretais/prevenção & controle , Lesões Pré-Cancerosas/cirurgia , Cuidados Pré-Operatórios/métodos , Catárticos/administração & dosagem , Colonoscopia/normas , Pesquisa sobre Serviços de Saúde , Humanos , Cuidados Pré-Operatórios/normas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...