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1.
J Emerg Med ; 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32354588

RESUMO

BACKGROUND: The anatomic course of the phrenic nerve runs in the fascia covering the anterior scalene muscle. Interscalene blocks are commonly performed by an anesthesiologist for shoulder surgery, such as a rotator cuff repair, total shoulder replacement, humeral fracture, or other arm surgery. Phrenic nerve palsy or paralysis is a known complication from interscalene block and is covered in multiple case reports and series in both Anesthesia and Neurosurgical literature, but only one case report in the Emergency Medicine literature. CASE REPORT: This case involves a 57-year-old man who had an uncomplicated arthroscopic rotator cuff repair with placement of interscalene block under care of anesthesia. He was discharged with a pain pump in place and then subsequently presented to the Emergency Department (ED) later that same day for evaluation of dyspnea. Using point-of-care ultrasound, his right diaphragm did not appear to be moving. Chest x-ray study revealed an elevated right hemidiaphragm. He was diagnosed with iatrogenic right phrenic nerve paralysis from interscalene block. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergent diagnosis of phrenic nerve paralysis in the ED is complicated by a distressed patient and need for quick intervention. Most formal tests for this diagnosis are not immediately available to emergency physicians. Ultrasound is a rapid and reproducible, noninvasive resource with high sensitivity and specificity, making it an ideal imaging modality for the emergent evaluation of possible phrenic nerve palsy or paralysis.

2.
Diagn Pathol ; 15(1): 57, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32414387

RESUMO

BACKGROUND: Digital multiplex gene expression profiling is overcoming the limitations of many tissue-processing and RNA extraction techniques for the reproducible and quantitative molecular classification of disease. We assessed the effect of different skin biopsy collection/storage conditions on mRNA quality and quantity and the NanoString nCounter™ System's ability to reproducibly quantify the expression of 730 immune genes from skin biopsies. METHODS: Healthy human skin punch biopsies (n = 6) obtained from skin sections from four patients undergoing routine abdominoplasty were subject to one of several collection/storage protocols, including: i) snap freezing in liquid nitrogen and transportation on dry ice; ii) RNAlater (ThermoFisher) for 24 h at room temperature then stored at - 80 °C; iii) formalin fixation with further processing for FFPE blocks; iv) DNA/RNA shield (Zymo) stored and shipped at room temperature; v) placed in TRIzol then stored at - 80 °C; vi) saline without RNAse for 24 h at room temperature then stored at - 80 °C. RNA yield and integrity was assessed following extraction via NanoDrop, QuantiFluor with RNA specific dye and a Bioanalyser (LabChip24, PerkinElmer). Immune gene expression was analysed using the NanoString Pancancer Immune Profiling Panel containing 730 genes. RESULTS: Except for saline, all protocols yielded total RNA in quantities/qualities that could be analysed by NanoString nCounter technology, although the quality of the extracted RNA varied widely. Mean RNA integrity was highest from samples that were placed in RNALater (RQS 8.2 ± 1.15), with integrity lowest from the saline stored sample (RQS < 2). There was a high degree of reproducibility in the expression of immune genes between all samples with the exception of saline, with the number of detected genes at counts < 100, between 100 and 1000 and > 10,000 similar across extraction protocols. CONCLUSIONS: A variety of processing methods can be used for digital immune gene expression profiling in mRNA extracted from skin that are comparable to snap frozen skin specimens, providing skin cancer clinicians greater opportunity to supply skin specimens to tissue banks. NanoString nCounter technology can determine gene expression in skin biopsy specimens with a high degree of sensitivity despite lower RNA yields and processing methods that may generate poorer quality RNA. The increased sensitivity of digital gene expression profiling continues to expand molecular pathology profiling of disease.

3.
Cell Host Microbe ; 27(5): 710-724.e7, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32407709

RESUMO

The rational design of dengue virus (DENV) vaccines requires a detailed understanding of the molecular basis for antibody-mediated immunity. The durably protective antibody response to DENV after primary infection is serotype specific. However, there is an incomplete understanding of the antigenic determinants for DENV type-specific (TS) antibodies, especially for DENV serotype 3, which has only one well-studied, strongly neutralizing human monoclonal antibody (mAb). Here, we investigated the human B cell response in children after natural DENV infection in the endemic area of Nicaragua and isolated 15 DENV3 TS mAbs recognizing the envelope (E) glycoprotein. Functional epitope mapping of these mAbs and small animal prophylaxis studies revealed a complex landscape with protective epitopes clustering in at least 6-7 antigenic sites. Potently neutralizing TS mAbs recognized sites principally in E glycoprotein domains I and II, and patterns suggest frequent recognition of quaternary structures on the surface of viral particles.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32372540

RESUMO

The direct Friedel-Crafts-type coupling and dedinitrogenation reactions of vinyldiazo compounds with aromatic compounds using a metal-free strategy are described. This acid-catalyzed methodology is efficient for the formation of α-diazo-ß-carbocations (vinyldiazonium ions), vinyl carbocations, and allylic or homoallylic carbocation species via vinyldiazo compounds. By choosing suitable nucleophilic reagents to selectively capture these intermediates, both trisubstituted α,ß-unsaturated esters, ß-indole-substituted diazo esters, and dienes are obtained in good to high yields and selectivities. Experimental insights implicate a reaction mechanism involving the selective protonation of vinyldiazo compounds and the subsequent release of dinitrogen to form vinyl cations that undergo intramolecular 1,3- and 1,4- hydride transfer processes as well as fragmentation.

5.
J Org Chem ; 85(5): 3728-3741, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-31990547

RESUMO

Oxidative cleavage reactions of arylalkenes by tert-butyl hydroperoxide that occur by free radical processes provide access to carboxylic acid or ketone products. However, the pathway to these cleavage products is complex, initiated by regioselective oxygen radical addition to the carbon-carbon double bond. Subsequent reactions of the initially formed benzyl radical lead eventually to carbon-carbon cleavage. Thorough investigations of these reactions have identified numerous reaction intermediates that are on the pathways to final product formation, and they have identified a new synthetic methodology for the synthesis of peroxy radical addition-induced hydroperoxide formation.

6.
Nat Commun ; 10(1): 5328, 2019 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-31757976

RESUMO

Coupling reactions of amines and alcohols are of central importance for applications in chemistry and biology. These transformations typically involve the use of a reagent, activated as an electrophile, onto which nucleophile coupling results in the formation of a carbon-nitrogen or a carbon-oxygen bond. Several promising reagents and procedures have been developed to achieve these bond forming processes in high yields with excellent stereocontrol, but few offer direct coupling without the intervention of a catalyst. Herein, we report the synthesis of chiral donor-acceptor azetines by highly enantioselective [3 + 1]-cycloaddition of enoldiazoacetates with aza-ylides and their selective coupling with nitrogen and oxygen nucleophiles via 3-azetidinones to form amino acid derivatives, including those of peptides and natural products. The overall process is general for a broad spectrum of nucleophiles, has a high degree of electronic and steric selectivity, and retains the enantiopurity of the original azetine.

7.
J Am Chem Soc ; 141(42): 16643-16650, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31574223

RESUMO

α-Aminoradicals undergo halogen atom abstraction to form halomethyl radicals in reactions initiated by the combination of tert-butyl hydroperoxide, aliphatic trialkylamine, halocarbon, and copper(I) iodide. The formation of the α-aminoradical circumvents preferential hydrogen atom transfer in favor of halogen atom transfer, thereby releasing the halomethyl radical for addition to alkenes. The resulting radical addition products add the tert-butylperoxy group to form α-peroxy-ß,ß-dichloropropylbenzene products that are convertible to their corresponding ß,ß-dichloro-alcohols and to novel pyridine derivatives. Computational analysis clearly explains the deviation from traditional HAT of chloroform and also establishes formal oxidative addition/reductive elimination as the lowest energy pathway.

8.
BMC Med Inform Decis Mak ; 19(1): 180, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488135

RESUMO

BACKGROUND: The Grog Survey App is a visual and interactive tablet computer-based survey application. It has been shown to be an accurate and acceptable tool to help Indigenous Australians describe what they drink. METHODS: The Grog Survey App was used to enquire into patterns of drinking in a stratified sample of Indigenous Australians in urban and remote/regional sites during testing of the App. The App asked about the last four drinking occasions in the past 12 months, including preferred alcohol types and containers; and symptoms of alcohol dependence, based on ICD-11 descriptions. Drinking patterns are presented here using medians and interquartile ranges, and the thresholds set out by the Australian National and Health and Medical Research Council guidelines. Patterns of consumption are compared by gender and remoteness, using Wilcoxon rank-sum test to compare medians. Logistic regressions tested whether alcohol types and drinking containers varied by remoteness. RESULTS: In this stratified sample most people either consumed nothing (21.7%), or consumed quantities which placed them at short- (95.6%) or long-term risk (47.8%) of harms. Drinkers in remote areas were more likely to drink beer, but less likely to drink pre-mixed spirits. 'Stubbies' and other beer glasses were popular in urban areas, compared with 'slabs' (cases of beer) in remote/regional areas. The use of improvised containers (i.e. empty juice bottles) did not vary by remoteness. Nearly one in six (15%) current drinkers reported experiencing at least two symptoms of alcohol dependence at least monthly. Average drinks per day was the consumption measure most highly correlated with each dependence symptom (r = 0.34-0.38). CONCLUSIONS: The App was able to capture a wide range of preferred alcohol types and containers, and demonstrate a diversity in how alcohol is consumed. This detail was captured in a relative brief survey delivered using an interactive and appealing tablet computer-based application.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Grupo com Ancestrais Oceânicos , Autorrelato , Software , Adulto , Austrália , Computadores de Mão , Feminino , Comportamentos Relacionados com a Saúde , Inquéritos Epidemiológicos , Humanos , Modelos Logísticos , Masculino , Projetos de Pesquisa
9.
Angew Chem Int Ed Engl ; 58(45): 16188-16192, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31496021

RESUMO

The all-cis stereoisomers of tetrasubstituted azetidine-2-carboxylic acids and derivatives that possess three chiral centers have been prepared in high yield and stereocontrol from silyl-protected Z-γ-substituted enoldiazoacetates and imido-sulfur ylides by asymmetric [3+1]-cycloaddition using chiral sabox copper(I) catalysis followed by Pd/C catalytic hydrogenation. Hydrogenation of the chiral p-methoxybenzyl azetine-2-carboxylates occurs with both hydrogen addition to the C=C bond and hydrogenolysis of the ester.

10.
Crit Rev Food Sci Nutr ; : 1-6, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31397170

RESUMO

The combination of levulinic acid and sodium dodecyl sulfate (SDS) in recent years has shown considerable promise as an antimicrobial intervention. Both ingredients have been designated by the U.S. Food and Drug Administration (FDA) as Generally Recognized as Safe (GRAS) for being used as a flavoring agent and multipurpose food additive, respectively. The use of levulinic acid and SDS alone has limited antimicrobial efficacy on tested microorganisms, and synergism between levulinic acid and SDS has been observed. The postulated mechanism of action of the synergistic effect is presented. The antimicrobial efficacy of levulinic acid plus SDS remains high even when organic materials are present. The other features, including penetration, foamability, and being readily soluble, extend its potential applications to disinfection of difficult-to-access areas and control of foodborne pathogens both in a planktonic state and in a biofilm. These features indicate that the levulinic acid plus SDS combination may have the potential to be applied within the food processing environment on a large scale.

11.
Angew Chem Int Ed Engl ; 58(36): 12502-12506, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31322789

RESUMO

A chiral copper(I) complex catalyzes reactions of symmetric diaziridines with enol diazo compounds, which react through N-N bond ring opening in a formal [3+3] cycloaddition to form four chiral centers with high stereocontrol. A broad spectrum of bridged dinitrogen heterocycles were obtained in high yields and excellent diastereo- and enantioselectivities from γ-substituted enol diazoacetates, while their geometrical isomers gave different enantioselectivities. Donor-acceptor cyclopropenes formed from the geometrical isomers of the γ-substituted enol diazoacetates underwent catalytic ring opening to give only the Z isomer of the metalloenolcarbene intermediate, provided excellent yields and selectivities for the 1,5-diazabicyclo[n.3.1]non-2-ene derivatives.

12.
Muscle Nerve ; 60(2): 147-154, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31136007

RESUMO

INTRODUCTION: We previously reported our amyotrophic lateral sclerosis (ALS) video televisit experience. Here we report on video televisit versus in-clinic costs, adjusting for perceived medical usefulness (MU). METHODS: We take the patient-perspective and a focused institutional-perspective. Costs are adjusted for patient/caregiver and physician perceptions of visit MU. The base-case reflects our outpatient ALS practice. RESULTS: In the base-case, from the patient perspective, in-clinic visits cost $1,116 and video televisits cost $89 ($119 after MU-adjustment). From the institutional perspective, clinic visits cost $799, and video televisits cost $354 ($472 after MU-adjustment). Adjusted cost-savings per televisit are $997 (patient) and $327 (institution). Sensitivity analyses on 5 variables accounted for uncertainty in base-case assumptions. CONCLUSIONS: Video televisits provide marked adjusted cost-savings for patients and institutions. Adjusted costs are sensitive to perceived MU of video televisits. Future research should explore the ability of video televisits to reduce healthcare resource usage. Muscle Nerve 60: 147-154, 2019.


Assuntos
Esclerose Amiotrófica Lateral/economia , Telemedicina/economia , Comunicação por Videoconferência/economia , Assistência Ambulatorial , Esclerose Amiotrófica Lateral/terapia , Cuidadores , Redução de Custos , Efeitos Psicossociais da Doença , Custos e Análise de Custo , Habitação/economia , Humanos , Licença Médica/economia , Viagem/economia
13.
J Oral Maxillofac Surg ; 77(8): 1687-1694, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30991020

RESUMO

PURPOSE: Intraoral scanners (IOSs), which create digital "impressions" of dental arches, have become popular for prosthetic and orthodontic applications. Adoption in oral and maxillofacial surgery (OMS) practices has been slower, likely because of high implementation costs and low-volume use. The purpose of this study was to evaluate costs for introduction of an IOS into an OMS practice. The authors hypothesized that digital impressions would be more efficient in time and cost compared with conventional impressions and that implementation costs would be offset within 1 year. MATERIALS AND METHODS: This was a prospective study that included patients who had digital impressions during the first year after introduction of an IOS to the practice. Conventional alginate impressions obtained at the same visit were included for comparison. Variables included time for each step in each impression process, IOS experience of the operator obtaining the impression, and associated costs. Per-arch costs for each technique were calculated using time-driven activity-based costing methodology. RESULTS: Sixty-three digital impressions and 31 conventional impressions were included. Mean total times for digital and conventional impressions were 14.1 ± 1.3 and 19.4 ± 4.0 minutes per arch, respectively. On a per-patient basis (2 arches for digital impressions and 4 arches for conventional impressions because of the inability to create duplicate stone models from each alginate impression), total impression times were 24.8 ± 2.7 minutes for digital and 67.2 ± 14.8 minutes for conventional impressions. Total calculated costs for digital and conventional impressions were $21.42 and $29.40 per arch and $37.66 and $102.10 per patient, respectively. In a practice with 2 patients for impressions per working day (500 per year), it would take 1.04 years to offset the purchase of the IOS; with 5 sets of impressions per day (1,250 per year), it would take 5 months. CONCLUSION: Digital impressions are more efficient and cost effective than standard impressions, and implementation costs can be offset within the first year.

14.
J Craniofac Surg ; 30(6): e539-e542, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30939559

RESUMO

PURPOSE: Craniofacial anthropometry is a valuable tool for characterization of facial dysmorphology and evaluation of treatment outcomes. Databases of normal anthropometric ranges are limited for infants. The aim of this study is to establish normative data for craniofacial anthropometric measurements in Caucasian infants. METHODS: This is a prospective cross-sectional study including Caucasian infants (≤12 months old) that were recruited from a pediatric medicine practice and Boston Children's Hospital. Infants with craniofacial deformities, trauma or operations were excluded. The sample was stratified by age (in months) into 4 groups: 0 to 3, 3.1 to 6, 6.1 to 9, and 9.1 to 12. Three dimensional (3D) photographs were obtained for all subjects. Forty-five standard anthropometric points were plotted, and 37 measurements were made on the 3D photographs. Two evaluators independently performed all measurements. One examiner repeated the measurements on 25% of the subjects. Intraclass correlation coefficients (ICC) were calculated to assess inter-rater and intra-rater agreement. RESULTS: Thirty-three subjects were enrolled in the study. The mean age for the entire sample was 6.3 ±â€Š3.0 months, and 17 subjects (52%) were female. The mean ages (months) for each group were: 1.9 ±â€Š0.7 for group 1 (n = 6); 4.4 ±â€Š0.7 for group 2 (n = 8); 7.5 ±â€Š1.1 for group 3 (n = 11); and 9.9 ±â€Š1.0 for group 4 (n = 8). Descriptive statistics are presented for each group. Inter- and intra-rater agreements were acceptable (ICC >0.6) for 21 anthropometric measurements. CONCLUSIONS: This study generated normative craniofacial anthropometric measurements for Caucasian infants. These data can be used in the interpretation of measurements for research studies evaluating craniofacial anomalies in this population.


Assuntos
Antropometria , Face/anatomia & histologia , Algoritmos , Antropometria/métodos , Biometria , Anormalidades Craniofaciais , Estudos Transversais , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Imageamento Tridimensional/métodos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Valores de Referência , Reprodutibilidade dos Testes
15.
Aust N Z J Public Health ; 43(2): 120-130, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30908856

RESUMO

OBJECTIVE: A history of alcohol and other drug (AoD) use is common among men entering prison and often linked to the crime for which they are imprisoned. This is the first systematic review of prison-based, behavioural AoD treatment programs for more than a decade and the first that reviews the methodological quality of evaluations. This review aims to create an understanding of the quality of research in this field and identify the most effective AoD use treatment for men in prison. METHODS: A PRISMA-compliant systematic review of international, peer-reviewed research published between January 1995 and December 2015. The Dictionary for Effective Public Health Practice Project was used to assess the methodological quality of papers. RESULTS: A total of 25 relevant papers were identified, of which 12 were rated as methodologically sound. Four of these measured post-release AoD use and three reported statistically significant reductions in AoD use. CONCLUSIONS: Although there is relatively little methodologically strong evidence of the impact of prison-based AoD treatment, and no Australian papers studies, current best-evidence practice is Cognitive behavioural therapy delivered in Therapeutic Community (TC) settings. Implications for public health: Prison-based TC treatment should be available to people in prison who have a history of AoD use.


Assuntos
Terapia Comportamental/métodos , Prisioneiros , Transtornos Relacionados ao Uso de Substâncias/terapia , Crime , Humanos , Masculino , Prisões , Transtornos Relacionados ao Uso de Substâncias/psicologia , Comunidade Terapêutica , Resultado do Tratamento
16.
Org Biomol Chem ; 17(17): 4183-4195, 2019 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-30924829

RESUMO

This review describes catalytic asymmetric cycloaddition reactions of silyl-protected enoldiazo compounds for the construction of highly functionalized carbo- and heterocycles which possess one or more chiral center(s). The enoldiazo compound or its derivative, donor-acceptor cyclopropene, form electrophilic vinylogous metal carbene intermediates that combine stepwise with nucleophilic dipolar reactants to form products from [3 + 1]-, [3 + 2]-, [3 + 3]-, [3 + 4]-, and [3 + 5]-cycloaddition, generally in high yield and with exceptional stereocontrol and regioselectivity.


Assuntos
Compostos Azo/síntese química , Cobre/química , Compostos Azo/química , Catálise , Reação de Cicloadição , Estrutura Molecular , Estereoisomerismo
17.
Ir J Med Sci ; 188(4): 1269-1274, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30706295

RESUMO

BACKGROUND: Early-onset group B Streptococcus (EOGBS/GBS) infection remains a significant cause of neonatal morbidity and mortality. AIMS: Aiming to improve antimicrobial stewardship and reduce unnecessary maternal and infant exposure to intrapartum antibiotic prophylaxis (IAP), this study assessed the clinical use of a commercially available GBS polymerase chain reaction (PCR) assay for term women with pre-labour rupture of membranes. METHODS: This was a retrospective study in a tertiary level maternity unit of term women with pre-labour rupture of membranes (ROM), without any clinical suspicion of infection performed between November and December 2017. GBS PCR tests were cross-referenced with patient clinical data. PCR test results, the impact of testing on antibiotic administration, pyrexia in labour, induction, interventional delivery rates and neonatal outcomes were analysed. RESULTS: Of 200 patients included in the study, 29 were positive (14.5%) and 166 were negative (83%), with five invalid results (2.5%). One hundred and twenty three women had > 18-h ruptured membranes and 86 women (70%) who would have been eligible for IAP based on risk factors avoided antibiotic therapy following a negative PCR test. There were no significant differences in induction or interventional delivery rates between GBS-positive and GBS-negative women following PCR testing. During the study period, there were no cases of EOGBS. CONCLUSIONS: In a centre adhering to a risk-factor-based GBS policy, the introduction of limited rapid GBS screening for term women with pre-labour rupture of membranes resulted in a clinically significant reduction in prophylactic antibiotic use.


Assuntos
Antibacterianos/uso terapêutico , Ruptura Prematura de Membranas Fetais/microbiologia , Complicações Infecciosas na Gravidez/diagnóstico , Infecções Estreptocócicas/diagnóstico , Adulto , Antibioticoprofilaxia/métodos , Feminino , Humanos , Recém-Nascido , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Gravidez , Estudos Retrospectivos , Fatores de Risco , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus agalactiae/isolamento & purificação , Adulto Jovem
18.
Plast Reconstr Surg ; 143(4): 1136-1145, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30676503

RESUMO

BACKGROUND: The goal of this study was to determine upper-extremity function and health-related quality of life in a cohort of adults with Apert syndrome. METHODS: Twenty-two adults with Apert syndrome completed the Disabilities of the Arm, Shoulder, and Hand survey; the 36-Item Short-Form Health Survey; and a semistructured interview. One surgeon administered the Jebsen Hand Function Test and measured sensation, joint motion, and strength. RESULTS: Median Disabilities of the Arm, Shoulder, and Hand score was 16.9, which indicated slightly greater disability than the population norm of 10.1. Median 36-Item Short-Form Health Survey scores were 54.5 for mental health and 57.0 for physical health-both more favorable than population norms. Total Jebsen Hand Function Test scores for dominant hand were 69.2 seconds for men and 64.7 seconds for women versus 37.8 seconds for population norms of both sexes. More complex syndactyly resulted in worse metacarpophalangeal joint motion but no significant difference in Disabilities of the Arm, Shoulder, and Hand; 36-Item Short-Form Health Survey; or other functional results. There was no difference in self-reported outcomes between patients with four (n = 8) versus five digits (n = 14) in each hand. CONCLUSIONS: In this cohort of adults with Apert syndrome, self-reported assessment of disability was more favorable than measured functional data would suggest. Despite significant functional deficits, the participants in this study had adapted remarkably well.


Assuntos
Acrocefalossindactilia/fisiopatologia , Extremidade Superior/fisiologia , Atividades Cotidianas , Adaptação Fisiológica , Adulto , Estudos de Coortes , Avaliação da Deficiência , Feminino , Humanos , Estilo de Vida , Masculino , Qualidade de Vida , Adulto Jovem
19.
Proc Natl Acad Sci U S A ; 116(5): 1591-1596, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30642974

RESUMO

Zika virus (ZIKV) is a major human pathogen and member of the Flavivirus genus in the Flaviviridae family. In contrast to most other insect-transmitted flaviviruses, ZIKV also can be transmitted sexually and from mother to fetus in humans. During recent outbreaks, ZIKV infections have been linked to microcephaly, congenital disease, and Guillain-Barré syndrome. Neutralizing antibodies have potential as therapeutic agents. We report here a 4-Å-resolution cryo-electron microscopy structure of the ZIKV virion in complex with Fab fragments of the potently neutralizing human monoclonal antibody ZIKV-195. The footprint of the ZIKV-195 Fab fragment expands across two adjacent envelope (E) protein protomers. ZIKV neutralization by this antibody is presumably accomplished by cross-linking the E proteins, which likely prevents formation of E protein trimers required for fusion of the viral and cellular membranes. A single dose of ZIKV-195 administered 5 days after virus inoculation showed marked protection against lethality in a stringent mouse model of infection.


Assuntos
Anticorpos Monoclonais/imunologia , Epitopos/imunologia , Infecção por Zika virus/imunologia , Zika virus/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Microscopia Crioeletrônica/métodos , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Vacinação/métodos , Proteínas do Envelope Viral/imunologia
20.
Org Lett ; 21(1): 40-44, 2019 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-30550288

RESUMO

Enoldiazosulfones undergo [3 + 3]-cycloaddition with nitrones when catalyzed by copper(I) catalysts, but not with dirhodium(II) catalysts. Under mild reaction conditions with chiral bisoxazoline ligands, copper(I) catalysts produce 1,2-oxazine-sulfone derivatives in high yields and enantioselectivities. Dirhodium(II) catalysts form stable donor-acceptor cyclopropenes that undergo uncatalyzed [3 + 2]-cycloaddition reactions with nitrones.

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