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1.
Infant Ment Health J ; 41(6): 811-820, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32589319

RESUMO

My Baby's First Teacher is an intervention designed specifically for parents with infants staying in emergency homeless shelters. Infants are overrepresented in shelter populations and face considerable risk to their development, including mental health. We utilized a randomized controlled design across three family shelters to evaluate the program's effectiveness with 24 dyads assigned to the intervention compared to 21 dyads in care-as-usual. Dyads were randomized by round at each site to account for shelter effects. We used path analysis to illustrate change over time and in relation to intervention assignment.


El Primer Maestro de mi Bebé es una intervención diseñada específicamente para progenitores con infantes que se alojan en refugios de emergencia para personas sin casa. En la población de los refugios, los infantes están sobrerrepresentados y enfrentan un considerable riesgo en cuanto a su desarrollo, incluyendo la salud mental. Utilizamos un diseño de control al azar a través de tres refugios de familias para evaluar la eficacia del programa con 24 díadas asignadas al grupo de intervención que fueron comparadas con 21 díadas bajo el cuidado usual. A las díadas se les colocó al azar por etapas en cada lugar para tener en cuenta los efectos del refugio. Usamos un análisis de trayectoria para ilustrar el cambio a través del tiempo y en relación con la asignación de intervención. Resultados claves: los resultados indicaron mejoras en la observada sensibilidad de progenitor-infante relacionada con la intervención en el lugar, con un control en cuanto a los niveles iniciales de sensibilidad. Los resultados fueron consistentes entre un modelo de intención de tratar y un modelo para probar la participación cierta en la intervención. No encontramos ningún efecto significativo para el estrés de crianza o la ansiedad del progenitor, aunque las tendencias sugirieron más altos puntajes para las familias de la intervención. Implicaciones para la práctica y las políticas: presentamos los resultados considerando retos específicos en contextos de casos sin casa para la salud mental infantil. Este trabajo puede servir de base para los esfuerzos de quienes proveen servicios y encuentran familias que experimentan el estar sin casa, así como también las políticas sobre los recursos para programaciones en albergues de emergencia.


Le Premier Enseignant de Mon Bébé est une intervention conçue spécialement pour les parents dont les bébés restent dans des foyers d'urgence pour sans-abris. Les bébés sont sur-représentés dans les populations de ces foyers et ils font face à un risque considérable pour leur développement, y compris pour ce qui concerne leur santé mentale. Nous avons utilisé un schéma expérimental contrôlé pour 3 trois foyers familiaux afin d'évaluer l'efficacité du programme avec 24 dyades désignées pour l'intervention comparé à 21 dyades dans le groupe de soins habituels. Les dyades ont été randomisées par ronde sur chaque site afin de contrôler les effets du foyer. Nous avons utilisé une analyse causale pour illustrer le changement au fil du temps et en relation au groupe d'intervention. Constatations Clés: Résultats a indiqué des améliorations dans la réaction observée parent-bébé liée à l'intervention en fin d'étude, contrôlant les niveaux initiaux de réaction. Les résultats sont cohérents entre un modèle intention-de-traiter et un modèle testant la véritable participation à l'intervention. Nous n'avons trouvé aucun effet important pour le stress de parentage ou la détresse du parent, bien que des tendances suggèrent des scores plus élevés pour les familles d'intervention. Nous présentons des résultats en considérant les défis uniques aux contextes de la vie des sans-abris pour la santé mentale du nourrisson. Ce travail peut orienter les efforts des prestataires de services qui rencontrent des familles faisant l'expérience d'une vie sans abri ainsi que les lois et pratiques concernant les ressources pour des programmes dans des foyers d'accueil d'urgence.


Assuntos
Pessoas Mal Alojadas/psicologia , Relações Pais-Filho , Pais/psicologia , Adolescente , Adulto , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Masculino , Poder Familiar/psicologia , Adulto Jovem
2.
J Am Chem Soc ; 141(25): 9837-9853, 2019 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-31144503

RESUMO

Piscidins are histidine-enriched antimicrobial peptides that interact with lipid bilayers as amphipathic α-helices. Their activity at acidic and basic pH in vivo makes them promising templates for biomedical applications. This study focuses on p1 and p3, both 22-residue-long piscidins with 68% sequence identity. They share three histidines (H3, H4, and H11), but p1, which is significantly more permeabilizing, has a fourth histidine (H17). This study investigates how variations in amphipathic character associated with histidines affect the permeabilization properties of p1 and p3. First, we show that the permeabilization ability of p3, but not p1, is strongly inhibited at pH 6.0 when the conserved histidines are partially charged and H17 is predominantly neutral. Second, our neutron diffraction measurements performed at low water content and neutral pH indicate that the average conformation of p1 is highly tilted, with its C-terminus extending into the opposite leaflet. In contrast, p3 is surface bound with its N-terminal end tilted toward the bilayer interior. The deeper membrane insertion of p1 correlates with its behavior at full hydration: an enhanced ability to tilt, bury its histidines and C-terminus, induce membrane thinning and defects, and alter membrane conductance and viscoelastic properties. Furthermore, its pH-resiliency relates to the neutral state favored by H17. Overall, these results provide mechanistic insights into how differences in the histidine content and amphipathicity of peptides can elicit different directionality of membrane insertion and pH-dependent permeabilization. This work features complementary methods, including dye leakage assays, NMR-monitored titrations, X-ray and neutron diffraction, oriented CD, molecular dynamics, electrochemical impedance spectroscopy, surface plasmon resonance, and quartz crystal microbalance with dissipation.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Histidina/química , Bicamadas Lipídicas/metabolismo , Tensoativos/metabolismo , Sequência de Aminoácidos , Animais , Peptídeos Catiônicos Antimicrobianos/química , Proteínas de Peixes/química , Proteínas de Peixes/metabolismo , Peixes , Fluoresceínas/metabolismo , Corantes Fluorescentes/metabolismo , Concentração de Íons de Hidrogênio , Bicamadas Lipídicas/química , Simulação de Dinâmica Molecular , Permeabilidade/efeitos dos fármacos , Fosfatidilcolinas/química , Fosfatidilgliceróis/química , Tensoativos/química
3.
Biochim Biophys Acta Biomembr ; 1859(2): 135-145, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27814978

RESUMO

Apolipoprotein B (apoB) is a large amphipathic protein that is the structural scaffold for the formation of several classes of lipoproteins involved in lipid transport throughout the body. The goal of the present study was to identify specific domains in the apoB sequence that contribute to its lipid binding properties. A sequence analysis algorithm was developed to identify stretches of hydrophobic amino acids devoid of charged amino acids, which are referred to as hydrophobic cluster domains (HCDs). This analysis identified 78 HCDs in apoB with hydrophobic stretches ranging from 6 to 26 residues. Each HCD was analyzed in silico for secondary structure and lipid binding properties, and a subset was synthesized for experimental evaluation. One HCD peptide, B38, showed high affinity binding to both isolated HDL and LDL, and could exchange between lipoproteins. All-atom molecular dynamics simulations indicate that B38 inserts 3.7Å below the phosphate plane of the bilayer. B38 forms an unusual α-helix with a broad hydrophobic face and polar serine and threonine residues on the opposite face. Based on this structure, we hypothesized that B38 could efflux cholesterol from cells. B38 showed a 12-fold greater activity than the 5A peptide, a bihelical Class A amphipathic helix (EC50 of 0.2658 vs. 3.188µM; p<0.0001), in promoting cholesterol efflux from ABCA1 expressing BHK-1 cells. In conclusion, we have identified novel domains within apoB that contribute to its lipid biding properties. Additionally, we have discovered a unique amphipathic helix design for efficient ABCA1-specific cholesterol efflux.


Assuntos
Apolipoproteínas B/química , Apolipoproteínas B/metabolismo , Lipídeos/química , Estrutura Secundária de Proteína/fisiologia , Transportador 1 de Cassete de Ligação de ATP/química , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Aminoácidos/química , Aminoácidos/metabolismo , Sítios de Ligação/fisiologia , Células Cultivadas , HDL-Colesterol/química , HDL-Colesterol/metabolismo , LDL-Colesterol/química , LDL-Colesterol/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Peptídeos/química , Peptídeos/metabolismo , Ligação Proteica/fisiologia
4.
Biophys J ; 111(6): 1248-1257, 2016 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-27653483

RESUMO

An all-atom molecular dynamics simulation of the archetype barrel-stave alamethicin (alm) pore in a 1,2-dioleoyl-sn-glycero-3-phosphocholine bilayer at 313 K indicates that ∼7 µs is required for equilibration of a preformed 6-peptide pore; the pore remains stable for the duration of the remaining 7 µs of the trajectory, and the structure factors agree well with experiment. A 5 µs simulation of 10 surface-bound alm peptides shows significant peptide unfolding and some unbinding, but no insertion. Simulations at 363 and 413 K with a -0.2 V electric field yield peptide insertion in 1 µs. Insertion is initiated by the folding of residues 3-11 into an α-helix, and mediated by membrane water or by previously inserted peptides. The stability of five alm pore peptides at 413 K with a -0.2 V electric field demonstrates a significant preference for a transmembrane orientation. Hence, and in contrast to the cationic antimicrobial peptide described in the following article, alm shows a strong preference for the inserted over the surface-bound state.


Assuntos
Alameticina/química , Antibacterianos/química , Bicamadas Lipídicas/química , Alameticina/metabolismo , Animais , Antibacterianos/metabolismo , Peptídeos Catiônicos Antimicrobianos/química , Campos Eletromagnéticos , Proteínas de Peixes/química , Peixes , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Glicerilfosforilcolina/análogos & derivados , Glicerilfosforilcolina/química , Interações Hidrofóbicas e Hidrofílicas , Simulação de Dinâmica Molecular , Fosfatidilcolinas , Ligação Proteica , Conformação Proteica em alfa-Hélice , Dobramento de Proteína , Trichoderma , Viscosidade
5.
Biophys J ; 111(6): 1258-1266, 2016 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-27653484

RESUMO

Antimicrobial peptides (AMPs) that disrupt bacterial membranes are promising therapeutics against the growing number of antibiotic-resistant bacteria. The mechanism of membrane disruption by the AMP piscidin 1 was examined with multimicrosecond all-atom molecular dynamics simulations and solid-state NMR spectroscopy. The primary simulation was initialized with 20 peptides in four barrel-stave pores in a fully hydrated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol bilayer. The four pores relaxed to toroidal by 200 ns, only one porelike structure containing two transmembrane helices remained at 26 µs, and none of the 18 peptides released to the surface reinserted to form pores. The simulation was repeated at 413 K with an applied electric field and all peptides were surface-bound by 200 ns. Trajectories of surface-bound piscidin with and without applied fields at 313 and 413 K and totaling 6 µs show transient distortions of the bilayer/water interface (consistent with (31)P NMR), but no insertion to transmembrane or pore states. (15)N chemical shifts confirm a fully surface-bound conformation. Taken together, the simulation and experimental results imply that transient defects rather than stable pores are responsible for membrane disruption by piscidin 1, and likely other AMPs.


Assuntos
Peptídeos Catiônicos Antimicrobianos/química , Proteínas de Peixes/química , Animais , Peptídeos Catiônicos Antimicrobianos/metabolismo , Proteínas de Peixes/metabolismo , Peixes , Bicamadas Lipídicas/química , Simulação de Dinâmica Molecular , Ressonância Magnética Nuclear Biomolecular , Fosfatidilcolinas/química , Fosfatidilgliceróis/química , Conformação Proteica em alfa-Hélice , Estabilidade Proteica , Propriedades de Superfície , Água/química
6.
J Membr Biol ; 248(3): 455-67, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25292264

RESUMO

The initial steps of membrane disruption by antimicrobial peptides (AMPs) involve binding to bacterial membranes in a surface-bound (S) orientation. To evaluate the effects of lipid composition on the S state, molecular dynamics simulations of the AMPs piscidin 1 (p1) and piscidin 3 (p3) were carried out in four different bilayers: 3:1 DMPC/DMPG, 3:1 POPC/POPG, 1:1 POPE/POPG, and 4:1 POPC/cholesterol. In all cases, the addition of 1:40 piscidin caused thinning of the bilayer, though thinning was least for DMPC/DMPG. The peptides also insert most deeply into DMPC/DMPG, spanning the region from the bilayer midplane to the headgroups, and thereby only mildly disrupting the acyl chains. In contrast, the peptides insert less deeply in the palmitoyl-oleoyl containing membranes, do not reach the midplane, and substantially disrupt the chains, i.e., the neighboring acyl chains bend under the peptide, forming a basket-like conformation. Curvature free energy derivatives calculated from the simulation pressure profiles reveal that the peptides generate positive curvature in membranes with palmitoyl and oleoyl chains but negative curvature in those with myristoyl chains. Curvature inductions predicted with a continuum elastic model follow the same trends, though the effect is weaker, and a small negative curvature induction is obtained in POPC/POPG. These results do not directly speak to the relative stability of the inserted (I) states or ease of pore formation, which requires the free energy pathway between the S and I states. Nevertheless, they do highlight the importance of lipid composition and acyl chain packing.


Assuntos
Peptídeos Catiônicos Antimicrobianos/química , Proteínas de Peixes/química , Dimiristoilfosfatidilcolina/química , Simulação de Dinâmica Molecular , Fosfatidilcolinas/química , Fosfatidiletanolaminas/química , Fosfatidilgliceróis/química , Estrutura Secundária de Proteína , Termodinâmica
7.
PLoS Comput Biol ; 10(7): e1003739, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25058418

RESUMO

A module for fast determination of reduction potentials, E°, of redox-active proteins has been implemented in the CHARMM INterface and Graphics (CHARMMing) web portal (www.charmming.org). The free energy of reduction, which is proportional to E°, is composed of an intrinsic contribution due to the redox site and an environmental contribution due to the protein and solvent. Here, the intrinsic contribution is selected from a library of pre-calculated density functional theory values for each type of redox site and redox couple, while the environmental contribution is calculated from a crystal structure of the protein using Poisson-Boltzmann continuum electrostatics. An accompanying lesson demonstrates a calculation of E°. In this lesson, an ionizable residue in a [4Fe-4S]-protein that causes a pH-dependent E° is identified, and the E° of a mutant that would test the identification is predicted. This demonstration is valuable to both computational chemistry students and researchers interested in predicting sequence determinants of E° for mutagenesis.


Assuntos
Biologia Computacional/educação , Biologia Computacional/métodos , Transporte de Elétrons , Internet , Proteínas/química , Proteínas/metabolismo , Oxirredução , Termodinâmica
8.
J Am Chem Soc ; 136(9): 3491-504, 2014 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-24410116

RESUMO

While antimicrobial peptides (AMPs) have been widely investigated as potential therapeutics, high-resolution structures obtained under biologically relevant conditions are lacking. Here, the high-resolution structures of the homologous 22-residue long AMPs piscidin 1 (p1) and piscidin 3 (p3) are determined in fluid-phase 3:1 phosphatidylcholine/phosphatidylglycerol (PC/PG) and 1:1 phosphatidylethanolamine/phosphatidylglycerol (PE/PG) bilayers to identify molecular features important for membrane destabilization in bacterial cell membrane mimics. Structural refinement of (1)H-(15)N dipolar couplings and (15)N chemical shifts measured by oriented sample solid-state NMR and all-atom molecular dynamics (MD) simulations provide structural and orientational information of high precision and accuracy about these interfacially bound α-helical peptides. The tilt of the helical axis, τ, is between 83° and 93° with respect to the bilayer normal for all systems and analysis methods. The average azimuthal rotation, ρ, is 235°, which results in burial of hydrophobic residues in the bilayer. The refined NMR and MD structures reveal a slight kink at G13 that delineates two helical segments characterized by a small difference in their τ angles (<10°) and significant difference in their ρ angles (~25°). Remarkably, the kink, at the end of a G(X)4G motif highly conserved among members of the piscidin family, allows p1 and p3 to adopt ρ angles that maximize their hydrophobic moments. Two structural features differentiate the more potent p1 from p3: p1 has a larger ρ angle and less N-terminal fraying. The peptides have comparable depths of insertion in PC/PG, but p3 is 1.2 Å more deeply inserted than p1 in PE/PG. In contrast to the ideal α-helical structures typically assumed in mechanistic models of AMPs, p1 and p3 adopt disrupted α-helical backbones that correct for differences in the amphipathicity of their N- and C-ends, and their centers of mass lie ~1.2-3.6 Å below the plane defined by the C2 atoms of the lipid acyl chains.


Assuntos
Peptídeos Catiônicos Antimicrobianos/química , Proteínas de Peixes/química , Bicamadas Lipídicas/química , Interações Hidrofóbicas e Hidrofílicas , Imersão , Cristais Líquidos/química , Simulação de Dinâmica Molecular , Fosfatidilcolinas/química , Fosfatidilgliceróis/química , Estrutura Secundária de Proteína
9.
Diabet Med ; 31(1): 102-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23869945

RESUMO

AIM: The aim of this study was to explore the cognitive representations of peripheral neuropathy and self-reported foot-care behaviour in an Australian sample of people with diabetes and peripheral neuropathy. METHODS: This cross-sectional study was undertaken with 121 participants with diabetes and peripheral neuropathy. Cognitive representations of peripheral neuropathy were measured by the Patients' Interpretation of Neuropathy questionnaire and two aspects of self-foot-care behaviour were measured using a self-report questionnaire. Hierarchical cluster analysis using the average linkage method was used to identify distinct illness schemata related to peripheral neuropathy. RESULTS: Three clusters of participants were identified who exhibited distinct illness schemata related to peripheral neuropathy. One cluster had more misperceptions about the nature of peripheral neuropathy, one cluster was generally realistic about the nature of their condition and the final cluster was uncertain about their condition. The cluster with high misperceptions of their condition undertook more potentially damaging foot-care behaviours than the other clusters (F = 4.98; P < 0.01). CONCLUSIONS: People with diabetes and peripheral neuropathy have different illness schemata that may influence health-related behaviour. Education aimed at improving foot-care behaviour and foot-health outcomes should be tailored to specific illness schemata related to peripheral neuropathy.


Assuntos
Cognição , Pé Diabético/psicologia , Comportamentos Relacionados com a Saúde , Doenças do Sistema Nervoso Periférico/psicologia , Autocuidado , Idoso , Austrália/epidemiologia , Análise por Conglomerados , Estudos Transversais , Pé Diabético/epidemiologia , Escolaridade , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Doenças do Sistema Nervoso Periférico/epidemiologia , Fatores de Risco , Autocuidado/psicologia , Autorrelato , Inquéritos e Questionários
10.
Microb Genom ; 10(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38787376

RESUMO

Lyme disease (LD), caused by spirochete bacteria of the genus Borrelia burgdorferi sensu lato, remains the most common vector-borne disease in the northern hemisphere. Borrelia outer surface protein A (OspA) is an integral surface protein expressed during the tick cycle, and a validated vaccine target. There are at least 20 recognized Borrelia genospecies, that vary in OspA serotype. This study presents a new in silico sequence-based method for OspA typing using next-generation sequence data. Using a compiled database of over 400 Borrelia genomes encompassing the 4 most common disease-causing genospecies, we characterized OspA diversity in a manner that can accommodate existing and new OspA types and then defined boundaries for classification and assignment of OspA types based on the sequence similarity. To accommodate potential novel OspA types, we have developed a new nomenclature: OspA in silico type (IST). Beyond the ISTs that corresponded to existing OspA serotypes 1-8, we identified nine additional ISTs that cover new OspA variants in B. bavariensis (IST9-10), B. garinii (IST11-12), and other Borrelia genospecies (IST13-17). The IST typing scheme and associated OspA variants are available as part of the PubMLST Borrelia spp. database. Compared to traditional OspA serotyping methods, this new computational pipeline provides a more comprehensive and broadly applicable approach for characterization of OspA type and Borrelia genospecies to support vaccine development.


Assuntos
Antígenos de Superfície , Proteínas da Membrana Bacteriana Externa , Lipoproteínas , Doença de Lyme , Antígenos de Superfície/genética , Proteínas da Membrana Bacteriana Externa/genética , Vacinas Bacterianas , Borrelia burgdorferi/genética , Borrelia burgdorferi/classificação , Grupo Borrelia Burgdorferi/genética , Grupo Borrelia Burgdorferi/classificação , Simulação por Computador , Genoma Bacteriano , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Lipoproteínas/genética , Doença de Lyme/microbiologia , Filogenia , Sorogrupo
11.
Biochemistry ; 52(18): 3022-4, 2013 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-23607577

RESUMO

The pH dependence of the reduction potential E° for a metalloprotein indicates that the protonation state of at least one residue near the redox site changes and may be important for its activity. The responsible residue is usually identified by site-specific mutagenesis, which may be time-consuming. Here, the titration of E° for Chromatium vinosum high-potential iron-sulfur protein is predicted to be in good agreement with experiment using density functional theory and Poisson-Boltzmann calculations if only the sole histidine undergoes changes in protonation. The implementation of this approach into CHARMMing, a user-friendly web-based portal, allows users to identify residues in other proteins causing similar pH dependence.


Assuntos
Concentração de Íons de Hidrogênio , Chromatium/química , Modelos Moleculares , Oxirredução
12.
Phys Rev Lett ; 110(3): 037403, 2013 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-23373951

RESUMO

We show that distributed Bragg reflector GaAs/AlAs vertical cavities designed to confine photons are automatically optimal to confine phonons of the same wavelength, strongly enhancing their interaction. We study the impulsive generation of intense coherent and monochromatic acoustic phonons by following the time evolution of the elastic strain in picosecond-laser experiments. Efficient optical detection is assured by the strong phonon backaction on the high-Q optical cavity mode. Large optomechanical factors are reported (~THz/nm range). Pillar cavities based in these structures are predicted to display picogram effective masses, almost perfect sound extraction, and threshold powers for the stimulated emission of phonons in the range µW-mW, opening the way for the demonstration of phonon "lasing" by parametric instability in these devices.

13.
Data Brief ; 50: 109607, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37823067

RESUMO

The data presented in this article were collected in the field at an experimental station in southern France under a Mediterranean climate. Experiments were conducted under three plastic walk-in tunnels used as blocks with organic farming practices over two successive years in a completely randomized design. The aim was to compare the intercropping of sweet pepper with basil, onion, lettuce, parsley or French bean to a sole crop of sweet pepper used as a control. The dataset provides information on cultural practices with details on inputs and working times used to estimate economic costs. The data also describe the climatic conditions under tunnels as well as the dynamics of soil nitrate concentration and water tension over time through treatments. Yields, economic benefits and the rates of products with visual defects are presented. In addition, some variables applied exclusively to sweet pepper crops, namely nitrate concentration in petiole sap, growth parameters, abundance of aerial pests and beneficials, incidence of root necrosis, arbuscular mycorrhizal fungi colonization rates and diversity in roots. The field dataset is made publicly available to allow free and easy access for the scientific and professional community to enable analysis and reuse. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

14.
Photoacoustics ; 30: 100472, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36950519

RESUMO

Ultrahigh-frequency acoustic-phonon resonators usually require atomically flat interfaces to avoid phonon scattering and dephasing, leading to expensive fabrication processes, such as molecular beam epitaxy. Mesoporous thin films are based on inexpensive wet chemical fabrication techniques that lead to relatively flat interfaces regardless the presence of nanopores. Here, we report mesoporous titanium dioxide-based acoustic resonators with resonances up to 90 GHz, and quality factors from 3 to 7. Numerical simulations show a good agreement with the picosecond ultrasonics experiments. We also numerically study the effect of changes in the speed of sound on the performance of the resonator. This change could be induced by liquid infiltration into the mesopores. Our findings constitute the first step towards the engineering of building blocks based on mesoporous thin films for reconfigurable optoacoustic sensors.

15.
mBio ; 13(4): e0086922, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-35862764

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to represent a global health emergency as a highly transmissible, airborne virus. An important coronaviral drug target for treatment of COVID-19 is the conserved main protease (Mpro). Nirmatrelvir is a potent Mpro inhibitor and the antiviral component of Paxlovid. The significant viral sequencing effort during the ongoing COVID-19 pandemic represented a unique opportunity to assess potential nirmatrelvir escape mutations from emerging variants of SARS-CoV-2. To establish the baseline mutational landscape of Mpro prior to the introduction of Mpro inhibitors, Mpro sequences and its cleavage junction regions were retrieved from ~4,892,000 high-quality SARS-CoV-2 genomes in the open-access Global Initiative on Sharing Avian Influenza Data (GISAID) database. Any mutations identified from comparison to the reference sequence (Wuhan-Hu-1) were catalogued and analyzed. Mutations at sites key to nirmatrelvir binding and protease functionality (e.g., dimerization sites) were still rare. Structural comparison of Mpro also showed conservation of key nirmatrelvir contact residues across the extended Coronaviridae family (α-, ß-, and γ-coronaviruses). Additionally, we showed that over time, the SARS-CoV-2 Mpro enzyme remained under purifying selection and was highly conserved relative to the spike protein. Now, with the emergency use authorization (EUA) of Paxlovid and its expected widespread use across the globe, it is essential to continue large-scale genomic surveillance of SARS-CoV-2 Mpro evolution. This study establishes a robust analysis framework for monitoring emergent mutations in millions of virus isolates, with the goal of identifying potential resistance to present and future SARS-CoV-2 antivirals. IMPORTANCE The recent authorization of oral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antivirals, such as Paxlovid, has ushered in a new era of the COVID-19 pandemic. The emergence of new variants, as well as the selective pressure imposed by antiviral drugs themselves, raises concern for potential escape mutations in key drug binding motifs. To determine the potential emergence of antiviral resistance in globally circulating isolates and its implications for the clinical response to the COVID-19 pandemic, sequencing of SARS-CoV-2 viral isolates before, during, and after the introduction of new antiviral treatments is critical. The infrastructure built herein for active genetic surveillance of Mpro evolution and emergent mutations will play an important role in assessing potential antiviral resistance as the pandemic progresses and Mpro inhibitors are introduced. We anticipate our framework to be the starting point in a larger effort for global monitoring of the SARS-CoV-2 Mpro mutational landscape.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Antivirais/metabolismo , Proteases 3C de Coronavírus , Cisteína Endopeptidases/metabolismo , Combinação de Medicamentos , Humanos , Lactamas , Leucina , Nitrilas , Pandemias , Prolina , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Ritonavir , SARS-CoV-2/genética , Proteínas não Estruturais Virais/metabolismo
16.
J Adolesc Health ; 70(5): 706-713, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34955356

RESUMO

We sought to aggregate common barriers and facilitators to screening adolescents for sensitive health topics (e.g., depression, chlamydia) in primary care, as well as those that are unique to a given health topic. We conducted a literature search of three databases (PsycInfo, MEDLINE, and CINAHL) and reference lists of included articles. Studies focused on barriers and facilitators to screening adolescents (ages 12-17 years) for sensitive health topics in primary care that are recommended by national guidelines. Articles were peer-reviewed, presented empirical data, and were published in English in 2006-2021. We coded barriers and facilitators using the Consolidated Framework for Implementation Research, a well-established framework within implementation science. In total, 39 studies met inclusion criteria and spanned several health topics: depression, suicide, substance use, HIV, and chlamydia. We found common barriers and facilitators to screening across health topics, with most relating to characteristics of the primary care clinics (e.g., time constraints). Other factors relevant to screening implementation ranged from confidentiality concerns to clinician knowledge. Barriers and facilitators specific to certain health topics, such as the availability of on-site laboratories for HIV screening, were also noted. Findings can guide refinements to screening implementation.


Assuntos
Infecções por HIV , Programas de Rastreamento , Adolescente , Criança , Humanos , Atenção Primária à Saúde
17.
Behav Ther ; 53(6): 1191-1204, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36229116

RESUMO

Clinician fidelity to cognitive behavioral therapy (CBT) is an important mechanism by which desired clinical outcomes are achieved and is an indicator of care quality. Despite its importance, there are few fidelity measurement methods that are efficient and have demonstrated reliability and validity. Using a randomized trial design, we compared three methods of assessing CBT adherence-a core component of fidelity-to direct observation, the gold standard. Clinicians recruited from 27 community mental health agencies (n = 126; M age = 37.69 years, SD = 12.84; 75.7% female) were randomized 1:1:1 to one of three fidelity conditions: self-report (n = 41), chart-stimulated recall (semistructured interviews with the chart available; n = 42), or behavioral rehearsal (simulated role-plays; n = 43). All participating clinicians completed fidelity assessments for up to three sessions with three different clients that were recruited from clinicians' caseloads (n = 288; M age = 13.39 years SD = 3.89; 41.7% female); sessions were also audio-recorded and coded for comparison to determine the most accurate method. All fidelity measures had parallel scales that yielded an adherence maximum score (i.e., the highest-rated intervention in a session), a mean of techniques observed, and a count total of observed techniques. Results of three-level mixed effects regression models indicated that behavioral rehearsal produced comparable scores to observation for all adherence scores (all ps > .01), indicating no difference between behavioral rehearsal and observation. Self-report and chart-stimulated recall overestimated adherence compared to observation (ps < .01). Overall, findings suggested that behavioral rehearsal indexed CBT adherence comparably to direct observation, the gold-standard, in pediatric populations. Behavioral rehearsal may at times be able to replace the need for resource-intensive direct observation in implementation research and practice.


Assuntos
Terapia Cognitivo-Comportamental , Adolescente , Adulto , Criança , Terapia Cognitivo-Comportamental/métodos , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Projetos de Pesquisa , Autorrelato
18.
Implement Res Pract ; 3: 26334895221114664, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37091084

RESUMO

Background: The current gold standard for measuring fidelity (specifically, adherence) to cognitive behavioral therapy (CBT) is direct observation, a costly, resource-intensive practice that is not feasible for many community organizations to implement regularly. Recent research indicates that behavioral rehearsal (i.e., role-play between clinician and individual with regard to session delivery) and chart-stimulated recall (i.e., brief structured interview between clinician and individual about what they did in session; clinicians use the client chart to prompt memory) may provide accurate and affordable alternatives for measuring adherence to CBT in such settings, with behavioral rehearsal yielding greater correspondence with direct observation. Methods: Drawing on established causal theories from social psychology and leading implementation science frameworks, this study evaluates stakeholders' intention to use behavioral rehearsal and chart-stimulated recall. Specifically, we measured attitudes, self-efficacy, and subjective norms toward using each, and compared these factors across the two methods. We also examined the relationship between attitudes, self-efficacy, subjective norms, and intention to use each method. Finally, using an integrated approach we asked stakeholders to discuss their perception of contextual factors that may influence beliefs about using each method. These data were collected from community-based supervisors (n = 17) and clinicians (n = 66). Results: Quantitative analyses suggest moderately strong intention to use both methods across stakeholders. There were no differences in supervisors' or clinicians' attitudes, self-efficacy, subjective norms, or intention across methods. More positive attitudes and greater reported subjective norms were associated with greater reported intention to use either measure. Qualitative analyses identified participants' specific beliefs about using each fidelity measure in their organization, and results were organized using the Consolidated Framework for Implementation Research. Conclusions: Strategies are warranted to overcome or minimize potential barriers to using fidelity measurement methods and to further increase the strength of intention to use them.Plain Language Summary: The best way to measure fidelity, or how closely a clinician follows the protocol, to Cognitive Behavioral Therapy (CBT) is watching the session. This is an expensive practice that is not feasible for many community organizations to do regularly. Recent research indicates that behavioral rehearsal, or a role-play between the clinician and individual with regard to session delivery, and chart-stimulated recall, or a brief discussion between an individual and the clinician about what they did in session with the clinician having access to the chart to help them remember, may provide accurate and affordable alternatives for measuring fidelity to CBT. We just completed a study demonstrating that both methods are promising, with behavioral rehearsal offering scores that are the most similar to watching the session. Drawing on established theories from social psychology and leading implementation science frameworks, this study evaluates future supervisor and clinician motivation to use these fidelity measurement methods. Specifically, we measured supervisor (n = 17) and clinician (n = 66) attitudes, norms, self-efficacy, intentions, and anticipated barriers and facilitators to using each of these fidelity measurement tools. Quantitative and qualitative analyses suggest similar intention to use both methods, and concerns about barriers to using each method. Further research is warranted to minimize the burden associated with implementing fidelity measurement methods and deploying strategies to increase use.

19.
AIDS Care ; 23(8): 971-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21400307

RESUMO

OBJECTIVE: Geographic location may be related to the receipt of quality HIV health care services. Clinical outcomes and health care utilization were evaluated in rural, urban, and peri-urban patients seen at high-volume US urban-based HIV care sites. METHODS: Zip codes for 8773 HIV patients followed in 2005 at seven HIV Research Network sites were categorized as rural (population <10,000), peri-urban (10,000-100,000), and urban (>100,000). Clinical and demographic characteristics, inpatient and outpatient (OP) utilization, AIDS-defining illness rates, receipt of highly active antiretroviral therapy (HAART), opportunistic infection (OI) prophylaxis usage, and virologic suppression were compared among patients, using χ(2) tests for categorical variables, t-tests for means, and logistic regression for HAART utilization. RESULTS: HIV-infected rural (n=170) and peri-urban (n=215) patients were less likely to be Black or Hispanic than urban HIV patients. Peri-urban subjects were more likely to report MSM as their HIV risk factor than rural or urban subjects. Age, gender, CD4 or HIV-RNA distribution, virologic suppression, HAART usage, or OI prophylaxis did not differ by geographic location. In multivariate analysis, rural and peri-urban patients were less likely to have four or more annual outpatient visits than urban patients. Rural patients were less likely to receive HAART if they were Black. Overall, geographic location (as defined by home zip code) did not affect receipt of HAART or OI prophylaxis. CONCLUSION: Although demographic and health care utilization differences were seen among rural, peri-urban, and urban HIV patients, most HIV outcomes and medication use were comparable across geographic areas. As with HIV care for urban-dwelling patients, areas for improvement for non-urban HIV patients include access to HAART among minorities and injection drug users.


Assuntos
Terapia Antirretroviral de Alta Atividade/estatística & dados numéricos , Infecções por HIV/terapia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Serviços de Saúde Rural/estatística & dados numéricos , Serviços Urbanos de Saúde/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Etnicidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade da Assistência à Saúde , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
20.
J Foot Ankle Res ; 14(1): 26, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33827640

RESUMO

BACKGROUND: Acute Charcot Neuroarthropathy (CN) is a destructive condition that is characterised by acute fractures, dislocations and joint destruction in the weight-bearing foot. The acute phase is often misdiagnosed and can rapidly lead to devastating health outcomes. Early diagnosis and management of CN is imperative to attenuate progression of this condition. Consequently, timely evidence-based assessment, diagnosis and management of acute CN is imperative. OBJECTIVE: To identify the factors that impact the delivery of evidence-based care in assessment, diagnosis and management of people with acute CN. METHOD: Systematic searches were conducted in four databases to identify studies in English that included factors that impact the delivery of evidence-based care in the assessment, diagnosis and management of people with acute CN. Articles and consensus/guideline documents were assessed for inclusion by the researchers and disagreements were resolved through consensus. Additionally backward citation searching was used to source other potentially relevant documents. Information relevant to the research question was extracted and thematic analyses were performed using qualitative synthesis. RESULTS: Thirty-two articles and four additional consensus/guideline documents were included for data extraction and analyses. Information related to the research question was of expert opinion using the National Health and Medical Research Council (NHMRC) Levels of Evidence guidelines. Themes explaining practices that deviated from evidence-based care in assessment, diagnosis and management of acute CN centred around patient, health professional and health organisation/environmental. Delay to diagnosis is particularly influenced by the patient's knowledge of when to seek help, practitioner knowledge in knowing how to recognise and refer for appropriate immediate care, confusion in imaging and offloading and geographical and local health service resources to appropriately manage the condition. CONCLUSION: Individual and health professional awareness and geographical barriers are key challenges to the effective delivery of evidence-based assessment, diagnosis and management of people with acute CN. Acute CN represents a medical emergency warranting the need for expedited assessment, diagnosis and management by appropriately trained health professionals in the appropriate.


Assuntos
Artropatia Neurogênica , Prática Clínica Baseada em Evidências , Acessibilidade aos Serviços de Saúde , Doença Aguda , Gerenciamento Clínico , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde/psicologia , Humanos , Avaliação de Sintomas
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