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1.
Diabetes Ther ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861136

RESUMO

INTRODUCTION: This study assessed experiences, attitudes, and behaviors of people with diabetes (PwD) regarding diabetes self-management and glucose control, and their level of awareness, knowledge, and attitudes toward time in range (TIR). METHODS: This quantitative survey was conducted using an online questionnaire across seven countries. Respondents were PwD classified into three subgroups: type 1 (T1), type 2 insulin (T2 insulin), and type 2 not on insulin (T2 N/insulin). RESULTS: Respondents included 621 people in the T1, 780 people in the T2 insulin, and 735 people in the T2 N/insulin subgroups. Awareness of TIR was low, particularly in the T2 N/insulin subgroup (T1 53%, T2 insulin 29%, T2 N/insulin 9%). Despite a lower current use of continuous glucose monitoring (CGM) among the T2 insulin and T2 N/insulin participants (38% and 9%, respectively), versus T1 participants (64%), most (> 70%) were positive toward utilizing new tools and measures to self-manage blood glucose. Recommendations from their healthcare professionals (HCPs) were cited as a strong motivator to try new measures for analyzing glucose levels. The main barriers cited were limited access to CGM and lack of understanding of TIR benefits. Cost was the main reason given by ≥ 40% of respondents for stopping CGM use. CONCLUSIONS: There is an unmet need in diabetes management, and TIR and CGM offer a potential solution. PwD are motivated to manage their blood glucose levels and are positive toward utilizing new tools and measures to achieve this goal. HCPs play a pivotal role in informing and guiding PwD on new measures for analyzing glucose.

2.
Cureus ; 16(4): e57903, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38725792

RESUMO

Vascular tumors of the breast are rare, but benign hemangiomas are the most common type. Capillary hemangiomas are a subset of benign vascular tumors that involve smaller vessel sizes. They are difficult to diagnose with mammography and ultrasound, as they lack pathognomonic features and are frequently not seen. MRI is the most sensitive imaging tool. The lesions appear similar to angiosarcoma or ductal carcinoma in situ on imaging, which further complicates the diagnosis. A biopsy of the lesions is required for a definitive diagnosis. In this report, a 49-year-old female with newly diagnosed breast cancer is incidentally found to have a capillary hemangioma on staging breast MRI that was confirmed with a biopsy and excised along with the primary breast cancer with a partial mastectomy. The imaging findings of breast hemangioma on mammography, ultrasound, and MRI are also reviewed and described in this report.

3.
EES Catal ; 2(2): 664-674, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38464594

RESUMO

Photoelectrodes with FTO/Au/Sb2Se3/TiO2/Au architecture were studied in photoelectrochemical CO2 reduction reaction (PEC CO2RR). The preparation is based on a simple spin coating technique, where nanorod-like structures were obtained for Sb2Se3, as confirmed by SEM images. A thin conformal layer of TiO2 was coated on the Sb2Se3 nanorods via ALD, which acted as both an electron transfer layer and a protective coating. Au nanoparticles were deposited as co-catalysts via photo-assisted electrodeposition at different applied potentials to control their growth and morphology. The use of such architectures has not been explored in CO2RR yet. The photoelectrochemical performance for CO2RR was investigated with different Au catalyst loadings. A photocurrent density of ∼7.5 mA cm-2 at -0.57 V vs. RHE for syngas generation was achieved, with an average Faradaic efficiency of 25 ± 6% for CO and 63 ± 12% for H2. The presented results point toward the use of Sb2Se3-based photoelectrodes in solar CO2 conversion applications.

4.
Neuropeptides ; 104: 102413, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38335798

RESUMO

The measurement of neuropeptides using small electrodes for high spatial resolution would provide us with localized information on the release of neuromolecules. The release of Neuropeptide Y (NPY) is related to different neurological diseases such as stress, obesity, and PTSD, among others. In this conference paper, we electrodeposited polypyrrole on carbon fiber microelectrodes in the presence of NPY to develop a molecularly imprinted polypyrrole sensitive to NPY. Optimization of the electrodeposition process resulted in the full coverage of the polymer with nucleation sites on the carbon fiber ridges, achieving completion by the seventh cycle. Electrodeposition was performed for five cycles, and using cyclic voltammetry (CV), we studied the change in the oxidation current peak for polypyrrole due to the presence of NPY. We also observed a change in capacitance due to the presence of NPY, which was studied by electrochemical impedance spectroscopy (EIS). A linear correlation was found between the oxidation peak and the concentration of NPY between 50 ng/mL and 1000 ng/mL. In addition, a linear correlation was also found between microelectrode capacitance and the concentration of NPY between 50 ng/mL and 1000 ng/mL at 100 kHz.


Assuntos
Neuropeptídeo Y , Polímeros , Fibra de Carbono , Microeletrodos , Neuropeptídeo Y/análise , Polímeros/química , Pirróis
5.
J Biosci ; 482023.
Artigo em Inglês | MEDLINE | ID: mdl-37671533

RESUMO

An important preventive measure to mitigate the COVID-19 pandemic is vaccine implementation. In creating vaccines, evoking neutralizing antibody (NAb) production is the main objective. This review determines and compares the NAb titers produced by COVID-19 vaccine recipients based on the vaccine type and the manner of administration. This review includes published articles on studies with healthy participants with a minimum age of 18 years, without previous infections, and those who were given Emergency Use License (EUL) vaccines from WHO. Bias assessment was performed using the Cochrane Risk of Bias and the Newcastle- Ottawa Scale. In all the studies, 40.82% of the primary doses were viral vector platforms. For booster doses, 50% were mRNA platforms. Messenger RNA (mRNA) vaccines have higher titers as homologous than as heterologous vaccines. However, inactivated vaccines and viral vector vaccines have lower titers as homologous than as heterologous vaccines. Meanwhile, subunit vaccines lack data for their titers. Based on the antibody titers, homologous mRNA vaccines are more viral-protective than their heterologous counterparts. Heterologous inactivated and viral vector vaccines are more protective than homologous combinations, mainly when mRNA is the other type in those heterologous combinations. This is because mRNA vaccines elicit higher immunogenicity compared to other types.


Assuntos
COVID-19 , Vacinas Virais , Humanos , Adolescente , Vacinas contra COVID-19 , Pandemias , RNA Mensageiro , Vacinas de mRNA
6.
Cureus ; 15(6): e40349, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37456443

RESUMO

Neuroectodermal disease involves abnormalities that arise from the ectodermal origin, such as the nervous system, eyeball, retina, and skin. Due to the rarity of the disease, it is often underdiagnosed or misdiagnosed. In this study, the researcher presents two cases of pediatric patients with no fetomaternal complications who presented with focal seizures as their initial complaint. During the examination, varying skin color pigmentation and an abnormal neurophysical examination were observed. Cranial imaging showed hemimegalencephaly and voltage asymmetry on EEG. Skin biopsy was performed on both cases, which revealed basketweave orthokeratosis. The combination of a triad of intractable epilepsy, developmental delay, and cutaneous lesion prompted the consideration of a neuroectodermal disease. The study shows two cases of hypomelanosis of Ito and nevus syndrome, both of which may be due to mTOR and RAS pathways, respectively.

7.
Risk Manag Healthc Policy ; 16: 677-697, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37077534

RESUMO

Objective: The objective of this systematic review was to analyze published literature from the last five years to assess facilitators and barriers to the adoption of mHealth as interventions to treat and manage HIV for PLHIV (people living with HIV). The primary outcomes were physical and mental conditions. The secondary outcomes were behavior based (substance use, care engagement, and healthy habits). Methods: Four databases (PubMed, CINAHL, Web of Science, and ScienceDirect) were queried on 9/2/2022 for peer-reviewed studies on the treatment and management of PLHIV with mHealth as the intervention. The review was conducted in accordance with the Kruse Protocol and reported in accordance with PRISMA 2020. Results: Five mHealth interventions were identified across 32 studies that resulted in improvements in physical health, mental health, care engagement, and behavior change. mHealth interventions offer both convenience and privacy, meet a digital preference, increase health knowledge, decrease healthcare utilization, and increase quality of life. Barriers are cost of technology and incentives, training of staff, security concerns, digital literacy gap, distribution of technology, technical issues, usability, and visual cues are not available over the phone. Conclusion: mHealth offers interventions to improve physical health, mental health, care engagement, and behavior for PLHIV. There are many advantages to this intervention and very few barriers to its adoption. The barriers are strong, however, and should be addressed through policy. Further research should focus on specific apps for younger versus older PLHIV, based on preferences and the digital literacy gap.

8.
Proc Natl Acad Sci U S A ; 120(11): e2219523120, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36893269

RESUMO

The continuous evolution of SARS-CoV-2 variants complicates efforts to combat the ongoing pandemic, underscoring the need for a dynamic platform for the rapid development of pan-viral variant therapeutics. Oligonucleotide therapeutics are enhancing the treatment of numerous diseases with unprecedented potency, duration of effect, and safety. Through the systematic screening of hundreds of oligonucleotide sequences, we identified fully chemically stabilized siRNAs and ASOs that target regions of the SARS-CoV-2 genome conserved in all variants of concern, including delta and omicron. We successively evaluated candidates in cellular reporter assays, followed by viral inhibition in cell culture, with eventual testing of leads for in vivo antiviral activity in the lung. Previous attempts to deliver therapeutic oligonucleotides to the lung have met with only modest success. Here, we report the development of a platform for identifying and generating potent, chemically modified multimeric siRNAs bioavailable in the lung after local intranasal and intratracheal delivery. The optimized divalent siRNAs showed robust antiviral activity in human cells and mouse models of SARS-CoV-2 infection and represent a new paradigm for antiviral therapeutic development for current and future pandemics.


Assuntos
COVID-19 , Humanos , Animais , Camundongos , RNA Interferente Pequeno/genética , COVID-19/terapia , SARS-CoV-2/genética , Antivirais/farmacologia , Antivirais/uso terapêutico , Oligonucleotídeos , Pulmão
9.
J Diabetes Sci Technol ; : 19322968221149041, 2023 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-36710452

RESUMO

BACKGROUND: Derived time in range (dTIR), calculated from self-monitored blood glucose (SMBG-dTIR) profiles, has demonstrated correlation with risk of cardiovascular and microvascular complications. This post hoc analysis of the DUAL V and DUAL VIII trials aimed to compare dTIR with an insulin degludec/liraglutide fixed-ratio combination (IDegLira) versus insulin glargine 100 units/mL (glargine U100) in people with type 2 diabetes (T2D). MATERIALS AND METHODS: Nine-point SMBG profiles were taken more than 24 hours at baseline and end of trial (EOT: 26 weeks [DUAL V] and 104 weeks [DUAL VIII]) and used to derive the percentage of readings within target range (70-180 mg/dL). Estimated treatment differences (ETDs, IDegLira-glargine U100) were analyzed using analysis of covariance, with treatment as fixed effects and baseline response as a covariate. RESULTS: ETDs for change from baseline to EOT in dTIR were significantly greater with IDegLira versus glargine U100 in DUAL V (4.18%, P = .027) and DUAL VIII (5.17%, P = .001). The proportions of people achieving ≥70% dTIR at EOT with IDegLira and glargine U100, respectively, were 62% and 60% in DUAL V (P = .7541), and 50% and 26% in DUAL VIII (P < .0001). The proportion achieving a ≥5% increase in dTIR from baseline to EOT with IDegLira and glargine U100 was 63% in both groups in DUAL V (P = .9043), and 44% and 25%, respectively, in DUAL VIII (P < .0001). CONCLUSIONS: IDegLira was associated with significantly greater increases in dTIR versus basal insulin alone in people with T2D. TRIAL ID(S): ClinicalTrials.gov, NCT01952145 (DUAL V); ClinicalTrials.gov, NCT02501161 (DUAL VIII).

10.
Healthcare (Basel) ; 11(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36673533

RESUMO

The United States healthcare industry has witnessed a number of hospitals declare bankruptcy. This has a meaningful impact on local communities with vast implications on access, cost, and quality of care available. In our research, we seek to determine what contemporary structural and operational factors influence a bankruptcy outcome, and craft predictive models to guide healthcare leaders on how to best avoid bankruptcy in the future. In this exploratory study we performed, a single-year cross-sectional analysis of short-term acute care hospitals in the United States and subsequently developed three predictive models: logistic regression, a linear support vector machine (SVM) model with hinge function, and a perceptron neural network. Data sources include Definitive Healthcare and Becker's Hospital Review 2019 report with 3121 observations of 32 variables with 27 observed bankruptcies. The three models consistently indicate that 18 variables have a significant impact on predicting hospital bankruptcy. Currently, there is limited literature concerning financial forecasting models and knowledge detailing the factors associated with hospital bankruptcy. By having tailored knowledge of predictive factors to establish a sound financial structure, healthcare institutions at large can be empowered to take proactive steps to avoid financial distress at the organizational level and ensure long-term financial viability.

11.
Front Immunol ; 13: 995412, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36172366

RESUMO

Anti-COVID antibody therapeutics have been developed but not widely used due to their high cost and escape of neutralization from the emerging variants. Here, we describe the development of VHH-IgA1.1, a nanobody IgA fusion molecule as an inhalable, affordable and less invasive prophylactic and therapeutic treatment against SARS-CoV-2 Omicron variants. VHH-IgA1.1 recognizes a conserved epitope of SARS-CoV-2 spike protein Receptor Binding Domain (RBD) and potently neutralizes major global SARS-CoV-2 variants of concern (VOC) including the Omicron variant and its sub lineages BA.1.1, BA.2 and BA.2.12.1. VHH-IgA1.1 is also much more potent against Omicron variants as compared to an IgG Fc fusion construct, demonstrating the importance of IgA mediated mucosal protection for Omicron infection. Intranasal administration of VHH-IgA1.1 prior to or after challenge conferred significant protection from severe respiratory disease in K18-ACE2 transgenic mice infected with SARS-CoV-2 VOC. More importantly, for cost-effective production, VHH-IgA1.1 produced in Pichia pastoris had comparable potency to mammalian produced antibodies. Our study demonstrates that intranasal administration of affordably produced VHH-IgA fusion protein provides effective mucosal immunity against infection of SARS-CoV-2 including emerging variants.


Assuntos
COVID-19 , Imunoglobulina A , SARS-CoV-2 , Anticorpos de Domínio Único , Enzima de Conversão de Angiotensina 2 , Animais , Anticorpos Antivirais/farmacologia , Epitopos/química , Humanos , Imunoglobulina A/farmacologia , Imunoglobulina G , Camundongos , Anticorpos de Domínio Único/farmacologia , Glicoproteína da Espícula de Coronavírus
12.
Viruses ; 14(7)2022 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-35891350

RESUMO

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, causing surges, breakthrough infections, and devastating losses-underscoring the importance of identifying SARS-CoV-2 antivirals. A simple, accessible human cell culture model permissive to SARS-CoV-2 variants is critical for identifying and assessing antivirals in a high-throughput manner. Although human alveolar A549 cells are a valuable model for studying respiratory virus infections, they lack two essential host factors for SARS-CoV-2 infection: angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). SARS-CoV-2 uses the ACE2 receptor for viral entry and TMPRSS2 to prime the SARS-CoV-2 spike protein, both of which are negligibly expressed in A549 cells. Here, we report the generation of a suitable human cell line for SARS-CoV-2 studies by transducing human ACE2 and TMPRSS2 into A549 cells. We show that subclones highly expressing ACE2 and TMPRSS2 ("ACE2plus" and the subclone "ACE2plusC3") are susceptible to infection with SARS-CoV-2, including the delta and omicron variants. These subclones express more ACE2 and TMPRSS2 transcripts than existing commercial A549 cells engineered to express ACE2 and TMPRSS2. Additionally, the antiviral drugs EIDD-1931, remdesivir, nirmatrelvir, and nelfinavir strongly inhibit SARS-CoV-2 variants in our infection model. Our data show that ACE2plusC3 cells are highly permissive to SARS-CoV-2 infection and can be used to identify anti-SARS-CoV-2 drugs.


Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Células A549 , Enzima de Conversão de Angiotensina 2/genética , Antivirais/farmacologia , Humanos , Peptidil Dipeptidase A/metabolismo , SARS-CoV-2/genética , Serina Endopeptidases/genética , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo
13.
Cell Rep ; 39(11): 110952, 2022 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-35675811

RESUMO

Sequence homology between SARS-CoV-2 and common-cold human coronaviruses (HCoVs) raises the possibility that memory responses to prior HCoV infection can affect T cell response in COVID-19. We studied T cell responses to SARS-CoV-2 and HCoVs in convalescent COVID-19 donors and identified a highly conserved SARS-CoV-2 sequence, S811-831, with overlapping epitopes presented by common MHC class II proteins HLA-DQ5 and HLA-DP4. These epitopes are recognized by low-abundance CD4 T cells from convalescent COVID-19 donors, mRNA vaccine recipients, and uninfected donors. TCR sequencing revealed a diverse repertoire with public TCRs. T cell cross-reactivity is driven by the high conservation across human and animal coronaviruses of T cell contact residues in both HLA-DQ5 and HLA-DP4 binding frames, with distinct patterns of HCoV cross-reactivity explained by MHC class II binding preferences and substitutions at secondary TCR contact sites. These data highlight S811-831 as a highly conserved CD4 T cell epitope broadly recognized across human populations.


Assuntos
COVID-19 , SARS-CoV-2 , Alelos , Linfócitos T CD4-Positivos , Vacinas contra COVID-19 , Epitopos de Linfócito T , Antígenos HLA , Humanos , Receptores de Antígenos de Linfócitos T , Vacinas de mRNA
14.
Anal Chem ; 93(2): 973-980, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33297678

RESUMO

Aptamer-modified microelectrodes for Neuropeptide Y measurement by electrochemical impedance spectroscopy was described here. The advantages of using carbon fiber or platinum microelectrodes are because they are promising materials with high electrical conductivity, chemical stability, and high surface area that can be easily modified on their surface. The immobilization and biofouling were studied and compared using EIS. Moreover, the adsorption of NPY to the aptamer-modified microelectrodes was also demonstrated by EIS. Changes of -ω*Zimag, an impedance factor that gives information of the capacitance, is directly correlated with concentrations. A widely linear range was obtained from 10 to 1000 ng/mL of NPY. This method was able to detect NPY without performing a redox reaction by adsorption at the surface of the microelectrodes, with the specificity provided by aptamer functionalization of the microelectrode surface.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais , Espectroscopia Dielétrica , Neuropeptídeo Y/análise , Fibra de Carbono/química , Microeletrodos , Platina/química , Propriedades de Superfície
15.
Cad Saude Publica ; 35(10): e00065118, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31596393

RESUMO

The study aimed to investigate the population's perceptions of generic drugs compared to original brand-name drugs in Peruvian hospitals. Participation included 4,914 persons 18 years and older in 13 cities in Peru, categorized as Lima, large cities, and small cities. The study explored socioeconomic and demographic characteristics and perceptions of generics in comparison to brand-name drugs. In determining the associations for each intersection of variables, the authors calculated the prevalence ratios (PR) and 95% confidence intervals (95%CI), using crude and adjusted Poisson regression with robust variance with Stata 14.0. Of the 4,914 participants, 46.7% felt that generics are less effective than brand-name drugs and 49.3% had recommended or would recommend generics to other people; multivariate analysis showed that individuals with income less than PEN 1,000 (USD 300) were prone to recommending a generic drug (PR = 1.36; 95%CI: 1.14-1.63). The results indicate that the Peruvian population still has mistaken concepts and low acceptance of generic drugs, and the study should serve to develop health policies that ensure low cost and quality when choosing medicines.


El objetivo del estudio fue conocer la percepción de la población con respecto a medicamentos genéricos, frente a los medicamentos de marca, en hospitales del Perú. Participaron del estudio 4.914 personas mayores de 18 años, de 13 ciudades del Perú; clasificándolas en Lima, grandes y pequeñas ciudades. Se exploraron características socioeconómicas, demográficas y de percepción de medicamentos genéricos, en comparación con los medicamentos de marca. Determinando las asociaciones para cada cruce de variables, se calcularon razones de prevalencias (RP) y sus intervalos del 95% de confianza (IC95%), usando regresiones de Poisson crudas y ajustadas con varianza robusta con Stata 14.0. De los 4.914 participantes, el 46,7% estaban de acuerdo con que los medicamentos genéricos son menos eficaces que los medicamentos de marca, el 49,3% ha recomendado o recomendaría a otras personas el uso de medicamentos genéricos, además, el análisis multivariado encontró que las personas que tenían un ingreso económico menor a PEN 1.000 estaban predispuestas a recomendar un medicamento genérico (RP = 1,36; IC95%: 1,14-1,63). Los resultados ponen en manifiesto que la población peruana aún tiene conceptos equívocos y baja aceptación a los medicamentos genéricos. El presente estudio debería servir para desarrollar políticas de salud, que velen por el bajo costo y calidad a la hora de escoger un medicamento.


O objetivo do estudo foi conhecer a percepção da população a respeito dos medicamentos genéricos frente aos medicamentos de marca em hospitais do Peru. Participaram 4.914 pessoas maiores de 18 anos, de 13 cidades do Peru; foram classificadas em Lima, além de grandes e pequenas cidades. Foram exploradas as características socioeconômicas, demográficas e de percepção de medicamentos genéricos em comparação com os medicamentos de marca. Determinando as associações para cada intersecção de variáveis, foram calculadas as razões de prevalências (RP) e seus intervalos de 95% de confiança (IC95%), usando regressões de Poisson brutas e ajustadas com variância robusta com Stata 14.0. Dos 4.914 participantes, um 46,7% estavam de acordo com que os medicamentos genéricos são menos eficazes do que os medicamentos de marca, um 49,3% tem recomendado o recomendaria a outras pessoas o uso de medicamentos genéricos, além disso, a análise multivariada encontrou que as pessoas que tinham um ingresso econômico menor a PEN 1.000 eram propensas a recomendar um medicamento genérico (RP = 1,36; IC95%: 1,14-1,63). Os resultados manifestam que a população peruana ainda tem conceitos equívocos e baixa aceitação dos medicamentos genéricos, e o presente estudo deveria servir para desenvolver políticas de saúde, que assegurem o baixo custo e a qualidade na hora de escolher um medicamento.


Assuntos
Uso de Medicamentos , Medicamentos Genéricos , Adolescente , Adulto , Estudos Transversais , Prescrições de Medicamentos , Uso de Medicamentos/economia , Medicamentos Genéricos/economia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Peru , Fatores Socioeconômicos , Adulto Jovem
16.
J Spec Oper Med ; 19(3): 14-16, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31539427

RESUMO

Presumptive antirelapse therapy (PART) with primaquine for Plasmodium vivax malaria postdeployment is an important component of the US military Force Health Protection plan. While primaquine is well tolerated in the majority of cases, we present a unique case of an active duty Army Ranger without glucose-6-phosphatase dehydrogenase or cytochrome b5 reductase (b5R) deficiencies who developed symptomatic methemoglobinemia while taking PART following a deployment to Afghanistan.


Assuntos
Metemoglobinemia/induzido quimicamente , Metemoglobinemia/diagnóstico , Militares , Primaquina/toxicidade , Campanha Afegã de 2001- , Diagnóstico Tardio , Humanos
17.
Eur J Immunol ; 49(8): 1167-1185, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31020640

RESUMO

Human herpes virus 6B (HHV-6B) is a widespread virus that infects most people early in infancy and establishes a chronic life-long infection with periodic reactivation. CD4 T cells have been implicated in control of HHV-6B, but antigenic targets and functional characteristics of the CD4 T-cell response are poorly understood. We identified 25 naturally processed MHC-II peptides, derived from six different HHV-6B proteins, and showed that they were recognized by CD4 T-cell responses in HLA-matched donors. The peptides were identified by mass spectrometry after elution from HLA-DR molecules isolated from HHV-6B-infected T cells. The peptides showed strong binding to matched HLA alleles and elicited recall T-cell responses in vitro. T-cell lines expanded in vitro were used for functional characterization of the response. Responding cells were mainly CD3+ CD4+ , produced IFN-γ, TNF-α, and low levels of IL-2, alone or in combination, highlighting the presence of polyfunctional T cells in the overall response. Many of the responding cells mobilized CD107a, stored granzyme B, and mediated specific killing of peptide-pulsed target cells. These results highlight a potential role for polyfunctional cytotoxic CD4 T cells in the long-term control of HHV-6B infection.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Herpesvirus Humano 6/fisiologia , Infecções por Roseolovirus/imunologia , Apresentação de Antígeno , Antígenos Virais/metabolismo , Linfócitos T CD4-Positivos/virologia , Células Cultivadas , Citotoxicidade Imunológica , Mapeamento de Epitopos , Antígeno HLA-DR3/metabolismo , Humanos , Epitopos Imunodominantes , Interferon gama/metabolismo , Ativação Linfocitária , Espectrometria de Massas , Peptídeos/metabolismo
18.
Cad. Saúde Pública (Online) ; 35(10): e00065118, 2019. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1039392

RESUMO

Resumen: El objetivo del estudio fue conocer la percepción de la población con respecto a medicamentos genéricos, frente a los medicamentos de marca, en hospitales del Perú. Participaron del estudio 4.914 personas mayores de 18 años, de 13 ciudades del Perú; clasificándolas en Lima, grandes y pequeñas ciudades. Se exploraron características socioeconómicas, demográficas y de percepción de medicamentos genéricos, en comparación con los medicamentos de marca. Determinando las asociaciones para cada cruce de variables, se calcularon razones de prevalencias (RP) y sus intervalos del 95% de confianza (IC95%), usando regresiones de Poisson crudas y ajustadas con varianza robusta con Stata 14.0. De los 4.914 participantes, el 46,7% estaban de acuerdo con que los medicamentos genéricos son menos eficaces que los medicamentos de marca, el 49,3% ha recomendado o recomendaría a otras personas el uso de medicamentos genéricos, además, el análisis multivariado encontró que las personas que tenían un ingreso económico menor a PEN 1.000 estaban predispuestas a recomendar un medicamento genérico (RP = 1,36; IC95%: 1,14-1,63). Los resultados ponen en manifiesto que la población peruana aún tiene conceptos equívocos y baja aceptación a los medicamentos genéricos. El presente estudio debería servir para desarrollar políticas de salud, que velen por el bajo costo y calidad a la hora de escoger un medicamento.


Abstract: The study aimed to investigate the population's perceptions of generic drugs compared to original brand-name drugs in Peruvian hospitals. Participation included 4,914 persons 18 years and older in 13 cities in Peru, categorized as Lima, large cities, and small cities. The study explored socioeconomic and demographic characteristics and perceptions of generics in comparison to brand-name drugs. In determining the associations for each intersection of variables, the authors calculated the prevalence ratios (PR) and 95% confidence intervals (95%CI), using crude and adjusted Poisson regression with robust variance with Stata 14.0. Of the 4,914 participants, 46.7% felt that generics are less effective than brand-name drugs and 49.3% had recommended or would recommend generics to other people; multivariate analysis showed that individuals with income less than PEN 1,000 (USD 300) were prone to recommending a generic drug (PR = 1.36; 95%CI: 1.14-1.63). The results indicate that the Peruvian population still has mistaken concepts and low acceptance of generic drugs, and the study should serve to develop health policies that ensure low cost and quality when choosing medicines.


Resumo: O objetivo do estudo foi conhecer a percepção da população a respeito dos medicamentos genéricos frente aos medicamentos de marca em hospitais do Peru. Participaram 4.914 pessoas maiores de 18 anos, de 13 cidades do Peru; foram classificadas em Lima, além de grandes e pequenas cidades. Foram exploradas as características socioeconômicas, demográficas e de percepção de medicamentos genéricos em comparação com os medicamentos de marca. Determinando as associações para cada intersecção de variáveis, foram calculadas as razões de prevalências (RP) e seus intervalos de 95% de confiança (IC95%), usando regressões de Poisson brutas e ajustadas com variância robusta com Stata 14.0. Dos 4.914 participantes, um 46,7% estavam de acordo com que os medicamentos genéricos são menos eficazes do que os medicamentos de marca, um 49,3% tem recomendado o recomendaria a outras pessoas o uso de medicamentos genéricos, além disso, a análise multivariada encontrou que as pessoas que tinham um ingresso econômico menor a PEN 1.000 eram propensas a recomendar um medicamento genérico (RP = 1,36; IC95%: 1,14-1,63). Os resultados manifestam que a população peruana ainda tem conceitos equívocos e baixa aceitação dos medicamentos genéricos, e o presente estudo deveria servir para desenvolver políticas de saúde, que assegurem o baixo custo e a qualidade na hora de escolher um medicamento.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Adulto Jovem , Medicamentos Genéricos/economia , Uso de Medicamentos/economia , Peru , Prescrições de Medicamentos , Fatores Socioeconômicos , Conhecimentos, Atitudes e Prática em Saúde , Estudos Transversais , Hospitais , Pessoa de Meia-Idade
19.
J Infect Dis ; 215(5): 818-823, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28011910

RESUMO

Antibodies that mediate antibody-dependent cellular cytotoxicity (ADCC) against avian influenza virus subtypes, including H7N9 and H5N1, have been detected in human sera. Using NK cell activation and NK cytotoxicity assays, we compared ADCC-mediating antibodies (ADCC-Abs) in sera collected from healthy infants, children and adults against H7N9 virus-infected cells and recombinant hemagglutinin (HA), neuraminidase (NA), and nucleoprotein (NP) proteins. High titers of ADCC-Abs against H7N9 virus-infected cells were detected in sera from adults and children but not infants. ADCC-Abs titers directed against H7N9 HA or NA proteins. Further analysis showed that ADCC-Abs titers were significantly higher toward H7N9 NP, as compared with H7N9 HA or NA proteins, and correlated strongly with ADCC-Abs titers against H7N9 virus-infected cells. Indeed, ADCC-Abs to NPs of seasonal H1N1 and H3N2 viruses correlated strongly with ADCC-Abs to H7N9 NP, suggesting that seasonal influenza infections and vaccinations may induce these cross-reactive antibodies. Targeting ADCC-Abs to internal proteins may be a potential mechanism of universal vaccine design.


Assuntos
Anticorpos Antivirais/imunologia , Citotoxicidade Celular Dependente de Anticorpos , Proteínas de Ligação a RNA/imunologia , Proteínas do Core Viral/imunologia , Adolescente , Adulto , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Reações Cruzadas , Hemaglutininas/sangue , Hemaglutininas/imunologia , Humanos , Lactente , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Virus da Influenza A Subtipo H5N1 , Subtipo H7N9 do Vírus da Influenza A , Vacinas contra Influenza/uso terapêutico , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Células Matadoras Naturais/imunologia , Pessoa de Meia-Idade , Neuraminidase/sangue , Neuraminidase/imunologia , Proteínas do Nucleocapsídeo , Proteínas de Ligação a RNA/sangue , Proteínas Recombinantes/sangue , Proteínas Recombinantes/imunologia , Proteínas do Core Viral/sangue , Adulto Jovem
20.
Cell Host Microbe ; 19(6): 800-13, 2016 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-27281570

RESUMO

Pathogenic H7N9 avian influenza viruses continue to represent a public health concern, and several candidate vaccines are currently being developed. It is vital to assess if protective antibodies are induced following vaccination and to characterize the diversity of epitopes targeted. Here we characterized the binding and functional properties of twelve H7-reactive human antibodies induced by a candidate A/Anhui/1/2013 (H7N9) vaccine. Both neutralizing and non-neutralizing antibodies protected mice in vivo during passive transfer challenge experiments. Mapping the H7 hemagglutinin antigenic sites by generating escape mutant variants against the neutralizing antibodies identified unique epitopes on the head and stalk domains. Further, the broadly cross-reactive non-neutralizing antibodies generated in this study were protective through Fc-mediated effector cell recruitment. These findings reveal important properties of vaccine-induced antibodies and provide a better understanding of the human monoclonal antibody response to influenza in the context of vaccines.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Subtipo H7N9 do Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/farmacologia , Animais , Anticorpos Monoclonais/biossíntese , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Modelos Animais de Doenças , Cães , Feminino , Células HEK293 , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/virologia
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