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1.
J Public Health Manag Pract ; 30(1): E31-E40, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37966959

RESUMO

OBJECTIVE: In this study, we sought to understand patterns of childhood vaccinations in the United States across socioeconomic and racial/ethnic groups over a 12-year period to identify interventions that improve immunization equity and inform public health practice. DESIGN: We conducted an explanatory, sequential, mixed-methods study. US state- and county-level immunization data were analyzed to understand trends in immunization coverage among racial/ethnic groups. Qualitative interviews with public health and community leaders were used to explain trends, gain insight into routine childhood immunization interventions, and understand local contexts and data limitations. PARTICIPANTS AND SETTING: Secondary data were used from the National Immunization Survey-Child (NIS) public use data sets (2007 and 2019). Eligible participants for qualitative interviews were routine childhood immunization stakeholders from selected counties in North Carolina, Washington, and Arizona. MAIN OUTCOME MEASURE: Our integrated findings report trends and probability of children aged 19 months to 3 years being fully vaccinated (measles-mumps-rubella [MMR], diphtheria and tetanus toxoids and acellular pertussis [DTaP], hepatitis B [Hep B]), interventions, and recommendations to improve routine childhood immunization coverage and equity. RESULTS: Vaccination coverage remained high and relatively stable between 2007 and 2019; however, there were differences across racial/ethnic groups. Public health leaders identified key interventions that effectively improved vaccine equity and coverage, including data quality improvement, tailored interventions for specific populations, multisector partnerships, addressing common barriers, and data limitations. Participants also identified the critical role of state policies, public health funding, and community vaccine norms. CONCLUSIONS: Variability persists in vaccination coverage and equity across states, race/ethnicity, and socioeconomic status despite decades of interventions. Vaccine stakeholders should use our findings to improve coverage and reduce disparities. Equitable improvements can be realized through policy change, data tracking/infrastructure improvements, and tailored interventions. Furthermore, local partners are critical in improving vaccine coverage and equitable interventions to disrupt disparities that long hold true for vaccine-preventable diseases.


Assuntos
Vacinas contra Difteria, Tétano e Coqueluche Acelular , Vacinação , Humanos , Estados Unidos , Lactente , Imunização , Cobertura Vacinal , Programas de Imunização , Esquemas de Imunização
2.
Sensors (Basel) ; 23(14)2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37514594

RESUMO

This paper presents a study of the performances of different Mach-Zehnder modulation technologies with applications in microwave polarimeters based on a near-infrared (NIR) frequency up-conversion stage, allowing for optical correlation and signal detection at a wavelength of 1550 nm. Commercial Mach-Zehnder modulators (MZMs) are traditionally implemented using LiNbO3 technology, which does not enable integration for the fabrication of MZMs. In this work, we propose the use of an alternative technology based on InP, which allows for integration in the fabrication process. In this way, it is possible to obtain advantages in terms of bandwidth, cost, and size reductions, which yield results that are very interesting for wide-band applications such as microwave instrumentation for the study of the cosmic microwave background (CMB). Here, we describe and compare the modulation performances of different MZMs, with one commercial unit presenting a higher bandwidth than those in previous works, and another three InP integrated units provided by the Fraunhofer Institute for Telecommunications, Heinrich-Hertz-Institute (HHI). Then, these modulators were coupled to a microwave polarimeter demonstrator, which has also been presented previously, to compare the polarization measurement performances of each of the MZMs.

3.
Sensors (Basel) ; 23(5)2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36904617

RESUMO

Cosmic Microwave Background (CMB) B-modes detection is the main focus of future CMB experiments because of the valuable information it contains, particularly to probe the physics of the very early universe. For this reason, we have developed an optimized polarimeter demonstrator sensitive to the 10-20 GHz band in which the signal received by each antenna is modulated into a Near Infrared (NIR) laser by a Mach-Zehnder modulator. Then, these modulated signals are optically correlated and detected using photonic back-end modules consisting of voltage-controlled phase shifters, a 90-degree optical hybrid, a pair of lenses, and an NIR camera. During laboratory tests, a 1/f-like noise signal related to the low phase stability of the demonstrator has been found experimentally. To solve this issue, we have developed a calibration method that allows us to remove this noise in an actual experiment, until obtaining the required accuracy level in the measurement of polarization.

4.
Sensors (Basel) ; 22(20)2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36298431

RESUMO

This paper presents a polarization calibration method applied to a microwave polarimeter demonstrator based on a near-infrared (NIR) frequency up-conversion stage that allows both optical correlation and signal detection at a wavelength of 1550 nm. The instrument was designed to measure the polarization of cosmic microwave background (CMB) radiation from the sky, obtaining the Stokes parameters of the incoming signal simultaneously, in a frequency range from 10 to 20 GHz. A linearly polarized input signal with a variable polarization angle is used as excitation in the polarimeter calibration setup mounted in the laboratory. The polarimeter systematic errors can be corrected with the proposed calibration procedure, achieving high levels of polarization efficiency (low polarization percentage errors) and low polarization angle errors. The calibration method is based on the fitting of polarization errors by means of sinusoidal functions composed of additive or multiplicative terms. The accuracy of the fitting increases with the number of terms in such a way that the typical error levels required in low-frequency CMB experiments can be achieved with only a few terms in the fitting functions. On the other hand, assuming that the calibration signal is known with the required accuracy, additional terms can be calculated to reach the error levels needed in ultrasensitive B-mode polarization CMB experiments.

5.
Sensors (Basel) ; 21(10)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34066074

RESUMO

In this work, the use of a calibration satellite (L2-CalSat) flying in formation with a Cosmic Microwave Background (CMB) polarization mission in an orbit located at the second Lagrange point, is proposed. The new generation of CMB telescopes are expected to reach unprecedented levels of sensitivity to allow a very precise measurement of the B-mode of polarization, the curl-like polarization component expected from gravitational waves coming from Starobinski inflationary models. Due to the CMB polarized signal weakness, the instruments must be subjected to very precise calibration processes before and after launching. Celestial sources are often used as external references for calibration after launch, but these sources are not perfectly characterized. As a baseline option, L2-CalSat is based on the CubeSat standard and serves as a perfectly known source of a reference signal to reduce polarization measurements uncertainty. A preliminary design of L2-CalSat is described and, according to the scanning strategy followed by the telescope, the influence of the relative position between the spacecrafts in the calibration process is studied. This new calibration element will have a huge impact on the performance of CMB space missions, providing a significant improvement in the measurements accuracy without requiring new and costly technological developments.

6.
Sensors (Basel) ; 19(8)2019 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-31010121

RESUMO

This paper presents a 10 to 20 GHz bandwidth microwave polarimeter demonstrator, based on the implementation of a near-infra-red frequency up-conversion stage that allows both the optical correlation, when operating as a synthesized-image interferometer, and signal detection, when operating as a direct-image instrument. The proposed idea is oriented towards the implementation of ultra-sensitive instruments presenting several dozens or even thousands of microwave receivers operating in the lowest bands of the cosmic microwave background. In this work, an electro-optical back-end module replaces the usual microwave detection stage with Mach-Zehnder modulators for the frequency up-conversion, and an optical stage for the signals correlation and detection at near-infra-red wavelengths (1550 nm). As interferometer, the instrument is able to correlate the signals of large-format instruments, while operating as a direct imaging instrument also presents advantages in terms of the possibility of implementing the optical back end by means of photonic integrated circuits to achieve reductions in cost, weight, size, and power consumption. A linearly polarized input wave, with a variable polar angle, is used as a signal source for laboratory tests. The receiver demonstrator has proved its capabilities of being used as a new microwave-photonic polarimeter for the study of the lowest bands of cosmic microwave background.

7.
Artigo em Inglês | MEDLINE | ID: mdl-28358290

RESUMO

The removal of three emerging contaminants (ECs) (amitriptyline hydrochloride (AH), methyl salicylate (MS) and 2-phenoxyethanol (PE)) dissolved in several water matrices by means of their adsorption onto powdered activated carbon (PAC) and granular activated carbon (GAC) has been investigated. When dissolved in ultrapure water, adsorption of the ECs followed the trend of AH > MS > PE, with a positive effect of the adsorbent dose. According to the analysis of the adsorption isotherms and adsorption kinetics, PAC showed strongly higher adsorption efficiency in both capacity and velocity of the adsorption, in agreement with its higher mesoporosity. Equilibrium isotherm data were fitted by Langmuir and Freundlich models. Pseudo-second order kinetics modeled very successfully the adsorption process. Finally, the effect of the presence of dissolved organic matter (DOM) in the water matrices (ultrapure water, surface water and two effluents from wastewater treatment plants) on the adsorption of the selected ECs onto PAC was established, as well as its performance on the removal of water quality parameters. Results show a negative effect of the DOM content on the adsorption efficiency. Over 50% of organic matter was removed with high PAC doses, revealing that adsorption onto PAC is an effective technology to remove both micro-pollutants and DOM from water matrices.


Assuntos
Carvão Vegetal/química , Modelos Teóricos , Águas Residuárias/química , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Adsorção , Amitriptilina/análise , Amitriptilina/química , Etilenoglicóis/análise , Etilenoglicóis/química , Substâncias Húmicas/análise , Cinética , Porosidade , Salicilatos/análise , Salicilatos/química , Poluentes Químicos da Água/química , Qualidade da Água
8.
Eur Respir J ; 48(2): 350-8, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27390278

RESUMO

Numerous studies have shown that oxidative stress accelerates telomere shortening in several lung pathologies. Since oxidative stress is involved in the pathophysiology of α1-antitrypsin deficiency (AATD), we hypothesised that telomere shortening would be accelerated in AATD patients. This study aimed to assess telomere length in AATD patients and to study its association with α1-antitrypsin phenotypes.Telomere length, telomerase activity, telomerase reverse transcriptase (hTERT) expression and biomarkers of oxidative stress were measured in 62 children and teenagers (aged 2-18 years) diagnosed with AATD and 18 controls (aged 3-16 years).Our results show that intermediate-risk (MZ; SZ) and high-risk (ZZ) AATD patients have significantly shorter telomeres and increased oxidative stress than controls. Correlation studies indicate that telomere length was related to oxidative stress markers in AATD patients. Multiple hypothesis testing revealed an association between telomere length, telomerase activity, hTERT expression and AATD phenotypes; high-risk patients showed shorter telomeres, lower hTERT expression and decreased telomerase activity than intermediate-risk and low-risk patients.AATD patients show evidence of increased oxidative stress leading to telomere attrition. An association between telomere and α1-antitrypsin phenotypes is observed suggesting that telomere length could be a promising biomarker for AATD disease progression.


Assuntos
Encurtamento do Telômero , Telômero/ultraestrutura , Deficiência de alfa 1-Antitripsina/genética , Adolescente , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Pulmão/metabolismo , Masculino , Estresse Oxidativo , Fenótipo , Espirometria , Telomerase/genética , Deficiência de alfa 1-Antitripsina/metabolismo
9.
BMC Infect Dis ; 15: 295, 2015 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-26220420

RESUMO

BACKGROUND: Under-reporting of tuberculosis (TB) cases complicates disease control, hinders contact tracing and alters the accuracy of epidemiological data, including disease burden. The objective of the present study is to evaluate the proportion of unreported TB cases in Spanish healthcare facilities and to identify the associated factors. METHODS: A multi-center retrospective study design was employed. The study included TB cases diagnosed in 16 facilities during 2011-2012. These cases were compared to those reported to the corresponding public health departments. Demographic, microbiological and clinical data were analyzed to determine the factors associated with unreported cases. Associated factors were analyzed on a bivariate level using the x(2) test and on a multivariate level using a logistic regression. Odds ratios (OR) and 95 % confidence intervals (CI) were calculated. RESULTS: Of the 592 TB cases included in the study, 85 (14.4 %) were not reported. The percentage of unreported cases per healthcare center ranged from 0-45.2 %. The following variables were associated to under-reporting at a multivariate level: smear-negative TB (OR = 1.87; CI:1.07-3.28), extrapulmonary disease (OR = 2.07; CI:1.05-4.09) and retired patients (OR = 3.04; CI:1.29-7.18). A nurse case manager was present in all of the centers with 100 % reporting. The percentage of reported cases among the smear-positive cases was 9.4 % and 19.4 % (p = 0.001) among the rest of the study population. Smear-positive TB was no associated to under-reporting. CONCLUSIONS: It is important that TB Control Programs encourage thorough case reporting to improve disease control, contact tracing and accuracy of epidemiological data. The help from a TB nurse case manager could improve the rate of under-reporting.


Assuntos
Notificação de Doenças , Tuberculose/epidemiologia , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Hospitais , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Espanha , Tuberculose/diagnóstico , Adulto Jovem
10.
Sensors (Basel) ; 15(8): 19124-39, 2015 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-26251906

RESUMO

This paper presents preliminary polarization measurements and systematic-error characterization of the Thirty Gigahertz Instrument receiver developed for the QUIJOTE experiment. The instrument has been designed to measure the polarization of Cosmic Microwave Background radiation from the sky, obtaining the Q, U, and I Stokes parameters of the incoming signal simultaneously. Two kinds of linearly polarized input signals have been used as excitations in the polarimeter measurement tests in the laboratory; these show consistent results in terms of the Stokes parameters obtained. A measurement-based systematic-error characterization technique has been used in order to determine the possible sources of instrumental errors and to assist in the polarimeter calibration process.

12.
Heliyon ; 10(14): e34906, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39149088

RESUMO

Background: Numerous social and behavioral factors have been implicated in vaccination coverage. There is no single measure that describes a country's ability to improve or maintain its immunization coverage. Methods: We estimated the "Vaccination Improvement Potential" (VIP) by taking the geometric mean of 13 different indicators on health financing, vaccine confidence, and socio-demographics for more than 200 countries across 30 years. Potential VIP Index values range from 0 to 1, with a higher score indicating greater potential to improve or maintain high vaccination rates. Findings: In 1990, the mean VIP score was 0.49 (range = 0.13 to 0.86). In 2019, the mean score was 0.59 (range = 0.25 to 0.84). Consistent high performers included countries in Western Europe and high-income North America and East Asia. Important differences in subcomponents of the index drove major trends including vaccine hesitancy in Western Europe and Asia as well as lower levels of per capita health spending and development assistance in sub-Saharan Africa. Interpretation: The VIP Index is a first-of-its-kind tool for understanding the capacity that exists in a country to realize improved immunization rates. It is a new resource that can guide researchers, policymakers, and health officials to more effectively deploy resources to realize improvements in vaccination coverage, assess the impact of those improvements, and identify countries that might require additional support to improve vaccine coverage. Funding: Merck Sharp & Dohme Corp.

13.
Allergy Asthma Clin Immunol ; 19(1): 34, 2023 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-37088840

RESUMO

BACKGROUND: Scientific evidence on patients with multimorbid type 2 asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) from a united airways disease (UAD) perspective remains scarce, despite the frequent coexistence of these entities. We aimed to generate expert consensus-based recommendations for the management of UAD patients. METHODS: Using a two-round Delphi method, Spanish expert allergists, pulmonologists and otolaryngologists expressed their agreement on 32 statements (52 items) on a 9-point Likert scale, classified as appropriate (median 7-9), uncertain (4-6) or inappropriate (1-3). Consensus was considered when at least two-thirds of the panel scored within the range containing the median. RESULTS: A panel of 30 experts reached consensus on the appropriateness of 43 out of the 52 (82.7%) items. The usefulness of certain biomarkers (tissue and peripheral blood eosinophil count, serum total IgE, and fraction of exhaled nitric oxide [FeNO]) in the identification and follow-up of type 2 inflammation, and assessment of the response to biologics, were agreed. Some of these biomarkers were also associated with disease severity and/or recurrence after endoscopic sinus surgery (ESS). Consensus was achieved on treatment strategies related to the prescription of anti-IL-4/IL-13 or anti-IgE agents, concomitant treatment with systemic corticosteroids, and combining or switching to biologics with a different mechanism of action, considering a number of UAD clinical scenarios. CONCLUSION: We provide expert-based recommendations to assist in clinical decision-making for the management of patients with multimorbid type 2 asthma and CRSwNP. Specific clinical trials and real-world studies focusing on the single-entity UAD are required to address controversial items.

14.
Arch Bronconeumol ; 57(7): 457-463, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35698951

RESUMO

INTRODUCTION: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition resulting in lung and liver disease with a great clinical variability. MicroRNAs have been identified as disease modifiers; therefore miRNA deregulation could play an important role in disease heterogeneity. Members of miR-320 family are involved in regulating of multiple processes including inflammation, and have potential specific binding sites in the 3'UTR region of SERPINA1 gene. In this study we explore the involvement of miR-320c, a member of this family, in this disease. METHODS: Firstly in vitro studies were carried out to demonstrate regulation of SERPINA1 gene by miR-320. Furthermore, the expression of miR-320c was analyzed in the blood of 98 individuals with different AAT serum levels by using quantitative PCR and expression was correlated to clinical parameters of the patients. Finally, HL60 cells were used to analyze induction of miR-320c in inflammatory conditions. RESULTS: Overexpression of miR-320 members in human HepG2 cells led to inhibition of SERPINA1 expression. Analysis of miR-320c expression in patient's samples revealed significantly increased expression of miR-320c in individuals with pulmonary disease. Additionally, HL60 cells treated with the pro-inflammatory factor lipopolysaccharide (LPS) showed increase in miR-320c expression, suggesting that miR-320c responds to inflammation. CONCLUSION: Our findings demonstrate that miR-320c inhibits SERPINA1 expression in a hepatic cell line and its levels in blood are associated with lung disease in a cohort of patients with different AAT serum levels. These results suggest that miR-320c can play a role in AAT regulation and could be a biomarker of inflammatory processes in pulmonary diseases.


Assuntos
Pneumopatias , MicroRNAs , Deficiência de alfa 1-Antitripsina , alfa 1-Antitripsina , Regiões 3' não Traduzidas , Humanos , Inflamação/genética , Pulmão , Pneumopatias/genética , MicroRNAs/genética , alfa 1-Antitripsina/genética , Deficiência de alfa 1-Antitripsina/genética
15.
J Racial Ethn Health Disparities ; 7(5): 937-948, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32040841

RESUMO

Latina immigrant women in the U.S. are at increased risk for poor mental health status, due to socioeconomic- and immigration-related stressors. We sought to describe the mechanisms linking immigration-related stressors and mental health, including how the current social and political climate affects women's mental health status, and which coping strategies are used to maintain well-being. We conducted four focus groups with Latina immigrants (N = 58) recruited through local community-based organizations. We drew on the stages of migration framework to guide our study design and analysis. Focus group transcripts were analyzed to identify emergent themes across groups. On average, focus group participants were 35.5 years old and had lived in the U.S. for 12.5 years. Most were from Mexico. Participants reported immigration-related stressors including unsafe migration, worry about immigration enforcement, broken social ties, and limited access to health and social services. In the face of these stressors, they relied on transnational social networks and connections with other Latina immigrant women. Social ties with family in the U.S. also helped them alleviate social isolation and overcome barriers to social services. Those who were mothers expressed that their children were a source of encouragement and comfort with feelings of stress. Immigration policies that contribute to unsafe migration, worry about immigration enforcement, limited social ties, and limited access to social services were associated with increased stress among Latina immigrants who participated in the focus groups. These participants could benefit from increased access to mental health care and community-based programs that connect them to resources.


Assuntos
Adaptação Psicológica , Emigrantes e Imigrantes/psicologia , Emigração e Imigração/legislação & jurisprudência , Hispânico ou Latino/psicologia , Estresse Psicológico/etnologia , Adulto , Emigrantes e Imigrantes/estatística & dados numéricos , Feminino , Grupos Focais , Hispânico ou Latino/estatística & dados numéricos , Humanos , México/etnologia , Estresse Psicológico/psicologia
16.
J Clin Med ; 9(7)2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32708262

RESUMO

BACKGROUND: Nebulised antibiotics are habitually used in patients with bronchiectasis, but the use of dry powder inhaled antibiotics (DPIA) in these patients is extremely limited. This study seeks to analyse the efficacy and safety of DPIA in bronchiectasis patients. MATERIAL AND METHODS: Multi-centre study of historic cohorts. All the hospital centres in Spain were contacted in order to collect data on patients with a diagnosis of bronchiectasis who had taken at least one dose of DPIA. Its efficacy was analysed in clinical, functional and microbiological terms by comparing the year before and the year after the prescription of DPIA. Adverse effects and variables associated with these effects, or any need to withdraw the drug, were also analysed. RESULTS: 164 patients from 33 Spanish centres were included; 86% and 14% of these were treated with dry powder colistin and tobramycin, respectively. Chronic bronchial infection by Pseudomonas aeruginosa was present in 86% of these patients, and DPIA significantly reduced the number of exacerbations, the quantity and purulence of sputum and the isolation of pathogenic microorganisms. The most common adverse effect was cough (40%), particularly in cases of Chronic Obstructive Pulmonary Disease (COPD) and a previous cough and in those patients who had difficulties in handling the device. These factors were associated with a higher level of withdrawal of the treatment. There were no serious adverse effects. CONCLUSIONS: Our study suggests that DPIA are clinically efficacious and safe for treating bronchiectasis patients. Cough was shown to be the most common side-effect and reason for withdrawal of the treatment.

17.
BMJ Glob Health ; 5(11)2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33148539

RESUMO

INTRODUCTION: Understanding how to deliver interventions more effectively is a growing emphasis in Global Health. Simultaneously, health system strengthening is a key component to improving delivery. As a result, it is challenging to evaluate programme implementation while reflecting real-world complexity. We present our experience in using a health systems modelling approach as part of a mixed-methods evaluation and describe applications of these models. METHODS: We developed a framework for how health systems translate financial inputs into health outcomes, with in-country and international experts. We collated available data to measure framework indicators and developed models for malaria in Democratic Republic of the Congo (DRC), and tuberculosis in Guatemala and Senegal using Bayesian structural equation modelling. We conducted several postmodelling analyses: measuring efficiency, assessing bottlenecks, understanding mediation, analysing the cascade of care and measuring subnational effectiveness. RESULTS: The DRC model indicated a strong relationship between shipment of commodities and utilisation thereof. In Guatemala, the strongest model coefficients were more evenly distributed. Results in Senegal varied most, but pathways related to community care had the strongest relationships. In DRC, we used model results to estimate the end-to-end cost of delivering commodities. In Guatemala, we used model results to identify potential bottlenecks and understand mediation. In Senegal, we used model results to identify potential weak links in the cascade of care, and explore subnationally. CONCLUSION: This study demonstrates a complementary modelling approach to traditional evaluation methods. Although these models have limitations, they can be applied in a variety of ways to gain greater insight into implementation and functioning of health service delivery.


Assuntos
Infecções por HIV , Malária , Tuberculose , Teorema de Bayes , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Humanos , Malária/epidemiologia , Senegal/epidemiologia , Tuberculose/diagnóstico , Tuberculose/epidemiologia
18.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32439252

RESUMO

INTRODUCTION: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition resulting in lung and liver disease with a great clinical variability. MicroRNAs have been identified as disease modifiers; therefore miRNA deregulation could play an important role in disease heterogeneity. Members of miR-320 family are involved in regulating of multiple processes including inflammation, and have potential specific binding sites in the 3'UTR region of SERPINA1 gene. In this study we explore the involvement of miR-320c, a member of this family, in this disease. METHODS: Firstly in vitro studies were carried out to demonstrate regulation of SERPINA1 gene by miR-320. Furthermore, the expression of miR-320c was analyzed in the blood of 98 individuals with different AAT serum levels by using quantitative PCR and expression was correlated to clinical parameters of the patients. Finally, HL60 cells were used to analyze induction of miR-320c in inflammatory conditions. RESULTS: Overexpression of miR-320 members in human HepG2 cells led to inhibition of SERPINA1 expression. Analysis of miR-320c expression in patient's samples revealed significantly increased expression of miR-320c in individuals with pulmonary disease. Additionally, HL60 cells treated with the pro-inflammatory factor lipopolysaccharide (LPS) showed increase in miR-320c expression, suggesting that miR-320c responds to inflammation. CONCLUSION: Our findings demonstrate that miR-320c inhibits SERPINA1 expression in a hepatic cell line and its levels in blood are associated with lung disease in a cohort of patients with different AAT serum levels. These results suggest that miR-320c can play a role in AAT regulation and could be a biomarker of inflammatory processes in pulmonary diseases.

19.
Orphanet J Rare Dis ; 13(1): 114, 2018 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-29996870

RESUMO

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition that leads to decreased circulating alpha-1 antitrypsin (AAT) levels, significantly increasing the risk of serious lung and/or liver disease in children and adults, in which some aspects remain unresolved. METHODS: In this review, we summarise and update current knowledge on alpha-1 antitrypsin deficiency in order to identify and discuss areas of controversy and formulate questions that need further research. RESULTS: 1) AATD is a highly underdiagnosed condition. Over 120,000 European individuals are estimated to have severe AATD and more than 90% of them are underdiagnosed. CONCLUSIONS: 2) Several clinical and etiological aspects of the disease are yet to be resolved. New strategies for early detection and biomarkers for patient outcome prediction are needed to reduce morbidity and mortality in these patients; 3) Augmentation therapy is the only specific approved therapy that has shown clinical efficacy in delaying the progression of emphysema. Regrettably, some countries reject registration and reimbursement for this treatment because of the lack of larger randomised, placebo-controlled trials. 4) Alternative strategies are currently being investigated, including the use of gene therapy or induced pluripotent stem cells, and non-augmentation strategies to prevent AAT polymerisation inside hepatocytes.


Assuntos
Deficiência de alfa 1-Antitripsina/metabolismo , Deficiência de alfa 1-Antitripsina/patologia , alfa 1-Antitripsina/metabolismo , Animais , Fibrose/metabolismo , Fibrose/patologia , Humanos , Paniculite/metabolismo , Paniculite/patologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Vasculite/metabolismo , Vasculite/patologia
20.
Rev Sci Instrum ; 88(4): 044702, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28456241

RESUMO

In this paper, a microwave interferometer prototype with a near-infra-red optical correlator is proposed as a solution to get a large-format interferometer with hundreds of receivers for radio astronomy applications. A 10 Gbits/s Lithium Niobate modulator has been tested as part of an electro-optic correlator up-conversion stage that will be integrated in the interferometer prototype. Its internal circuitry consists of a single-drive modulator biased by a SubMiniature version A (SMA) connector allowing to up-convert microwave signals with bandwidths up to 12.5 GHz to the near infrared band. In order to characterize it, a 12 GHz tone and a bias voltage were applied to the SMA input using a polarization tee. Two different experimental techniques to stabilize the modulator operation point in its minimum optical carrier output power are described. The best achieved results showed a rather stable spectrum in amplitude and wavelength at the output of the modulator with an optical carrier level 23 dB lower than the signal of interest. On the other hand, preliminary measurements were made to analyze the correlation stage, using 4f and 6f optical configurations to characterize both the antenna/fiber array configuration and the corresponding point spread function.

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