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Background: Polymerized allergoids conjugated with mannan represent a novel approach of allergen immunotherapy targeting dendritic cells. In this study, we aimed to determine the optimal dose of mannan-allergoid conjugates derived from grass pollen (Phleum pratense and Dactylis glomerata) administered via either the subcutaneous or sublingual route. Methods: A randomized, double-blind, placebo-controlled trial with a double-dummy design was conducted, involving 162 participants across 12 centers in Spain. Subjects were randomly allocated to one of nine different treatment groups, each receiving either placebo or active treatment at doses of 500, 1,000, 3,000, or 5,000 mTU/mL over four months. Each participant received five subcutaneous (SC) doses of 0.5 mL each, every 30 days, and a daily sublingual (SL) dose of 0.2 mL. Participants who received active treatment through SC, received placebo through SL. Participants who received active treatment through SL, received placebo SC. One Group, as control, received bot SC and SL placebo. The primary efficacy outcome was the improvement in titrated nasal provocation tests (NPT) at the end of the study compared to baseline. Secondary outcomes included specific antibody (IgG4, IgE) and cellular (IL-10 producing and regulatory T cell) responses. All adverse events and side reactions were recorded and assessed. Results: Post-treatment, the active groups showed improvements in NPT ranging from 33% to 53%, with the highest doses showing the greatest improvements regardless of the administration route. In comparison, the placebo group showed a 12% improvement. Significant differences over placebo were observed at doses of 3,000 mTU/mL (p=0.049 for SL, p=0.015 for SC) and 5,000 mTU/mL (p=0.011 for SL, p=0.015 for SC). A dose-dependent increase in IgG4 was observed following SC administration, and an increase in IL-10 producing cells for both routes of administration. No serious systemic or local adverse reactions were recorded, and no adrenaline was required. Conclusion: Grass pollen immunotherapy with mannan-allergoid conjugates was found to be safe and efficacious in achieving the primary outcome, whether administered via the subcutaneous or sublingual routes, at doses of 3,000 and 5,000 mTU/mL. Clinical trial registration: https://www.clinicaltrialsregister.eu/ctr-search (EudraCT), identifier 2014-005471-88; https://www.clinicaltrials.gov, identifier NCT02654223.
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Alérgenos , Alergoides , Dessensibilização Imunológica , Mananas , Poaceae , Pólen , Imunoterapia Sublingual , Humanos , Masculino , Feminino , Adulto , Pólen/imunologia , Mananas/administração & dosagem , Alérgenos/imunologia , Alérgenos/administração & dosagem , Imunoterapia Sublingual/métodos , Imunoterapia Sublingual/efeitos adversos , Injeções Subcutâneas , Poaceae/imunologia , Pessoa de Meia-Idade , Dessensibilização Imunológica/métodos , Dessensibilização Imunológica/efeitos adversos , Método Duplo-Cego , Rinite Alérgica Sazonal/terapia , Rinite Alérgica Sazonal/imunologia , Administração Sublingual , Resultado do Tratamento , Adulto Jovem , Imunoglobulina E/imunologiaRESUMO
Background: Recurrent urinary tract infection (rUTI) remains a major health burden for women. A randomized, double-blind, placebo-controlled trial (RCT; NCT02543827) reported that female patients with rUTI receiving a sublingual vaccine, MV140, had a reduction in rUTI and increase in UTI-free rate compared with placebo. Objective: To determine the impact of MV140 on the personal burden of disease in women with rUTI using secondary endpoint data from the pivotal RCT evaluating MV140. Design setting and participants: In the primary RCT, female patients with rUTI enrolled in Spain and UK (from October 2015 to April 2019) were randomized to placebo (6 mo) or MV140 (3 or 6 mo), and followed for 12 mo. Individuals analyzed in this secondary analysis included those in the placebo and 3-mo (recommended dose) groups. Intervention: A polybacterial sublingual vaccine, MV140 (four inactivated whole-cell bacteria-Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, and Enterococcus faecalis), or placebo. Outcome measurements and statistical analysis: Symptom severity scoring, antibiotic use, safety, and multiple aspects of quality of life (QoL; Short-Form Questionnaire [SF-36]) were assessed. Results and limitations: Compared with the placebo group (n = 76), the 3-mo vaccinated group (n = 74) experienced fewer overall UTI symptoms (mean symptom score 102.2 ± 222.9 vs 194.2 ± 178.8; p = 0.0002), fewer days on antibiotics (12.4 ± 17.7 vs 28.7 ± 25.2; p = 0.0001), and improved total, general, and physical SF-36 QoL improvement (differences in means for total SF-36 score 15.7; 95% confidence interval [CI] 8.80, 22.64; p < 0.0001), with only social function QoL showing no impact (4.07; 95% CI -4.93, 13.08; p = 0.3744). Conclusions: Three months of MV140 is associated with a reduction of the personal burden of UTI by reducing overall UTI symptoms and antibiotic use, improving QoL in women with rUTI. Patient summary: Three months of MV140 vaccine, which has previously been shown to reduce the risk of urinary tract infection safely, is associated with a reduction in the personal burden of disease.
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Respiratory tract infections (RTIs) are among the most common and important problems in clinical medicine, making antibiotics the gold standard therapeutic option regardless of their frequent viral etiology. Their excessive and inappropriate use contributes to the rapid rise of antibiotic resistance and underscores the need for alternative strategies, especially when dealing with recurrent RTIs. Prevention is the ideal alternative, but specific vaccines targeting a wide range of respiratory pathogens are scarce. MV130 is a sublingual bacterial vaccine that induces trained immunity and provides non-specific protection against respiratory pathogens in various clinical settings according to the concept of TIbV (Trained Immunity-based Vaccine). A retrospective real-world study (RWS) was conducted to evaluate the annual incidence of RTIs and the consumption of antibiotics before and after the administration of MV130, using data sourced from the medical records of 599 patients (186 children and 413 adults) who suffered from recurrent RTIs. The median number of infectious episodes in children was significantly reduced by more than 70% from 5 episodes (interquartile range (IQR) 4.0-6.0) to 1 (IQR, 0.0-2.0) (p < 0.001) after MV130. Similarly, in adults, the median number of episodes before MV130 immunization was 5 (IQR, 4.0-6.0), which dropped by more than 80% to 1 (IQR, 0.0-1.0) during the year following MV130 immunization (p < 0.001). The median number of antibiotic courses also significantly decreased for both children and adults by over 80% (p < 0.001). This RWS showed that MV130 is an effective strategy for the prevention of respiratory infections and the reduction of associated antibiotic consumption.
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Antimony sulfide (Sb2S3) and antimony selenide (Sb2Se3) compounds have attracted considerable attention for applications in different optoelectronic devices due to their notable optical and electrical properties, and due to the strong anisotropy of these properties along different crystallographic directions. However, the efficient use of these promising compounds still requires significant efforts in characterization of their fundamental properties. In the present study, Raman scattering and spectroscopic ellipsometry were used to investigate the vibrational and optical properties of Sb2Se3 and Sb2S3 bulk polycrystals grown by the modified Bridgman method. The first technique proved the presence of the desired Sb2S3 and Sb2Se3 phases in the analyzed ingots and confirmed the absence of any preferential crystallographic orientation at the measured surface of the samples. Spectroscopic ellipsometry was performed using a multi-oscillator Tauc-Lorentz dispersion model, and yielded a complex dielectric function of chalcogenides over the range 1.0-4.6 eV with a three phase model (ambient, surface and bulk materials). Finally, spectral data on the refractive index, the extinction coefficient, the absorption coefficient and the reflectivity at normal incidence, R, were obtained, which serve as a reference for the optical modeling of optoelectronic devices based on polycrystalline Sb2S3 and Sb2Se3 compounds.
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BACKGROUND: Polymerized allergens conjugated to non-oxidized mannan (PM-allergoids) are novel vaccines targeting dendritic cells (DCs). Previous experimental data indicate that PM-allergoids are readily taken up by DCs and induce Treg cells. This first-in-human study was aimed to evaluate safety and to find the optimal dose of house dust mite PM-allergoid (PM-HDM) administered subcutaneously (SC) or sublingually (SL). METHODS: In a randomized, double-blind, double-dummy, placebo-controlled trial, 196 subjects received placebo or PM-HDM at 500, 1000, 3000, or 5000 mannan-conjugated therapeutic units (mTU)/mL in 9-arm groups for 4 months. All subjects received 5 SC doses (0.5 ml each) every 30 days plus 0.2 ml SL daily. The primary efficacy outcome was the improvement of titrated nasal provocation tests (NPT) with D. pteronyssinus at baseline and at the end of the study. All adverse events and reactions were recorded and assessed. Secondary outcomes were the combination of symptom and medication scores (CSMS) and serological markers. RESULTS: No moderate or severe adverse reactions were reported. Subjects improving the NPT after treatment ranged from 45% to 62% in active SC, 44% to 61% in active SL and 16% in placebo groups. Statistical differences between placebo and active groups were all significant above 500 mTU, being the highest with 3000 mTU SL (p = 0.004) and 5000 mTU SC (p = 0.011). CSMS improvement over placebo reached 70% (p < 0.001) in active 3000 mTU SC and 40% (p = 0.015) in 5000 mTU SL groups. CONCLUSIONS: PM-HDM immunotherapy was safe and successful in achieving primary and secondary clinical outcomes in SC and SL at either 3000 or 5000 mTU/ml.
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Imunoterapia Sublingual , Vacinas , Alérgenos , Alergoides , Animais , Antígenos de Dermatophagoides , Dermatophagoides pteronyssinus , Método Duplo-Cego , Humanos , Mananas , Pyroglyphidae , Imunoterapia Sublingual/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Recurrent urinary tract infections (UTIs), which consist of three or more episodes in 1 year or two or more infections in 6 months, affect 5% to 10% of women. MV140, a sublingual preparation of whole-cell inactivated bacteria, has shown clinical benefit in observational studies. This trial examined treatment with MV140 to prevent recurrent UTI. METHODS: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group 1-year trial, 240 women 18 to 75 years of age from Spain and the United Kingdom with recurrent UTI were allocated to receive MV140 for 3 or 6 months or placebo for 6 months in a 1:1:1 ratio. The primary end point was the number of UTIs in the 9-month study period after 3 months of intervention. Key secondary end points were the percentage of women who were UTI free over the above period, time to UTI onset, and health-related quality of life. RESULTS: The median (interquartile range) of UTI episodes was 3.0 (0.5 to 6.0) for placebo compared with 0.0 (0.0 to 1.0) in both groups receiving MV140 (P<0.001). Among women treated with placebo, 25% (95% confidence interval [CI], 15% to 35%) were free of UTIs compared with 56% (95% CI, 44% to 67%) and 58% (95% CI, 44% to 67%) of women who received 3 and 6 months of MV140 treatment, respectively. A total of 205 AEs in 101 participants were registered (81, 76, and 48 in the placebo, 3-month MV140, and 6-month MV140 groups, respectively). CONCLUSIONS: In this controlled trial of modest size and duration, MV140 showed promising clinical efficacy in reducing recurrent UTI in women suffering from this condition. Adverse effects were not clinically limiting. (Funded by Inmunotek S.L. and Syner-Med [Pharmaceutical Products] Ltd.; ClinicalTrials.gov number, NCT02543827.)
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Infecções Urinárias , Humanos , Infecções Urinárias/prevenção & controle , Feminino , Pessoa de Meia-Idade , Adulto , Método Duplo-Cego , Administração Sublingual , Idoso , Adolescente , Adulto Jovem , Prevenção Secundária/métodos , Qualidade de VidaRESUMO
INTRODUCTION: Developmental dysplasia of the hip is a common cause of disability among children. Early detection leads to better prognosis. There are some risk factors that increase the possibility of developing a dysplasia. But not every child with developmental dysplasia has them. This means that physical examination is still very useful to detect them. However, based on clinical findings, the amount of requested ultrasound seems higher than it would be necessary. METHODS: Retrospective cohort study of infants born in a single tertiary care centre. Babies in which hip ultrasound was performed were included. During the period of study, patients with diagnosis of developmental hip dysplasia were also included, as well as the amount of ultrasounds requested during this period, and their efficiency. RESULTS: Out of the 456 newborns included, 530 hip ultrasounds were performed. Just 3 of the total 12 dysplasias had risk factors. The others were diagnosed through clinical examination. CONCLUSIONS: Screening protocols are useful to detect hip dysplasia but clinical examination is very important to detect those cases without risk factors. However, the number of tests is higher than expected according to the diagnosed dysplasias.
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Displasia do Desenvolvimento do Quadril , Luxação Congênita de Quadril , Criança , Feminino , Luxação Congênita de Quadril/diagnóstico , Humanos , Lactente , Recém-Nascido , Exame Físico , Estudos Retrospectivos , UltrassonografiaRESUMO
INTRODUCTION: Developmental dysplasia of the hip is a common cause of disability among children. Early detection leads to better prognosis. There are some risk factors that increase the possibility of developing a dysplasia. But not every child with developmental dysplasia has them. This means that physical examination is still very useful to detect them. However, based on clinical findings, the amount of requested ultrasound seems higher than it would be necessary. METHODS: Retrospective cohort study of infants born in a single tertiary care centre. Babies in which hip ultrasound was performed were included. During the period of study, patients with diagnosis of developmental hip dysplasia were also included, as well as the amount of ultrasounds requested during this period, and their efficiency. RESULTS: Out of the 456 new-borns included, 530 hip ultrasounds were performed. Just 3 of the total 12 dysplasias had risk factors. The others were diagnosed through clinical examination. CONCLUSIONS: Screening protocols are useful to detect hip dysplasia but clinical examination is very important to detect those cases without risk factors. However, the number of tests is higher than expected according to the diagnosed dysplasias.
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BACKGROUND: Clitoral artery Doppler has been used as an objective technique to measure changes in genital women response. However, the technique has not been fully validated, and arterial volume flow has never been used as an outcome measure. AIMS: To validate the technique clitoral artery Doppler measured in a sagittal section and explore arterial volume flow as a new parameter in clitoral Doppler. METHODS: We examined 90 healthy volunteers by clitoral artery Doppler using the sagittal section approach described by Battaglia et al in 2008. We calculated intraobserver, interobserver, and intraobserver intersession variability and reliability for all Doppler parameters and described and validated arterial volume flow as a new parameter in clitoral artery Doppler. OUTCOMES: We calculated peak systolic velocity (PSV), time-averaged maximum velocity, time-averaged mean velocity, end-diastolic velocity, pulsatility index, resistance index, and volume flow (v-flow) in all groups. We conducted reliability analyses using the intraclass correlation coefficient for agreement. We explored differences between and within observers and calculated agreement limits using the Bland-Altman test. RESULTS: The intraclass correlation coefficient analysis showed correlation values higher than 0.75 (good reliability) for most of the variables and higher than 0.60 (moderate reliability) for the remaining ones. There were statistically significant differences between PSV and time-averaged maximum velocity in the intraobserver intersession measurements. For the remaining groups and variables, no statistically significant differences were observed. Bland-Altman analyses showed that the limits of agreement were acceptable and the regressions were not significant. The v-flow parameter also showed good reliability and low variability between groups. CLINICAL IMPLICATIONS: We found that PSV was not a good outcome measure because of its high intraobserver and intersession variability. Moreover, it is possible to measure v-flow in the clitoral artery using the sagittal technique described by Battaglia et al, and it seems that this measure is reliable and reproducible. This could be the best parameter to assess clinical changes. STRENGTHS & LIMITATIONS: This study provided full validation of the sagittal section approach and of a new parameter, v-flow, which could beuseful for assessing clitoral blood flow. The main limitation of the study is its retrospective nature for validating v-flow. CONCLUSION: We found that clitoral artery Doppler measured using a sagittal approach is a valid and reliable technique for studying clitoral blood flow in women. The v-flow variable is a promising and reliable parameter for measuring changes in clitoral blood flow. Pérez MF, Agís IF, La Calle Marcos P, et al. Validation of a Sagittal Section Technique for Measuring Clitoral Blood Flow: Volume Flow - A New Parameter in Clitoral Artery Doppler. J Sex Med 2020;17:1109-1117.
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Clitóris , Ultrassonografia Doppler , Artérias , Velocidade do Fluxo Sanguíneo , Clitóris/diagnóstico por imagem , Feminino , Humanos , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
The introduction of the alkaline-earth element Magnesium (Mg) into Cu2ZnSn(S,Se)4 (CTZSSe) is explored in view of potential photovoltaic applications. Cu2Zn1-xMgxSn(S,Se)4 absorber layers with variable Mg content x = 0 1 are deposited using the solution approach with dimethyl sulfoxide solvent followed by annealing in selenium atmosphere. For heavy Mg alloying with x = 0.55 1 the phase separation into Cu2SnSe3, MgSe2, MgSe and SnSe2 occurs in agreement with literature predictions. A lower Mg content of x = 0.04 results in the kesterite phase as confirmed by XRD and Raman spectroscopy. A photoluminescence maximum is red-shifted by 0.02 eV as compared to the band-gap and a carrier concentration NCV of 1 × 1016 cm-3 is measured for a Mg-containing kesterite solar cell device. Raman spectroscopy indicates that structural defects can be reduced in Mg-containing absorbers as compared to the Mg-free reference samples, however the best device efficiency of 7.2% for a Mg-containing cell measured in this study is lower than those frequently reported for the conventional Na doping.
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INTRODUCTION: Early-onset neonatal sepsis refers to an infection which starts during the first 72hours of birth, and can lead to significant morbidity and mortality. Scientific evidence shows that infected infants present with symptoms during the first hours after delivery. There has been a significant decrease in this condition with the implementation of guidelines for its prevention. However, International guidelines still recommend the evaluation of these infants using painful tests. MATERIAL AND METHODS: A prospective cohort study was conducted on all asymptomatic infants born at>35 weeks gestation with one or more risk factors in a single tertiary care centre from 2011 to 2015. They were periodically observed in newborn nursery from admission until discharge looking for signs of infection. RESULTS: Out of the 9,424 babies born during this period, 1425 were included in the study. A total of 53 infants were admitted to the neonatal unit, half of them because of sepsis suspicion. Finally, just 7 were discharged with the diagnosis of sepsis. All these 7 presented with symptoms during their first 72hours of life. No sepsis was reported in asymptomatic infants. CONCLUSIONS: Truly infected infants present with symptoms during their first hours of life. This study supports the observation of infants at risk as a safe practice to detect early-onset sepsis.
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Infecções/diagnóstico , Triagem Neonatal , Feminino , Humanos , Recém-Nascido , Infecções/epidemiologia , Masculino , Estudos Prospectivos , Fatores de RiscoRESUMO
In this work, we propose a method to improve electro-optical and structural parameters of light-absorbing kesterite materials. It relies on the application of weak power hydrogen plasma discharges using electromagnetic field of radio frequency range, which improves homogeneity of the samples. The method allows to reduce strain of light absorbers and is suitable for designing solar cells based on multilayered thin film structures. Structural characteristics of tetragonal kesterite Cu2ZnSn(S, Se)4 structures and their optical properties were studied by Raman, infrared, and reflectance spectroscopies. They revealed a reduction of the sample reflectivity after RF treatment and a modification of the energy band structure.
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A novel approach to incorporate cobalt atoms into a magnetite single crystal is demonstrated by a combination of x-ray spectro-microscopy, low-energy electron diffraction, and density-functional theory calculations. Co is deposited at room temperature on the reconstructed magnetite (001) surface filling first the subsurface octahedral vacancies and then occupying adatom sites on the surface. Progressive annealing treatments at temperatures up to 733 K diffuse the Co atoms into deeper crystal positions, mainly into octahedral ones with a marked inversion level. The oxidation state, coordination, and magnetic moments of the cobalt atoms are followed from their adsorption to their final incorporation into the bulk, mostly as octahedral Co(2+). This precise control of the near-surface Co atoms location opens up the way to accurately tune the surface physical and magnetic properties of mixed spinel oxides.
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In a recent publication by Abou-Ras et al., various techniques for the analysis of elemental distribution in thin films were compared, using the example of a 2-µm thick Cu(In,Ga)Se2 thin film applied as an absorber material in a solar cell. The authors of this work found that similar relative Ga distributions perpendicular to the substrate across the Cu(In,Ga)Se2 thin film were determined by 18 different techniques, applied on samples from the same identical deposition run. Their spatial and depth resolutions, their measuring speeds, their availabilities, as well as their detection limits were discussed. The present work adds two further techniques to this comparison: laser-induced breakdown spectroscopy and grazing-incidence X-ray fluorescence analysis.
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This work presents results from high-resolution scanning transmission electron microscopy and electron energy-loss spectroscopy on twin boundaries (TBs) and nontwin grain boundaries (GBs) in Cu(In,Ga)Se(2) thin films. It is shown that the atomic reconstruction is different for different symmetries of the grain boundaries. We are able to confirm the model proposed by Persson and Zunger [Phys. Rev. Lett. 91, 266401 (2003)] for Se-Se-terminated Σ3 {112} TBs, showing Cu depletion and In enrichment in the two atomic planes closest to the TB. On the contrary, Cu depletion without In enrichment is detected for a cation-Se-terminated TB. At nontwin GBs, always a strong anticorrelation of Cu and In signals is detected suggesting that the formation of In(Cu) or Cu(In) antisites within a very confined region of smaller than 1 nm is an essential element in the reconstruction of these GBs.
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Los cambios presentados en el actual modelo de atención en salud requiere de la comprensión del funcionamiento del Sistema General de Seguridad Social en Salud-SGSSS-; de igual manera, el consiguiente impacto de la situación económica y laboral sobre la práctica odontológica debe generar en la profesión una mirada critica hacia la prestación de los servicios de salud bucal actualmente. Se realizó un estudio de corte transversal, cuyo objetivo fue describir los cambios económicos y laborales que se han presentado en el ejercicio profesional de la Odontología, a partir del Sistema General de Seguridad Social en Salud. Para este fin se utilizó la base de datos de los egresados del Colegio Odontológico Colombiano correspondiente a los años de 1979, contactando 60 egresados a quienes se aplicó una encuesta estructurada que evaluara aspectos económico, laboral, de conocimientos acerca del modelo de Seguridad Social en Salud y la apreciación sobre la calidad del servicio. Los resultados obtenidos revelaron una marcada tendencia a la contratación por servicios prestados y dependencia laboral, disminución en el ingreso promedio y marginal en la práctica odontológica, a pesar de ser esta la principal fuente de ingresos; los odontólogos expresaron inconformidad con la forma de contratación; así mismo, evidenciaron reducción en el número de pacientes en la consulta privada, disminución de los ingresos y movilización o vinculación en las EPS e IPS. El conocimiento acerca del Sistema de Seguridad Social en Salud resultó ser deficiente. El conocimiento insuficiente acerca del actual sistema de salud en Colombia, las condiciones de contratación y el deterioro de la calidad de los servicios, se constituyen en los principales problemas percibidos por los odontólogos encuestados...
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Militares , Saúde Bucal , Previdência Social , Colômbia , Odontologia , Aplicação da LeiRESUMO
CuIn(1-x)Ga(x)Se2 [CIGS; x=Ga/(In+Ga)] thin films are among of the best candidates as absorber materials for solar cell applications. The material quality and main properties of the polycrystalline absorber layer are critically influenced by deviations in the stoichiometry, particularly in the Cu/(In+Ga) atomic ratio. In this work a simple, sensitive and accurate method has been developed for the quantitative determination of these thin films by inductively coupled plasma optical emission spectrometry (ICP-OES). The proposed method involves an acid digestion of the samples to achieve the complete solubilization of CIGS, followed by the analytical determination by ICP-OES. A digestion procedure with 50% HNO3 alone or in the presence of 10% HCl was performed to dissolve those thin films deposited on glass or Mo-coated glass substrates, respectively. Two analytical lines were selected for each element (Cu 324.754 and 327.396 nm, Ga 294.364 and 417.206 nm, In 303.936 and 325.609 nm, Se 196.090 and 203.985 nm, and Mo 202.030 and 379.825 nm) and a study of spectral interferences was performed which showed them to be suitable, since they offered a high sensitivity and no significant inter-element interferences were detected. Detection limits for all elements at the selected lines were found to be appropriate for this kind of application, and the relative standard deviations were lower than 1.5% for all elements with the exception of Se (about 5%). The Cu/(In+Ga) atomic ratios obtained from the application of this method to CIGS thin films were consistent with the study of the structural and morphological properties by X-ray diffraction (XRD) and scanning electron microscopy (SEM).