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The aim of this work is to test whether the use of a transparent capsule affects the residual capsule weight after inhalation as a surrogate of the inhaled delivered dose for patients with non-reversible chronic airway disease. Researchers conducted an observational cross-sectional study with patients using a single-dose dry powder inhaler. The weight of the capsule was measured with a precision microbalance before and after inhalation. Ninety-one patients were included, of whom 63 (69.2%) used a transparent capsule. Inhalation with a transparent capsule achieved a weight decrease of 30.1% vs 8.6% for devices with an opaque capsule (P Key words: chronic obstructive airway diseases; dry powder inhalers; dry powder capsules; clinical outcomes, https://doi.org/10.1370/afm.3147 INTRODUCTION One of the factors considered most important by patients when using inhaled medications is the verification of the dose taken. (1) Additionally, critical errors in dose delivery have [...]

Introduction: Immune-based diagnostic tests for tuberculosis (TB) have suboptimal sensitivity in children and cannot differentiate between latent infection (LTBI) and active disease. This study evaluated the diagnostic potential of a broad range of biomarkers of tissue damage and inflammation in unstimulated plasma in children. Methods: We analyzed 17 biomarkers in 15 non–M. tuberculosis (MTB)-infected controls and 33 children with TB infection (LTBI, n = 8; probable TB, n = 19; confirmed TB, n = 6). Biomarker concentrations were measured using a Luminex magnetic bead–based platform and multiplex sandwich immunoassays. Concentrations, correlations and diagnostic accuracy assessments were conducted among patient groups. Results: Confirmed TB cases had significantly higher concentrations of IFN-γ and IL-2 and higher IFN-γ/MCP-1 and IL-2/MCP-1 ratios compared to LTBI and non–MTB-infected children. Among children with confirmed TB, there was a strong correlation between IFN-γ and IL-10 (r = 0.95; p

Different physicochemical factors have an influence on wine quality, for instance, quantity of grapes, PH, temperature, and humidity over the growing season. However, despite the weather conditions of the season, the product, grapes, is deposited in the wineries. At that time, a set of analyses are conducted to determine some chemical parameters of the grapes. This work is focused on the chemical parameters obtained at wineries to establish a method to pay farmers according to quality parameters. These parameters have been determined by the technicians at wineries, that is, the experts on wine, as well as market expectations. The idea behind this work is to introduce policies that promote quality instead of quantity, bringing about a change in the mentality of the farmers. These policies pay attention to water consumption or reduction in fertilizers that, of course, affect the chemical parameters of wine but also the sustainability of the sector and the region, in this case, Castilla-La Mancha in Spain. The application developed in this work, called DICAUVACOOP, not only promotes good practices but also introduces penalties. On the other hand, the calculations of each campaign are stored in databases that allow users to conduct comparisons among different campaigns showing the data in a Geographic Information System (GIS) as a decision-making support tool. Another effect of this process is to improve the visibility and brand positioning of Castilla-La Mancha wines on the world stage.

El adobe es resistente a cambios súbitos de temperatura y al fuego, actuando como una eficaz barrera térmica y acústica en la construcción de viviendas. Este artículo investiga las propiedades térmicas, de resistencia, compresión, plasticidad y absorción del adobe biocompósito, proponiendo que la combinación de adobe con bagazo de agave mejora significativamente su eficiencia en comparación con los bloques compuestos de zacate, fibra de agave y tierra. El estudio se realizó en una zona productora de mezcal y adobe tradicional en el Estado de México, en línea con los principios de la economía circular. Los resultados indican que el adobe enriquecido con bagazo de agave presenta varias mejoras en sus propiedades físicas y mecánicas, lo que reduce su impacto ambiental. Esta investigación resalta la importancia del adobe como elemento fundamental en la revaloración de la arquitectura de tierra, contribuyendo al fomento de la identidad patrimonial edificada.

María Torres-Durán,1 José Luis López-Campos,2,3 Myriam Calle Rubio,4 Carmen Montero-Martínez,5 Ana Priegue Carrera,6 Rosanel Amaro Rodríguez,7 Miriam Barrecheguren,8 María Ángeles Barrio Guirado,9 Francisco Javier Callejas-González,10 Francisco Casas-Maldonado,11 Layla Diab-Cáceres,12 Pilar García-Meseguer,9 José María Hernández-Pérez,13 Lourdes Lázaro-Asegurado,14 Cristina Martínez-González,15 Carlos Martínez Rivera,16 Francisco Javier Michel,17 José-Bruno Montoro-Ronsano,18 Raquel Sánchez,19 Marta Ortiz-Pica,20 Isabel Parra,21 José Pablo Quintero García,22 María del Rosario Ruiz-Serrano-de la Espada,23 Begoña Tortajada-Goitia,24 Marc Miravitlles8 1Pneumology Department, Hospital Álvaro Cunqueiro, NeumoVigo I+i Research Group, IIS Galicia Sur, Vigo, Spain; 2Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain; 3Medical and Surgery Unit for Respiratory Diseases, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, Seville, Spain; 4Pneumology Department, Research Institute of Hospital Clínico San Carlos (IdISSC), Department of Medicine, Faculty of Medicine, University Complutense of Madrid, Madrid, Spain; 5Pneumology Department, Hospital Universitario de A Coruña, A Coruña, Spain; 6Nursing Unit, Hospital Álvaro Cunqueiro, Pontevedra, Spain; 7Pneumology Department, Hospital Clínic, Barcelona, Spain; 8Pneumology Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain; 9Nursung Unit, Hospital Universitari Vall d’Hebron, Barcelona, Spain; 10Pneumology Department, Complejo Hospitalario Universitario de Albacete, Albacete, Spain; 11Pneumology Department, Hospital Universitario Clínico San Cecilio, Granada, Spain; 12Pneumology Department, Hospital Universitario 12 de Octubre, Madrid, Spain; 13Pneumology Department, Hospital Universitario Nuestra Señora de La Candelaria, Santa Cruz de Tenerife, Tenerife, Spain; 14Pneumology Department, Complejo Asistencial Universitario de Burgos, Burgos, Spain; 15Instituto de Investigación Sanitaria del Principado de Asturias (FINBA-ISPA) Oviedo, Oviedo, Spain; 16Pneumology Department, Hospital Universitario Germans Trías I Pujol, Institut d’investigació Germans Trias i Pujol (IGTP), Badalona, Spain; 17Pneumology Department, Hospital Universitario Donostia, Donostia, Spain; 18Hospital Pharmacy Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain; 19Pneumology Department, Hospital Universitario Basurto, Bilbao, Spain; 20Nursing Unit, Hospital Clínico San Carlos, Madrid, Spain; 21Pneumology Department, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain; 22Hospital Pharmacy Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain; 23Nursing Unit, Hospital Universitario Virgen del Rocío, Sevilla, Spain; 24Hospital Pharmacy Department, Hospital Costa del Sol, Málaga, SpainCorrespondence: María Torres-Durán, Tel +34986811111, Email maria.luisa.torres.duran@sergas.esPurpose: Administration of exogenous alpha-1 antitrypsin (AAT) is the only specific therapy for the management of pulmonary morbidity in patients with AAT deficiency. It requires weekly or biweekly intravenous infusions, which may impact patient independence and quality of life. Self-administration of AAT therapy is an alternative to reduce the burden for patients who require AAT therapy. We presented herein experts’ recommendations for the implementation of a program for the self-administration of AAT.Methods: This project was conducted using a modified nominal group technique and was undertaken in two online meetings involving the participation of 25 experts: specialists in pulmonology (n=17), nurses (n=5) and hospital pharmacists (n=3).Results: The following issues were discussed, and several recommendations were agreed upon on the following topics: a) patient profile and clinical evaluation, establishing selection criteria that should include clinical as well as social criteria; b) role of health care professionals, suggested roles for specialists in pulmonology, nurses, and hospital pharmacists; c) training by the nurse, including recommendations before initiating the training and the content of the training sessions; and d) logistic issues and follow-up, adherence, and patient support.Conclusion: We expect this proposal to increase awareness of this therapeutic alternative and facilitate the implementation of self-administration programs, thus contributing to optimizing the patient experience with AAT therapy. Further research on the outcomes of these programs, especially from the patient perspective, will also help to improve their design and implementation.Keywords: alpha-1 antitrypsin deficiency, disease burden, augmentation therapy, self-administration

This is a descriptive study using healthcare claims data from patients with T2DM from public and private healthcare insurance companies providing services in Puerto Rico in 2013, aimed to estimate the prevalence of comorbidities in this population. Descriptive analyses were performed by sociodemographic, and type of service variables using frequency and percent for categorical data or means (+/-SD) or median (IQR) for continuous variables. Chi-square, Fisher exact or two-sample t-tests were used for comparisons. A total of 3,100,636 claims were identified from 485,866 adult patients with T2DM. Patients older than 65 years represented 48% of the study population. Most patients were women (57%) and had private health insurance (77%). The regions of Metro Area (17%) and Caguas (16%) had the higher number of persons living with T2DM. The overall estimated prevalence of T2DM was 17.4%. The number of claims per patient ranged from 1 to 339. A mean of 6.3 claims (SD±9.99) and a median of 3 claims (Q1 1- Q3 8) per subject were identified. Of the 3,100,636 claims most (74%) were related to the diagnosis of diabetes (59%) and associated to outpatient services (88%). The most prevalent comorbidities were hypertension (48%), hyperlipidemia (41%), neuropathy (21%); renal disease (15%), and retinopathy (13%). A high prevalence and co-prevalence of comorbidities and use of healthcare services were identified in patients with T2DM, especially in older adults. Since most comorbidities were due to diabetes-related conditions, this analysis highlights the importance of early diagnosis and adequate management of T2DM patients to avoid preventable burden to the patient and to the healthcare system.

Abstract Identification of Nocardia and Mycobacterium species by matrix‐assisted laser desorption/ionization‐time of flight mass spectrometry (MALDI‐TOF MS) is still a challenging task that requires both suitable protein extraction procedures and extensive databases. This study aimed to evaluate the VITEK MS Plus system coupled with updated RUO (v4.17) and IVD (v3.2) databases for the identification of Nocardia spp. and Mycobacterium spp. clinical isolates. Sample preparation was carried out using the VITEK MS Mycobacterium/Nocardia kit for protein extraction. From 90 Nocardia spp. isolates analysed, 86 (95.6%) were correctly identified at species or complex level using IVD and 78 (86.7%) using RUO. Only two strains were misidentified as other species pertaining to the same complex. Among the 106 non‐tuberculous Mycobacterium clinical isolates tested from a liquid culture medium, VITEK MS identified correctly at species or complex level 96 (90.6%) isolates in the IVD mode and 89 (84.0%) isolates in the RUO mode. No misidentifications were detected. Although the IVD mode was unable to differentiate members of the M. fortuitum complex, the RUO mode correctly discriminated M. peregrinum and M. septicum. The robustness and accuracy showed by this system allow its implementation for routine identification of these microorganisms in clinical laboratories.

ABSTRACT Mycobacterium abscessus (MABS) is the most pathogenic and drug-resistant rapidly growing mycobacteria. However, studies on MABS epidemiology, especially those focusing on subspecies level, are scarce. We aimed to determine MABS subspecies distribution and its correlation with phenotypic and genotypic antibiotic profiles. A retrospective multicenter study of 96 clinical MABS isolates in Madrid between 2016 to 2021 was conducted. Identification at the subspecies level and resistance to macrolides and aminoglycosides were performed by the GenoType NTM-DR assay. The MICs of 11 antimicrobials tested against MABS isolates were determined using the broth microdilution method (RAPMYCOI Sensititer titration plates). Clinical isolates included 50 (52.1%) MABS subsp. abscessus; 33 (34.4%) MABS subsp. massiliense; and 13 (13.5%) MABS subsp. bolletii. The lowest resistance rates corresponded to amikacin (2.1%), linezolid (6.3%), cefoxitin (7.3%), and imipenem (14.6%), and the highest to doxycycline (100.0%), ciprofloxacin (89.6%), moxifloxacin (82.3%), cotrimoxazole (82.3%), tobramycin (81.3%), and clarithromycin (50.0% at day 14 of incubation). Regarding tigecycline, although there are no susceptibility breakpoints, all strains but one showed MICs ≤ 1 μg/mL. Four isolates harbored mutations at positions 2058/9 of the rrl gene, one strain harbored a mutation at position 1408 of the rrl gene, and 18/50 harbored the T28C substitution at erm(41) gene. Agreement of the GenoType results with clarithromycin and amikacin susceptibility testing was 99.0% (95/96). The rate of MABS isolates showed an upward trend during the study period, being M. abscessus subsp. abscessus the most frequently isolated subspecies. Amikacin, cefoxitin, linezolid, and imipenem showed great in vitro activity. The GenoType NTM-DR assay provides a reliable and complementary tool to broth microdilution for drug resistance detection. IMPORTANCE Infections caused by Mycobacterium abscessus (MABS) are increasingly being reported worldwide. Identifying MABS subspecies and assessing their phenotypic resistance profiles are crucial for optimal management and better patient outcomes. M. abscessus subspecies differ in erm(41) gene functionality, which is a critical determinant of macrolide resistance. Additionally, resistance profiles of MABS and the subspecies distribution can vary geographically, highlighting the importance of understanding local epidemiology and resistance patterns. This study provides valuable insights into the epidemiology and resistance patterns of MABS and its subspecies in Madrid. Elevated resistance rates were observed for several recommended antimicrobials, emphasizing the need for cautious drug use. Furthermore, we assessed the GenoType NTM-DR assay, which examines principal mutations in macrolides and aminoglycosides resistance-related genes. We observed a high level of agreement between the GenoType NTM-DR assay and the microdilution method, indicating its usefulness as an initial tool for early initiation of appropriate therapy.

Resumen: Introducción: La escala modificada Rankin (mRS) es la principal herramienta para la valoración funcional tras un evento cerebrovascular. Recientemente, fue validado en inglés, el cuestionario simplificado de la mRS (smRSq) telefónico, consiguiendo una escala basada en la mRS, más sencilla, fiable y con buena reproductibilidad telefónica. Nuestro objetivo es validar en castellano el cuestionario smRSq telefónico. Método: Se realizó un estudio de cohortes prospectivo, evaluando a 50 pacientes, a los 3 meses de haber sufrido un ictus isquémico. Se evaluó el cuestionario smRSq en castellano por teléfono y posteriormente de forma presencial la mRS mediante entrevista estructurada, el cuestionario smRSq y la SIS-16 (Stroke Impact Scale-16). Se estudió la fiabilidad interobservador, test-retest y la validez de constructo y de criterio. Resultados: La fiabilidad interobservador obtuvo una correlación muy alta (k = 0,810); la fiabilidad test-retest y la validez de criterio respecto a la entrevista estructurada de la mRS de forma presencial, obtuvieron una correlación alta (k = 0,639 y k = 0,759) y la validez de constructo respecto a la SIS-16, obtuvo una correlación lineal alta (coeficiente de Spearman = -0,728). Conclusiones: El cuestionario smRSq telefónico en castellano es una herramienta fiable, rápida y sencilla para la obtención del estado funcional de los pacientes tras un evento cerebrovascular, basado en la mRS. Abstract: Introduction: The modified Rankin Scale (mRS) is the main functional assessment tool used after stroke. The simplified mRS questionnaire (smRSq) has recently been validated in English, and represents a simpler, reliable scale with an excellent reproducibility via telephone. The present study aims to validate a Spanish-language version of the telephone smRSq. Method: We conducted a prospective cohort study, assessing 50 patients 3 months after they presented an ischaemic stroke. We assessed the Spanish-language smRSq by telephone and in person, the mRS with a structured interview, the Spanish-language smRSq, and the Stroke Impact Scale-16. Inter-rater reliability, test-retest reliability, construct validity, and criterion validity were assessed. Results: Inter-rater reliability showed strong agreement (k = 0.810); test-retest reliability and criterion validity showed moderate agreement (k = 0.639 and k = 0.759, respectively), and construct validity showed moderate agreement (Spearman correlation coefficient = –0.728). Conclusions: The Spanish-language telephone smRSq is reliable and simple, and saves time in the functional assessment after a stroke.

Different physicochemical factors have an influence on wine quality, for instance, quantity of grapes, PH, temperature, and humidity over the growing season. However, despite the weather conditions of the season, the product, grapes, is deposited in the wineries. At that time, a set of analyses are conducted to determine some chemical parameters of the grapes. This work is focused on the chemical parameters obtained at wineries to establish a method to pay farmers according to quality parameters. These parameters have been determined by the technicians at wineries, that is, the experts on wine, as well as market expectations. The idea behind this work is to introduce policies that promote quality instead of quantity, bringing about a change in the mentality of the farmers. These policies pay attention to water consumption or reduction in fertilizers that, of course, affect the chemical parameters of wine but also the sustainability of the sector and the region, in this case, Castilla-La Mancha in Spain. The application developed in this work, called DICAUVACOOP, not only promotes good practices but also introduces penalties. On the other hand, the calculations of each campaign are stored in databases that allow users to conduct comparisons among different campaigns showing the data in a Geographic Information System (GIS) as a decision-making support tool. Another effect of this process is to improve the visibility and brand positioning of Castilla-La Mancha wines on the world stage. [ABSTRACT FROM AUTHOR]

The 1,8-Diazaanthracene-2,9,10-triones, their 5,8-dihydro derivatives, and 1,8-diazaanthracene-2,7,9,10-tetraones, structurally related to the diazaquinomycin family of natural products, were synthesized in a regioselective fashion employing Diels–Alder strategies. These libraries were studied for their cytotoxicity in a variety of human cancer cell lines in order to establish structure–activity relationships. From the results obtained, we conclude that some representatives of the 1,8-diazaanthracene-2,9,10-trione framework show potent and selective cytotoxicity against solid tumors. Similar findings were made for the related 1-azaanthracene-2,9,10-trione derivatives, structurally similar to the marcanine natural products, which showed improved activity over their natural counterparts. An enantioselective protocol based on the use of a SAMP-related chiral auxiliary derived was developed for the case of chiral 5-substituted 1,8-diazaanthracene-2,9,10-triones, and showed that their cytotoxicity was not enantiospecific.

Background Interferon-y Release Assays (IGRA) reversions have been reported in different clinical scenarios for the diagnosis of tuberculosis (TB) infection. This study aimed to determine the rate of QuantiFERON-TB Gold Plus (QFT-Plus) reversions during contact investigation as a potential strategy to reduce the number of preventive treatments. Methods Prospective, multicentre cohort study of immunocompetent adult contacts of patients with pulmonary TB tested with QFT-Plus. Contacts with an initial positive QFT-Plus (QFT-i) underwent a second test within 4 weeks (QFT-1), and if negative, underwent a repeat test 4 weeks later (QFT-2). Based on the QFT-2 result, we classified cases as sustained reversion if they remained negative and as temporary reversion if they turned positive. Results We included 415 contacts, of whom 96 (23.1%) had an initial positive test (QFT-i). Following this, 10 had negative QFT-1 results and 4 (4.2%) of these persisted with a negative result in the QFT-2 (sustained reversions). All four sustained reversions occurred in contacts with IFN-γ concentrations between ≥0.35 and ≤0.99 IU•mL-1 in one or both QFT-i tubes. Conclusion In this study, TB contact investigations rarely reveal QFT-Plus reversion. These results do not support retesting cases with an initial positive result to reduce the number of preventive treatments.

IntroductionSince the COVID-19 outbreak, specific mRNA-based anti-SARS-CoV-2 vaccines have been developed and distributed worldwide. Because this is the first time that mRNA vaccines have been used, there are several questions regarding their capacity to confer immunity and the durability of the specific anti-SARS-CoV-2 response. Therefore, the objective of this study was to recruit a large cohort of healthcare workers from the Gregorio Marañón Hospital vaccinated with the mRNA-1273 or BNT126b2 vaccines and to follow-up on IgG anti-RBD levels at 8 months post-vaccination.MethodsWe recruited 4,970 volunteers and measured IgG anti-RBD antibodies on days 30 and 240 post-vaccination.ResultsWe observed that both vaccines induced high levels of antibodies on day 30, while a drastic wane was observed on day 240, where mRNA-1273 vaccinated induced higher levels than BNT162b2. Stratifying by vaccine type, age, gender, and comorbidities, we identified that older mRNA-1273-vaccinated volunteers had higher antibody levels than the younger volunteers, contrary to what was observed in the BNT162b2-vaccinated volunteers.DiscussionIn conclusion, we observed that mRNA-1273 has a higher capacity to induce a humoral response than BNT162b2 and that age is a factor in the specific response.

The aim of this work is to test whether the use of a transparent capsule affects the residual capsule weight after inhalation as a surrogate of the inhaled delivered dose for patients with non-reversible chronic airway disease. Researchers conducted an observational cross-sectional study with patients using a single-dose dry powder inhaler. The weight of the capsule was measured with a precision microbalance before and after inhalation. Ninety-one patients were included, of whom 63 (69.2%) used a transparent capsule. Inhalation with a transparent capsule achieved a weight decrease of 30.1% vs 8.6% for devices with an opaque capsule (P <0.001). These data reinforce the need to provide patients with mechanisms that verify the correct inhalation technique. [ABSTRACT FROM AUTHOR]

ABSTRACT Detection of mixed Mycobacterium tuberculosis (MTB) infections is essential, particularly when resistance mutations are present in minority bacterial populations that may affect patients’ disease evolution and treatment. Whole-genome sequencing (WGS) has extended the amount of key information available for the diagnosis of MTB infection, including the identification of mixed infections. Having genomic information at diagnosis for early intervention requires carrying out WGS directly on the clinical samples. However, few studies have been successful with this approach due to the low representation of MTB DNA in sputa. In this study, we evaluated the ability of a strategy based on specific MTB DNA enrichment by using a newly designed capture platform (MycoCap) to detect minority variants and mixed infections by WGS on controlled mixtures of MTB DNAs in a simulated sputum genetic background. A pilot study was carried out with 12 samples containing 98% of a DNA pool from sputa of patients without MTB infection and 2% of MTB DNA mixtures at different proportions. Our strategy allowed us to generate sequences with a quality equivalent to those obtained from culture: 62.5× depth coverage and 95% breadth coverage (for at least 20× reads). Assessment of minority variant detection was carried out by manual analysis and allowed us to identify heterozygous positions up to a 95:5 ratio. The strategy also automatically distinguished mixed infections up to a 90:10 proportion. Our strategy efficiently captures MTB DNA in a nonspecific genetic background, allows detection of minority variants and mixed infections, and is a promising tool for performing WGS directly on clinical samples. IMPORTANCE We present a new strategy to identify mixed infections and minority variants in Mycobacterium tuberculosis by whole-genome sequencing. The objective of the strategy is the direct detection in patient sputum; in this way, minority populations of resistant strains can be identified at the time of diagnosis, facilitating identification of the most appropriate treatment for the patient from the first moment. For this, a platform for capturing M. tuberculosis-specific DNA was designed to enrich the clinical sample and obtain quality sequences.