Evaluation of radiological capacity and usage in paediatric TB diagnosis: A mixed-method protocol of a comparative study in Mozambique, South Africa and Spain.

INTRODUCTION: Tuberculosis remains one of the top ten causes of mortality globally. Children accounted for 12% of all TB cases and 18% of all TB deaths in 2022. Paediatric TB is difficult to diagnose with conventional laboratory tests, and chest radiographs remain crucial. However, in low-and middle-income countries with high TB burden, the capacity for radiological diagnosis of paediatric TB is rarely documented and data on the associated radiation exposure limited. METHODS: A multicentre, mixed-methods study is proposed in three countries, Mozambique, South Africa and Spain. At the national level, official registry databases will be utilised to retrospectively compile an inventory of licensed imaging resources (mainly X-ray and Computed Tomography (CT) scan equipment) for the year 2021. At the selected health facility level, three descriptive cross-sectional standardised surveys will be conducted to assess radiology capacity, radiological imaging diagnostic use for paediatric TB diagnosis, and radiation protection optimization: a site survey, a clinician-targeted survey, and a radiology staff-targeted survey, respectively. At the patient level, potential dose optimisation will be assessed for children under 16 years of age who were diagnosed and treated for TB in selected sites in each country. For this component, a retrospective analysis of dosimetry will be performed on TB and radiology data routinely collected at the respective sites. National inventory data will be presented as the number of units per million people by modality, region and country. Descriptive analyses will be conducted on survey data, including the demographic, clinical and programmatic characteristics of children treated for TB who had imaging examinations (chest X-ray (CXR) and/or CT scan). Dose exposure analysis will be performed by children's age, gender and disease spectrum. DISCUSSION: As far as we know, this is the first multicentre and multi-national study to compare radiological capacity, radiation protection optimization and practices between high and low TB burden settings in the context of childhood TB management. The planned comparative analyses will inform policy-makers of existing radiological capacity and deficiencies, allowing better resource prioritisation. It will inform clinicians and radiologists on best practices and means to optimise the use of radiological technology in paediatric TB management.

Rate of severe and fatal infections in a cohort of patients with interstitial lung disease associated with rheumatoid arthritis: a multicenter prospective study.

Objective: To describe severe infection, foci of infection, microorganisms, associated factors, and impact on mortality in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Patients and methods: The study was based on a multicenter prospective cohort of patients with RA-ILD followed up from 2015 to 2023. The main outcome measures were incident severe infection and fatal infection. We evaluated infectious foci, etiologic agents, vaccination status, variables associated with lung function, and clinical-therapeutic variables in RA. The incidence rate (IR) for infection and mortality was calculated per 100 person-years, and 3 multivariate models were constructed to explore factors associated with infection. Results: We followed up 148 patients with RA-ILD for a median 56.7 months (699.3 person-years). During this period, 142 patients (96%) had at least 1 infection. A total of 368 infectious episodes were recorded, with an IR of 52.6 per 100 person-years. Of the 48 patients who died, 65% did so from infection. Respiratory infections were the most common first infection (74%), infection overall (74%), and fatal infection (80%) and were caused mostly by SARS CoV-2, Streptococcus pneumoniae, Pseudomonas aeruginosa, and influenza A virus. The factors associated with an increased risk of infection and death in patients with RA-ILD were age, inflammatory activity, and therapy with corticosteroids and immunosuppressants. Conclusion: Patients with RA-ILD have a high risk of serious infection, especially respiratory infection. Infection develops early, is recurrent, and is frequently fatal. The presence of associated factors such as advanced age, joint inflammation, and treatment highlight the importance of integrated and preventive medical care.

Psychometric Validation of the Patient-Reported Experience Measure (PREM) Questionnaire "HowRwe" in Patients With Respiratory Disease Receiving Home Respiratory Therapies.

Introduction: The patient experience is defined as all the interactions that occur between patients and the healthcare system. The experience of patients with respiratory disease with home respiratory treatments (HRT) is not captured in currently available Patient-Reported Outcome Measures (PROM). We present the psychometric validation of the Patient-Reported Experience Measure (PREM) 'HowRwe' in Spanish and for respiratory patients with HRT. Methods: After translation following ISPOR guidelines (International Society for Pharmacoeconomics and Outcomes Research), the questionnaire was administered to adult respiratory patients who were receiving treatment at Hospital Universitario de La Princesa. The administration was done in two stages with 6 months of difference between the pre- and post-test. Results: We studied 228 respiratory patients, with a mean (SD) age of 64.1 (13.2) years, 52.2% were men, 68.0% were married or coupled, and 56.6% were retired. Reliability coefficients of the scale were adequate, with α = .921 and Ω = .929 for pre-test, and α = .940 and Ω = .958 for post. The confirmatory factor analysis tested for pre- and post-intervention, showed an excellent overall fit: χ2(2) = 49.380 (p < .001), CFI = .941 and SRMR = .072; and χ2(2) = 37.579 (p < .001), CFI = .982 and SRMR = .046, respectively. No statistically significant associations were observed for neither age, adherence nor quality of life, except between HowRwe post-test and quality of life pre-test (r = .14 [.01,.26]; p = .035). No significant differences were found in sociodemographic variables. No differences in pre-test or post-test were found in effect of HRT. 85.6% of patients found the content of HowRwe "Useful", and the preferred channel to respond it were paper, app and email. Conclusions: The Spanish version of the 'HowRwe' questionnaire to measure the experience in respiratory patients with home respiratory treatments (HRT), has adequate psychometric properties and conceptual and semantic equivalence with the original English version.

Introducción: La experiencia del paciente se define como todas las interacciones que ocurren entre los pacientes y el sistema de salud. La experiencia de los pacientes con enfermedades respiratorias con terapias respiratorias domiciliarios (TRD) no se refleja en las Medidas de resultados informados por el paciente (PROM) disponibles actualmente. Presentamos la validación psicométrica de la Medida de Experiencia Reportada por el Paciente (PREM por sus siglas en inglés) 'HowRwe' en español y para pacientes respiratorios con TRD. Métodos: Después de la traducción siguiendo las pautas de ISPOR (Sociedad Internacional de Farmacoeconomía e Investigación de Resultados), el cuestionario se administró a pacientes respiratorios adultos que estaban recibiendo tratamiento en el Hospital Universitario de La Princesa. La administración se realizó en dos etapas con 6 meses de diferencia entre el pre y post test. Resultados: Se estudiaron 228 pacientes respiratorios, con una edad media (DE) de 64,1 ± 13,2 años, el 52,2% eran hombres, el 68,0% estaban casados o en pareja y el 56,6% eran jubilados. Los coeficientes de confiabilidad de la escala fueron adecuados, con α = .921 y Ω = .929 para el pretest, y α = .940 y Ω = .958 para el post. El análisis factorial confirmatorio testado para pre y postintervención, mostró un ajuste global excelente: χ2(2) = 49.380 (p < .001), CFI = .941 y SRMR = .072; y χ2(2) = 37,579 (p < .001), CFI = .982 y SRMR = .046, respectivamente. No se observaron asociaciones estadísticamente significativas ni para la edad, la adherencia ni para la calidad de vida, excepto entre HowRwe postest y calidad de vida pretest (r = .14 [.01,.26];p = .035). No se encontraron diferencias significativas en las variables sociodemográficas. No se encontraron diferencias en el efecto de la TRH en el pretest o postest. El 85,6% de los pacientes encontró "útil" el contenido de HowRwe y el canal preferido para responder fue el papel, la aplicación y el correo electrónico. Conclusiones: La versión española del cuestionario 'HowRwe' para medir la experiencia en pacientes respiratorios con tratamientos respiratorios domiciliarios (TRH), tiene adecuadas propiedades psicométricas y equivalencia conceptual y semántica con la versión original en inglés.

Extracellular Kir2.1C122Y Mutant Upsets Kir2.1-PIP2 Bonds and Is Arrhythmogenic in Andersen-Tawil Syndrome.

BACKGROUND: Andersen-Tawil syndrome type 1 is a rare heritable disease caused by mutations in the gene coding the strong inwardly rectifying K+ channel Kir2.1. The extracellular Cys (cysteine)122-to-Cys154 disulfide bond in the channel structure is crucial for proper folding but has not been associated with correct channel function at the membrane. We evaluated whether a human mutation at the Cys122-to-Cys154 disulfide bridge leads to Kir2.1 channel dysfunction and arrhythmias by reorganizing the overall Kir2.1 channel structure and destabilizing its open state. METHODS: We identified a Kir2.1 loss-of-function mutation (c.366 A>T; p.Cys122Tyr) in an ATS1 family. To investigate its pathophysiological implications, we generated an AAV9-mediated cardiac-specific mouse model expressing the Kir2.1C122Y variant. We employed a multidisciplinary approach, integrating patch clamping and intracardiac stimulation, molecular biology techniques, molecular dynamics, and bioluminescence resonance energy transfer experiments. RESULTS: Kir2.1C122Y mice recapitulated the ECG features of ATS1 independently of sex, including corrected QT prolongation, conduction defects, and increased arrhythmia susceptibility. Isolated Kir2.1C122Y cardiomyocytes showed significantly reduced inwardly rectifier K+ (IK1) and inward Na+ (INa) current densities independently of normal trafficking. Molecular dynamics predicted that the C122Y mutation provoked a conformational change over the 2000-ns simulation, characterized by a greater loss of hydrogen bonds between Kir2.1 and phosphatidylinositol 4,5-bisphosphate than wild type (WT). Therefore, the phosphatidylinositol 4,5-bisphosphate-binding pocket was destabilized, resulting in a lower conductance state compared with WT. Accordingly, on inside-out patch clamping, the C122Y mutation significantly blunted Kir2.1 sensitivity to increasing phosphatidylinositol 4,5-bisphosphate concentrations. In addition, the Kir2.1C122Y mutation resulted in channelosome degradation, demonstrating temporal instability of both Kir2.1 and NaV1.5 proteins. CONCLUSIONS: The extracellular Cys122-to-Cys154 disulfide bond in the tridimensional Kir2.1 channel structure is essential for the channel function. We demonstrate that breaking disulfide bonds in the extracellular domain disrupts phosphatidylinositol 4,5-bisphosphate-dependent regulation, leading to channel dysfunction and defects in Kir2.1 energetic stability. The mutation also alters functional expression of the NaV1.5 channel and ultimately leads to conduction disturbances and life-threatening arrhythmia characteristic of Andersen-Tawil syndrome type 1.

[What do we know and what should we know about the imbalances of doctors in Spain? Diagnosis and proposals. SESPAS Report 2024]. / ¿Qué sabemos y qué deberíamos saber sobre los desequilibrios de médicos en España? Diagnóstico y propuestas. Informe SESPAS 2024.

This article characterizes the main features of the supply, demand, and labor markets for physicians in Spain, with an international and territorial perspective. It also presents some of the results of the simulation model for specialist physicians with a 2035 horizon and proposes strategic and short-term lines of action in the planning, regulation, and management of health professionals in Spain, with a focus on specialist physicians. In Spain there are high rates of physicians and medical graduates, but low rates of nurses, compared to other developed countries. Approximately 30% of practicing physicians (not considering residents) practice only in the private network. In the last two decades, competition from the private sector for health professionals has intensified, competing with the public network, which is subject to an excessively rigid regulatory framework. There is currently a shortage of physicians in some specialties, particularly in family medicine, which urgently needs specific incentives to stimulate vocations. Numbers consider only part of the story. The imbalances in the educational and labor markets are not resolved by creating vacancies, but by reforming the regulatory framework, the incentive systems, and the slack in public management to compete with the private sector in attracting and retaining talent.

[Experiences in human resources planning for health: The case of physicians. Data and models. SESPAS Report 2024]. / Experiencias de planificación de recursos humanos para la salud. El caso de los médicos. Datos y modelos. Informe SESPAS 2024.

Virtually all developed countries conduct physician planning exercises. We can learn from successful experiences. The modeling and projection of supply is technically complex, but it is a technical matter, whereas the assessment of demand or need, and therefore the outcome in terms of deficit or surplus, requires standards, usually in population ratios, which are based on expert judgments and belong to the normative universe. One type of technical problem insufficiently solved is that of converting "heads" into full time equivalents. Fortunately, progress is being made in the right direction. We need more and better information, in particular the State Register of Health Professionals, but even with the limitations of the data, it is necessary to plan. The Ministry of Health, the Autonomous Regions and other professional and union organizations regularly carry out planning exercises. We have high rates of physicians and graduates, and low rates of nurses, a growing number of physicians in both public and private practice, and short-term deficits in some specialties, particularly family medicine, which urgently needs specific incentives to stimulate vocations. The numbers tell only part of the story. The imbalances in the educational and labor markets are not resolved by creating vacancies, but rather by reforming the regulatory framework, incentive systems and public management slack to compete with the private sector in attracting and retaining talent.

Time-restricted eating and supervised exercise for improving hepatic steatosis and cardiometabolic health in adults with obesity: protocol for the TEMPUS randomised controlled trial.

INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease is a major public health problem considering its high prevalence and its strong association with extrahepatic diseases. Implementing strategies based on an intermittent fasting approach and supervised exercise may mitigate the risks. This study aims to investigate the effects of a 12-week time-restricted eating (TRE) intervention combined with a supervised exercise intervention, compared with TRE or supervised exercise alone and with a usual-care control group, on hepatic fat (primary outcome) and cardiometabolic health (secondary outcomes) in adults with obesity. METHODS AND ANALYSIS: An anticipated 184 adults with obesity (50% women) will be recruited from Granada (south of Spain) for this parallel-group, randomised controlled trial (TEMPUS). Participants will be randomly designated to usual care, TRE alone, supervised exercise alone or TRE combined with supervised exercise, using a parallel design with a 1:1:1:1 allocation ratio. The TRE and TRE combined with supervised exercise groups will select an 8-hour eating window before the intervention and will maintain it over the intervention. The exercise alone and TRE combined with exercise groups will perform 24 sessions (2 sessions per week+walking intervention) of supervised exercise combining resistance and aerobic high-intensity interval training. All participants will receive nutritional counselling throughout the intervention. The primary outcome is change from baseline to 12 weeks in hepatic fat; secondary outcomes include measures of cardiometabolic health. ETHICS AND DISSEMINATION: This study was approved by Granada Provincial Research Ethics Committee (CEI Granada-0365-N-23). All participants will be asked to provide written informed consent. The findings will be disseminated in scientific journals and at international scientific conferences. TRIAL REGISTRATION NUMBER: NCT05897073.

The Kir2.1E299V mutation increases atrial fibrillation vulnerability while protecting the ventricles against arrhythmias in a mouse model of Short QT Syndrome type 3.

AIMS: Short QT Syndrome Type 3 (SQTS3) is a rare arrhythmogenic disease caused by gain-of-function mutations in KCNJ2, the gene coding the inward rectifier potassium channel Kir2.1. We used a multidisciplinary approach and investigated arrhythmogenic mechanisms in an in-vivo model of de-novo mutation Kir2.1E299V identified in a patient presenting an extremely abbreviated QT interval and paroxysmal atrial fibrillation. METHODS AND RESULTS: We used intravenous adeno-associated virus-mediated gene transfer to generate mouse models, and confirmed cardiac-specific expression of Kir2.1WT or Kir2.1E299V. On ECG, the Kir2.1E299V mouse recapitulated the QT interval shortening and the atrial-specific arrhythmia of the patient. The PR interval was also significantly shorter in Kir2.1E299V mice. Patch-clamping showed extremely abbreviated action potentials in both atrial and ventricular Kir2.1E299V cardiomyocytes due to lack of inward-going rectification and increased IK1 at voltages positive to -80 mV. Relative to Kir2.1WT, atrial Kir2.1E299V cardiomyocytes had a significantly reduced slope conductance at voltages negative to -80 mV. After confirming a higher proportion of heterotetrameric Kir2.x channels containing Kir2.2 subunits in the atria, in-silico 3D simulations predicted an atrial-specific impairment of polyamine block and reduced pore diameter in the Kir2.1E299V-Kir2.2WT channel. In ventricular cardiomyocytes, the mutation increased excitability by shifting INa activation and inactivation in the hyperpolarizing direction, which protected the ventricle against arrhythmia. Moreover, Purkinje myocytes from Kir2.1E299V mice manifested substantially higher INa density than Kir2.1WT, explaining the abbreviation in the PR interval. CONCLUSIONS: The first in-vivo mouse model of cardiac-specific SQTS3 recapitulates the electrophysiological phenotype of a patient with the Kir2.1E299V mutation. Kir2.1E299V eliminates rectification in both cardiac chambers but protects against ventricular arrhythmias by increasing excitability in both Purkinje-fiber network and ventricles. Consequently, the predominant arrhythmias are supraventricular likely due to the lack of inward rectification and atrial-specific reduced pore diameter of the Kir2.1E299V-Kir2.2WT heterotetramer.

BEhavioral Health Stratified Treatment (B.E.S.T.) to optimize transition to adulthood for youth with intellectual and/or developmental disabilities.

Youth with intellectual and/or developmental disabilities (IDD) often struggle with depression and anxiety, which adversely impacts transition to adulthood. Integrated behavioral health care coordination, wherein care coordinators and behavioral health specialists collaborate to provide systematic, cost-effective, patient-centered care, is a promising strategy to improve access to behavioral health services and address factors that impact transition to adulthood, including depression/anxiety symptoms. Current care coordination models (e.g., Title V Maternal and Child Health Bureau [MCHB]) do not include behavioral health services. The CHECK (Coordinated HealthCarE for Complex Kids) mental health model, hereby refined and renamed BEhavioral Health Stratified Treatment (B.E.S.T.), is a behavioral health intervention delivery program designed for integration into care coordination programs. This study aims to determine whether an integrated behavioral health care coordination strategy (i.e., MCHB care coordination plus B.E.S.T.) would be more acceptable and lead to better youth health and transition outcomes, relative to standard care coordination (i.e., MCHB care coordination alone). Results would guide future investment in improving outcomes for youth with IDD. This study is a two-arm randomized clinical trial of 780 transition-aged youth with IDD (13-20 years) to evaluate the comparable efficacy of MCHB Care Coordination alone vs. MCHB Care Coordination plus B.E.S.T. on the following outcomes: 1) decreased symptoms and episodes of depression and anxiety over time; 2) improved health behaviors, adaptive functioning and health related quality of life; 3) increased health care transition (HCT) readiness; and 4) improved engagement and satisfaction with care coordination among stakeholders.

Efficacy of different 8 h time-restricted eating schedules on visceral adipose tissue and cardiometabolic health: A study protocol.

BACKGROUND AND AIMS: To investigate the efficacy and feasibility of three different 8 h time-restricted eating (TRE) schedules (i.e., early, late, and self-selected) compared to each other and to a usual-care (UC) intervention on visceral adipose tissue (VAT) and cardiometabolic health in men and women. METHODS AND RESULTS: Anticipated 208 adults (50% women) aged 30-60 years, with overweight/obesity (25 ≤ BMI<40 kg/m2) and with mild metabolic impairments will be recruited for this parallel-group, multicenter randomized controlled trial. Participants will be randomly allocated (1:1:1:1) to one of four groups for 12 weeks: UC, early TRE, late TRE or self-selected TRE. The UC group will maintain their habitual eating window and receive, as well as the TRE groups, healthy lifestyle education for weight management. The early TRE group will start eating not later than 10:00, and the late TRE group not before 13:00. The self-selected TRE group will select an 8 h eating window before the intervention and maintain it over the intervention. The primary outcome is changes in VAT, whereas secondary outcomes include body composition and cardiometabolic risk factors. CONCLUSION: This study will determine whether the timing of the eating window during TRE impacts its efficacy on VAT, body composition and cardiometabolic risk factors and provide insights about its feasibility.

Efficacy of Transcranial Direct Current Stimulation on Pain Intensity and Functionality in Patients With Knee Osteoarthritis: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of the study is to investigate whether transcranial direct current stimulation is superior to control groups or other interventions for pain relief and improving functionality in knee osteoarthritis patients. METHODS: PubMed, the Physiotherapy Evidence Database, the Cochrane Library, ProQuest, and Scopus databases were searched from inception to July 2022 to identify randomized clinical trials. The main outcomes were subjective perception of pain intensity measured either with the visual analog scale or with the numeric rating scale; and the functionality, assessed with the Western Ontario and McMaster Universities Osteoarthritis Index. As secondary outcomes, pressure pain threshold, conditioned pain modulation, and its safety were evaluated. RESULTS: We identified 10 randomized clinical trials (634 participants). The results showed an important effect favoring transcranial direct current stimulation for pain relief (mean difference = -1.1 cm, 95% confident interval = -2.1 to -0.2) and for improving functionality (standardized mean difference = -0.6, 95% confident interval = -1.02 to -0.26). There was also a significant improvement in pressure pain threshold (mean difference = 0.9 Kgf/cm 2 , 95% confident interval = 0.1 to 1.6). The certainty of evidence according to Grades of Recommendation Assessment, Development and Evaluation was generally moderate. CONCLUSIONS: Our findings suggest that transcranial direct current stimulation is a safe treatment for reducing pain intensity, improving functionality, and the pressure pain thresholds in patients with knee osteoarthritis.

Bioanalytical sensors using the heat-transfer method HTM and related techniques.

This review provides an overview on bio- and chemosensors based on a thermal transducer platform that monitors the thermal interface resistance R th between a solid chip and the supernatant liquid. The R th parameter responds in a surprisingly strong way to molecular-scale changes at the solid-liquid interface, which can be measured thermometrically, using for instance thermocouples in combination with a controllable heat source. In 2012, the effect was first observed during on-chip denaturation experiments on complementary and mismatched DNA duplexes that differ in their melting temperature. Since then, the concept is addressed as heat-transfer method, in short HTM, and numerous applications of the basic sensing principle were identified. Functionalizing the chip with bioreceptors such as molecularly imprinted polymers makes it possible to detect neurotransmitters, inflammation markers, viruses, and environmental pollutants. In combination with aptamer-type receptors, it is also possible to detect proteins at low concentrations. Changing the receptors to surface-imprinted polymers has opened up new possibilities for quantitative bacterial detection and identification in complex matrices. In receptor-free variants, HTM was successfully used to characterize lipid vesicles and eukaryotic cells (yeast strains, cancer cell lines), the latter showing spontaneous detachment under influence of the temperature gradient inherent to HTM. We will also address modifications to the original HTM technique such as M-HTM, inverted HTM, thermal wave transport analysis TWTA, and the hot-wire principle. The article concludes with an assessment of the possibilities and current limitations of the method, together with a technological forecast.

Pain assessment and management among adult patients in a gynecology ward: a best practice implementation project.

OBJECTIVES: This project aimed to improve compliance with evidence-based practice in pain assessment and management in a gynecology ward. INTRODUCTION: Effective pain control is important to prevent the negative consequences of pain that is poorly managed. However, it remains undervalued and inadequately treated. Applying evidence-based practices to correctly evaluate and manage pain is essential to improve pain relief. METHODS: This project followed the JBI Evidence Implementation Framework. A baseline audit of 41 women admitted to the gynecology ward was conducted and measured against 5 best practice criteria, along with a patient satisfaction questionnaire. Targeted strategies were then implemented and a follow-up audit was conducted using the same criteria, methods, and sample size as the baseline audit. RESULTS: The baseline audit revealed gaps between current and best practice. Barriers to implementation were identified and strategies to resolve the barriers were designed and implemented (nurse education, informative materials, electronic patient records system improvements). Comprehensive pain assessment, including dynamic and static pain assessment, use of a validated tool, and education provided to patients and carers, improved in the follow-up audit. There was no change in patient satisfaction levels; however, the discrepancy between pain measured by nurses and pain measured by patients was reduced. CONCLUSIONS: The JBI methodology was useful in improving compliance with evidence-based practice criteria. It also facilitated adaptation to new barriers, such as the COVID-19 pandemic. Improving nurses' knowledge of pain assessment can lead to more accurate assessment. Inadequate records systems also made it difficult to record the care that was provided. Subsequent audits will assess sustainability and the project will be escalated to other wards.

Preclinical immune efficacy against SARS-CoV-2 beta B.1.351 variant by MVA-based vaccine candidates.

The constant appearance of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs) has jeopardized the protective capacity of approved vaccines against coronavirus disease-19 (COVID-19). For this reason, the generation of new vaccine candidates adapted to the emerging VoCs is of special importance. Here, we developed an optimized COVID-19 vaccine candidate using the modified vaccinia virus Ankara (MVA) vector to express a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein, containing 3 proline (3P) substitutions in the S protein derived from the beta (B.1.351) variant, termed MVA-S(3Pbeta). Preclinical evaluation of MVA-S(3Pbeta) in head-to-head comparison to the previously generated MVA-S(3P) vaccine candidate, expressing a full-length prefusion-stabilized Wuhan S protein (with also 3P substitutions), demonstrated that two intramuscular doses of both vaccine candidates fully protected transgenic K18-hACE2 mice from a lethal challenge with SARS-CoV-2 beta variant, reducing mRNA and infectious viral loads in the lungs and in bronchoalveolar lavages, decreasing lung histopathological lesions and levels of proinflammatory cytokines in the lungs. Vaccination also elicited high titers of anti-S Th1-biased IgGs and neutralizing antibodies against ancestral SARS-CoV-2 Wuhan strain and VoCs alpha, beta, gamma, delta, and omicron. In addition, similar systemic and local SARS-CoV-2 S-specific CD4+ and CD8+ T-cell immune responses were elicited by both vaccine candidates after a single intranasal immunization in C57BL/6 mice. These preclinical data support clinical evaluation of MVA-S(3Pbeta) and MVA-S(3P), to explore whether they can diversify and potentially increase recognition and protection of SARS-CoV-2 VoCs.

Geothermal food dehydrator system, operation and sensory analysis, and dehydrated pineapple quality.

Food dehydration is a preservation technique that guarantees its supply. Food like vegetables and fruits are traditionally dehydrated with natural gas or solar energy, however, this work demonstrates the feasibility of doing it with energy from a geothermal power plant in Nayarit, Mexico. Different species of pineapple (Miel, Cayenne, and Esmeralda) were dehydrated at different temperatures from 64 to 80°C and the safety of the product was subsequently verified, for these aerobic mesophiles (<230 ufc/g), total coliforms (<0.3 s.m.), molds and yeasts (<120 v.e.), and salmonella spp (Absent in 25 g), and results were obtained within the proposed specifications, which were generated taking as reference the national and international guidance standards. A sensory evaluation, a modified Flash Profile (mFP), was carried out with a group of judges trained in descriptive methodology, since a better consensus of responses was obtained, thus demonstrating the usability of mFP for food dehydration. The studies of pineapple allowed the evaluation of production with the DGA 200 technology, and the microbiological standards, as well as sensory and physicochemical parameters, were considering just to verify that product is suitable for human consumption. The technology is a system that takes advantage of the heat of the earth, with which it is possible to work 7 days a week or the entire pineapple season. Physicochemical changes caused by its dehydration with respect to the content of vitamin C, carbohydrates, and dietary fiber in the three species of dehydrated pineapple were measured. In the fresh samples, an average concentration of vitamin C 9 mg/100 g, carbohydrates 11.6 g sugar/100 g, and dietary fiber 0.96% were measured. The dehydrated samples presented an average value of vitamin C of 95 mg/100 g, carbohydrates 72.6 g sugar/100 g, and dietary fiber 8.6%, these results were similar to Mühlbauer and Müller, 2020, Drying atlas, drying kinetics and quality of agricultural products, Elsevier.

Evaluation of Social Determinants of Health in Nursing Education through Service Learning.

Background: This manuscript describes an in-state nursing student global health-care experience. The 2021 Rio Grande Valley service learning team at Louise Herrington School of Nursing at Baylor University traveled from Dallas to McAllen, Texas to volunteer in a COVID vaccination clinic and refugee respite center on the U.S.-Mexican border. Method: A competency-based evaluation utilized the American Association of Colleges of Nursing's The Essentials: Core Competencies for Professional Nursing Education Featured Concepts, with a focus on social determinants of health, as a framework. Results: The evaluation of the service learning trip through the lens of social determinants of health and the Core Competencies can serve as a guideline for the design of future trips. Conclusion: The Rio Grande Valley service learning trip contributed to nursing students' self-reports of competency in global health education, in identifying the social determinants of health that characterized the immigrants and refugees, and in service and advocacy.

Lung transcriptomics of K18-hACE2 mice highlights mechanisms and genes involved in the MVA-S vaccine-mediated immune response and protection against SARS-CoV-2 infection.

Unravelling the molecular mechanism of COVID-19 vaccines through transcriptomic pathways involved in the host response to SARS-CoV-2 infection is key to understand how vaccines work, and for the development of optimized COVID-19 vaccines that can prevent the emergence of SARS-CoV-2 variants of concern (VoCs) and future outbreaks. In this study, we investigated the effects of vaccination with a modified vaccinia virus Ankara (MVA)-based vector expressing the full-length SARS-CoV-2 spike protein (MVA-S) on the lung transcriptome from susceptible K18-hACE2 mice after SARS-CoV-2 infection. One dose of MVA-S regulated genes related to viral infection control, inflammation processes, T-cell response, cytokine production and IFN-γ signalling. Down-regulation of Rhcg and Tnfsf18 genes post-vaccination with one and two doses of MVA-S may represent a mechanism for controlling infection immunity and vaccine-induced protection. One dose of MVA-S provided partial protection with a distinct lung transcriptomic profile to healthy animals, while two doses of MVA-S fully protected against infection with a transcriptomic profile comparable to that of non-vaccinated healthy animals. This suggests that the MVA-S booster generates a robust and rapid antigen-specific immune response preventing virus infection. Notably, down-regulation of Atf3 and Zbtb16 genes in mice vaccinated with two doses of MVA-S may contribute to vaccine control of innate immune system and inflammation processes in the lungs during SARS-CoV-2 infection. This study shows host transcriptomic mechanisms likely involved in the MVA-S vaccine-mediated immune response against SARS-CoV-2 infection, which could help in improving vaccine dose assessment and developing novel, well-optimized SARS-CoV-2 vaccine candidates against prevalent or emerging VoCs.

Optimized vaccine candidate MVA-S(3P) fully protects against SARS-CoV-2 infection in hamsters.

The development of novel optimized vaccines against coronavirus disease 2019 (COVID-19) that are capable of controlling the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and the appearance of different variants of concern (VoC) is needed to fully prevent the transmission of the virus. In the present study, we describe the enhanced immunogenicity and efficacy elicited in hamsters by a modified vaccinia virus Ankara (MVA) vector expressing a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein [termed MVA-S(3P)]. Hamsters vaccinated with one or two doses of MVA-S(3P) developed high titers of S-binding IgG antibodies and neutralizing antibodies against the ancestral Wuhan SARS-CoV-2 virus and VoC beta, gamma, and delta, as well as against omicron, although with a somewhat lower neutralization activity. After SARS-CoV-2 challenge, vaccinated hamsters did not lose body weight as compared to matched placebo (MVA-WT) controls. Consistently, vaccinated hamsters exhibited significantly reduced viral RNA in the lungs and nasal washes, and no infectious virus was detected in the lungs in comparison to controls. Furthermore, almost no lung histopathology was detected in MVA-S(3P)-vaccinated hamsters, which also showed significantly reduced levels of proinflammatory cytokines in the lungs compared to unvaccinated hamsters. These results reinforce the use of MVA-S(3P) as a vaccine candidate against COVID-19 in clinical trials.