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La administración de busulfán es ampliamente utilizada como parte del régimen de acondicionamiento en pacientes que se van a someter a trasplante de células madre hematopoyéticas. Se recomienda monitorizar las concentraciones plasmáticas de busulfán con el fin de optimizar la dosis en cada paciente y minimizar su toxicidad. El objetivo del presente estudio es validar un método analítico sencillo, rápido y costo-efectivo para la cuantificación de busulfán en plasma por cromatografía líquida acoplada a espectrometría de masas en tándem de aplicabilidad en la práctica clínica.

Administration of busulfan is extending rapidly as a part of a conditioning regimen in patients undergoing hematopoietic stem cell transplantation (HSCT). Monitoring blood plasma levels of busulfan is recommended for identifying the optimal dose in patients and for minimizing toxicity. The aim of this research was to validate a simple, rapid, and cost-effective analytical tool for measuring busulfan in human plasma that would be suitable for routine clinical use. This novel tool was based on liquid chromatography coupled to mass spectrometry.

Irene Belmonte,1 Alexa Nuñez,1,2 Miriam Barrecheguren,1 Cristina Esquinas,1 Mònica Pons,3 Rosa M López-Martínez,4 Gerard Ruiz,4 Albert Blanco-Grau,4 Roser Ferrer,4 Joan Genescà,3,5 Marc Miravitlles,1,6 Francisco Rodríguez-Frías4 1Pneumology Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain; 2Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès). Barcelona, Spain; 3Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d’Hebron; Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain; 4Department of Clinical Biochemistry, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain; 5Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain; 6CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, SpainCorrespondence: Marc MiravitllesPneumology Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, P. Vall d’Hebron 119-129, Barcelona 08035, SpainEmail marcm@separ.esBackground: Alpha-1 antitrypsin deficiency (AATD) remains largely underdiagnosed despite recommendations of healthcare institutions and programmes designed to increase awareness. The objective was to analyse the trends in AATD diagnosis during the last 5 years in a Spanish AATD reference laboratory.Methods: This was a retrospective revision of all alpha-1 antitrypsin (AAT) determinations undertaken in our laboratory from 2015 to 2019. We analysed the number of AAT determinations performed and described the characteristics of the individuals tested, as well as the medical specialties and the reasons for requesting AAT determination.Results: A total of 3507 determinations were performed, of which 5.5% corresponded to children. A significant increase in the number of AAT determinations was observed from 349 in 2015 to 872 in 2019. Among the samples, 57.6% carried an intermediate AATD (50– 119 mg/dL) and 2.4% severe deficiency (< 50 mg/dL). The most frequent phenotype in severe AATD individuals was PI*ZZ (78.5%), and aminotransferase levels were above normal in around 43% of children and 30% of adults. Respiratory specialists requested the highest number of AAT determinations (31.5%) followed by digestive diseases and internal medicine (27.5%) and primary care physicians (19.7%). The main reason for AAT determination in severe AATD adults was chronic obstructive pulmonary disease (41.7%), but reasons for requesting AAT determination were not reported in up to 41.7% of adults and 58.3% of children.Conclusion: There is an increase in the frequency of AATD testing despite the rate of AAT determination remaining low. Awareness about AAT is probably increasing, but the reason for testing is not always clear.Keywords: alpha-1 antitrypsin deficiency, diagnosis, screening, lung disease

Cristina Esquinas,1,2 Sabina Janciauskiene,3 Ricardo Gonzalo,4 Gemma Mas de Xaxars,4 Beata Olejnicka,5 Irene Belmonte,6 Miriam Barrecheguren,1 Esther Rodriguez,1 Alexa Nuñez,1 Francisco Rodriguez-Frias,6 Marc Miravitlles1 1Pneumology Department, University Hospital Vall d’Hebron, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, 2Public Health, Mental, Maternal and Child Health Nursing Department, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; 3Department of Respiratory Medicine, Hannover Medical School, BREATH, German Center for Lung Research (DZL), Hannover, Germany; 4Statistics and Bioinformatics Unit (UEB), Vall d’Hebron Research Institute (VHIR), Barcelona, Spain; 5Department of Experimental Medical Science, Lund University, Lund, Sweden; 6Biochemistry Department, University Hospital Vall d’Hebron, Barcelona, Spain Introduction: COPD has complex etiologies involving both genetic and environmental determinants. Among genetic determinants, the most recognized is a severe PiZZ (Glu342Lys) inherited alpha1-antitrypsin deficiency (AATD). Nonetheless, AATD patients present a heterogeneous clinical evolution, which has not been completely explained by sociodemographic or clinical factors. Here we performed the gene expression profiling of blood cells collected from mild and severe COPD patients with PiZZ AATD. Our aim was to identify differences in messenger RNA (mRNA) and microRNA (miRNA) expressions that may be associated with disease severity. Materials and methods: Peripheral blood mononuclear cells from 12 COPD patients with PiZZ AATD (6 with severe disease and 6 with mild disease) were used in this pilot, high-throughput microarray study. We compared the cellular expression levels of RNA and miRNA of the 2 groups, and performed functional and enrichment analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene-ontology (GO) terms. We also integrated the miRNA and the differentially expressed putative target mRNA. For data analyses, we used the R statistical language R Studio (version 3.2.5). Results: The severe and mild COPD–AATD groups were similar in terms of age, gender, exacerbations, comorbidities, and use of augmentation therapy. In severe COPD–AATD patients, we found 205 differentially expressed genes (DEGs) (114 upregulated and 91 downregulated) and 28 miRNA (20 upregulated and 8 downregulated) compared to patients with mild COPD–AATD disease. Of these, hsa-miR-335-5p was downregulated and 12 target genes were involved in cytokine signaling, MAPK/mk2, JNK signaling cascades, and angiogenesis were much more highly expressed in severe compared with mild patients. Conclusions: Despite the small sample size, we identified downregulated miRNA (hsa-miR-335) and the activation of pathways related to inflammation and angiogenesis on comparing patients with severe vs mild COPD–AATD. Nonetheless, our findings warrant further validation in large studies. Keywords: alpha1-antitrypsin deficiency, COPD, gene expression, miRNAs, integrative analysis

Abstract Background Sub-Saharan African countries have a high burden of viral hepatitis and poor access to screening and care. The aim of this study was to evaluate the feasibility and acceptability of using the plasma separation card (PSC) for viral hepatitis B and C screening among people living with HIV (PLHIV) in Cameroon and Uganda. Methods This is a cross-sectional study carried out between 05/2021 and 03/2023 including 192 PLHIV in Cameroon (n = 104) and Uganda (n = 88). Basic sociodemographic variables and whole blood samples were collected. Adequate filling with blood of PSCs was used to determine feasibility together with participant responses to questions on acceptability. A logistic regression model was carried out to assess the relationship between PSC acceptability and factors of interest. Results 70% of participants reported PSC as an acceptable viral hepatitis screening tool, and it was significantly more accepted in Uganda than Cameroon (100% vs. 43.2%, p

Abstract X-ray sources have a strong social impact, being implemented for biomedical research, material and environmental sciences. Nowadays, compact and accessible sources are made using lasers. We report evidence of nontrivial spectral-angular correlations in a laser-driven betatron X-ray source. Furthermore, by angularly-resolved spectral measurements, we detect the signature of spatial phase modulations by the electron trajectories. This allows the lateral coherence function to be retrieved, leading to the evaluation of the coherence area of the source, determining its brightness. Finally, the proposed methodology allows the unprecedented reconstruction of the size of the X-ray source and the electron beam emittance in the two main emission planes in a single shot. This information will be of fundamental interest for user applications of new radiation sources.

Abstract Background Chronic infection with HBV is responsible for >50% of all hepatocellular cancer cases globally and disproportionately affects sub-Saharan African (sSA) countries. Migration from these countries to Europe has increased substantially in recent years, posing unique challenges to health systems. The aim of this study was to carry out a community-based intervention to increase HBV screening, vaccination, and linkage to care among sSA migrants in Catalonia, Spain. Methods This was a prospective cohort study. Participants ≥18 years were offered community-based HBV screening between 20/11/20 and 21/01/22. Rapid HBV testing and blood sample collection utilizing plasma separation cards were carried out and linkage to care was offered to all participants. HBV vaccination and post-test counseling were performed at a second visit in the community. The main outcome was the odds of those with current HBV infection being successfully linked to hepatology. Rates of completing the care cascade of this model were analyzed. Results In the present study, 444 people undergo screening, with 50.6% of participants showing evidence of past or current HBV infection, including an HBsAg prevalence of 9.2%. Migrants with current HBV infection exhibit 5.2 times higher odds of successful linkage to care compared to those in need of post-test counseling or vaccination. The study achieves a successful linkage to care rate of 72% for all participants, with specialist appointments arranged within 15.5 days. Conclusions This community-based HBV screening program provides evidence of a successful model for identifying and providing care, including vaccination, to west African migrants at high risk of HBV infection who may otherwise not engage in care.

Highly intense bunches of protons and ions with energies of several MeV/u can be generated with ultra-short laser pulses focused on solid targets. In the most common interaction regime, target normal sheath acceleration, the spectra of these particles are spread over a wide range following a Maxwellian distribution. We report on the design and testing of a magnetic chicane for the selection of protons within a limited energy window. This consisted of two successive, anti-parallel dipole fields generated by cost-effective permanent C-magnets with customized configuration and longitudinal positions. The chicane was implemented into the target vessel of a petawatt laser facility with constraints on the direction of the incoming laser beam and guidance of the outgoing particles through a vacuum port. The separation of protons and carbon ions within distinct energy intervals was demonstrated and compared to a ray tracing code. Measurements with radiochromic film stacks indicated the selection of protons within [2.4, 6.9] MeV, [5.0, 8.4] MeV, or ≥6.9 MeV depending on the lateral dispersion. A narrow peak at 4.8 MeV was observed with a time-of-flight detector.

Our aim was to develop an accurate, highly sensitive method for HBV genotype determination and detection of genotype mixtures. We examined the preS and 5′ end of the HBV X gene (5X) regions of the HBV genome using next-generation sequencing (NGS). The 1852 haplotypes obtained were subjected to genotyping via the Distance-Based discrimination method (DB Rule) using two sets of 95 reference sequences of genotypes A–H. In clinical samples from 125 patients, the main genotypes were A, D, F and H in Caucasian, B and C in Asian and A and E in Sub-Saharan patients. Genotype mixtures were identified in 28 (22.40%) cases, and potential intergenotypic recombination was observed in 29 (23.20%) cases. Furthermore, we evaluated sequence conservation among haplotypes classified into genotypes A, C, D, and E by computing the information content. The preS haplotypes exhibited limited shared conserved regions, whereas the 5X haplotypes revealed two groups of conserved regions across the genotypes assessed. In conclusion, we developed an NGS-based HBV genotyping method utilizing the DB Rule for genotype classification. We identified two regions conserved across different genotypes at 5X, offering promising targets for RNA interference-based antiviral therapies.

We present experimental results for the controlled mitigation of the electromagnetic pulses (EMPs) produced in the interactions of a 1 PW high-power 30 fs Ti:Sa laser VEGA-3 with solid-density targets transparent to laser-forward-accelerated relativistic electrons. This study aims at the band of very high frequencies (VHFs), i.e., those in the hundreds of MHz, which comprise the fundamental cavity modes of the rectangular VEGA-3 vacuum chamber. We demonstrate mode suppression by a tailoring of the laser-produced space charge distribution.