Association between Reactogenicity and Immunogenicity in a Vaccinated Cohort with Two mRNA SARS-CoV-2 Vaccines at a High-Complexity Reference Hospital: A Post Hoc Analysis on Immunology Aspects of a Prospective Cohort Study.

Enhancing our comprehension of mRNA vaccines may facilitate the future design of novel vaccines aimed at augmenting immune protection while minimising reactogenic responses. Before this design is carried out, it is important to determine whether adaptive immunity correlates with the reactogenicity profile of vaccines. We studied a large cohort that was vaccinated with mRNA vaccines to answer this question. This was an observational study with real-world data. Reactogenicity data were obtained from the VigilVacCOVID study. Immunogenicity (humoral and cellular) data were retrieved from health records. One main population (n = 215) and two subpopulations were defined (subpopulation 1, n = 3563; subpopulation 2, n = 597). Sensitivity analyses were performed with subpopulations 1 and 2 to explore the consistency of results. We analysed the association of the intensity and types of adverse reactions with the development and quantity of elicited antibody titres. As an exploratory analysis in subpopulation 1, we assessed the association between reactogenicity and cellular immunogenicity. A higher incidence of fever, malaise, and myalgia including severe cases was significantly associated with the development and quantity of positive antibody titres. No significant findings were observed with cellular immunity. We observed a positive association between immunogenicity and reactogenicity. These findings can be relevant for the future development of our understanding of how mRNA vaccines function.

A newborn Screening Programme for Inborn errors of metabolism in Galicia: 22 years of evaluation and follow-up.

BACKGROUND: There is a notable lack of harmonisation in newborn screening (NBS) programmes worldwide. The Galician programme for early detection of inborn errors of metabolism (IEM) was one of the first NBS programmes in Europe to incorporate mass spectrometry (July 2000). This programme currently screens for 26 IEMs in dried blood and urine samples collected 24-72 h after birth. RESULTS: In its 22-year history, this programme has analysed samples from 440,723 neonates and identified 326 cases of IEM with a prevalence of 1:1351. The most prevalent IEMs were hyperphenylalaninaemia (n = 118), followed by medium chain acyl-CoA dehydrogenase deficiency (MCADD, n = 26), galactosaemia (n = 20), and cystinurias (n = 43). Sixty-one false positives and 18 conditions related to maternal pathologies were detected. Urine samples have been identified as a useful secondary sample to reduce the rate of false positives and identify new defects. There were 5 false negatives. The overall positive value was 84.23%. The fatality rate over a median of 12.1 years of follow-up was 2.76%. The intelligence quotient of patients was normal in 95.7% of cases, and school performance was largely optimal, with pedagogic special needs assistance required in < 10% of cases. Clinical onset of disease preceded diagnosis in 4% of cases. The age at which first NBS report is performed was reduced by 4 days since 2021. CONCLUSIONS: This study highlights the benefits of collecting urine samples, reduce NBS reporting time and expanding the number of IEMs included in NBS programmes.

Traqueotomía versus traqueostomía, la necesidad de una aclaración lexicográfica / Tracheotomy versus tracheostomy, the need for lexicographical clarification

Con frecuencia se usan en el ámbito sanitario los términos traqueotomía y traqueostomía, pudiendo generar dudas entre los propios profesionales sobre qué definición corresponde a cada término o cuál de ellos debe considerarse más correcto en casos concretos. Se ha realizado una búsqueda de los términos «traqueotomía» y «traqueostomía» en los diccionarios generalistas en idioma español del Diccionario de la Real Academia Española (DRAE) y del Diccionario Histórico de la Lengua Española de la Real Academia Española (DHLE), y de los términos en inglés «tracheotomy» y «tracheostomy» en los diccionarios generalistas en idioma inglés del Oxford Dictionary, del Cambridge Dictionary y del Collins English Dictionary. Asimismo, se ha hecho una búsqueda en los diccionarios de términos médicos en español del Diccionario de Términos Médicos de la Real Academia Nacional de Medicina (DTM) y en inglés del Farlex Dictionary. Los términos se buscaron también en el buscador generalista de Internet Google®. Se analizaron las definiciones desde el punto de vista lexicográfico y etimológico. Las definiciones que aparecen en los diccionarios generalistas, tanto en español como en inglés, son imprecisas, limitadas y adolecen de ambigüedad por mezclar indicaciones desactualizadas con criterios alejados de la etimología. Sin embargo, las definiciones en los diccionarios de términos médicos en ambos idiomas están más ajustadas a la etimología. La traqueotomía identifica estrictamente el procedimiento quirúrgico de realización de una apertura en la cara anterior de la tráquea. La traqueostomía identifica la realización de un orificio que comunica la tráquea con el exterior e implica una modificación del tracto aéreo superior al proporcionar una entrada adicional de la vía respiratoria. Solo en las laringectomías totales la traqueostomía es la única vía de entrada al tracto aéreo. Ambos términos pueden utilizarse sinónimamente cuando una traqueotomía culmina con una traqueostomía. No convendrá utilizar el término traqueostomía cuando se produce el cierre de los planos al final del procedimiento y este no resulta en la creación de un estoma. Los traqueostomas pueden ser cualificados con adjetivos de tiempo de permanencia (temporal/permanente), tamaño (grande/pequeño), forma (redondo/elíptico), o profundidad por sí mismos, sin vincularse a ningún tipo de enfermedad o de indicación quirúrgica. No todos los traqueostomas permanentes tienen lugar en laringectomías totales ni tienen sistemáticamente un carácter irreversible.(AU)

In the healthcare field, the terms “traqueotomía” and “traqueostomía” are frequently used, often leading to confusion among professionals regarding the appropriate definition for each term or which one should be considered more correct in specific cases. A search was conducted for the terms “traqueotomía” and “traqueostomía” in general Spanish-language dictionaries such as the Dictionary of the Royal Spanish Academy (DRAE) and the Historical Dictionary of the Spanish Language of the Royal Spanish Academy (DHLE), as well as for the English terms “tracheotomy” and “tracheostomy” in English general dictionaries like the Oxford Dictionary, the Cambridge Dictionary, and the Collins English Dictionary. Additionally, searches were performed in medical dictionaries in both Spanish, specifically the Dictionary of Medical Terms of the National Academy of Medicine (DTM), and English, including the Farlex Dictionary. The terms were also explored using the Google search engine. Definitions were analyzed from both lexicographical and etymological perspectives. Definitions found in general dictionaries, in both Spanish and English, were found to be imprecise, limited, and ambiguous, as they mixed outdated indications with criteria that deviated from etymology. In contrast, definitions in medical dictionaries in both languages were more aligned with etymology. “Traqueotomía” strictly identifies the surgical procedure of creating an opening in the anterior face of the trachea. “Traqueostomía” identifies the creation of an opening that connects the trachea to the exterior, involving a modification of the upper airway by providing an additional entry for the respiratory pathway. “Traqueostomía” becomes the sole means of entry to the airway in total laryngectomies. Both terms can be used synonymously when a traqueotomía culminates in a traqueostomía. However, it is not appropriate to use the term “traqueostomía” when the procedure concludes with the closure of the planes and does not result in the creation of a stoma. Traqueostomas can be qualified with adjectives indicating permanence (temporary/permanent), size (large/small), shape (round/elliptical), or depth, without being linked to any specific disease or surgical indication. Not all permanent traqueostomas are the result of total laryngectomies, and they do not necessarily have an irreversible character systematically.(AU)

Characterization of the plasma proteomic profile of Fabry disease: Potential sex- and clinical phenotype-specific biomarkers.

Fabry disease (FD) is a X-linked rare lysosomal storage disorder caused by deficient α-galactosidase A (α-GalA) activity. Early diagnosis and the prediction of disease course are complicated by the clinical heterogeneity of FD, as well as by the frequently inconclusive biochemical and genetic test results that do not correlate with clinical course. We sought to identify potential biomarkers of FD to better understand the underlying pathophysiology and clinical phenotypes. We compared the plasma proteomes of 50 FD patients and 50 matched healthy controls using DDA and SWATH-MS. The >30 proteins that were differentially expressed between the 2 groups included proteins implicated in processes such as inflammation, heme and haemoglobin metabolism, oxidative stress, coagulation, complement cascade, glucose and lipid metabolism, and glycocalyx formation. Stratification by sex revealed that certain proteins were differentially expressed in a sex-dependent manner. Apolipoprotein A-IV was upregulated in FD patients with complications, especially those with chronic kidney disease, and apolipoprotein C-III and fetuin-A were identified as possible markers of FD with left ventricular hypertrophy. All these proteins had a greater capacity to identify the presence of complications in FD patients than lyso-GB3, with apolipoprotein A-IV standing out as being more sensitive and effective in differentiating the presence and absence of chronic kidney disease in FD patients than renal markers such as creatinine, glomerular filtration rate and microalbuminuria. Identification of these potential biomarkers can help further our understanding of the pathophysiological processes that underlie the heterogeneous clinical manifestations associated with FD.

Tracheotomy versus tracheostomy, the need for lexicographical clarification.

In the healthcare field, the terms "traqueotomía" and "traqueostomía" are frequently used, often leading to confusion among professionals regarding the appropriate definition for each term or which one should be considered more correct in specific cases. A search was conducted for the terms "traqueotomía" and "traqueostomía" in general Spanish-language dictionaries such as the Dictionary of the Royal Spanish Academy (DRAE) and the Historical Dictionary of the Spanish Language of the Royal Spanish Academy (DHLE), as well as for the English terms "tracheotomy" and "tracheostomy" in English general dictionaries like the Oxford Dictionary, the Cambridge Dictionary, and the Collins English Dictionary. Additionally, searches were performed in medical dictionaries in both Spanish, specifically the Dictionary of Medical Terms of the National Academy of Medicine (DTM), and English, including the Farlex Dictionary. The terms were also explored using the Google search engine. Definitions were analyzed from both lexicographical and etymological perspectives. Definitions found in general dictionaries, in both Spanish and English, were found to be imprecise, limited, and ambiguous, as they mixed outdated indications with criteria that deviated from etymology. In contrast, definitions in medical dictionaries in both languages were more aligned with etymology. "Traqueotomía" strictly identifies the surgical procedure of creating an opening in the anterior face of the trachea. "Traqueostomía" identifies the creation of an opening that connects the trachea to the exterior, involving a modification of the upper airway by providing an additional entry for the respiratory pathway. "Traqueostomía" becomes the sole means of entry to the airway in total laryngectomies. Both terms can be used synonymously when a traqueotomía culminates in a traqueostomía. However, it is not appropriate to use the term "traqueostomía" when the procedure concludes with the closure of the planes and does not result in the creation of a stoma. Traqueostomas can be qualified with adjectives indicating permanence (temporary/permanent), size (large/small), shape (round/elliptical), or depth, without being linked to any specific disease or surgical indication. Not all permanent traqueostomas are the result of total laryngectomies, and they do not necessarily have an irreversible character systematically.

Impact of SARS-CoV-2 Infection on Humoral and Cellular Immunity in a Cohort of Vaccinated Solid Organ Transplant Recipients.

The aim of the present study was to determine humoral and T-cell responses after four doses of mRNA-1273 vaccine in solid organ transplant (SOT) recipients, and to study predictors of immunogenicity, including the role of previous SARS-CoV-2 infection in immunity. Secondarily, safety was also assessed. Liver, heart, and kidney transplant recipients eligible for SARS-CoV-2 vaccination from three different institutions in Barcelona, Spain were included. IgM/IgG antibodies and T cell ELISpot against the S protein four weeks after receiving four consecutive booster doses of the vaccine were analyzed. One hundred and forty-three SOT recipients were included (41% liver, 38% heart, and 21% kidney). The median time from transplantation to vaccination was 6.6 years (SD 7.4). In total, 93% of the patients developed SARS-CoV-2 IgM/IgG antibodies and 94% S-ELISpot positivity. In total, 97% of recipients developed either humoral or cellular response (100% of liver recipients, 95% of heart recipients, and 88% of kidney recipients). Hypogammaglobulinemia was associated with the absence of SARS-CoV-2 IgG/IgM antibodies and S-ELISpot reactivity after vaccination, whereas past symptomatic SARS-CoV-2 infection was associated with SARS-CoV-2 IgG/IgM antibodies and S-ELISpot reactivity. Local and systemic side effects were generally mild or moderate, and no recipients experienced the development of de novo DSA or graft dysfunction following vaccination.

Barriers and facilitators for adopting healthy lifestyles in breast cancer survivors: a scoping review protocol.

OBJECTIVE: This scoping review will identify barriers and facilitators for the adoption of 7 healthy lifestyle components by female breast cancer survivors. This will be achieved by mapping the World Cancer Research Fund/American Institute for Cancer Research recommendations and the Lifestyle Medicine pillars. INTRODUCTION: Adherence to healthy lifestyle components (including weight management, physical activity, healthy diet, restorative sleep, avoidance of risky substances, forming and maintaining healthy relationships, and stress management) may improve the quality of life of breast cancer survivors and reduce the risk of adverse patient outcomes. However, cancer survivors' adherence to recommendations of multiple healthy lifestyle components is low, and decreases over time. INCLUSION CRITERIA: The review will consider peer-reviewed studies investigating barriers and facilitators for adopting any of the 7 healthy lifestyle components by female adult (18+ years old) breast cancer survivors (ie, from the time of diagnosis) in community, hospital, and/or cancer care settings, without any geographical restrictions. All study designs and articles published in English will be included. METHODS: The review will follow the JBI methodology for scoping reviews. Databases to be searched will include MEDLINE (PubMed), Embase, CINAHL (EBSCOhost), PsycINFO (Ovid), and the Cochrane Library databases. Articles published from 2007 to the present will be considered since this was the year in which the World Cancer Research Fund/American Institute for Cancer Research recommendations were published. Two independent reviewers will screen the retrieved articles and extract the data. Barriers and facilitators for each lifestyle component will be grouped according to the Theoretical Domain Framework. A narrative summary will explicate the charted data. REVIEW REGISTRATION: Open Science Framework https://osf.io/cn3va.

Hazards of swine slurry: Heavy metals, bacteriology, and overdosing-Physicochemical models to predict the nutrient value.

In this work, 124 samples of slurry from 32 commercial farms of three animal categories (lactating sows, nursery piglets, and growing pigs) were studied. The samples were collected in summer and winter over two consecutive years and analyzed for physicochemical properties, macronutrient and micronutrient, heavy metals, and major microbiological indicators. The results were found to be influenced by farm type and to deviate especially markedly in nursery piglets, probably as a consequence of differences in pig age, diet, and management. The main potential hazards of the slurries can be expected to arise from their high contents in heavy metals (Cu and Zn), especially in the nursery piglet group, and from the high proportion of samples testing positive for Salmonella spp. (66%). Linear and nonlinear predictive equations were developed for each animal category and the three as a whole. Dry matter, which was highly correlated with N, CaO, and MgO contents, proved the best predictor of fertilizer value. Using an additional predictor failed to improve the results but nonlinear and farm-specific equations did. Rapid on-site measurements can improve the accuracy of fertilizer value estimates and help optimize the use of swine slurry as a result.

Ayudas diagnósticas y diagnóstico diferencial de la enfermedad de Pompe / Diagnostic aids and differential diagnosis of Pompe disease

Introducción: La enfermedad de Pompe (EP) o glucogenosis tipo II es una enfermedad autosómica recesiva causada por mutaciones en el gen GAA que codifica para la proteína alfa-1,4-glucosidasa. Su deficiencia lleva a un almacenamiento anormal de glucógeno en los lisosomas de varias células, a través de los diferentes tejidos, lo que causa un compromiso musculoesquelético predominante. Contenidos: Los fenotipos de la enfermedad dependen de las variantes genéticas y de los niveles de la actividad enzimática residual. La enfermedad se presenta como EP de inicio infantil, EP de inicio tardío y EP intermedio, por lo que es de suma importancia su diagnóstico temprano, por medio de estudios moleculares como la secuenciación de Sanger y la secuenciación de nueva generación. Conclusiones: Se ha demostrado, mediante diferentes estudios, que las variaciones genéticas pueden diferir entre etnias, y es importante su caracterización molecular para determinar el tratamiento más adecuado, de acuerdo con el estado del material inmunológico de reacción cruzada (CRIM).

Introduction: Pompe disease (PD) or Glycogenosis Type II is a rare autosomal recessive disease caused by mutations in the GAA gene that codes for the alpha-1,4-glucosidase protein. Its deficiency leads to abnormal glycogen storage in the lysosomes of various cells throughout the different tissues causing a predominant musculoskeletal compromise. Contents: The phenotypes of the disease depend on the genetic variants and the levels of residual enzyme activity, presenting as infantile-onset PD, late-onset PD, and intermediate PD; Therefore, early diagnosis of the disease through molecular studies such as Sanger sequencing and new generation sequencing is of utmost importance. Conclusions: It has been shown through different studies that genetic variations can vary between ethnic groups and the molecular characterization of the variants is important to determine the most appropriate treatment depending on the state of the cross-reactive immunological material (CRIM)

An interregional measles outbreak in Spain with nosocomial transmission, November 2017 to July 2018.

Given sustained high vaccination coverage and enhanced surveillance for measles, Spain has been free of endemic measles transmission since 2014, achieving elimination certification from the World Health Organization in 2017. In November 2017, measles was introduced through an imported case travelling to the Valencian Community, causing an interregional outbreak. Here, we describe the outbreak using data reported to the national epidemiological surveillance network. The outbreak involved 154 cases (67 males, 87 females) notified in four regions; 148 were laboratory-confirmed and six epidemiologically linked. Most cases were adults aged 30-39 (n = 62, 40.3%) years. Sixty-two cases were hospitalised (40.3%) and 35 presented complications (22.7%). Two thirds of the cases (n = 102) were unvaccinated including 11 infants (≤ 1 year) not yet eligible for vaccination. The main route of transmission was nosocomial; at least six healthcare facilities and 41 healthcare workers and support personnel were affected. Sequencing of the viral nucleoprotein C-terminus (N450) identified genotype B3, belonging to the circulating MVs/Dublin.IRL/8.16-variant. Control measures were implemented, and the outbreak was contained in July 2018. The outbreak highlighted that raising awareness about measles and improving the vaccination coverage in under-vaccinated subgroups and personnel of healthcare facilities are key measures for prevention of future outbreaks.

Maturity-onset diabetes of the young in a large Portuguese cohort.

AIMS: Monogenic forms of diabetes that develop with autosomal dominant inheritance are classically aggregated in the Maturity-Onset Diabetes of the Young (MODY) categories. Despite increasing awareness, its true prevalence remains largely underestimated. We describe a Portuguese cohort of individuals with suspected monogenic diabetes who were genetically evaluated for MODY-causing genes. METHODS: This single-center retrospective cohort study enrolled patients with positive genetic testing for MODY between 2015 and 2021. Automatic sequencing and, in case of initial negative results, next-generation sequencing were performed. Their clinical and molecular characteristics were described. RESULTS: Eighty individuals were included, 55 with likely pathogenic/pathogenic variants in one of the MODY genes and 25 MODY-positive family members, identified by cascade genetic testing. The median age at diabetes diagnosis was 23 years, with a median HbA1c of 6.5%. The most frequently mutated genes were identified in HNF1A (40%), GCK (34%) and HNF4A (13%), followed by PDX1, HNF1B, INS, KCNJ11 and APPL1. Thirty-six unique variants were found (29 missense and 7 frameshift variants), of which ten (28%) were novel. CONCLUSIONS: Our data highlights the importance of genetic testing in the diagnosis of MODY and the establishment of its subtypes, leading to more personalized treatment and follow-up strategies.

Cost-Effectiveness Analysis of Pertuzumab Plus Trastuzumab and Docetaxel Compared With Trastuzumab and Docetaxel in the Adjuvant Treatment of Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer in Colombia.

OBJECTIVES: The addition of pertuzumab to the scheme of docetaxel plus trastuzumab (TH) in patients with metastatic breast cancer with overexpression of human epidermal growth factor receptor 2 increases survival. Nevertheless, this addition could represent a high cost for the health system of a middle-income country such as Colombia. Therefore, it is necessary to evaluate the efficiency of the pertuzumab plus TH (PTH) scheme in comparison with TH. METHODS: A partitioned survival model-based cost-utility analysis was performed. Progression-free survival and overall survival curves for each scheme were obtained from the CLEOPATRA study. The time horizon was 30 years with a discount rate of 5% for costs and quality-adjusted life-years. Total direct costs were calculated using national tariffs. Utilities were obtained from external sources. Model uncertainty was evaluated by deterministic and probabilistic sensitivity analysis. A willingness to pay value of 5180 US dollars was used. RESULTS: The discounted total average costs of TH and PTH were $24 109 and $60 846, respectively. These regimens' average life-years were 5.78 and 8.38, and their quality-adjusted life-years were 3.28 and 4.51, respectively. The incremental cost-effectiveness ratio was $29 867. One-way sensitivity analysis showed that the cost of pertuzumab was the variable that explained the uncertainty in the model. The probability that PTH is cost-effective in the probabilistic sensitivity analysis is 0.0724. CONCLUSIONS: The addition of pertuzumab to the TH regimen in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer has a low probability of being cost-effective from the payer's perspective in the Colombian health system.

Analysis of Prevalence and Predictive Factors of Long-Lasting Olfactory and Gustatory Dysfunction in COVID-19 Patients.

BACKGROUND: Although smell and taste disorders are highly prevalent symptoms of COVID-19 infection, the predictive factors leading to long-lasting chemosensory dysfunction are still poorly understood. METHODS: 102 out of 421 (24.2%) mildly symptomatic COVID-19 patients completed a second questionnaire about the evolution of their symptoms one year after the infection using visual analog scales (VAS). A subgroup of 69 patients also underwent psychophysical evaluation of olfactory function through UPSIT. RESULTS: The prevalence of chemosensory dysfunction decreased from 82.4% to 45.1% after 12 months, with 46.1% of patients reporting a complete recovery. Patients older than 40 years (OR = 0.20; 95% CI: [0.07, 0.56]) and with a duration of loss of smell longer than four weeks saw a lower odds ratio for recovery (OR = 0.27; 95% CI: [0.10, 0.76]). In addition, 28 patients (35.9%) reported suffering from parosmia, which was associated with moderate to severe taste dysfunction at the baseline (OR = 7.80; 95% CI: [1.70, 35.8]). Among the 69 subjects who underwent the UPSIT, 57 (82.6%) presented some degree of smell dysfunction, showing a moderate correlation with self-reported VAS (r = -0.36, p = 0.0027). CONCLUSION: A clinically relevant number of subjects reported persistent chemosensory dysfunction and parosmia one year after COVID-19 infection, with a moderate correlation with psychophysical olfactory tests.

Genotypic and Phenotypic Study of Antiviral Resistance Mutations in Refractory Cytomegalovirus Infection.

BACKGROUND: This study describes the genotypic and phenotypic characterization of novel human cytomegalovirus (HCMV) genetic variants of a cohort of 94 clinically resistant HCMV patients. METHODS AND RESULTS: Antiviral-resistant mutations were detected in the UL97, UL54, and UL56 target genes of 25 of 94 (26.6%) patients. The genotype-phenotype correlation study resolved the status of 5 uncharacterized UL54 deoxyribonucleic acid polymerase (G441S, A543V, F460S, R512C, A928T) and 2 UL56 terminase (F345L, P800L) mutations found in clinical isolates. A928T conferred high, triple resistance to ganciclovir, foscarnet, and cidofovir, and A543V had 10-fold reduced susceptibility to cidofovir. Viral growth assays showed G441S, A543V, F345L, and P800L impaired viral growth capacities compared with wild-type AD169 HCMV. Three-dimensional modeling predicted A543V and A928T phenotypes but not R512C, reinforcing the need for individual characterization of mutations by recombinant phenotyping. CONCLUSIONS: Extending mutation databases is crucial to optimize treatments and to improve the assessment of patients with resistant/refractory HCMV infection.

Rapid Molecular Diagnosis of Genetically Inherited Neuromuscular Disorders Using Next-Generation Sequencing Technologies.

Neuromuscular diseases are genetically highly heterogeneous, and differential diagnosis can be challenging. Over a 3-year period, we prospectively analyzed 268 pediatric and adult patients with a suspected diagnosis of inherited neuromuscular disorder (INMD) using comprehensive gene-panel analysis and next-generation sequencing. The rate of diagnosis increased exponentially with the addition of genes to successive versions of the INMD panel, from 31% for the first iteration (278 genes) to 40% for the last (324 genes). The global mean diagnostic rate was 36% (97/268 patients), with a diagnostic turnaround time of 4-6 weeks. Most diagnoses corresponded to muscular dystrophies/myopathies (68.37%) and peripheral nerve diseases (22.45%). The most common causative genes, TTN, RYR1, and ANO5, accounted for almost 30% of the diagnosed cases. Finally, we evaluated the utility of the differential diagnosis tool Phenomizer, which established a correlation between the phenotype and molecular findings in 21% of the diagnosed patients. In summary, comprehensive gene-panel analysis of all genes implicated in neuromuscular diseases facilitates a rapid diagnosis and provides a high diagnostic yield.

Surveillance of influenza B severe hospitalized cases during 10 seasons in Catalonia: Does the lineage make a difference?

Influenza B viruses circulate in two lineages (B/Victoria and B/Yamagata). Although classically affecting children, recently it has shown a high rate of infection and increased hospitalization in the elderly. To describe and analyze the clinical and epidemiological characteristics of severe hospitalized laboratory-confirmed influenza B virus (SHLCI-B) cases in Catalonia associated with mismatch from Influenza B virus strain included in the trivalent influenza vaccine (TIV). SHLCI-B was registered by the influenza sentinel surveillance system of Catalonia (PIDIRAC) during ten surveillance seasons from 2010 to 2020. Variables age, comorbidities, and vaccination status were recorded. Vaccine effectiveness was estimated as (1-OR) for intensive care unit (ICU) admission. Statistical significance was established at p < 0.05. A total of 1159 SHLCI-B were registered, of these 68.2% (791) corresponded to the 2017-2018 season; 21.8% (253) were admitted to ICU and 13.8% (160) were exitus; 62.5% (725) cases occurred in those aged >64 years; most frequent risk factor was cardiovascular disease (35.1%, 407) followed by chronic pulmonary obstructive disease-COPD (24.6%, 285) and diabetes (24.1%, 279). In four seasons, the predominant circulating lineage was B/Victoria, in two seasons the B/Yamagata lineage and four seasons had no IBV activity. Four seasons presented discordance with the strain included within the TIV. Vaccine effectiveness (VE) to prevent ICU admission was 31% (95% confidence interval [CI]: 4%-51%; p = 0.03); being 29% (95% CI: -3% to 51%) in discordant and 43% (95% CI:-43% to 77%) in concordant seasons. Significant differences were observed in the number of affected aged > 64 years (odds ratio [OR] = 2.5; 95% CI: 1.9-3.4; p < 0.001) and in patients with heart disease (OR = 2.40 95% CI: 1.7-3.4; p < 0.001), COPD (OR = 1.6 95% CI: 1.1-2.3; p = 0.01), and diabetes (OR = 1.5 95% CI: 1.1-2.1; p = 0.04) between discordant and concordant seasons. The increase in hospitalization rate in people> 64 years of age and those presenting comorbidities in seasons with circulating influenza B virus belonging to a lineage discordant with the strain included in the TIV and the decrease of VE to prevent ICU admissions evidence the vital need to administer the quadrivalent influenza vaccine regardless of the findings of predominant circulation in the previous season.

Dye decomposition and air de-pollution performance of TiO2/SiO2 and N-TiO2/SiO2 photocatalysts coated on Portland cement mortar substates.

In this study, the newly synthesized TiO2 and N doped TiO2 clusters were added to silica sol to synthesize N-TiO2/SiO2 composites via the sol-gel method. Afterwards, the prepared sols were applied by brushing on portland cement. Doping with nitrogen significantly increased the absorption of TiO2 towards the visible region, thus, increasing the photocatalytic activity. SEM characterization of the treated samples showed that the clusters were distributed in form of aggregates on the samples' surface. The self-cleaning and air de-polluting performances were assessed through methylene blue degradation and the oxidation of nitrogen oxide, resulting in methylene blue (MB) removal of 85% and 78% after 60 min of irradiation for SN10TiO2 and STiO2, respectively. Regarding air de-pollution performance, the newly synthesized photocatalysts showed the ability of NOx reduction. However, their efficiency was somewhat lower, in which 23.81% of NO has been oxidized by the sample SN10TiO2, while SP25 showed a total NO conversion of 38.98%. The powdered xerogels of the newly synthesized nanoparticles revealed high photocatalytic efficiency concerning NO oxidation, resulting in a higher performance compared to those obtained by the xerogel containing P25.

Transcriptomic analysis of patients with clinical suspicion of maturity-onset diabetes of the young (MODY) with a negative genetic diagnosis.

BACKGROUND: Diagnosis of mature-onset diabetes of the young (MODY), a non-autoimmune monogenic form of diabetes mellitus, is confirmed by genetic testing. However, a positive genetic diagnosis is achieved in only around 50% of patients with clinical characteristics of this disease. RESULTS: We evaluated the diagnostic utility of transcriptomic analysis in patients with clinical suspicion of MODY but a negative genetic diagnosis. Using Nanostring nCounter technology, we conducted transcriptomic analysis of 19 MODY-associated genes in peripheral blood samples from 19 patients and 8 healthy controls. Normalized gene expression was compared between patients and controls and correlated with each patient's biochemical and clinical variables. Z-scores were calculated to identify significant changes in gene expression in patients versus controls. Only 7 of the genes analyzed were detected in peripheral blood. HADH expression was significantly lower in patients versus controls. Among patients with suspected MODY, GLIS3 expression was higher in obese versus normal-weight patients, and in patients aged < 25 versus > 25 years at diabetes onset. Significant alteration with respect to controls of any gene was observed in 57.9% of patients. CONCLUSIONS: Although blood does not seem to be a suitable sample for transcriptomic analysis of patients with suspected MODY, in our study, we detected expression alterations in some of the genes studied in almost 58% of patients. That opens the door for future studies that can clarify the molecular cause of the clinic of these patients and thus be able to maintain a more specific follow-up and treatment in each case.