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Abstract The characteristics of the host are crucial in the final outcome of COVID-19. Herein, the influence of genetic and clinical variants in COVID-19 severity was investigated in a total of 1350 patients. Twenty-one single nucleotide polymorphisms of genes involved in SARS-CoV-2 sensing as Toll-like-Receptor 7, antiviral immunity as the type I interferon signalling pathway (TYK2, STAT1, STAT4, OAS1, SOCS) and the vasoactive intestinal peptide and its receptors (VIP/VIPR1,2) were studied. To analyse the association between polymorphisms and severity, a model adjusted by age, sex and different comorbidities was generated by ordinal logistic regression. The genotypes rs8108236-AA (OR 0.12 [95% CI 0.02–0.53]; p = 0.007) and rs280519-AG (OR 0.74 [95% CI 0.56–0.99]; p = 0.03) in TYK2, and rs688136-CC (OR 0.7 [95% CI 0.5–0.99]; p = 0.046) in VIP, were associated with lower severity; in contrast, rs3853839-GG in TLR7 (OR 1.44 [95% CI 1.07–1.94]; p = 0.016), rs280500-AG (OR 1.33 [95% CI 0.97–1.82]; p = 0.078) in TYK2 and rs1131454-AA in OAS1 (OR 1.29 [95% CI 0.95–1.75]; p = 0.110) were associated with higher severity. Therefore, these variants could influence the risk of severe COVID-19.

Introduction: The vertical transmission rate (VTR) of HIV has decreased to less than 2% in high-income countries, in spite of which perinatal infections continue to occur. We present data from the national cohort of pregnant women living with HIV and their children in Spain. The objectives were to describe the characteristics of this population, evaluate the VTR of HIV, the safety of antiretroviral therapy (ART) and the prevalence of coinfection. Patients and methods: Multicentre prospective, observational and descriptive study with participation of 62 hospitals. The sample included pegnant women living with HIV whose children were born between January 2020 and December 2022. We collected prospective data on the characteristics of mothers and children using an online questionnaire (REDCap web application). Results: The study included 414 mother-child dyads. Most mothers were immigrants (227/349; 65.1%). The main route of HIV infection was heterosexual transmission (160/402; 39.8%), followed by vertical transmission (44/402; 10.9%). The diagnosis was made before conception in 313/389 women (80.4%), 394/402 (98%) received ART during pregnancy and 356/402 (89.3%) had an undetectable viral load at the time of delivery. The delivery was vaginal in 230/388 children (59.3%). The proportion of preterm birth was 11.1%. The most frequent neonatal prophylaxis approach was monotherapy with zidovudine (358/414; 86.5%). There were 3 cases of vertical transmission of HIV (95% CI, 0%–1.54%). Only one newborn was breastfed. Conclusions: At present, most women living with HIV in Spain receive the diagnosis before conception, are of foreign ancestry and achieve good control of the infection. Although the VTR is very low in Spain, there are still infections that could be prevented with early diagnosis and treatment. Resumen: Introducción: La tasa de transmisión materno-infantil (TMI) del VIH ha disminuido a menos del 2% en países desarrollados, a pesar de lo cual siguen produciéndose infecciones. Se presentan los datos de la Cohorte Nacional Española de mujeres embarazadas que viven con VIH y sus hijos. Los objetivos fueron describir sus características, evaluar la TMI de VIH, la seguridad del tratamiento antirretroviral (TAR) y la prevalencia de coinfecciones. Pacientes y métodos: Estudio descriptivo, observacional, prospectivo y multicéntrico con participación de 62 hospitales. Se incluyeron las embarazadas cuyos hijos nacieron entre enero 2020 y diciembre 2022. Se recogieron prospectivamente características de las madres y niños en REDCap. Resultados: Hubo 414 pares madre-niño. Las madres fueron migrantes 227/349 (65,1%). La principal vía de adquisición del VIH fue la heterosexual (160/402; 39,8%), seguido de la TMI (44/402; 10,9%). En 313/389 (80,4%) el diagnóstico fue previo al embarazo, 394/402 (98%) recibieron TAR durante la gestación y 356/402 (89,3%) presentaba carga viral indetectable al parto. Hubo 230/388 (59,3%) neonatos nacidos por parto vaginal. La tasa de prematuridad fue 11,1%. La profilaxis neonatal más empleada (358/414; 86,5%) fue monoterapia con zidovudina. Hubo 3 casos de TMI del VIH (0,72% (IC 95%; 0%–1,54%), todos ellos con infección intraútero. Todos menos 1 recibieron lactancia artificial. Conclusiones: Actualmente las mujeres que viven con VIH en nuestro medio son migrantes, diagnosticadas mayoritariamente antes de la gestación, y logran adecuada situación inmunovirológica. Aunque la tasa de TMI es muy baja en nuestro país continúan ocurriendo infecciones prevenibles con diagnóstico y tratamiento más precoces.

Thyroid carcinoma originating in Struma Ovarii (SO) is a rare thyroid ectopic cancer that accounts for 0.01% of all ovarian malignancies and is associated with hyperthyroidism in less than 15% of cases. In a 44-year-old patient with pelvic pain, the CT scan revealed a solid-cystic formation in the ovarium. A left oophorectomy was performed and showed a borderline serous tumor and papillary thyroid carcinoma (‘thyroid carcinoma originating in Struma Ovarii’) measuring 10 cm. Thyroid function was assessed, and hyperthyroidism was diagnosed. Surgical complementation and a pelvic re-approach were performed. The histological findings showed a papillary thyroid carcinoma in the uterine serosa and the right adnexa. Thyroid function was re-evaluated, and despite normal thyroid function, the TRAb test remained positive. The patient underwent total thyroidectomy and radioiodine therapy (RIT), after which the TRAb test became negative. During 3 years of follow-up, no evidence of tumor was observed. In our case of thyroid carcinoma originating in SO, hyperthyroidism was treated with ovarian surgery, total thyroidectomy, and RIT. It is worth noting that thyroid function was normalized after ovarian surgery, but the TRAb test only became negative after total thyroidectomy. We hope to draw attention to the importance of evaluating thyroid function in patients with SO and treating high-risk SO patients with RIT after total thyroidectomy to achieve disease remission.

Abstract The dataset presents a 43 year-long reanalysis of pollen seasons for three major allergenic genera of trees in Europe: alder (Alnus), birch (Betula), and olive (Olea). Driven by the meteorological reanalysis ERA5, the atmospheric composition model SILAM predicted the flowering period and calculated the Europe-wide dispersion pattern of pollen for the years 1980–2022. The model applied an extended 4-dimensional variational data assimilation of in-situ observations of aerobiological networks in 34 European countries to reproduce the inter-annual variability and trends of pollen production and distribution. The control variable of the assimilation procedure was the total pollen release during each flowering season, implemented as an annual correction factor to the mean pollen production. The dataset was designed as an input to studies on climate-induced and anthropogenically driven changes in the European vegetation, biodiversity monitoring, bioaerosol modelling and assessment, as well as, in combination with intra-seasonal observations, for health-related applications.

Abstract Metabolic plasticity is a hallmark of cancer, and metabolic alterations represent a promising therapeutic target. Since cellular metabolism is controlled by membrane traffic at multiple levels, we investigated the involvement of TBC1 domain-containing proteins (TBC1Ds) in the regulation of cancer metabolism. These proteins are characterized by the presence of a RAB-GAP domain, the TBC1 domain, and typically function as attenuators of RABs, the master switches of membrane traffic. However, a number of TBC1Ds harbor mutations in their catalytic residues, predicting biological functions different from direct regulation of RAB activities. Herein, we report that several genes encoding for TBC1Ds are expressed at higher levels in triple-negative breast cancers (TNBC) vs. other subtypes of breast cancers (BC), and predict prognosis. Orthogonal transcriptomics/metabolomics analysis revealed that the expression of prognostic TBC1Ds correlates with elevated glycolytic metabolism in BC cell lines. In-depth investigations of the three top hits from the previous analyses (TBC1D31, TBC1D22B and TBC1D7) revealed that their elevated expression is causal in determining a glycolytic phenotype in TNBC cell lines. We further showed that the impact of TBC1D7 on glycolytic metabolism of BC cells is independent of its known participation in the TSC1/TSC2 complex and consequent downregulation of mTORC1 activity. Since TBC1D7 behaves as an independent prognostic biomarker in TNBC, it could be used to distinguish good prognosis patients who could be spared aggressive therapy from those with a poor prognosis who might benefit from anti-glycolytic targeted therapies. Together, our results highlight how TBC1Ds connect disease aggressiveness with metabolic alterations in TNBC. Given the high level of heterogeneity among this BC subtype, TBC1Ds could represent important tools in predicting prognosis and guiding therapy decision-making.

Abstract Objective Biallelic mutations in PRDX3 have been linked to autosomal recessive spinocerebellar ataxia type 32. In this study, which aims to contribute to the growing body of knowledge on this rare disease, we identified two unrelated patients with mutations in PRDX3. We explored the impact of PRDX3 mutation in patient skin fibroblasts and the role of the gene in neurodevelopment. Methods We performed trio exome sequencing that identified mutations in PRDX3 in two unrelated patients. We also performed functional studies in patient skin fibroblasts and generated a “crispant” zebrafish (Danio rerio) model to investigate the role of the gene during nervous system development. Results Our study reports two additional patients. Patient 1 is a 19‐year‐old male who showed a novel homozygous c.525_535delGTTAGAAGGTT (p. Leu176TrpfsTer11) mutation as the genetic cause of cerebellar ataxia. Patient 2 is a 20‐year‐old male who was found to present the known c.425C>G/p. Ala142Gly variant in compound heterozygosity with the p. Leu176TrpfsTer11 one. While the fibroblast model failed to recapitulate the pathological features associated with PRDX3 loss of function, our functional characterization of the prdx3 zebrafish model revealed motor defects, increased susceptibility to reactive oxygen species‐triggered apoptosis, and an impaired oxygen consumption rate. Conclusions We identified a new variant, thereby expanding the genetic spectrum of PRDX3‐related disease. We developed a novel zebrafish model to investigate the consequences of prdx3 depletion on neurodevelopment and thus offered a potential new tool for identifying new treatment opportunities.

Abstract Background The concept of quality in health care has evolved, placing greater importance on the patient’s needs, culture, and social context, as well as their participation in clinical decision-making, as highlighted by Mead and Bower’s Person-Centered Care Model. The aim of the present study was to design and validate an instrument to assess the extent to which healthcare services provided by PEMEX (Petróleos Mexicanos) offer person-centered care according to user perceptions. Methods The first phase comprised the development of 57 items based on the analysis of responses from an open-ended questionnaire administered to 30 users of Pemex healthcare services. This questionnaire was designed considering the four factors of the person-centered care model, however, the high correlation between the 4 factors (i.e., r ≥ .80) indicated an overfactoring effect and consequently an increase in the risk of overfitting. Therefore, an exhaustive analysis of the instrument was performed, starting with the review of the individual behavior of each item, and carrying out exploratory and confirmatory factor analysis. Using a sample of 330 individuals, an exploratory factor analysis was perfomed. Afterward, a confirmatory factorial analysis was carried out with 335 participants. Finally, a new confirmatory factorial analysis included 130 participants due to the refinements made in the previous phase. Internal consistency was assessed using Cronbach’s α and McDonald’s ω at every phase. Results The exploratory factor analysis retained 35 items in a single factor that accounted for 49% of the variance with an internal consistency of Cronbach’s α and McDonald’s ω = 0.97. Because the factorial structure by confirmatory factorial analysis was unsatisfactory, the initial model was refined, leading to the retention of 11 items and a final model with adjustment index of χ2 = 127.53, χ2/gl = 2.89, RMSEA = 0.07, IC RMSEA 0.06 to 0.09, TLI = 0.95 and CFI = 0.96, with an internal consistency of Cronbach’s α and McDonald’s ω = 0.93. Due to the refinements, a new confirmatory factorial analysis was conducted with suitable goodness-of-fit criteria in most items (χ2 = 151.44, χ2/gl = 3.43, RMSEA = 0.13, IC RMSEA 0.11 to 0.16, TLI = 0.93 and CFI = 0.94), resulting in a Cronbach’s α and McDonald’s ω = 0.98. Conclusions The instrument exhibits suitable psychometric properties to be employed to measure the degree to which medical care is patient centered. This instrument represents a strategy for promoting an innovative healthcare model.

Abstract Deep neural networks can improve the quality of fluorescence microscopy images. Previous methods, based on Convolutional Neural Networks (CNNs), require time-consuming training of individual models for each experiment, impairing their applicability and generalization. In this study, we propose a novel imaging-transformer based model, Convolutional Neural Network Transformer (CNNT), that outperforms CNN based networks for image denoising. We train a general CNNT based backbone model from pairwise high-low Signal-to-Noise Ratio (SNR) image volumes, gathered from a single type of fluorescence microscope, an instant Structured Illumination Microscope. Fast adaptation to new microscopes is achieved by fine-tuning the backbone on only 5–10 image volume pairs per new experiment. Results show that the CNNT backbone and fine-tuning scheme significantly reduces training time and improves image quality, outperforming models trained using only CNNs such as 3D-RCAN and Noise2Fast. We show three examples of efficacy of this approach in wide-field, two-photon, and confocal fluorescence microscopy.

This paper addresses the problem of how Spanish digital media reported income inequality during the first year of the COVID-19 pandemic. In this way, the goal was to study the framing of definition, contextual aspects, and depth. For this article, a tool was designed to analyse the content of the items. An analysis of news published by six digital media in Spain from March 2020 to February 2021 was conducted using content analysis. Within a sample of 2727 media stories in which there was a connection between the coronavirus and inequality, a stratified sample was used (n = 958) according to the content production by quarter and by media. The results of this study show that income inequality was the most common type of inequality reported in the media, and they cantered more on the micro level. Also, it appeared to be linked to the social gap and showed poverty as the main consequence. The frame was focused on social issues, international and national contexts, and expert sources. Finally, different levels of depth can be observed in the news items analysed, depending on the frame.

Abstract Non-neovascular or dry age-related macular degeneration (AMD) is a multi-factorial disease with degeneration of the aging retinal-pigmented epithelium (RPE). Lysosomes play a crucial role in RPE health via phagocytosis and autophagy, which are regulated by transcription factor EB/E3 (TFEB/E3). Here, we find that increased AKT2 inhibits PGC-1α to downregulate SIRT5, which we identify as an AKT2 binding partner. Crosstalk between SIRT5 and AKT2 facilitates TFEB-dependent lysosomal function in the RPE. AKT2/SIRT5/TFEB pathway inhibition in the RPE induced lysosome/autophagy signaling abnormalities, disrupted mitochondrial function and induced release of debris contributing to drusen. Accordingly, AKT2 overexpression in the RPE caused a dry AMD-like phenotype in aging Akt2 KI mice, as evident from decline in retinal function. Importantly, we show that induced pluripotent stem cell-derived RPE encoding the major risk variant associated with AMD (complement factor H; CFH Y402H) express increased AKT2, impairing TFEB/TFE3-dependent lysosomal function. Collectively, these findings suggest that targeting the AKT2/SIRT5/TFEB pathway may be an effective therapy to delay the progression of dry AMD.

Abstract This article explores whether the implementation of the B-Learning (BL) and Flipped Classroom (FC) methodologies, using the ICT tool Edpuzzle, in the mandatory subject of Didactics of Plastic Expression in the Early Childhood Education teacher training programme leads to improvements in their education as future teachers. To address this investigation, two different pedagogical interventions were proposed: Unit 1 (U1), implementing BL, and Unit 2 (U2) through traditional lectures. For the analysis, a qualitative methodology using the focus group technique was employed. The results revealed high satisfaction among students regarding U1, implying that the use of ICT through the implementation of BL and FC methodologies has created a more dynamic and enriching educational environment, thereby enhancing their learning.

Abstract Aims A higher risk of cancer among patients with heart failure (HF) has been suggested in recent community‐based studies. This study aimed to investigate the impact of HF during hospitalization with acute coronary syndrome (ACS) on the long‐term cancer risk. Methods and results The study included 572 patients admitted with ACS to three Italian hospitals, discharged cancer‐free, and prospectively followed for 24 years or until death. All but three patients completed the follow‐up, which represented 6440 person‐years (mean age: 66 ± 12 years; 70% males). Baseline HF was diagnosed in 192 (34%) patients. A total of 129 (23%) patients developed cancer (103 without HF and 26 with HF), and 107 (19%) patients died due to it (81 without HF and 26 with HF). The incidence rates for cancer onset and cancer death were not different according to HF status. Cox regression analysis revealed no association between HF or left ventricular ejection fraction (LVEF) and cancer risk. In addition, no difference in cancer risk was observed among patients with HF with preserved ejection fraction, HF with mildly reduced ejection fraction, and HF with reduced ejection fraction. In competing risk regression analysis, the risk of cancer onset associated with HF was sub‐hazard ratio (SHR) 0.47 [95% confidence interval (CI): 0.30–0.72; P = 0.001] and SHR 1.02 (95% CI: 1.01–1.04; P = 0.002) with LVEF. Results were the same in the adjusted model. Yet the fully adjusted model showed an attenuated association between cancer death and HF (SHR: 0.63; 95% CI: 0.37–1.05; P = 0.08) and LVEF (SHR: 1.02; 95% CI: 0.99–1.06; P = 0.08). Consistent results were obtained after using propensity score matching analysis that created 192 pairs. A negative interaction between age and HF and a positive interaction between age and LVEF for cancer risk have also been found. Conclusions An inverse association between baseline HF and long‐term cancer risk has been observed among the ABC Study on heart disease patients who were followed for 24 years after ACS.

BackgroundNeonatologists and clinical neurophysiologists face challenges with the current electrodes used for long-duration amplitude-integrated electroencephalography (aEEG) in neonatal intensive care units (NICU), limiting the capacity to diagnose brain damage.ObjectivesThe objectives of this study were to develop methods for comparing the performance of different electrodes to be used in aEEG. The comparison was done between a newly designed neonate-specific electrode, aCUP-E, with commercial liquid gel electrodes used in amplitude-integrated electroencephalography (aEEG). The comparison included impedance stability, electrode survival, recording quality, usability, and satisfaction of NICU staff.MethodsaEEG recordings with bipolar montage was used, with one hemisphere fitted with commercial electrodes and the other with aCUP-E electrodes, alternated among subjects. Continuous impedance and raw EEG data were collected over a minimum of 24 h, and signal processing was performed using Python and MATLAB.Main resultsaCUP-E electrodes demonstrated superior performance, including: Increased impedance stability and electrode survival, enhanced recording quality with fewer artifacts, high correlation in signal capture between electrodes during optimal brain activity segments, higher signal-to-noise ratio (SNR) across varying impedance levels, greater staff satisfaction and ease of use. Moreover, Kaplan-Meier curves indicated a higher survival rate for aCUP-E electrodes over 24 h compared to commercial electrodes. Impedance variability analysis showed statistically significant stability improvements for aCUP-E.ConclusionaCUP-E electrodes outperform commercial liquid gel electrodes in impedance stability, electrode survival, and recording quality. These results suggest that aCUP-E electrodes could significantly enhance aEEG utilization in diagnosing and treating neonatal brain conditions in NICUs. Future improvements to the aCUP-E electrode may further reduce artifacts and increase electrode longevity, potentially leading to a significant improvement in neonatal brain monitoring by means of aEEG.

PURPOSEThe optimal treatment sequence for hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC) after progression on first-line cyclin-dependent kinase 4/6 inhibitor (CDKi) and endocrine therapy is unclear. Clinical and biological factors influencing treatment choices and outcomes in the second-line setting need to be elucidated.MATERIALS AND METHODSThis is a retrospective analysis of a real-world cohort including patients with HR+/HER2– ABC who received CDKi and endocrine therapy in the first-line setting and progressed, requiring second-line treatment. Clinical and biological factors were analyzed to evaluate their association with daily treatment decisions and the prognostic role of progression-free survival (PFS) in the second-line setting.RESULTSTwo hundred thirty-five patients were included. Second-line treatments were hormone therapy (HT) based in 60% and chemotherapy based in 40% of patients. The second-line median PFS was 6.6 months, with no difference between treatment types. In multivariable analysis, postmenopausal status, lower Ki-67 expression, and non–de novo stage IV disease were associated with improved second-line (2L) PFS. Menopausal status significantly interacted with treatment type, with reduced PFS in premenopausal patients receiving HT-based treatments (4.7 v 8.7 months, P = .00045).CONCLUSIONIn our study, treatment decisions reflected the current algorithm incorporated in our clinical guidelines, and prior treatment response was the most relevant factor to determine 2L treatment decision. Menopausal status interacted with the subsequent therapy efficacy in this setting. Hence, we consider that menopausal status should be routinely evaluated in the subgroup analysis of clinical trials.

Introduction: Treatment of calcium (Ca) and vitamin D (VD) deficiency (VDD) is crucial for health, especially in bone conditions, such as low bone mineral density (BMD) and osteoporosis. Despite updates in clinical guideline recommendations, no studies have evaluated the efficacy and safety of administering 2000 IU of cholecalciferol combined with calcium. Thus, the main objective of this study was to evaluate VD levels following treatment with Ca 600 mg/ cholecalciferol 2000 IU in real-life clinical practice. Methods: This multicenter, retrospective, observational study included 302 adult patients receiving Ca 600 mg/D3 2000 IU orodispersible tablets, daily for ≥24 weeks. The primary outcome was 25-hydroxivitamin D [25(OH)D] serum levels following treatment. Key secondary outcomes included changes in serum 25(OH)D levels and other bone metabolism (BM) parameters, safety and tolerability. The protocol was approved by a Research Ethics Committee. Results: 285 patients were evaluated (mean age [SD]: 67.4 [12.6] years old; 88.4 % women; basal serum 25(OH)D: 20.0 [8.6] ng/mL); 80.7 % reported previous history of osteoporosis/low BMD (osteopenia) and 37.2 % had received other Ca/VD prior to start study treatment. Median treatment duration was 38.5 weeks [range 24.0–82.4]. Overall, 94.4 % of patients increased serum 25(OH)D following treatment to a mean of 36.3 [11.8] ng/mL (p

Gender-based violence is a global scourge advancing unchecked, penetrating all social and cultural strata. Physical, sexual and emotional abuse seriously affects women's freedom, with consequences not only psychological and physical but also economic, in the form of health, labour, legal and police costs. Therefore, society demands effective governmental measures based on respect for human rights and aimed at promoting equality to avoid intimidation and ill-treatment. This paper proposes to carry out a bibliometric analysis of the literature to investigate the state of the art of public policy and gender violence or domestic violence or violence against women to detect the patterns of behaviour that have marked the lines of study over the last two decades (2001–2022), by analysing a sample of 355 articles. The results reveal that scientific production has grown exponentially recently, with Brazil and the USA having the most significant involvement. Furthermore, three clearly differentiated lines of research are evident: the detection of risk factors and prevention measures; feminist movements aimed at empowering women, seeking their independence; and the qualification of care services supported by public policies. However, they all have the same objective, to achieve gender homogeneity and stop any type of violence against women and girls.

Abstract Background The increase in life expectancy and long-lived individuals is a challenge for public health and provides an opportunity to understand the determinants of longevity. However, few studies have addressed the factors associated with the health status and quality of life in a long-lived individual population. We described the perceived health, clinical status, quality of life, and dependency for activities of daily living in a representative population in Castile and Leon, Spain. Methods A sample of 759 long-lived individuals aged 95 years and older was studied by the Health Sentinel Network of Castile and Leon (Spain) through a health examination and a structured questionnaire covering quality of life (EQ-5D-3), lifestyle habits, diet, working life and family health. A blood sample was taken for the study of biological and genetic markers. Chi Square and logistic regression OR with 95% confidence intervals were used to analyze the determinants of the long-lived individuals’ health status. The significant level for the bivariate analysis was established at 0.05. Results Perceived health was good, very good or excellent in 64.2%, while only 46.0% had a quality-of-life index above 0.5 (ranging from 0 to 1) and 44.1% maintained acceptable independence for activities of daily living. Quality-of-life index was higher in the oldest, (OR 7.98 [2,32-27.41]) above 100 years compared to those under 98, and men had better values for independence than women (OR 2.43 [1.40–4.29]). Cardiovascular diseases were the most prevalent (85.5%), but neurological and mental diseases and vision problems had the highest impact on quality of life and independence. Conclusion The long-lived individuals of Castile and Leon have a relatively well-preserved health status, although the perception of health is higher than that describing their quality of life and dependence. The quality of life was higher in the oldest age group and showed differences according to sex, with a better quality of life in men. Public health policies and programs should take in account the differences by sex and age as well as the prevention and control of the main conditions related with poor quality of life or dependence. Future research must include the interaction among genetic, socioeconomic, environmental, and other clinical factors in the quality of life and disability of long-lived individuals.

Introduction and objective: Several studies have suggested that the hospitalization rate for COVID-19 in children and adolescents may reflect the prevalence of the infection rather than the severity of the disease. The aim of this study was to describe the clinical features of hospitalised paediatric patients with SARS-CoV-2 infection in order to understand if the infection was the reason for admission. Methods: Retrospective cohort study including patients aged 0–18 years with SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) admitted to a tertiary care children’s hospital in Spain between 01/01/2020 and 12/31/2021. Results: 228 patients were included, corresponding to 150 cases of COVID-related admission (SARS-CoV-2 infection as main cause of hospitalization) and 78 of non-COVID-related admission (SARS-CoV-2 infection unrelated to the hospitalization).In the group of COVID-related admissions, 58 patients had comorbidities. Forty-nine patients had acute respiratory disease (pneumonia, bronchospasm or bronchiolitis). Multisystem inflammatory syndrome in children was diagnosed in 27 and was significantly more frequent in the first year of the pandemic (wild type virus). Eighty percent of patients with acute respiratory disease needed respiratory support, mostly low-flow oxygen therapy. The severity of the disease was similar in all virus variants. Two patients (both with severe comorbidities) died from COVID-related conditions. Conclusions: In our study, one third of the patients were admitted with SARS-CoV-2 infection but not because of it. Acute respiratory disease was less frequent and had a better prognosis compared to the adult population, while MIS-C was a major cause of morbidity and hospitalization. The fatality rate was extremely low. Resumen: Introducción y objetivo: Varios estudios han sugerido que la tasa de hospitalización por COVID-19 en niños y adolescentes puede reflejar la prevalencia de la infección más que la gravedad de la enfermedad. El objetivo de este estudio fue describir las características clínicas de pacientes pediátricos hospitalizados con infección por SARS-CoV-2, con el fin de comprender si este fue el principal motivo de ingreso. Métodos: Estudio de cohortes retrospectivo que incluyó a pacientes de 0 a 18 años con infección por SARS-CoV-2 o síndrome inflamatorio multisistémico pediátrico vinculado a SARS-CoV-2 (SIM-PedS), ingresados en un hospital infantil de tercer nivel en España entre el 01/01/2020 y el 31/12/2021. Resultados: Se incluyeron 228 pacientes: 150 fueron ingresos causados por COVID (infección por SARS-CoV-2 como principal causa de hospitalización) y 78 fueron ingresos no causados por COVID (infección por SARS-CoV-2 no relacionada con la hospitalización). Entre los ingresos causados por COVID, 58 pacientes tenían comorbilidades. 49 pacientes cursaron con enfermedad respiratoria aguda (neumonía, broncoespasmo o bronquiolitis). 27 pacientes fueron diagnosticados de SIM-PedS; este diagnóstico se observó con más frecuencia durante el primer año de la pandemia (variante wild type). El 80% de los pacientes con enfermedad respiratoria aguda necesitaron algún tipo de soporte respiratorio, principalmente oxígeno de bajo flujo. La gravedad de la enfermedad fue similar con todas las variantes del virus. Dos pacientes (ambos con comorbilidades graves) fallecieron por afecciones relacionadas con la COVID-19. Conclusiones: En nuestro estudio, un tercio de los pacientes fueron hospitalizados con infección por SARS-CoV-2 pero no a causa de ella. La enfermedad respiratoria aguda tuvo menos incidencia y mejor pronóstico que en la población adulta, mientras que el SIM-PedS fue una causa importante de morbilidad y hospitalización. La mortalidad fue extremadamente baja.

Abstract Background The endothelial nitric oxide synthase (eNOS) gene deficiency is known to cause impaired coronary vasodilating capability in animal models. In the general clinical population, the eNOS gene polymorphisms, able to affect eNOS activity, were associated with cardiometabolic risk features and prevalence of coronary artery disease (CAD). Aim To investigate the association of eNOS Glu298Asp gene polymorphism, cardiometabolic profile, obstructive CAD and inducible myocardial ischemia in patients with suspected stable CAD. Methods A total of 506 patients (314 males; mean age 62 ± 9 years) referred for suspected CAD was enrolled. Among these, 325 patients underwent stress ECG or cardiac imaging to assess the presence of inducible myocardial ischemia and 436 patients underwent non-invasive computerized tomography or invasive coronary angiography to assess the presence of obstructive CAD. Clinical characteristics and blood samples were collected for each patient. Results In the whole population, 49.6% of patients were homozygous for the Glu298 genotype (Glu/Glu), 40.9% heterozygotes (Glu/Asp) and 9.5% homozygous for the 298Asp genotype (Asp/Asp). Obstructive CAD was documented in 178/436 (40.8%) patients undergoing coronary angiography while myocardial ischemia in 160/325 (49.2%) patients undergoing stress testing. Patients with eNOS Asp genotype (Glu/Asp + Asp/Asp) had no significant differences in clinical risk factors and in circulating markers. Independent predictors of obstructive CAD were age, gender, obesity, and low HDL-C. Independent predictors of myocardial ischemia were gender, obesity, low HDL-C and Asp genotype. In the subpopulation in which both stress tests and coronary angiography were performed, the Asp genotype remained associated with increased myocardial ischemia risk after adjustment for obstructive CAD. Conclusion In this population, low-HDL cholesterol was the only cardiometabolic risk determinant of obstructive CAD. The eNOS Glu298Asp gene polymorphism was significantly associated with inducible myocardial ischemia independently of other risk factors and presence of obstructive CAD.

Objective: The main objective of the present study was to evaluate the expression of nuclear orphan receptors in the development of Uterine Cervical Cancer (UCC). The principal cause of dysplastic changes in cervical epithelium is the presence of the human papilloma virus leading to the development of cervical intraepithelial neoplasia I (CIN I), high-grade lesions (CIN II and CIN III) and, finally, invasive cancer. Despite the existence of various treatments and vaccines, there is still a high mortality rate. There is evidence of the participation of a group of nuclear receptors called orphans in the development of various diseases, including cancer. Study design: The expression levels of the orphan receptors NR4A1, NR4A2, and NR4A3 were measured using real-time polymerase chain reaction (RT-PCR) in samples obtained through colposcopy from forty-five patients who attended the Medical Oncology Specialties Unit (UNEME) in Mexicali, B.C. Results: Forty-five cervical biopsy results were obtained, indicating cervicitis, CIN I, or CIN III, none of them CIN II. Our results showed that orphan receptors expressed in a specific manner depending on the degree of premalignant lesions. NR4A1 overexpressed in cervicitis (p 0.05). Conclusion: Our data suggest, for the first time, that nuclear receptors might be involved in the various stages that precede the development of invasive UCC.

ABSTRACTVaccine co-administration is a useful strategy for improving vaccine coverage and adherence. In Italy, an update to the national immunization program (NIP) in 2023 included recommendations for co-administration of pediatric vaccines, including the four-component vaccine for meningococcus B (4CMenB), pneumococcal conjugate vaccine (PCV), hexavalent vaccines, and oral rotavirus vaccines. Safety is a major concern when considering vaccine co-administration; therefore, a literature review of the available evidence on 4CMenB co-administration with PCV, hexavalent/pentavalent, and rotavirus vaccines was performed. Of 763 publications screened, two studies were reviewed that reported safety data on 4CMenB co-administration with PCV, hexavalent/pentavalent, and rotavirus vaccines in infants aged 0–24 months. Overall, these studies supported that there were no significant safety signals when co-administering 4CMenB with PCV, hexavalent/pentavalent, and rotavirus vaccines, compared with individual vaccination. This review provides key insights for healthcare professionals on the tolerability of co-administering 4CMenB with routine vaccines.

Background Fecal shedding of SARS-CoV-2 occurs during infection, particularly in pediatric populations. The gut microbiota are associated with resistance to enteric pathogens. COVID-19 is associated with alterations to the gut microbiome. We hypothesized that the gut microbiome of infants born to SARS-CoV-2+ mothers differs between infants with and without fecal shedding of the virus. Methods We enrolled 10 infants born to SARS-CoV-2+ mothers. We used qPCR on fecal RNA to test for SARS-CoV-2 and 16S rRNA gene sequencing of the V4 region to assess the gut microbiome. Infant SARS-CoV-2 status from nasal swabs was abstracted from medical records. Results Of the 10 included infants, nine were tested for SARS-CoV-2 by nasal swab with 1 testing positive. Four infants, including the nasal swab positive infant, had at least one sample with detectable levels of SARS-CoV-2 fecal shedding. Detection of both SARS-CoV-2 genes in feces was associated with increased gut alpha diversity compared to no detection by a linear mixed effects model (p

BackgroundHereditary Spastic Paraplegias (HSP) are genetic neurodegenerative disorders affecting the corticospinal tract. No established neuroimaging biomarker is associated with this condition.MethodsA total of 46 patients affected by HSP, genetically and clinically evaluated and tested with SPRS scores, and 46 healthy controls (HC) matched by age and gender underwent a single-voxel Magnetic Resonance Spectroscopy sampling (MRS) of bilateral pre-central and pre-frontal regions. MRS data were analyzed cross-sectionally (at T0 and T1) and longitudinally (T0 vs. T1).ResultsStatistically significant data showed that T0 mI/Cr in the pre-central areas of HSP patients was higher than in HC. In the left (L) pre-central area, NAA/Cr was significantly lower in HSP than in HC. In the right (R) pre-frontal area, NAA/Cr was significantly lower in HSP patients than in HC. HSP SPG4 subjects had significantly lower Cho/Cr concentrations in the L pre-central area compared to HC. Among the HSP subjects, non-SPG4 patients had significantly higher mI/Cr in the L pre-central area compared to SPG4 patients. In the R pre-frontal area, NAA/Cr was reduced, and ml/Cr was higher in non-SPG4 patients compared to SPG4 patients. Comparing “pure” and “complex” forms, NAA/Cr was higher in pHSP than in cHSP in the R pre-central and R pre-frontal areas. The longitudinal analysis, which involved fewer patients (n = 30), showed an increase in mI/Cr concentration in the L pre-frontal area among HSP subjects with respect to baseline. The patients had significantly higher SPRS scores at follow-up, with a significant positive correlation between SPRS scores and mI/Cr in the L pre-central area, while in bilateral pre-frontal areas, lower SPRS scores corresponded to higher NAA/Cr concentrations. To explore the discriminating power of MRS in correctly identifying HSP and controls, an inference tree methodology classified HSP subjects and controls with an overall accuracy of 73.9%, a sensitivity of 87.0%, and a specificity of 60.9%.ConclusionThis pilot study indicates that brain MRS is a valuable approach that could potentially serve as an objective biomarker in HSP.

Se examinó el impacto del contenido de harina de pituca (Colocasia esculenta L.) en las propiedades fisicoquímicas y aceptabilidad del pan tipo chachapoyano. La formulación del pan implicó la sustitución de harina de trigo con harina de pituca en 15/85, 20/80 y 25/75 y un grupo de control 0/100 harina de pituca/harina de trigo (HP/HT). Se realizaron análisis fisicoquímicos, farinográficos y alveográficos en las diferentes formulaciones de harina, mientras que el pan resultante fue evaluado en términos de propiedades fisicoquímicas y calidad sensorial, incluyendo aroma, color y textura. En la obtención del pan chachapoyano con harina de pituca se empleó un diseño completo al azar (DCA). Se realizó la comparación entre tratamientos se hizo mediante la prueba t de Student a una significancia del 0,05. Además, se empleó un Diseño de Bloques Completamente al Azar (DBCA) para evaluar la variable aceptabilidad, utilizando la prueba Tukey, con un nivel de significancia del 0,05. Según los resultados farinográficos, la harina de pituca fue clasificada como no panificable. No obstante, en términos alveográficos, la mezcla de harina 15/85 mostró similitudes cercanas al grupo de control, tanto en la harina como en el pan final.

Abstract Metabolic alterations in cancers can be exploited for diagnostic, prognostic, and therapeutic purposes. This is exemplified by 18F‐fluorodeoxyglucose (FDG)‐positron emission tomography (FDG‐PET), an imaging tool that relies on enhanced glucose uptake by tumors for diagnosis and staging. By performing transcriptomic analysis of breast cancer (BC) samples from patients stratified by FDG‐PET, a 54‐gene signature (PETsign) is identified that recapitulates FDG uptake. PETsign is independently prognostic of clinical outcome in luminal BCs, the most common and heterogeneous BC molecular subtype, which requires improved stratification criteria to guide therapeutic decision‐making. The prognostic power of PETsign is stable across independent BC cohorts and disease stages including the earliest BC stage, arguing that PETsign is an ab initio metabolic signature. Transcriptomic and metabolomic analysis of BC cells reveals that PETsign predicts enhanced glycolytic dependence and reduced reliance on fatty acid oxidation. Moreover, coamplification of PETsign genes occurs frequently in BC arguing for their causal role in pathogenesis. CXCL8 and EGFR signaling pathways feature strongly in PETsign, and their activation in BC cells causes a shift toward a glycolytic phenotype. Thus, PETsign serves as a molecular surrogate for FDG‐PET that could inform clinical management strategies for BC patients.

Introduction: Bloom syndrome is a rare autosomal recessive disorder characterized by chromosomal instability caused by mutations in the BLM gene that increase the risk of developing neoplasia, particularly at an early age. Bloom syndrome is typically characterized by short stature, photosensitivity, telangiectatic erythema, learning difficulties, immunodeficiency, and malignancy. Case report: We report a case of an adolescent girl with short stature and recurrent infections, who does not present typical erythematous sun-sensitive skin lesions to the face and whose high-pitched voice led to the diagnosis of BS caused by a novel L753X mutation. Discussion: To date, she has not presented with any malignancy or characteristic malar rash.

Durable serological memory following vaccination is critically dependent on the production and survival of long-lived plasma cells (LLPCs). Yet, the factors that control LLPC specification and survival remain poorly resolved. Using intravital two-photon imaging, we find that in contrast to most plasma cells (PCs) in the bone marrow (BM), LLPCs are uniquely sessile and organized into clusters that are dependent on APRIL, an important survival factor. Using deep, bulk RNA sequencing, and surface protein flow-based phenotyping, we find that LLPCs express a unique transcriptome and phenotype compared to bulk PCs, fine-tuning expression of key cell surface molecules, CD93, CD81, CXCR4, CD326, CD44, and CD48, important for adhesion and homing. Conditional deletion of Cxcr4 in PCs following immunization leads to rapid mobilization from the BM, reduced survival of antigen-specific PCs, and ultimately accelerated decay of antibody titer. In naïve mice, the endogenous LLPCs BCR repertoire exhibits reduced diversity, reduced somatic mutations, and increased public clones and IgM isotypes, particularly in young mice, suggesting LLPC specification is non-random. As mice age, the BM PC compartment becomes enriched in LLPCs, which may outcompete and limit entry of new PCs into the LLPC niche and pool.

En Valderredible, la educación primaria en el siglo XVIII era escasa, con algunas escuelas benéficas, pero la Constitución de 1812 y la Ley de Instrucción Primaria de 1838 intentaron ampliarla. Aunque se mejoró la alfabetización desde 1912, el trabajo infantil y la idiosincrasia rural limitaron la asistencia. Durante la Dictadura de Primo de Ribera se crearon trece escuelas, pero la red republicana se redujo drásticamente en Valderredible. La musealización de la antigua escuela de Castrillo de Valdelomar destaca la importancia de la educación rural, honrando la labor de maestros y comunidad. La recreación de un aula antigua y la exhibición de objetos transmiten la importancia de la educación en el desarrollo comunitario a las generaciones presentes y futuras.

SUMMARY Thyroglobulin (Tg) levels are important to predict recurrence in differentiated thyroid cancer patients. However, false-positive results can hence the request of unnecessary tests and treatments. We reported two cases of interference in thyroglobulin measurement and the workup to investigate them. Both patients achieved an excellent response to therapy after total thyroidectomy and one patient had also received radioiodine treatment. During the follow-up, Tg levels increased and there was no evidence of recurrent disease in the imaging studies. The Tg levels by the Access platform were positive but the results by Elecsys platform and LC-MS/MS were undetectable, leading to the hypothesis of heterophile antibodies (HAbs) interference. The possibility of HAbs interference must be considered when the Tg levels do not fit in the clinical picture. The measurement of Tg by another immunoassay or by LC-MS/MS may be useful in these situations.

Summary: Background: Vitiligo is a chronic autoimmune disease characterised by depigmented skin patches, which can pose substantial psychosocial challenges particularly in individuals with dark skin tones. Despite its impact on quality of life, there is an absence of standardised global epidemiological data. We sought to address this gap with the present study. Methods: In this study we did a systematic review and modelling analysis to estimate the global, regional, and national prevalence and incidence of vitiligo. We did a comprehensive search of nine digital libraries (PubMed, Embase, Web of Science, Scientific Electronic Library Online, KCI Korean Journal Database, Russian Science Citation Index, Western Pacific Region Index Medicus, Informit, and Health Research and Development Information Network) from inception up to May 25, 2023. We included cross-sectional or cohort studies reporting the incidence rate or prevalence of vitiligo, or data from which incidence rate or prevalence could be calculated, in the general population of a country or area of a country. Summary estimate data were extracted. A main outcome was to estimate the worldwide, regional, and country-specific lifetime prevalence of vitiligo diagnosed by physicians or dermatologists among the general population and in adults and children (as per age groups defined in included studies). We used a Bayesian hierarchical linear mixed model to estimate prevalence, and calculated number of affected individuals using the UN population structure in 2022. In estimating lifetime prevalence, studies reporting point or period prevalence were excluded. Our other main outcome was to estimate incidence rates of vitiligo, but due to a small number of studies, the data on incidence were presented in a descriptive summary. This study was registered on PROSPERO, CRD42023390433. Findings: Our search identified 22 192 records, of which 90 studies met our inclusion criteria. Of these studies, six focused on the incidence of vitiligo, 79 reported on the prevalence of vitiligo, and five provided data on both incidence and prevalence. 71 studies reported on lifetime prevalence. In the most recent years studied, incidence rates in the general population ranged from 24·7 cases (95% CI 24·3–25·2) per 100 000 person-years in South Korea in 2019, to 61·0 cases (60·6–61·4) in the USA in 2017. In individual studies, incidence rates showed an increasing trend over the periods studied. The global lifetime prevalence of vitiligo diagnosed by a physician or dermatologist was estimated at 0·36% (95% credible interval [CrI] 0·24–0·54) in the general population (28·5 million people [95% CrI 18·9–42·6]), 0·67% (0·43–1·07) in the adult population (37·1 million adults [23·9–58·9]), and 0·24% (0·16–0·37) in the child population (5·8 million children [3·8–8·9]). Vitiligo prevalence was higher in adults than in children across all regions. Central Europe and south Asia reported the highest prevalence (0·52% [0·28–1·07] and 0·52% [0·33–0·82], respectively, in the general population). Interpretation: This study highlights the need for standardised epidemiological data collection globally to inform public health policies and improve vitiligo diagnosis and management. Emphasis on the impact on individuals with darker skin tones is crucial to reducing stigma and improving quality of life. Furthermore, our study highlights the need to conduct more research in regions and populations that have been historically under-represented, to effectively address the worldwide burden of vitiligo. Funding: None.

Abstract Lysosomes have emerged as critical regulators of cellular homeostasis. Here we show that the lysosomal protein TMEM55B contributes to restore cellular homeostasis in response to oxidative stress by three different mechanisms: (1) TMEM55B mediates NEDD4-dependent PLEKHM1 ubiquitination, causing PLEKHM1 proteasomal degradation and halting autophagosome/lysosome fusion; (2) TMEM55B promotes recruitment of components of the ESCRT machinery to lysosomal membranes to stimulate lysosomal repair; and (3) TMEM55B sequesters the FLCN/FNIP complex to facilitate translocation of the transcription factor TFE3 to the nucleus, allowing expression of transcriptional programs that enable cellular adaptation to stress. Knockout of tmem55 genes in zebrafish embryos increases their susceptibility to oxidative stress, causing early death of tmem55-KO animals in response to arsenite toxicity. Altogether, our work identifies a role for TMEM55B as a molecular sensor that coordinates autophagosome degradation, lysosomal repair, and activation of stress responses.

Abstract Background Oropharyngeal dysphagia (OD), a common symptom in the elderly, uses commercial thickener (CT) as part of its treatment. This is often accompanied of dislike and poor compliance. Aim Describe adherence to CT and possible differences according to dwelling location in an area of influence of approximately 400.0000 inhabitants. Methods Cohort prospective observational study. Randomized patients from Nutrition and Dietetic (NDU)-database (4 calls-interviews/year). Variables: Age, diagnostic, gender, dwelling/location: Home (H) / Nursing Home (NH), viscosity (nectar, honey, pudding), days with CT. Adherence measured with a questionnaire, considering implementation of treatment by combining CT use and consumption data, categorised in three groups good, moderate and poor. Change in patterns (improvement, maintenance, worsening) and non-adherence reasons. Results One hundred sixty-eight patients recruited with indicated viscosity: Nectar 39.7%, honey 29.3% and pudding 30.8%. Average age of 82.6 ± 11.1 years; 57.8% women (46.4% at H vs. 67% at NH, p

Abstract Patients with corticosteroid-refractory acute graft-versus-host disease (aGVHD) have a low one-year survival rate. Identification and validation of novel targetable kinases in patients who experience corticosteroid-refractory-aGVHD may help improve outcomes. Kinase-specific proteomics of leukocytes from patients with corticosteroid-refractory-GVHD identified rho kinase type 1 (ROCK1) as the most significantly upregulated kinase. ROCK1/2 inhibition improved survival and histological GVHD severity in mice and was synergistic with JAK1/2 inhibition, without compromising graft-versus-leukemia-effects. ROCK1/2-inhibition in macrophages or dendritic cells prior to transfer reduced GVHD severity. Mechanistically, ROCK1/2 inhibition or ROCK1 knockdown interfered with CD80, CD86, MHC-II expression and IL-6, IL-1β, iNOS and TNF production in myeloid cells. This was accompanied by impaired T cell activation by dendritic cells and inhibition of cytoskeletal rearrangements, thereby reducing macrophage and DC migration. NF-κB signaling was reduced in myeloid cells following ROCK1/2 inhibition. In conclusion, ROCK1/2 inhibition interferes with immune activation at multiple levels and reduces acute GVHD while maintaining GVL-effects, including in corticosteroid-refractory settings.

Following developments in destandardisation of linguistic norms in non-standard Arabic writing practices (Mejdell 2017), the present study aims to analyse formal intermediate registers emerging in Moroccan written productions. Using colloquial Arabic (ʿĀmmiyya) in writing is increasing, also in Morocco (Kebede & Hinds 2016; Caubet 2017a-b, 2018; Miller 2017), where Dāriǧa (Moroccan Arabic) combined with Fuṣḥā (Standard Arabic), both in oral and written interactions (Mixed Arabic) is also emerging in more or less formal productions. Recently, Moroccan publications, such as Elmedlaoui’s (2019) monograph al-ʿArabiyyatu ad-Dāriǧatu (a comprehensive description of Dāriǧa in Dāriǧa, and in Arabic script), corroborate the interest on “middle/educated” Arabic (intermediate registers of Moroccan Arabic, mixing Fuṣḥā and Dāriǧa in formal, but ordinary, interactions among educated speakers). Based on syntactic descriptions in Elmedlaoui (2019), the present study aims at analysing the stylistic variation of (middle/educated) Dāriǧa in a corpus of 346 articles and its corresponding 2176 comments of Goud (a Moroccan online newspaper expressing in Moroccan Arabic). Quantitative and qualitative approaches in analysing declarative sentences and genitive constructions, allow to observe contrasting trends. As opposed to the syntactic (and artificial) regularities described in al-ʿArabiyyatu ad-Dāriǧatu, Goud’s written production shows syntactic and stylistic heterogeneous features of middle/educated (written) Dāriǧa.

The cider-making industry in Asturias generates between 9000 and 12,000 tons of apple pomace per year. This by-product, the remains of the apple pressing, and made up of peel, flesh, seeds and stems, is a valuable material, containing substantial amounts of antioxidant compounds associated with healthy properties. Polyphenols such as dihydrochalcones and quercetin glycosides, and triterpenic acids, among which ursolic acid is a major compound, are the main antioxidant families described in apple pomace. The simultaneous recovery of those families has been accomplished by low frequency ultrasound-assisted extraction. Working extraction conditions were optimised by response surface methodology (RSM): time, 5.1 min; extractant composition, 68% ethanol in water; solid/liquid ratio, 1/75 and ultrasonic wave amplitude, 90%. This procedure was further applied to analyse those components in the whole apple pomace (WAP), apple peel (AP) and apple flesh (AF). On average, dry WAP contained almost 1300 µg/g of flavonols, 1200 µg/g of dihydrochalcones and 4200 µg/g of ursolic acid. These figures increased in the apple peel to, respectively 2500, 1400 and 8500 µg/g dry matter. Two linear multivariate regression models allowed the antioxidant activity of apple by-products to be predicted on the basis of their bioactive composition. The results derived from this study confirm the potential of industrial cider apple pomace as a source of high-value bioactive compounds, and the feasibility of the ultrasound-assisted extraction technique to recover those components in a simple and efficient way.

Background: Physiotherapy plays a key role in managing fibromyalgia, a multifaceted disorder, through a combination of active and passive treatments. The purpose of this review is to compare the efficacy of “hands-off” treatments alone versus the combination of “hands-off” and “hands-on” therapies. Methods: MEDLINE (PubMed), CENTRAL, and Embase were searched. English-language randomized controlled trials involving adults with fibromyalgia were included. The included studies were divided into subgroups to reduce the possible heterogeneity. We calculated the standardized mean difference or mean difference with 95% confidence intervals for the continuous data according to the outcome measures. We used the risk ratio for dichotomous data of the drop-out rate of the studies. Results: We included and analyzed seven RCTs. The meta-analysis showed no significant results in the outcomes, pain, QoL, health status, and drop-out rate. We found significant results (p < 0.001) in favor of combining “hands-off” and “hands-on” treatments for the rest quality (SMD 0.72, 95% CI 0.35 to 1.09). Conclusions: This review increases the treatment options available for clinicians. Up to now, the main guidelines on managing fibromyalgia suggest only approaches based on “hands-off” treatments. These findings suggest that other approaches based on mixed interventions combining “hands-off” and “hands-on” treatments did not reduce the patient outcomes. Moreover, the mixed intervention led to better results for the patients’ sleep quality than the “hands-off” treatments alone.

The loss of one of the two copies of the 9 bp tandem repeat sequence (CCCCCTCTA) located in the small non-coding region between the cytochrome oxidase II (COII) and the lysine tRNA genes in human mtDNA has been reported to be polymorphic in Asian, Oceanian and Sub-Saharan African populations, but it has rarely been observed in Europe. In this study, we will evaluate the possible association between the MIC9D polymorphism and cognitive disorders. A genetic analysis of unrelated Sicilian patients with cognitive deficits was performed to identify the 9 bp deletion MIC9D polymorphism. The MIC9D polymorphism was found in six patients, whereas this variant was absent in control individuals without cognitive deficits. The patients with the MIC9D polymorphism exhibited more complex clinical presentations; in particular, all had neuromuscular disorders and five also presented with behavioral disorders. The present study suggests a potential association between the MIC9D polymorphism and cognitive impairment with concurrent neuromuscular and behavioral involvement.

Glycine, the simple amino acid, is a key component of muscle metabolism with proven cytoprotective effects and hypothetical benefits as a therapeutic nutrient. Cell, in vitro, and animal studies suggest that glycine enhances protection against muscle wasting by activating anabolic pathways and inhibiting proteolytic gene expression. Some evidence indicates that glycine supplementation may enhance peak power output, reduce lactic acid accumulation during high-intensity exercise, and improve sleep quality and recovery. This literature review critically explores glycine’s potential as an ergogenic aid and its relevance to muscle regeneration, muscle strength, endurance exercise performance, and sleep quality. It also underscores key areas for future research. It is concluded that more randomized controlled clinical trials in humans are needed to confirm glycine’s potential as a dietary supplement to support muscle function, recovery, and overall athletic performance as an ergogenic aid and to establish nutritional recommendations for athletic performance. Also, it is essential to consider that high doses (>500 mg/kg of body mass) could induce cytotoxic effects and contribute to acute glutamate toxicity.

Microplastics contamination is growing globally, being a risk for different environmental compartments including animals and humans. At present, some Spanish beaches and coasts have been affected by discharges of these pollutants, which have caused a serious environmental problem. Therefore, efficient strategies to remove microplastics (MPs) from environmental samples are needed. In this study, the application of three magnetic materials, namely iron oxide (Fe3O4) and the composites Fe3O4@Ag and Fe3O4@Ag@L-Cysteine, to remove MPs, specifically polystyrene (PS), from water samples has been assessed. The magnetic nanoparticles were synthesized and characterized by field effect scanning electron microscopy with energy dispersive X-ray spectroscopy detection (FESEM-EDX). Experimental conditions such as temperature, time, and pH during the removal process were assessed for the different adsorbent materials. The removal rate was calculated by filtering the treated water samples and counting the remaining MPs in the water using ImageJ software. The strongest removal efficiency (100%) was shown using Fe3O4@Ag@L-Cysteine for PS at 50 mg L−1 within 15 min of the separation process at room temperature and a neutral pH. A thermodynamic study demonstrated that the developed MPs elimination strategy was a spontaneous and physisorption process. Coated Fe3O4 magnetic nanoparticles were demonstrated to be an efficient adsorbent for MP removal in aquatic environments and their use a promising technique for the control of MPs contamination.

Glucosidases are important enzyme largely used in food industry; for this reason, different research studies have been aimed at investigating new producing microorganisms and cheap growth medium that can help to minimize their production costs and time. Food by-products and wastes are considered low-cost substrates that can play an important role from the perspective of a circular economy concept. Brewer’s spent grain (BSG) is the most abundant by-product of beer production that, thanks to its chemical and nutritional composition, has recently been re-evaluated for its application in various sectors. The aim of the present study was to induce the production of β-glucosidase in Wickerhamomyces anomalus BS91 using BSG as the main component. The results obtained during our research show that BSG is an attractive by-product of beer industry that can be used for the production of glucosidase. Enzyme activity obtained using this microorganism was equal to 369.7 ± 8.0 U/mL, six time greater than that observed in conventional nutritional medium (59.0 ± 5.7 U/mL). Also, we conducted additional research concerning β-glucosidase localization, and the obtained results show that the enzyme is tightly bound to the yeast cell wall, and this can probably greatly affect its stability since it is being protected by the cell wall itself.

INTRODUCCIÓN. La educación artística influye beneficiosamente en el desarrollo integral del ser humano. Sin embargo, existe una carencia por lo que respecta a su investigación, como también lo es respecto al conocimiento de estas ventajas. Por ese motivo, es de especial relevancia examinar la actitud de los futuros maestros sobre el arte, o de forma más concreta, en cuanto a su didáctica. No obstante, hasta el momento no se han encontrado escalas que evalúen, desde una metodología cuantitativa, las actitudes con respecto a la Didáctica de la Expresión Plástica. Por ese motivo, este trabajo tuvo como objetivo diseñar y validar la Escala breve de Actitudes sobre la Didáctica de la Expresión Plástica (EADEP) y observar la invarianza entre sexos. MÉTODO. Para ello, se partió de una muestra de 190 futuros docentes (Medad = 20.05; DT = 3.67) para un primer estudio y 790 (Medad = 19.88; DT= 4.03) para un segundo. RESULTADOS. El primero de ellos arrojó un factor para la EADEP con adecuadas propiedades psicométricas. El segundo de ellos indicó un buen ajuste de los datos para la estructura unidimensional de la EADEP, manteniéndose invariante en función del sexo. CONCLUSIÓN. Se ofrece, por tanto, un instrumento de medida válido y fiable para la actitud hacia la Didáctica de la Expresión Plástica y se reflexiona sobre la necesidad de aumentar los estudios en este campo.

El artículo busca estimar la participación y el tiempo dedicados por las personas de 12 años y más de nuestro país al trabajo no remunerado de los hogares, para el Estado de México, y localidades rurales. Ello con el fin de aproximarnos al conocimiento de la organización familiar de personas en territorios rurales que permitan detectar necesidades y recursos disponibles para satisfacerlas, poniendo además en relieve las desigualdades de género en el desempeño de las actividades cotidianas. Utilizamos la Encuesta Intercensal 2015 y la Encuesta Nacional sobre Uso del Tiempo 2019, fuentes de datos que cuentan con esta información de participación y tiempo dedicados a actividades para el mercado y para el hogar, remunerados y no remunerados, enfocando la atención en territorios rurales y en la entidad mexiquense. Los resultados permiten reflexionar sobre la desigual distribución del trabajo no remunerado de los hogares, haciendo especial énfasis en el trabajo de cuidado, por edad y género.

IntroductionSerine proteases play a critical role during SARS-CoV-2 infection. Therefore, polymorphisms of transmembrane protease serine 2 (TMPRSS2) and serpine family E member 1 (SERPINE1) could help to elucidate the contribution of variability to COVID-19 outcomes.MethodsTo evaluate the genetic variants of the genes previously associated with COVID-19 outcomes, we performed a cross-sectional study in which 1536 SARS-CoV-2-positive participants were enrolled. TMPRSS2 (rs2070788, rs75603675, rs12329760) and SERPINE1 (rs2227631, rs2227667, rs2070682, rs2227692) were genotyped using the Open Array Platform. The association of polymorphisms with disease outcomes was determined by logistic regression analysis adjusted for covariates (age, sex, hypertension, type 2 diabetes, and obesity).ResultsAccording to our codominant model, the GA genotype of rs2227667 (OR=0.55; 95% CI = 0.36-0.84; p=0.006) and the AG genotype of rs2227667 (OR=0.59; 95% CI = 0.38-0.91; p=0.02) of SERPINE1 played a protective role against disease. However, the rs2227692 T allele and TT genotype SERPINE1 (OR=1.45; 95% CI = 1.11-1.91; p=0.006; OR=2.08; 95% CI = 1.22-3.57; p=0.007; respectively) were associated with a decreased risk of death. Similarly, the rs75603675 AA genotype TMPRSS2 had an OR of 1.97 (95% CI = 1.07-3.6; p=0.03) for deceased patients. Finally, the rs2227692 T allele SERPINE1 was associated with increased D-dimer levels (OR=1.24; 95% CI = 1.03-1.48; p=0.02).DiscussionOur data suggest that the rs75603675 TMPRSS2 and rs2227692 SERPINE1 polymorphisms are associated with a poor outcome. Additionally, rs2227692 SERPINE1 could participate in hypercoagulable conditions in critical COVID-19 patients, and this genetic variant could contribute to the identification of new pharmacological targets and treatment strategies to block the inhibition of TMPRSS2 entry into SARS-CoV-2.

IntroductionThe situation generated by the recent pandemic has had several effects on education, one of them being the necessary but hasty efforts of teachers and students to adapt to the demands of a virtual classroom environment. Thus, it is essential to promote the development of digital competencies in future teachers, enabling them to create effective learning situations in the digital medium. Moreover, the European university curriculum includes a set of specific competencies (specific to each degree) and a series of generic competencies, many of which are related to emotional intelligence. Our work emerges from these specific premises and the more general need to develop emotional skills and learning abilities in virtual environments for future educators.MethodsThe sample comprised 240 students in higher education, pursuing a bachelor’s degree in education at the University of Alicante, Spain (68.3% were female and average age of the participants was 19.43 years SD = 4.127). Using a quasi-experimental design with pretests, posttests, and a control group, we present the effects of an online program aimed at improving the emotional skills and academic achievement of future teachers in higher education. In this study, a 30-h emotional intelligence training program was implemented. Since the student sample was grouped into different classes, we analyzed, using a generalized linear mixed-effects model, whether students who took the program showed a significant improvement in their academic achievement at the end of their studies, compared to those who did not take it.ResultsThe findings show a significant improvement in the academic achievement at the end of the bachelor’s degree studies of the students in the experimental group.DiscussionThese results open up a field of possibilities for the implementation of this type of training using virtual environments, enabling interventions to enhance the emotional development of the teaching staff (and, subsequently, in their students), develop their teaching careers adequately, and employ the ideal strategies to address educational programs. Looking ahead, the integration of emotional development programs that incorporate emerging technology into university curricula could enhance the preparation of educators profoundly and create adaptable learning environments for contemporary students.

Objetivo: conocer dentro del proyecto May Measurement Month (MMM), la situación de la presión arterial (PA) en la población española, difundir la importancia de su medida periódica y estimar la prevalencia de hipertensión enmascarada (HEN). Métodos: estudio descriptivo transversal en farmacias comunitarias españolas durante mayo de 2019. Sujetos: usuarios adultos que consentían participar. Variables: presión arterial sistólica (PAS), presión arterial diastólica (PAD) en milímetros de mercurio (mmHg), frecuencia cardíaca (FC) en latidos/minuto (lat/min). A los participantes con PA ≥130/85 y

O artigo apresenta uma discussão teórica sobre as situações vivenciadas por estudantes imigrantes da Venezuela e do Haiti em uma escola pública de Manaus (Brasil). O objetivo geral foi debater sobre as potencialidades e dificuldades enfrentadas por eles no cotidiano escolar. Para a análise dessa problemática, formulamos as seguintes questões: a) Como se deu a inclusão desses estudantes imigrantes em uma realidade completamente diferente da sua? b) Como superar alguns desafios, tais como as dificuldades linguísticas, o isolamento e o bullying ? c) Como a equipe pedagógica atuou para minimizar os problemas de adaptação desses alunos? Para investigar, nós utilizamos elementos qualitativos e descritivos e, como procedimento, optamos por uma revisão bibliográfica sobre interculturalidade e sobre os direitos dos imigrantes à educação no Brasil. Além disso, refletimos sobre as experiências vividas e registradas através da observação na referida escola pública. Concluiu-se que, apesar de obstáculos como a dificuldade no uso da língua portuguesa, a diferença de costumes e a ausência de uma política de serviços específica, os imigrantes venezuelanos e haitianos se integram e participam da vida escolar, ainda que de modo parcial.

Abstract Background Dementia affects ability to remember, think, or make decisions that interfere with doing everyday activities. There is no cure, therefore any prevention or delay of the onset is of importance. This study aims to investigate the association between zoster and influenza vaccinations and the risk of developing dementia. Methods We conducted a retrospective population-based cohort study using electronic health records from 1469 general practices contributing to the Clinical Practice Research Datalink (CPRD) Aurum database with linked hospital episode statistics (HES) and Office for National Statistics (ONS) mortality records. We built two 'matched cohorts': zoster vaccine (854,745 exposed individuals) matched with 8.8 million comparators without a history of zoster vaccination, and influenza vaccine (742,487 exposed individuals) matched with 7.12 million comparators without a history of vaccination as another comparator group. The cohorts were then followed to assess the association of exposure (vaccine) with outcome (dementia diagnosis). Results Zoster vaccination was associated with a lower risk of dementia diagnosis (adjusted hazard ratio (HR) 0.78 with 95% CI: 0.77–0.79), Alzheimer’s diagnosis (adjusted HR 0.91 with 95% CI: 0.89–0.92 and other types of dementia (adjusted HR 0.71 with 95% CI: 0.69–0.72). Influenza vaccination also was associated with a slightly reduced hazard of dementia risk (adjusted HR 0.96 with 95% CI: 0.94–0.97). Conclusion Both zoster vaccine for prevention of shingles / herpes zoster and influenza vaccine to prevent influenza were associated with diminished risk of dementia, with the zoster association appearing more pronounced.

Background/purpose(s): During a viral infection, the immune response is mediated by the toll-like receptors and myeloid differentiation Factor 88 (MyD88) that play an important role sensing infections such as SARS-CoV-2 which has claimed the lives of more than 6.8 million people around the world. Methods: We carried out a cross-sectional with a population of 618 SARS-CoV-2-positive unvaccinated subjects and further classified based on severity: 22% were mild, 34% were severe, 26% were critical, and 18% were deceased. Toll Like Receptor 7 (TLR7) single-nucleotide polymorphisms (rs3853839, rs179008, rs179009, and rs2302267) and MyD88 (rs7744) were genotyped using TaqMan OpenArray. The association of polymorphisms with disease outcomes was performed by logistic regression analysis adjusted by covariates. Results: A significant association of rs3853839 and rs7744 of the TLR7 and MyD88 genes, respectively, was found with COVID-19 severity. The G/G genotype of the rs3853839 TLR7 was associated with the critical outcome showing an Odd Ratio = 1.98 (95% IC = 1.04–3.77). The results highlighted an association of the G allele of MyD88 gene with severe, critical and deceased outcomes. Furthermore, in the dominant model (AG + GG vs. AA), we observed an Odd Ratio = 1.70 (95% CI = 1.02–2.86) with severe, Odd Ratio = 1.82 (95% CI = 1.04–3.21) with critical, and Odd Ratio = 2.44 (95% CI = 1.21–4.9) with deceased outcomes. Conclusion: To our knowledge this work represents an innovative report that highlights the significant association of TLR7 and MyD88 gene polymorphisms with COVID-19 outcomes and the possible implication of the MyD88 variant with D-dimer and IFN-α concentrations.

Terpenoids are a large class of natural secondary plant metabolites which are highly diverse in structure, formed from isoprene units (C-5), associated with a wide range of biological properties, including antioxidant, antimicrobial, anti-inflammatory, antiallergic, anticancer, antimetastatic, antiangiogenesis, and apoptosis induction, and are considered for potential application in the food, cosmetics, pharmaceutical, and medical industries. In plants, terpenoids exert a variety of basic functions in growth and development. This review gives an overview, highlighting the current knowledge of terpenoids and recent advances in our understanding of the organization, regulation, and diversification of core and specialized terpenoid metabolic pathways and addressing the most important functions of volatile and non-volatile specialized terpenoid metabolites in plants. A comprehensive description of different aspects of plant-derived terpenoids as a sustainable source of bioactive compounds, their biosynthetic pathway, the several biological properties attributed to these secondary metabolites associated with health-promoting effects, and their potential industrial applications in several fields will be provided, and emerging and green extraction methods will also be discussed. In addition, future research perspectives within this framework will be highlighted. Literature selection was carried out using the National Library of Medicine, PubMed, and international reference data for the period from 2010 to 2024 using the keyword “terpenoids”. A total of 177,633 published papers were found, of which 196 original and review papers were included in this review according to the criteria of their scientific reliability, their completeness, and their relevance to the theme considered.