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Abstract Accurate detection of post-refractive ectasia susceptibility is essential during preoperative evaluation for laser vision correction (LVC) due to the risk of progressive corneal ectasia and vision decline post-surgery. Despite improved screening and a reduced incidence from 0.66 to 0.033%, iatrogenic ectasia remains a concern due to the severe vision loss it can cause, highlighting the need for more accurate detection tools. A new optimized version of the Belin/Ambrósio Enhanced Ectasia Display version 4 (BAD-D v4) was developed and validated across 26 international centers to enhance the detection of keratoconus and very asymmetric ectasia and to assess the risk of post-refractive ectasia. Analyzing a dataset of 3,886 eyes from 3,351 patients, including normal, keratoconus (KC), and cases with very asymmetric ectasia (VAE) categories, having one eye with normal topography (VAE-NT and the fellow eye with clinical ectasia (VAE-E). The study utilized an optimized logistic regression algorithm improving diagnostic accuracy. The BAD-D v4 showed superior efficacy in differentiating normal eyes from ectatic conditions, with Area Under the Receiver Operating Characteristic Curve (AUROC) scores of 0.997 and 0.998 in training and testing samples for normal versus clinical ectasia. Additionally, in Normal vs. Disease (KC + VAE), the AUROC was 0.974 and 0.966, and in the challenging Normal vs. VAE-NT diverse group, it scored 0.905 and 0.858. These results outperformed the current version (BAD-D v3) and were comparable to the Pentacam Random Forest Index in all tested scenarios, highlighting the potential of BAD-D v4 in early ectasia detection, without altering the index scale or the end-user experience.

Abstract Background Mobile phones are essential tools worldwide, including for the academic training of medical students. However, their role in Latin America (LATAM) remains underexplored. This study aimed to evaluate cell phone use and its applicability in the academic training of medical students in LATAM. Methods A cross-sectional online survey was conducted among undergraduate medical students from seven Latin American countries between December 2023 and February 2024. The study assessed academic smartphone use across five types of applications: medical apps, knowledge updating apps, academic podcast apps, video streaming apps, and social media apps. Results A total of 1,590 medical students participated, with 63.6% being women, 21.2% third-year students, and 55.0% from private universities. Nearly all participants (98.4%) owned a mobile phone, and 88.2% used them for academic purposes. The most common academic use was for viewing academic content videos (82.9%). A significant association was found between academic cell phone use and progression through medical studies, with fifth-year students being the most likely to use their phones for academic purposes (OR = 4.517, 95% CI = 1.843–11.075). Students in the clinical stage of education were also more likely to rely on smart phones for academic purposes (OR = 2.090, 95% CI = 1.500–2.911). Conversely, public university students were less likely to use their phones for academic purposes compared to private university students (OR = 0.714, 95% CI = 0.522–0.977). Additionally, students who perceived that their academic preparation would be more difficult without a cell phone were more likely to use it for academic purposes (OR = 2.157, 95% CI = 1.463–3.181). Conclusions These results suggest the importance of incorporating smartphones into the educational frameworks of medical schools and universities in Latin America, with a particular emphasis on academic video content applications, which already capture the attention and preference of medical students.

Abstract This study aims to develop a Machine Learning model to assess the risks faced by COVID-19 patients in a hospital setting, focusing specifically on predicting the complications leading to Intensive Care Unit (ICU) admission or mortality, which are minority classes compared to the majority class of discharged patients. We operate within a multiclass framework comprising three distinct classes, and address the challenge of dataset imbalance, a common source of model bias. To effectively manage this, we introduce the Multi-Thresholding meta-algorithm (MTh), an innovative output-level methodology that extends traditional thresholding from binary to multiclass classification. This methodology dynamically adjusts class probabilities using misclassification costs, making it highly effective in imbalanced datasets. Our approach is further enhanced by integrating the simplicity, transparency, and effectiveness of Bayesian networks to create a robust predictive model. Using patient admission data, the model accurately identifies key risk and protective factors for COVID-19 outcomes. Our findings indicate that certain patient characteristics, such as high Charlson Index and pre-existing conditions, significantly influence the risk of ICU admission and mortality. Moreover, we introduce an explanatory model that elucidates the interrelationships among these factors, demonstrating the influence of therapeutic limits on the overall risk assessment of COVID-19 patients. Overall, our research provides a significant contribution to the field of Machine Learning by offering a novel solution for multiclass classification in the context of imbalanced datasets. This model not only enhances predictive accuracy but also supports critical decision-making processes in healthcare, potentially improving patient outcomes and optimizing clinical resource allocation.

Abstract The immune cellular landscape from the gastric mucosa remains largely unknown despite its relevance in several inflammatory conditions. Human gastric biopsies were obtained from the antrum, body and incisura from 10 individuals to obtain lamina propria mononuclear cells that were further characterized by spectral cytometry. Phenotypic hierarchical analyses identified a total of 52 different immune cell subsets within the human gastric mucosa revealing that T-cells (> 60%) and NK cells (> 20%) were the main populations. Within T-cells, CD4+ and CD8+ were equally represented with both subsets displaying mainly a memory and effector phenotype. NK cells, on the contrary, were largely of the early phenotype. No regional differences were observed for any subsets among the 3 locations. Following unsupervised analysis, a total of 82 clusters were found. Again, no differences were observed amongst locations although a great degree of inter-individual variability was found, largely influenced by the presence of H. pylori infection and dyspepsia. We have unraveled the human gastric immune cellular subset composition and a unique interindividual immune fingerprint with no inter-regional variations.

Abstract Diabetic nephropathy is one of the most frequent complications of diabetic patients and is the leading cause of end-stage renal disease worldwide. The complex physiopathology of this complication raises a challenge in the development of effective medical treatments. Therefore, a better understanding of this disease is necessary for producing more targeted therapies. In this work we propose human amylin as a possible mediator in the development of diabetic nephropathy. Islet amyloid polypeptide or amylin is a hormone co-secreted with insulin. The human isoform has the ability to fold and form amyloid aggregates in the pancreas of patients with type 2 diabetes mellitus, disrupting cellular homeostasis due to its ability to form pores in lipid bilayers. It has been described that hIAPP can be secreted and exported in extracellular vesicles outside the pancreas, being a plausible connecting mechanism between the β-cell and other peripheral tissues such as the kidney. Here, we demonstrate that tubular, podocytes and mesangial cells can incorporate hIAPP coming from β-cells. Then, this hIAPP can form aggregates inside these kidney cells, contributing to its failure. In order to study the consequences in vivo, we found amylin aggregates in the kidney of mice overexpressing hIAPP after feeding a high fat diet. In addition, we observed an increase in glomerulosclerosis index and inflammation. Specifically, there were significant changes in signalling pathways directly involved in the diabetic nephropathy such as an increased in mTORC1 signaling pathway, an alteration in mitochondrial dynamics and an increased in endoplasmic reticulum stress. All these results demonstrate the importance of hIAPP in the kidney and its possible contribution in the development of diabetic nephropathy.

Abstract Extractive fisheries and marine aquaculture share space and target species. Several regional-scale examples exist of escapees entering wild fisheries landings, yet no study has assessed the influence of aquaculture on landings at an ecosystem scale. We examined the effects of farmed fish escapes on fisheries using FAO data and published escape rates for Gilthead seabream (Sparus aurata) and European seabass (Dicentrarchus labrax). Seabream landings were significantly correlated with the estimated biomass of escaped seabream entering the wild. There was a similar pattern for seabass until 2005, but the overall relationship between landings and escapes was not significant due to the dramatic drop in catches in recent years. We argue that seabass escapees’ relatively high mortality, lower capturability, and minor ‘leaking’ from farms may obscure their influence on landings. Significant positive fisheries regime shifts were detected for both species, matching the onset of aquaculture in the Mediterranean and the period when escapees from aquaculture surpassed landings. Our results suggest that fish escapes of these two iconic species may mask wild stock overexploitation, confound stock assessments, alter genetic diversity, increase the risk of spreading pathogens and parasites, and compete with wild conspecifics while boosting fisheries landings.

Abstract The evolution of the COVID-19 pandemic has been associated with variations in clinical presentation and severity. Similarly, prediction scores may suffer changes in their diagnostic accuracy. The aim of this study was to test the 30-day mortality predictive validity of the 4C and SEIMC scores during the sixth wave of the pandemic and to compare them with those of validation studies. This was a longitudinal retrospective observational study. COVID-19 patients who were admitted to the Emergency Department of a Spanish hospital from December 15, 2021, to January 31, 2022, were selected. A side-by-side comparison with the pivotal validation studies was subsequently performed. The main measures were 30-day mortality and the 4C and SEIMC scores. A total of 27,614 patients were considered in the study, including 22,361 from the 4C, 4,627 from the SEIMC and 626 from our hospital. The 30-day mortality rate was significantly lower than that reported in the validation studies. The AUCs were 0.931 (95% CI: 0.90–0.95) for 4C and 0.903 (95% CI: 086–0.93) for SEIMC, which were significantly greater than those obtained in the first wave. Despite the changes that have occurred during the coronavirus disease 2019 (COVID-19) pandemic, with a reduction in lethality, scorecard systems are currently still useful tools for detecting patients with poor disease risk, with better prognostic capacity.

Abstract Aberrant caspase recruitment domain family member 14 (CARD14) signaling has been strongly associated with inflammatory skin conditions. CARD14 acts as a scaffold protein, ultimately activating the transcription factor NF-KB. Although primarily studied in the context of inflammation, recent research has suggested its potential implications in tumorigenesis. In this study, we gathered The Cancer Genome Atlas (TCGA) tumor data to gauge the involvement of CARD14 in cancer, including genetic alterations, expression patterns, survival correlations, immune cell infiltration and functional interactions across diverse cancer types. We found heightened CARD14 expression in most tumors and there was a significant correlation between CARD14 expression and the prognosis of patients for certain tumors. For instance, patients with higher CARD14 expression had a better prognosis in sarcoma, lung, cervix and head and neck cancers. Moreover, CARD14 expression positively correlated with neutrophil infiltration in most of the cancer types analyzed. Finally, enrichment analysis showed that epithelial development and differentiation pathways were involved in the functional mechanism of CARD14. Our results show that CARD14 may have the potential to become a prognostic biomarker in several cancers, hence, further prospective studies will be required for its validation.

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BackgroundThe current standard of interpretation provision is not efficacious or not acceptable to Deaf patients who communicate using sign language. In-person or video relay interpretation (VRI) sign language interpretation is largely unavailable. There are no clear data on the availability of VRI or in-person interpretation. Given the limited number of available sign language interpreters and the cost, VRI may be more available than in-person. Existing evidence tends to focus on assessing personal preferences of Deaf users regarding interpretation and interpreters’ preferences. Although respecting preferences is essential, there is a vacuum of knowledge on how the format of access to interpretation impacts the quality of communication between Deaf persons and health personnel. ObjectiveThis study aims to look at the effectiveness of the VRI system in improving communication outcomes between Deaf patients and doctors versus the available standard of care of the usual communication tools, including informal interpretation, lip- or note-reading, and using their mobile phones to contact a formal or informal interpreter, for Deaf patients aged 18 years and older in Bogota, Colombia. MethodsThis is a randomized controlled trial with a total sample size of 216 participants, divided into 2 groups: an intervention group, which receives a medical appointment using VRI, and a control group, which receives a medical appointment using standard communication. Both the Deaf participants and the health care professionals will be blinded to the allocation, as they will not know whether the appointment will involve VRI or standard communication until they arrive at the office. The primary outcome measure will be an assessment of communication using a Doctor-Patient Communication Scale. This scale was translated into Colombian Sign Language following a rigorous cultural adaptation and translation procedure. Furthermore, the database contains key clinical variables and recommendations provided by the doctor during a general medicine appointment. We will compute associations. ResultsRecruitment opened on August 24, 2023. As of July 2024, 180 participants had been enrolled. The intervention and data collection were finalized in October 2024. The findings of this study are expected to be submitted for publication in early 2025. ConclusionsThis study will provide rigorous evidence regarding information and communications technology intervention in health care, addressing empirical challenges in using inclusive research designs in public health. In addition, effective VRI models that address the challenges faced by Deaf people will be tested, implemented, and maintained in low- and middle-income countries. A disability-inclusive evaluative tool for quality communication mediated by VRI in health care is also tested. Ultimately, this will lead to evidence-based recommendations for implementing the Convention on the Rights of Persons with Disabilities (CRPD) in mobile health contexts. Trial RegistrationClinicalTrials.gov NCT05966623; https://clinicaltrials.gov/study/NCT05966623 International Registered Report Identifier (IRRID)DERR1-10.2196/64590

Summary: Background: Currently, there is no licensed treatment for chronic norovirus infections, but the use of intra-duodenally-delivered immunoglobulins is promising; nevertheless, varying results have limited their wide use. Little is known about the relationship between norovirus genetic diversity and treatment efficacy. Methods: We analyzed the norovirus within-host diversity and evolution in a cohort of 20 immunocompromised individuals using next-generation sequencing (NGS) and clone-based sequencing of the capsid (VP1) gene. Representative VP1s were expressed and their glycan receptor binding affinity and antigenicity were evaluated. Findings: The P2 domain, within the VP1, accumulated up to 30-fold more non-synonymous mutations than other genomic regions. Intra-host virus populations in these patients tended to evolve into divergent lineages that were often antigenically distinct. Several of these viruses were widely resistant to binding-blocking antibodies in immunoglobulin preparations. Notably, for one patient, a single amino-acid substitution in the P2 domain resulted in an immune-escape phenotype, and it was likely the main contributor to treatment failure. Furthermore, we found evidence for transmission of late-stage viruses between two immunocompromised individuals. Interpretation: The findings demonstrated that within-host noroviruses in chronic infections tend to evolve into antigenically distinct subpopulations. This antigenic evolution was likely caused by the remaining low immunity levels exerted by immunocompromised individuals, possibly undermining antiviral treatment. Our observations provide insights into norovirus (within-host) evolution and treatment. Funding: Erasmus MC grant mRACE, the European Union's Horizon 2020 research and innovation program under grant agreement No. 874735 (VEO), and the NWO STEVIN award (Koopmans).

We analyzed here how formin-like 1 β (FMNL1β), an actin cytoskeleton-regulatory protein, regulates microtubule-organizing center (MTOC) and multivesicular bodies (MVB) polarization and exosome secretion at an immune synapse (IS) model in a phosphorylation-dependent manner. IS formation was associated with transient recruitment of FMNL1β to the IS, which was independent of protein kinase C δ (PKCδ). Simultaneous RNA interference of all FMNL1 isoforms prevented MTOC/MVB polarization and exosome secretion, which were restored by FMNL1βWT expression. However, expression of the non-phosphorylatable mutant FMNL1βS1086A did not restore neither MTOC/MVB polarization nor exosome secretion to control levels, supporting the crucial role of S1086 phosphorylation in MTOC/MVB polarization and exosome secretion. In contrast, the phosphomimetic mutant, FMNL1βS1086D, restored MTOC/MVB polarization and exosome secretion. Conversely, FMNL1βS1086D mutant did not recover the deficient MTOC/MVB polarization occurring in PKCδ-interfered clones, indicating that S1086 FMNL1β phosphorylation alone is not sufficient for MTOC/MVB polarization and exosome secretion. FMNL1 interference inhibited the depletion of F-actin at the central region of the immune synapse (cIS), which is necessary for MTOC/MVB polarization. FMNL1βWT and FMNL1βS1086D, but not FMNL1βS1086A expression, restored F-actin depletion at the cIS. Thus, actin cytoskeleton reorganization at the IS underlies the effects of all these FMNL1β variants on polarized secretory traffic. FMNL1 was found in the IS made by primary T lymphocytes, both in T cell receptor (TCR) and chimeric antigen receptor (CAR)-evoked synapses. Taken together, these results point out a crucial role of S1086 phosphorylation in FMNL1β activation, leading to cortical actin reorganization and subsequent control of MTOC/MVB polarization and exosome secretion.

Objective To evaluate the impact of coadministering statins with direct oral anticoagulants (DOACs) on the risk of major bleeding events in patients with venous thromboembolism (VTE).Design Observational cohort analysis based on a multicentre international registry.Setting Data were extracted from the Registro Informatizado de Enfermedad TromboEmbolica Registry, which involves 205 centres across 27 countries.Participants A total of 73 659 patients diagnosed with VTE were classified based on their anticoagulant therapy (DOACs) versus low-molecular-weight heparin (LMWH) or vitamin K antagonists (VKAs) and concurrent use of statins.Methods Multivariable Cox proportional hazards models adjusted for confounding variables to assess the risk of major bleeding events stratified by the type of anticoagulant use and statin use.Results From October 2013 to February 2023, 73 659 patients were recruited: 2573 were statin users on DOACs, 14 090 were statin users on LMWH or VKA therapy, 10 088 were non-statin users on DOACs and 46 908 were non-statin users on LMWH or VKA therapy. Statin users were 10 years older and more likely to have hypertension, diabetes, renal failure or prior artery disease. During anticoagulation (median, 187 days), 1917 patients (2.6%) suffered major bleeding. Rates of major bleeding per 100 patient-years were 2.33 (95% CI 1.72 to 3.09), 3.75 (95% CI 3.43 to 4.10), 1.39 (95% CI 1.13 to 1.69) and 3.10 (95% CI 2.93 to 3.27), respectively. On multivariable analysis, patients treated with DOACs had a significantly lower risk of major bleeding compared with those on LMWH or VKA therapy (adjusted HR 0.59; 95% CI 0.48 to 0.74). The adjusted HR in statin users versus non-users was 1.03 (95% CI 0.92 to 1.14), while in statin users on DOACs versus the rest of patients, it was 1.18 (95% CI 0.79 to 1.76).Conclusions In patients with VTE receiving statins, long-term anticoagulation with DOACs was associated with a reduced risk of major bleeding, regardless of the statin use. These findings support the safety profile of DOACs over VKAs or LMWH in the management of VTE in patients requiring statins.

BackgroundChronic neck pain (CNP) needs attention to its physical, cognitive, and social dimensions. ObjectiveWe aimed to design a health education program (HEP) with a biopsychosocial approach for patients with CNP. MethodsA literature search on CNP, health education, and biopsychosocial models was carried out. Seven physiotherapists with expertise in HEPs and chronic pain participated in three teams that evaluated the literature and prepared a synthesis document in relation to the three target topics. Experts compiled the information obtained and prepared a proposal for an HEP with a biopsychosocial approach aimed at patients with CNP. This proposal was tested in the physiotherapy units of primary care health centers belonging to the East Assistance Directorate of Madrid, and suggestions were included in the final program. ResultsThe HEP for CNP with a biopsychosocial approach consists of 5 educational sessions lasting between 90 and 120 minutes, carried out every other day. Cognitive, emotional, and physical dimensions were addressed in all sessions, with particular attention to the psychosocial factors associated with people who have CNP. ConclusionsThe proposed HEP with a biopsychosocial approach emphasizes emotional management, especially stress, without neglecting the importance of physical and recreational exercises for the individual’s return to social activities. The objective of this program was to achieve a clinically relevant reduction in perceived pain intensity and functional disability as well as an improvement in quality of life in the short and medium term. Trial RegistrationClinicalTrials.gov NCT02703506; https://clinicaltrials.gov/study/NCT02703506 International Registered Report Identifier (IRRID)DERR1-10.2196/56632

In 2021, we identified a cluster of Elizabethkingia miricola cases in an intensive care unit in Spain. Because E. miricola is not considered a special surveillance agent in Spain, whole-genome sequencing was not performed. The bacterial source was not identified. All Elizabethkingia species should be listed as special surveillance bacteria.

Abstract Background The emergence of new SARS-CoV-2 variants and the waning of immunity raise concerns about vaccine effectiveness and protection against COVID-19. While antibody response has been shown to correlate with the risk of infection with the original variant and earlier variants of concern, the effectiveness of antibody-mediated protection against Omicron and the factors associated with protection remain uncertain. Methods We evaluated antibody responses to SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from Wuhan and variants of concern by Luminex and their role in preventing breakthrough infections 1 year after a third dose of mRNA vaccination, in a cohort of health care workers followed since the pandemic onset in Spain (N = 393). Data were analyzed in relation to COVID-19 history, demographic factors, comorbidities, vaccine doses, brand, and adverse events. Results Higher levels of anti-S IgG and IgA to Wuhan, Delta, and Omicron were associated with protection against vaccine breakthroughs (IgG against Omicron S antigen HR, 0.06, 95%CI, 0.26–0.01). Previous SARS-CoV-2 infection was positively associated with antibody levels and protection against breakthroughs, and a longer time since last infection was associated with lower protection. In addition, priming with BNT162b2 followed by mRNA-1273 booster was associated with higher antibody responses than homologous mRNA-1273 vaccination. Conclusions Data show that IgG and IgA induced by vaccines against the original strain or by hybrid immunization are valid correlates of protection against Omicron BA.1 despite immune escape and support the benefits of heterologous vaccination regimens to enhance antibodies and the prioritization of booster vaccination in individuals without recent infections.

Abstract Throughout pregnancy, the decidua is predominantly populated by NK lymphocytes expressing Killer immunoglobulin-like receptors (KIR) that recognize human leukocyte antigen-C (HLA-C) ligands from trophoblast cells. This study aims to investigate the association of KIR-HLA-C phenotypes in couples facing infertility, particularly recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF), in comparison to a reference population and fertile controls. This observational, non-interventional retrospective case–control study included patients consecutively referred to our Reproductive Immunology Unit from 2015 to 2019. We analyzed the frequencies of KIR and HLA-C genes. As control groups, we analyzed a reference Spanish population for KIR analysis and 29 fertile controls and their male partners for KIR and HLA-C combinations. We studied 397 consecutively referred women with infertility and their male partners. Among women with unexplained RPL (133 women) and RIF (176 women), the centromeric (cen)AA KIR genotype was significantly more prevalent compared to the reference Spanish population (p = 0.001 and 0.02, respectively). Furthermore, cenAA was associated with a 1.51-fold risk of RPL and a 1.2-fold risk of RIF. Conversely, the presence of BB KIR showed a lower risk of reproductive failure compared to non-BB KIR (OR: 0.12, p

Abstract Background Hereditary fructose intolerance (HFI) is a rare metabolic disease caused by aldolase B deficiency. The aim of our study was to analyse excipient tolerability in patients with HFI and other related diseases and to design mobile and website health applications to facilitate the search for drugs according to their tolerance. Results A total of 555 excipients listed in the Spanish Medicines Agency database (July 2023) were classified as suitable for HFI patients, suitable with considerations ((glucose and glucose syrup, intravenous sucrose, oral mannitol, polydextrose, gums and carrageenans, ethanol, sulfite caramel and vanilla), not recommended (intravenous mannitol) and contraindicated (fructose, oral sucrose, invert sugar, sorbitol, maltitol, lactitol, isomaltitol, fruit syrups, honey, sucrose esters and sorbitol esters). Glucose and glucose syrup were classified as suitable with considerations due to its possible fructose content and their potential endogenous fructose production. For other related intolerances, wheat starch was contraindicated and oatmeal was not recommended in celiac disease; oral lactose and lactose-based coprocessed excipient (Cellactose®) were not recommended in lactose intolerance; and glucose, invert sugar and oral sucrose were not recommended in diabetes mellitus. The applications were named IntoMed®. Results are listed in order of tolerability (suitable drugs appear first and contraindicated drugs at the end), and they are accompanied by a note detailing their classified excipients. If a drug contains excipients within different categories, the overall classification will be the most restrictive. The apps are also able to classify substances with the same criteria if they act as active ingredients. The tools exhibited good usability (82.07 ± 13.46 points on the System Usability Scale [range: 0-100]) on a sample of HFI patients, their families and health care professionals. Conclusions IntoMed® is a tool for finding information about the tolerability of drugs according to excipients for patients with HFI and other related intolerances, with good usability. It is a fast and reliable system that covers the current excipient legislation and expands on it with other specific information: HFI patients should be alert for excipients such as mannitol (especially in intravenous drugs), fruit syrups, honey, sulfite caramel or vanilla. Glucose might contain or produce fructose, and special precaution is needed because of potential errors in their composition.

Background: The main consequences of chronic hepatitis B virus (HBV) infections are cirrhosis and hepatocellular carcinoma (HCC), both associated with frequent hospitalization. The aim of this study was to analyze the impact of universal HBV vaccination in Spain on chronic HBV-related hospital discharges from 2005 to 2021. Methods: Using data from the Minimum Basic Data Set of the Spanish National Health System, we calculated the hospital discharge rate ratio (HDRR) and 95% confidence interval (CI) values for chronic HBV-related discharges between 2005 and 2021. For comparative purposes, we calculated the HDRR and 95% confidence interval (CI) values for the early (2005–2013) and later (2014–2021) periods and the vaccinated compared with unvaccinated cohorts for the 20–39 age group. Results: The hospital discharge rate per 1,000,000 people was 3.08 in 2005 and 4.50 in 2021 for HCC, and 4.81 in 2005 and 1.92 in 2021 for cirrhosis. Comparing the early and later periods, values were higher for HCC (HDRR 1.13; 95% CI: 1.06–1.20) and lower for cirrhosis (HDRR 0.56; 95% CI: 0.51–0.60). The rate for the 20–39 age group was lower for the vaccinated compared with the unvaccinated cohorts overall (HDRR 0.53; 95% CI: 0.45–0.62), for HCC (HDRR 0.66; 95% CI: 0.53–0.82), and for cirrhosis (HDRR 0.41; 95% CI: 0.33–0.53). Conclusions: This study describes the important impact, after 25 years, of universal HBV vaccination in Spain: cirrhosis hospital discharge rate was reduced, and the vaccinated cohorts, compared with the unvaccinated cohorts in the 20–39 age group, had a lower hospital discharge rate of both HCC and cirrhosis.

Icariin (ICA), one of the main active components of Herba Epimedii, is a natural prenylated flavonol glycoside that possesses a wide range of pharmacological effects, including antioxidant, antiosteoporotic, anti-aging, neuroprotective, immunomodulatory, antitumor, and aphrodisiac effects, and prevents numerous health disorders, such as cardiovascular diseases, osteoporosis, cancer, sexual dysfunction, menstrual disorders, neurodegenerative diseases, asthma, chronic inflammation, and diabetes. In the reproductive system, it has been observed that ICA may play a role in preserving fertility by regulating different signalling pathways, such as PI3K/AKT, which improves ovarian function, and ERα/Nrf2, which enhances testicular function and prevents ROS generation. In contrast, regulating the NF/kB signalling pathway causes anti-inflammatory effects, reducing spontaneous abortions. In this study, we review and examine the relevant literature on the therapeutic potential of ICA in reproduction, highlight the various mechanisms of action and limitations for the therapeutic applications of ICA, and summarise and highlight the existing preclinical research on its effects on male and female reproduction.

Background: During the COVID-19 pandemic, distinct population subsets, including pregnant women, have been differentially affected. While over 90% of COVID-19-infected pregnant women experience a benign course, a subset demonstrates marked clinical exacerbation. Symptomatic pregnant individuals, in particular, present a heightened risk of severe disease in comparison to their non-pregnant counterparts. Objective: The objective of this study is to systematically evaluate the epidemiological characteristics of COVID-19 in pregnant women, assess related maternal mortalities, ascertain the case fatality rate, and delineate associated risk factors. Design: This is a comprehensive population-based ecological study. Methodology: A population-based study was conducted to investigate the epidemiological patterns of COVID-19-associated morbidity and mortality in pregnant women in Ecuador from 27 February 2020 to 14 May 2021. Results: A total of 3274 positive COVID-19 cases were identified among pregnant women, with 22 official fatalities, yielding a case fatality rate of 0.67%. The majority of cases were of Mestizo ethnicity (92.66%); however, the highest case fatality rate was noted among indigenous pregnant women (case fatality rate = 1.25%), those aged between 40 and 44 years (case fatality rate = 2.68%), and those with a history of comorbidities (2.08%). Pregnant women residing at lower altitudes (2500 m), which stood at 0.17/100,000. Conclusion: The COVID-19 pandemic has profoundly impacted pregnant women in Ecuador during the first 14 months, particularly those with comorbidities, older age, and of indigenous ethnicity. These factors have heightened their vulnerability and susceptibility to severe COVID-19 infection and subsequent mortality. This underscores the urgency for comprehensive protective measures, including prioritization for vaccination. Further studies are needed to inform tailored prevention strategies and therapeutic interventions for these high-risk groups.

Objetivo: describir la percepción del cumplimiento de los atributos de la atención primaria de la salud en la población afroperuana durante la pandemia de COVID-19. Materiales y métodos: estudio observacional y transversal, realizado en seis ciudades del Perú, incluyendo a adultos afroperuanos, seleccionados con muestreo intencional. Se aplicó una encuesta en línea utilizando el Primary Care Assessment Tool (PCAT), armonizada para contexto iberoamericano, la cual evalúa atributos de la atención primaria como accesibilidad de los servicios, continuidad de la atención, participación comunitaria e idoneidad cultural, evaluándose con análisis descriptivo. Además, se exploraron factores relacionados como características sociodemográficas y clínicas empleando pruebas de hipótesis. Resultados: la mayoría de los entrevistados percibió un menor cumplimiento de los atributos de la atención primaria (94,8%). En particular, la orientación comunitaria y la continuidad de la atención fueron áreas problemáticas, 92,3 y 92,1%, respectivamente. No se encontró una correlación significativa entre la percepción de cumplimiento de la atención primaria y los factores sociodemográficos y clínicos con excepción del antecedente de tener COVID-19, quienes perciben un menor cumplimiento de los atributos de la atención primaria de salud. La fiabilidad global del PCAT fue de 0,93 con alfa de Cronbach. Conclusiones: existe una percepción generalmente baja de los servicios de atención primaria en la población afroperuana. Se requieren investigaciones futuras para explorar las causas subyacentes de estas percepciones y se deben hacer esfuerzos para mejorar el cumplimiento de los atributos de la atención primaria que se perciben como insuficientes, especialmente la accesibilidad y la continuidad de la atención.

A 73-year-old woman arrived at the ER claiming to be experiencing low back pain. To investigate the source of her pain, she was admitted to the Internal Medicine department. After a heterogeneous abdominal mass in the right upper quadrant was discovered by abdominal point-of-care ultrasonography (POCUS), it was confirmed by an abdominal CT scan, which also identified a metastatic lytic bone lesion in the L4. This finding is consistent with a malignant tumor of the right adrenal gland. POCUS was repeated right after the occurrence of dyspnea, and a 40x6 mm floating thrombus in the inferior vena cava was detected. A conservative approach with anticoagulants was chosen, with improvement of the clinical conditions. The diagnosis of adrenal carcinoma was ultimately made possible by the mass biopsy. POCUS is a safe, low-cost method that provides prompt results at the patient's bedside. We support the implementation of POCUS in all clinical departments, as it provides significant contributions to the assessment of prognosis and diagnosis.

Abstract Payments for Ecosystem Services (PES) provide conditional incentives for forest conservation. PES short-term effects on deforestation are well-documented, but we know less about program effectiveness when participation is sustained over time. Here, we assess the impact of consecutive renewals of PES contracts on deforestation and forest degradation in three municipalities of the Selva Lacandona (Chiapas, Mexico). PES reduced deforestation both after a single 5-year contract and after two consecutive contracts, but the impacts are only detectable in higher deforestation-risk parcels. Enrollment duration increases PES impact in these parcels, which suggests a positive cumulative effect over time. These findings suggest that improved spatial targeting and longer-term enrollment are key enabling factors to improve forest conservation outcomes in agricultural frontiers.

Abstract There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p

Abstract The development of high intensity petawatt lasers has created new possibilities for ion acceleration and nuclear fusion using solid targets. In such laser-matter interaction, multiple ion species are accelerated with broad spectra up to hundreds of MeV. To measure ion yields and for species identification, CR-39 solid-state nuclear track detectors are frequently used. However, these detectors are limited in their applicability for multi-ion spectra differentiation as standard image recognition algorithms can lead to a misinterpretation of data, there is no unique relation between track diameter and particle energy, and there are overlapping pit diameter relationships for multiple particle species. In this report, we address these issues by first developing an algorithm to overcome user bias during image processing. Second, we use calibration of the detector response for protons, carbon and helium ions (alpha particles) from 0.1 to above 10 MeV and measurements of statistical energy loss fluctuations in a forward-fitting procedure utilizing multiple, differently filtered CR-39, altogether enabling high-sensitivity, multi-species particle spectroscopy. To validate this capability, we show that inferred CR-39 spectra match Thomson parabola ion spectrometer data from the same experiment. Filtered CR-39 spectrometers were used to detect, within a background of ~ 2 × 1011 sr−1 J−1 protons and carbons, (1.3 ± 0.7) × 108 sr−1 J−1 alpha particles from laser-driven proton-boron fusion reactions.

El metaparadigma en enfermería es el conjunto de conceptos esenciales que identifican los fenómenos de interés para la enfermería. Este artículo tiene como objetivo proporcionar una mejor base para la comprensión de la importancia del desarrollo de metaparadigma que reflejen de modo adecuado la realidad de la práctica clínica propia de la Enfermería cubana. Se realizó un estudio de tipo teórico-reflexivo, apoyados por la observación sistemática, el razonamiento, la interpretación, y la sistematización de la práctica científica y complementados en una búsqueda bibliográfica en bases de datos como Pubmed, Cuiden® y Scielo y el análisis documental de las obras científicas relacionadas con el tema. Para lograr un cuerpo teórico en la ciencia del cuidado en Cuba, es imprescindible la delineación metaparadigmas que se ajusten a la realidad que viven los enfermeros y enfermeras cubanas lo que le brindara lo que favorecerá a que se brinden cuidados oportunos y de calidad.

Patients with interstitial lung disease (ILD) represent a vulnerable population against an acute SARS-CoV-2 infection. It has been observed that up to 80% of patients with ILD can develop post-COVID-19 symptomatology one year after. This secondary analysis aimed to, 1, compare serological biomarkers before and after surpassing a SARS-CoV-2 infection in individuals with interstitial lung disease (ILD) and, 2, to compare serological biomarkers between ILD patients who develop and those who do not develop post-COVID-19 symptoms. Seventy-six patients with ILD (40.4% women, age: 69, SD: 10.5 years) who survived a SARS-CoV-2 infection participated. High-resolution computerized tomography (CT) of the lungs, two pulmonary function tests (forced vital capacity (FVC) and diffusion value of carbon monoxide (DLCO)) and fourteen serological biomarkers were collected before and after SARS-CoV-2 infection. Participants were asked for the presence of post-COVID-19 symptomatology a mean of twelve (SD: eight) months after infection. Sixty patients (79%) showed post-COVID-19 symptoms (mean: 3.5, SD 1.1), with fatigue (68.4%), dyspnea (31.5%), and concentration loss (27.6%) being the most prevalent. Creatine phosphokinase (CPK) was the only biomarker showing differences in our study. In fact, CPK levels were higher after the acute SARS-CoV-2 infection (mean difference: 41.0, 95%CI 10.1 to 71.8, p = 0.03) when compared to before the infection. Thus, CPK levels were also higher in ILD patients with post-COVID-19 fatigue (mean difference: 69.7, 95%CI 12.7 to 126.7, p = 0.015) or with post-COVID-19 dyspnea (mean difference: 34.8, 95%CI 5.2 to 64.4, p = 0.025) than those patients without these post-COVID-19 symptoms. No significant changes in CT or functional pulmonary tests were observed after COVID-19 in patients with ILD. In conclusion, patients with ILD exhibited an increase in CPK levels after SARS-CoV-2 infection, albeit no changes in other serological biomarkers were identified. Similarly, the presence of post-COVID-19 fatigue or dyspnea was also associated with higher CPK levels in ILD patients. Studies investigating long COVID mechanisms in vulnerable populations such as ILD are needed.

(1) Background: The global coronavirus disease 2019 vaccination adapts to protect populations from emerging variants. This communication presents interim findings from the new Omicron XBB.1.16-adapted PHH-1V81 protein-based vaccine compared to an XBB.1.5-adapted mRNA vaccine against various acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains. (2) Methods: In a Phase IIb/III pivotal trial, adults previously vaccinated with a primary scheme and at least one booster dose of an EU-approved mRNA vaccine randomly received either the PHH-1V81 or BNT162b2 XBB.1.5 vaccine booster as a single dose. The primary efficacy endpoint assessed neutralization titers against the Omicron XBB.1.16 variant at day 14. Secondary endpoints evaluated neutralization titers and cellular immunity against different variants. Safety endpoints comprised solicited reactions up to day 7 post-vaccination and serious adverse events until the cut-off date of the interim analysis. Changes in humoral responses were assessed by pseudovirion-based or virus neutralization assays. (3) Results: At the cut-off date, immunogenicity assessments included 599 participants. Both boosters elicited neutralizing antibodies against XBB.1.16, XBB.1.5, and JN.1, with PHH-1V81 inducing a higher response for all variants. The PHH-1V8 booster triggers a superior neutralizing antibody response against XBB variants compared to the mRNA vaccine. A subgroup analysis consistently revealed higher neutralizing antibody responses with PHH-1V81 across age groups, SARS-CoV-2 infection history, and the number of prior vaccination shots. A safety analysis (n = 607) at the day 14 visit revealed favorable safety profiles without any serious vaccine-related adverse events. (4) Conclusions: PHH-1V81 demonstrates superiority on humoral immunogenicity compared to the mRNA vaccine against XBB variants and non-inferiority against JN.1 with a favorable safety profile and lower reactogenicity, confirming its potential as a vaccine candidate.

Background: Prehospital emergency medical services (EMS) are the main gateway for trauma patients. Recent advances in point-of-care testing and the development of early warning scores have allowed EMS to improve patient classification. We aimed to identify patients presenting with major trauma involving life-saving interventions (LSI) using the modified Sequential Organ Failure Assessment (mSOFA) score in the prehospital scenario, and to compare these results with those of other trauma scores. Methods: This was a prospective, ambulance-based, multicenter, training-validation study in trauma patients who were treated in a prehospital setting and subsequently transported to a hospital. The study involved six Advanced Life Support units, 38 Basic Life Support units, and four hospitals. The primary outcome was LSI performed at the scene or en route and intensive care unit (ICU) admission and all-cause two-day in-hospital mortality. We collected epidemiological variables, creatinine, lactate, base excess, international normalized ratio, and vital signs. Discriminative power (area under the receiver operating characteristic curve [AUC]), calibration (observed vs predicted outcome agreement), and decision-curve analysis (DCA, clinical utility) were used to assess the reliability of the mSOFA in comparison to other scores. Results: Between January 1, 2020–April 30, 2022, a total of 763 patients were selected. The mSOFA score’s AUC was 0.927 (95% confidence interval [CI] 0.898–0.957) for LSI, 0.845 (95% CI 0.808–0.882) for ICU admission, and 0.979 (95% CI 0.966–0.991) for two-day mortality. Conclusion: The mSOFA score outperformed the other scores, allowing a quick identification of high-risk patients. The routine implementation in EMS of mSOFA could provide critical support in the decision-making process in time-dependent trauma injuries.

Introducción: La autoestima es la valoración que las personas se hacen sobre sí mismas; manifiesta una actitud aprobatoria que señala la medida en que se consideran importantes, capaces, dignas y exitosas, es decir, un juicio de mérito. Objetivo: Evaluar el nivel de autoestima en adultos mayores. Métodos: Estudio observacional, descriptivo, de corte transversal en 59 pacientes. Se estudiaron las variables sexo, grupos de edades, antecedentes patológicos personales y nivel de autoestima. Resultados: Se observó mayor representación del rango etario entre los 71 y 80 años de edad (n= 29; 49,1 %), sexo femenino (n= 30; 50,8 %). El antecedente patológico personal más frecuente fue la hipertensión arterial; se observó predominio del nivel medio de autoestima (n= 38; 64,4 %) y ningún paciente con baja autoestima (n= 0). Conclusiones: El nivel de autoestima predominante en adultos mayores es medio.

The increasing availability of massive genetic sequencing data in the clinical setting has triggered the need for appropriate tools to help fully exploit the wealth of information these data possess. GFPrint™ is a proprietary streaming algorithm designed to meet that need. By extracting the most relevant functional features, GFPrint™ transforms high-dimensional, noisy genetic sequencing data into an embedded representation, allowing unsupervised models to create data clusters that can be re-mapped to the original clinical information. Ultimately, this allows the identification of genes and pathways relevant to disease onset and progression. GFPrint™ has been tested and validated using two cancer genomic datasets publicly available. Analysis of the TCGA dataset has identified panels of genes whose mutations appear to negatively influence survival in non-metastatic colorectal cancer (15 genes), epidermoid non-small cell lung cancer (167 genes) and pheochromocytoma (313 genes) patients. Likewise, analysis of the Broad Institute dataset has identified 75 genes involved in pathways related to extracellular matrix reorganization whose mutations appear to dictate a worse prognosis for breast cancer patients. GFPrint™ is accessible through a secure web portal and can be used in any therapeutic area where the genetic profile of patients influences disease evolution.

Many habitat-specialist organisms occur in distinct, patchy habitat, yet do not occupy all patches, and an important question is why apparently suitable habitat remains unoccupied. We examined factors influencing patch occupancy in near-threatened, little-known Diademed Plovers (Phegornis mitchellii), arguably the bird most specialized to life in High Andean peatlands. Andean peatlands are well-suited to occupancy modelling because they are discrete patches of humid habitat within a matrix of high-altitude steppe. We hypothesized that Diademed Plovers occupy preferably larger and more humid peatlands, and avoid peatlands used for grazing by llamas and vicuñas, which may trample vegetation and nests. From December 2021 to February 2022 (breeding season), we conducted plover occupancy surveys (2-4) on 40 peatlands at Lagunas de Vilama, a landscape of arid steppe and wetlands above 4,500 m in NW Argentina. We measured peatland size, grazing pressure, topographic and remotely-sensed variables that correlate with humidity, and incorporated these as covariates in occupancy models. Occupancy models showed that more than 50% of the studied peatlands were used by Diademed Plovers and most showed signs of reproduction, highlighting the importance of the Vilama Wetlands for Diademed Plover conservation. Within peatlands, Diademed Plovers were most often associated with headwaters. The top ranked occupancy model included constant detection, random spatial effects, and a single occupancy covariate: mean NDWI (Normalized Difference Water Index, an index correlated with water content and humidity) over the previous three years. Contrary to our prediction, Diademed Plovers preferred less water-saturated peatlands (lower NDWI), possibly to avoid nest flooding. This may be especially important in wet years, like the year when we conducted our surveys. Neither peatland size nor grazing by llamas and vicuñas affected peatland use by Diademed Plovers, suggesting that llama grazing at current levels may be compatible with plover conservation. For organisms that specialize on humid habitats, such as peatlands, factors affecting occupancy may vary temporally with variation in climate, and we recommend follow-up surveys across multi-year timescales to untangle the impact of climate on animals' use of humid habitats.

Introducción: La infección por el Virus de Inmunodeficiencia Humana, es un problema de salud en el mundo. En Cuba existen avances, se ha eliminado la transmisión prenatal desde el año 2013, aunque no se logra erradicar la epidemia. Objetivo: Implementar una intervención educativa sobre el Virus de Inmunodeficiencia Humana en estudiantes de preuniversitario. Métodos: Se realizó una intervención educativa en el Instituto Preuniversitario Urbano ¨República de Indonesia¨ en Guanajay, Artemisa. El universo fueron 343 estudiantes y de forma aleatoria se seleccionó una muestra de 60. Se aplicó un cuestionario para determinar el conocimiento sobre el agente causal, las vías de transmisión; las conductas de riesgo y las fuentes de información, antes y después de la intervención educativa. El programa educativo se realizó a través de conferencias, talleres y cine debate. Se utilizó la prueba estadística de Wilconxon para muestras relacionadas. Resultados: Predominó el género femenino en el 66.66 % y el grado de escolaridad onceno en el 58.33 %. Antes de la intervención el 61.33 % no conocían el agente causal, después se revirtió en un 75 %; en relación a las vías de transmisión el 86.66 % no las dominaban, invirtiéndose en el 70 %. Acerca de las medidas de prevención existió desconocimiento en el 88.33 %, modificándose en un 33.33 % y las conductas de riesgo se desconocían el 11.66 %, después se invirtió en un 81.66 %. Conclusiones: El programa de intervención educativa permite elevar los conocimientos sobre el Virus de Inmunodeficiencia Humana en los adolescentes.

Abstract We examine the differences in running performance demands and tactical individual actions for male amateur football wingers in four tactical formations: 4-2-3-1, 4-4-2, 3-5-2 and 3-4-2-1 during an entire season. Running demands were assessed in terms of: total distance run; distance traveled at 3 different speed ranges (Jogging, Running, and Sprinting); and number of accelerations registered in two different magnitude bands (Medium and High) while tactical individual actions were assessed through 3269 team match observations. 3-5-2 formation entails the highest running demands, exhibiting significant disparities in Jogging when compared to 4-2-3-1 and 3-5-2, in Sprinting when comparing 4-2-3-1 with both the 3-5-2 and the 3-4-2-1 formations. Moreover, the wingers in the 3-5-2 formation demonstrate the lowest scores in various tactical individual actions, including Shots: 3-5-2 vs. 3-4-2-1; Goal Area Shots: 3-5-2 vs. 3-4-2-1; and Dribbles: 3-5-2 vs. 3-4-2-1. Finally, wingers registered the highest levels of defensive tactical individual actions in 4-4-2 and 3-5-2. Findings suggest it would be of benefit for coaches to focus on formulating specific training plans to address the specific demands placed on wingers playing in these amateur matches and running performance demands and tactical individual actions should be considered together with tactical formation.

Abstract Background Anti-CGRP monoclonal antibodies have shown notable effectiveness and tolerability in migraine patients; however, data on their use in elderly patients is still lacking, as clinical trials have implicit age restrictions and real-world evidence is scarce. In this study, we aimed to describe the safety and effectiveness of erenumab, galcanezumab and fremanezumab in migraine patients over 65 years old in real-life. Methods In this observational real-life study, a retrospective analysis of prospectively collected data from 18 different headache units in Spain was performed. Migraine patients who started treatment with any anti-CGRP monoclonal antibody after the age of 65 years were included. Primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and medication intake frequencies by months 3 and 6, response rates, changes in patient-reported outcomes and reasons for discontinuation. As a subanalysis, reduction in monthly migraine days and proportion of adverse effects were also compared among the three monoclonal antibodies. Results A total of 162 patients were included, median age 68 years (range 65–87), 74.1% women. 42% had dyslipidaemia, 40.3% hypertension, 8% diabetes, and 6.2% previous cardiovascular ischaemic disease. The reduction in monthly migraine days at month 6 was 10.1 ± 7.3 days. A total of 25.3% of patients presented adverse effects, all of them mild, with only two cases of blood pressure increase. Headache and medication intake frequencies were significantly reduced, and patient-reported outcomes were improved. The proportions of responders were 68%, 57%, 33% and 9% for reductions in monthly migraine days ≥ 30%, ≥ 50%, ≥ 75% and 100%, respectively. A total of 72.8% of patients continued with the treatment after 6 months. The reduction in migraine days was similar for the different anti-CGRP treatments, but fewer adverse effects were detected with fremanezumab (7.7%). Conclusions Anti-CGRP mAbs are safe and effective treatments in migraine patients over 65 years old in real-life clinical practice. Graphical Abstract

Abstract The fatty acids profile has been playing a decisive role in recent years, thanks to technological, sensory and health demands from producers and consumers. The application of NIRS technique on fat tissues, could lead to more efficient, practical, and economical in the quality control. The study aim was to assess the accuracy of Fourier Transformed Near Infrared Spectroscopy technique to determine fatty acids composition in fat of 12 European local pig breeds. A total of 439 spectra of backfat were collected both in intact and minced tissue and then were analyzed using gas chromatographic analysis. Predictive equations were developed using the 80% of samples for the calibration, followed by full cross validation, and the remaining 20% for the external validation test. NIRS analysis of minced samples allowed a better response for fatty acid families, n6 PUFA, it is promising both for n3 PUFA quantification and for the screening (high, low value) of the major fatty acids. Intact fat prediction, although with a lower predictive ability, seems suitable for PUFA and n6 PUFA while for other families allows only a discrimination between high and low values.

The presence of medical comorbidities in women with psychotic disorders can lead to poor medical and psychiatric outcomes. Of all comorbidities, cardiovascular disease is the most frequent, and the one most likely to cause early death. We set out to review the evidence for cardiovascular risk factors (CRFs) in women with schizophrenia-related disorders and for interventions commonly used to reduce CRFs. Electronic searches were conducted on PubMed and Scopus databases (2017–2022) to identify papers relevant to our aims. A total of 17 studies fulfilled our inclusion criteria. We found that CRFs were prevalent in psychotic disorders, the majority attributable to patient lifestyle behaviors. We found some inconsistencies across studies with regard to gender differences in metabolic disturbances in first episode psychosis, but general agreement that CRFs increase at the time of menopause in women with psychotic disorders. Primary care services emerge as the best settings in which to detect CRFs and plan successive intervention strategies as women age. Negative symptoms (apathy, avolition, social withdrawal) need to be targeted and smoking cessation, a heart-healthy diet, physical activity, and regular sleep routines need to be actively promoted. The goal of healthier hearts for women with psychotic disorders may be difficult, but it is achievable.

Abstract The study of the GI-tract microbiota of spondylarthritis (SpA) patients has focused on the analysis of feces samples, that picture mostly the luminal microbiota. The aim of this study was to determine the contribution of mucosal and luminal microbiome to the gut dysbiosis in SpA, using colonoscopy aspiration lavages (CAL), a recent alternative for regional studies of the GI-tract. We analyzed 59 CAL (from sigmoid colon and distal ileum), and 41 feces samples, from 32 SpA patients and 7 healthy individuals, using 16S rRNA gene-targeted metataxonomic profiling. It was found high prevalence of GI-tract manifestations among SpA patients (65.3%). Metataxonomic profiling, confirmed CAL samples from the lower GI tract (colon or ileum) presented a distinctive and undifferentiated bacteriome and separate from that found in feces’ samples or in the beginning of the GI tract (oral cavity (OC)). Lower GI-tract samples and feces of SpA patients exhibited similar behavior to the microbiota of IBD group with reduced microbial richness and diversity, comparing to the healthy controls. Interestingly, it was found increase in proinflammatory taxa in SpA patients, such as Enterobacteriaceae family (mostly in the ileum), Succinivibrio spp. and Prevotella stercorea. Conversely, SpA patients presented significant decrease in the SCFA producers Coprococcus catus and Eubacterium biforme. Our data support the value of CAL samples for the regional study of GI-tract and contribute with information of potential “disruptor taxa” involved in the GI-tract associated disorders observed in SpA patients.

Abstract Continuous renal replacement techniques (CRRT) can induce complications and monitoring is crucial to ensure patient safety. We designed a prospective multicenter observational and descriptive study using the DIALYREG registry, an online database located on a REDCap web-based platform that allows real-time data analysis. Our main objective was to identify CRRT-related complications in our intensive care units (ICUs) and implement security measures accordingly. From January 2019 to December 2020, we included 323 patients with admission diagnoses of medical illness (54%), sepsis (24%), postoperative care (20%), and trauma (2%). CRRT indications were homeostasis (42%), oliguria (26%), fluid overload (15%), and hemodynamic optimization (13%). The median initial therapy dose was 30 ml/kg/h (IQR 25–40), and dynamic adjustment was performed in 61% of the treatments. Sets were anticoagulated with heparin (40%), citrate (38%) or no anticoagulation (22%). Citrate anticoagulation had several advantages: more frequent dynamic CRRT dose adjustment (77% vs. 58% with heparin and 56% without anticoagulation, p

The aim of this study was to evaluate and compare hepatitis A outbreak-associated healthcare and epidemiological surveillance costs in Spain in two types of autonomous regions during 2010–2018: (1) regions with a prevention strategy based on universal hepatitis A vaccination of children and vaccination of high-risk population groups (Catalonia) and (2) regions with a prevention strategy based on vaccinating high-risk population groups (Castile and Leon, Murcia, Navarra, Community of Madrid, Community of Valencia). Healthcare costs were determined based on the resources used to treat hepatitis A outbreak-associated cases and hospitalizations. Epidemiological surveillance costs were calculated from the resources used during surveillance activities. The ratios for total, healthcare and epidemiological surveillance costs (regions without universal hepatitis A vaccination of children vs. Catalonia) were used to compare the two hepatitis A prevention strategies. From 2010 to 2018, the total, healthcare and epidemiological surveillance costs per million population were 1.75 times (EUR 101,671 vs. EUR 58,032), 1.96 times (EUR 75,500 vs. EUR 38,516) and 1.34 times greater (EUR 26,171 vs. EUR 19,515) in regions without universal hepatitis A vaccination of children than in Catalonia, respectively. The ratios tended to increase over time during 2010–2018. In 2015–2018, total, healthcare and epidemiological surveillance costs per million population were 2.68 times (EUR 69,993 vs. EUR 26,158), 2.86 times (EUR 53,807 vs. EUR 18,825) and 2.21 times greater (EUR 16,186 vs. EUR 7333) in regions without universal hepatitis A vaccination of children than in Catalonia, respectively. These findings suggest that universal hepatitis A vaccination of children could reduce hepatitis A outbreak-associated costs.

The aim of this study was to analyse the impact of the introduction of universal adolescent HBV vaccination on the incidence of acute hepatitis B virus (HBV) infections. Acute HBV cases reported to the Spanish National Epidemiological Surveillance Network between 2005 and 2021 were included. For regions starting adolescent vaccination in 1991–1993 and in 1994–1996, HBV incidence rates were compared by calculating the incidence rate ratio (IRR) and 95% confidence interval (CI). We also analysed the 2017 Spanish national seroprevalence survey data. The overall acute HBV incidence per 100,000 persons was 1.54 in 2005 and 0.64 in 2021 (p < 0.001). The incidence in 2014–2021 was lower for regions that started adolescent vaccination in 1991–1993 rather than in 1994–1996 (IRR 0.76; 95% CI 0.72–0.83; p < 0.001). In the 20–29 age group, incidence in regions that started adolescent vaccination in 1991–1993 was also lower (IRR 0.87; 95% CI 0.77–0.98; p = 0.02 in 2005–2013 and IRR 0.71; 95% CI 0.56–0·90; p < 0.001 in 2014–2021). Anti-HBc prevalence in the 35–39 age group was lower in the regions that started vaccination earlier, although the difference was not statistically significant (p = 0.09). Acute HBV incidence decreased more in the young adult population in regions that began adolescent vaccination earlier. Maintaining high universal vaccination coverage in the first year of life and in at-risk groups is necessary to achieve HBV elimination by 2030.

AbstractIntroduction The clinical effect of domperidone against COVID-19 has been investigated in a double-blind phase III clinical trial (EudraCT number 2021-001228-17). Domperidone has shown in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential immudolatory properties through the stimulation of prolactin secretion.Patients and methods The efficacy of oral domperidone plus standard of care (SOC; n = 87) versus placebo plus SOC (n = 86) was evaluated in a 28-day randomized double-blind multicentre study in primary health care centres. A total of 173 outpatients with mild-to-moderate COVID-19 were included. Three daily doses of 10 mg (30 mg/day) of domperidone or placebo were administered for 7 days. Reduction of viral load on day 4 was the primary efficay endpoint. It was estimated in saliva samples by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), as the cycle thresholds detected ORF1ab, N Protein and S Protein genes.Results A significant reduction in the viral load was observed (p

Objective The aim was to explore the association of demographic and prehospital parameters with short-term and long-term mortality in acute life-threatening cardiovascular disease by using a hazard model, focusing on elderly individuals, by comparing patients under 75 years versus patients over 75 years of age.Design Prospective, multicentre, observational study.Setting Emergency medical services (EMS) delivery study gathering data from two back-to-back studies between 1 October 2019 and 30 November 2021. Six advanced life support (ALS), 43 basic life support and five hospitals in Spain were considered.Participants Adult patients suffering from acute life-threatening cardiovascular disease attended by the EMS.Primary and secondary outcome measures The primary outcome was in-hospital mortality from any cause within the first to the 365 days following EMS attendance. The main measures included prehospital demographics, biochemical variables, prehospital ALS techniques used and syndromic suspected conditions.Results A total of 1744 patients fulfilled the inclusion criteria. The 365-day cumulative mortality in the elderly amounted to 26.1% (229 cases) versus 11.6% (11.6%) in patients under 75 years old. Elderly patients (≥75 years) presented a twofold risk of mortality compared with patients ≤74 years. Life-threatening interventions (mechanical ventilation, cardioversion and defibrillation) were also related to a twofold increased risk of mortality. Importantly, patients suffering from acute heart failure presented a more than twofold increased risk of mortality.Conclusions This study revealed the prehospital variables associated with the long-term mortality of patients suffering from acute cardiovascular disease. Our results provide important insights for the development of specific codes or scores for cardiovascular diseases to facilitate the risk of mortality characterisation.

Introducción: Durante la pandemia de la COVID-19, la educación superior ha enfrentado la transición a la educación no presencial, con importante repercusión tanto en el rendimiento académico como en otros aspectos de la vida de los estudiantes. Objetivo: Aportar validez a la escala ACAD-COVID-19 y evaluar la percepción de los universitarios limeños acerca de las repercusiones académicas originadas por la pandemia de la COVID-19. Métodos: El estudio fue de diseño descriptivo y transversal, durante el año 2021. Se obtuvo una muestra conformada por 608 estudiantes del primer año académico de diferentes carreras, de 5 universidades de Lima. Se aplicó la escala ACAD-COVID-19 de 8 ítems y alternativas en escala Likert. Se realizaron análisis descriptivos y factoriales, utilizando SPSS versión 26.0. Resultados: Se evidenció que el instrumento es confiable. Se determinaron 3 factores, que pueden asociarse a las dimensiones académica, económica y el temor propio hacia enfermedad o muerte generada por la COVID-19. El 61,3 % de los estudiantes limeños manifiestan indiferencia respecto a la percepción sobre el impacto académico generado por el coronavirus, con un promedio general de los ítems de 3,21. La mayor media fue de la pregunta 5(3,47). Conclusiones: Se aportó validez a la escala ACAD-COVID-19 con su aplicación a la población universitaria limeña en un período de cuarentena durante el 2021. Los estudiantes, en general, manifestaron indiferencia en su percepción sobre el impacto académico generado por el coronavirus, aunque dentro de las repercusiones percibidas, predomina el miedo a enfermar al volver a las clases presenciales.

Abstract The aim of the present study is to produce flexible, flame-retardant, water-resistant and biodegradable composite materials. The ultimate goal of this research is to develop simple processes for the production of bio-based materials capable of replacing non-degradable substrates in printed circuit board. Cellulose was chosen as a renewable resource, and dissolved in 1-ethyl-3-methylimidazolium acetate ionic liquid to prepare a cellulosic continuous film. Since flame retardancy is an important criterion for electronic device applications and cellulose is naturally flammable, we incorporated ammonium polyphosphate (APP) as a flame-retardant filler to increase the flame retardancy of the produced materials. The developed material achieved a UL-94 HB rating in the flammability test, while the cellulose sample without APP failed the test. Two hydrophobic agents, ethyl 2-cyanoacrylate and trichloro(octadecyl)silane were applied by a simple dip-coating technique to impart hydrophobicity to the cellulose-APP composites. Dynamic mechanical analysis indicated that the mechanical properties of the cellulosic materials were not significantly affected by the addition of APP or the hydrophobic agents. Moreover, the biodegradability of the cellulosic materials containing APP increased owing to the presence of the cellulase enzyme. The hydrophobic coating slightly decreased the biodegradability of cellulose-APP, but it was still higher than that of pure cellulose film.

Abstract Cerebral ischemia is a condition affecting an increasing number of people worldwide, and the main cause of disability. Current research focuses on the search for neuroprotective drugs for its treatment, based on the molecular targets involved in the ischemic cascade. Nitrones are potent antioxidant molecules that can reduce oxidative stress. Here we report the neuroprotective properties and the antioxidant power of the six new quinolylnitrones (QNs) 1–6 for their potential application in stroke therapy. QNs 1–4 are 2-chloro-8-hydroxy-substituted QNs bearing N-t-butyl or N-benzyl substituents at the nitrone motif located at C3, whereas QN5 and QN6 are 8-hydroxy QNs bearing N-t-butyl or N-benzyl substituents at the nitrone motif located at C2, respectively. In vitro neuroprotection studies using QNs 1–6 in an oxygen-glucose-deprivation model of cerebral ischemia, in human neuroblastoma cell cultures, indicate that all QNs have promising neuroprotective, anti-necrotic, anti-apoptotic, and anti-oxidant properties against experimental ischemia–reperfusion in neuronal cultures. QN6 stands out as the most balanced nitrone out of all tested QNs, as it strongly prevents decreased neuronal metabolic activity (EC50 = 3.97 ± 0.78 μM), as well as necrotic (EC50 = 3.79 ± 0.83 μM) and apoptotic cell death (EC50 = 3.99 ± 0.21 μM). QN6 showed high capacity to decrease superoxide production (EC50 = 3.94 ± 0.76 μM), similar to its parent molecule α-phenyl-tert-butyl nitrone (PBN) and the well-known anti-oxidant molecule N-acetyl-l-cysteine (NAC). Thus, QN6 demonstrated the highest antioxidant power out of the other tested QNs. Finally, in vivo treatment with QN6 in an experimental permanent stroke model elicited a significant reduction (75.21 ± 5.31%) of the volume size of brain lesion. Overall, QN6 is a potential agent for the therapy of cerebral ischemia that should be further investigated.

Key messages 1. Development a prognostic index of poor renal evolution in patients with LN. 2. We use clinical, histological and laboratory factors 6 months after diagnosis and treatment 3. Effective tool in the early detection and management, easy to use in clinical practice