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Background: Hydroxychloroquine (HCQ) is a disease-modifying antirheumatic used in rheumatological diseases such as systemic lupus erythematosus. Long-term exposure to HCQ results in drug accumulation and predisposes to adverse effects. Case summary: We present the case of a 45-year-old woman with long-term treatment with HCQ who presented to the Emergency Department with acute heart failure. Transthoracic echocardiogram, previously normal, showed severe biventricular hypertrophy and biventricular systolic dysfunction. Cardiac magnetic resonance (CMR) confirmed the previous findings and showed elevated native T1 and T2 values, elevated extracellular volume, and extensive mid-wall late gadolinium enhancement (LGE). Infiltrative cardiomyopathy was suspected, and endomyocardial biopsy performed. Light microscopy showed myocyte hypertrophy and vacuolar change and absence of lymphocytic inflammatory infiltrates. The diagnosis of HCQ-induced cardiomyopathy was established, and the drug was withdrawn. A CMR performed 1 year later showed normal systolic function of both ventricles and normalization of T2 values, reflecting resolution of myocardial oedema. However, severe hypertrophy, elevated native T1 values, and LGE persisted. Discussion: Our case shows that although discontinuation of the drug stops the progression of the disease, established myocardial structural damage persists. Early diagnosis of this entity is therefore essential to improve prognosis.

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BACKGROUND: Several clinical signs in dermatoscopy are very characteristic of onychomycosis and can be a quick complement for the diagnosis of onychomycosis. OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy of dermatoscopy compared to microbiological culture and polymerase chain reaction (PCR), as well as the clinical signs associated with onychomycosis. METHODS: The clinical signs of 125 patients were assessed cross-sectionally using dermatoscopy, and a positive or negative result was assigned. A sample was then taken for PCR and microbiological culture. RESULTS: Of the 125 patients, 69.6% (87/125) had positive results when both laboratory tests were combined. When they were not combined, the prevalence was lower at 48% (60/125) with PCR and at 43.2% (54/125) with culture. Furthermore, 76.8% (96/125) were classified as positive with dermatoscopy with a sensitivity of 1, a specificity of 0.76, positive predictive value of 0.91 and negative predictive value of 1 (with 95% confidence intervals). Of the 96 dermatoscopy-positive samples, 36 were negative with PCR (p < 0.001), 42 were negative with culture (p < 0.001) and nine were negative when both tests were combined (p < 0.001). Clinical signs that were significantly associated with the presence of onychomycosis were subungual hyperkeratosis (dermatoscopy: p = 0.004, odds ratio (OR) = 2.438; PCR + microbiological culture: p = 0.004, OR = 3.221), subungual detritus (p = 0.033, OR = 3.01, only with dermatoscopy) and dermatophytoma (dermatoscopy: p = 0.049, OR = 3.02; PCR + microbiological culture: p = 0.022, OR = 2.40). CONCLUSIONS: The results suggest that dermatoscopy is a good tool for the diagnosis of onychomycosis but should be used as a complementary test or for screening patients to be sampled for laboratory testing. The combination of the three tests can lead to a reduction of false-positive and false-negative clinical and laboratory results. This allows for early diagnosis and specific treatment based on test results.

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Dermoscopía , Onicomicosis , Reacción en Cadena de la Polimerasa , Sensibilidad y Especificidad , Humanos , Onicomicosis/diagnóstico , Onicomicosis/microbiología , Estudios Transversales , Reacción en Cadena de la Polimerasa/métodos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Dermoscopía/métodos , Adulto Joven , Anciano de 80 o más Años , Adolescente , Técnicas Microbiológicas/métodos , Hongos/aislamiento & purificación , Hongos/genética , Valor Predictivo de las Pruebas

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Objective: To describe the perspectives of a group of COPD patients during the first outbreak of the COVID-19 pandemic and narrate the emotions and polarity (acceptance-rejection) regarding living with COPD during the pandemic. Design/methods: We used a novel application of lemmatization and thematic analysis of participants' narratives. A study was carried out with eight patients with moderate-severe-very severe COPD during the first outbreak of COVID-19 using purposive sampling. In-depth interviews and field notes from the researchers were used to collect data. A statistical content analysis (lemmatization) of the patients' narratives was performed. Additionally, inductive thematic analysis was used to identify emerging themes. This study was conducted following the guidelines of Consolidated Criteria/Standards for Reporting Qualitative Research. The study was conducted in accordance with the principles articulated in the WMA Declaration of Helsinki. Participants provided verbal informed consent prior to their inclusion as previously described. Results: The average age of our sample was 65 years, and 75% of the patients suffered from moderate COPD, 12.5% from severe COPD, and 12.5% from very severe COPD according to GOLD criteria. The lemmatized and sentiment analysis showed a predominance of positive emotions, and the polarity of the interviews indicated a very slight positive trend towards acceptance of the experience lived during the pandemic. Additionally, three main themes were identified: (1) Confinement and restriction measures, (2) COVID-19 and protective measures, and (3) Clinical care during the first outbreak of the pandemic. Conclusion: Patients experienced confinement with a feeling of security and protection. They strictly respect social distancing. They used masks, but these caused them to feel short of breath and fatigue, especially FFP2 masks. Half of the patients rejected the possibility of being vaccinated. Finally, they were very satisfied with the clinical care they received in the COPD unit of their hospital. Our results show that COPD patients have not experienced a negative impact of the COVID-19 pandemic.

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COVID-19 , Enfermedad Pulmonar Obstructiva Crónica , Investigación Cualitativa , Humanos , COVID-19/psicología , COVID-19/epidemiología , COVID-19/prevención & control , Enfermedad Pulmonar Obstructiva Crónica/psicología , Masculino , Anciano , Femenino , Persona de Mediana Edad , SARS-CoV-2 , Pandemias , Entrevistas como Asunto , Emociones

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A plantar wart is a benign hyperplasia that appears on the feet due to the human papillomavirus (HPV). One method used for the treatment of recalcitrant plantar warts, those lasting over 2 years or persisting after at least two treatment attempts, is the cantharidin (1%), podophyllin (5%), and salicylic acid (30%) formulation, also known as the CPS formulation. Although this method is in use, there are few studies on it. This study's objective was to ascertain its cure rate. For this retrospective observational study, we reviewed the medical records of patients treated with the CPS formulation at a podiatric clinic specializing in plantar wart treatment. Our sample size was 48 subjects. The CPS formulation had a cure rate of 62.5%. Out of the cured patients, 86.67% (26/30) required one or two applications. There was no observable correlation (p > 0.05) between wart resolution and virus biotype, evolution time, patient's morphological and clinical attributes, location, number of warts, or preceding treatments. The CPS formulation presents a relatively high efficacy rate for treating recalcitrant HPV plantar warts. Still, additional studies are necessary to evaluate its safety and efficiency.

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Cantaridina , Podofilino , Ácido Salicílico , Verrugas , Humanos , Cantaridina/uso terapéutico , Cantaridina/administración & dosificación , Verrugas/tratamiento farmacológico , Verrugas/virología , Estudios Retrospectivos , Masculino , Ácido Salicílico/uso terapéutico , Ácido Salicílico/administración & dosificación , Femenino , Adulto , Resultado del Tratamiento , Adulto Joven , Persona de Mediana Edad , Adolescente , Podofilino/uso terapéutico , Podofilino/administración & dosificación , Niño

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Although Essential Climate Variables (ECVs) have been widely adopted as important metrics for guiding scientific and policy decisions, the Earth Observation (EO) and Land Surface and Hydrologic Model (LSM/HM) communities have yet to treat terrestrial ECVs in an integrated manner. To develop consistent terrestrial ECVs at regional and continental scales, greater collaboration between EO and LSM/HM communities is needed. An essential first step is assessing the LSM/HM simulation uncertainty. To that end, we introduce a new hydrological reference dataset that comprises a range of 19 existing LSM/HM simulations that represent the current state-of-the-art of our LSM/HMs. Simulations are provided on a daily time step, covering Europe, notably the Rhine and Po river basins, alongside the Tugela river basin in Africa, and are uniformly formatted to allow comparisons across simulations. Furthermore, simulations are comprehensively validated with discharge, evapotranspiration, soil moisture and total water storage anomaly observations. Our dataset provides valuable information to support policy development and serves as a benchmark for generating consistent terrestrial ECVs through the integration of EO products.

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The study of the structural stability of carbonates under different pressure and temperature conditions is important for modeling the carbon budget in the Earth's interior and the stability of carbonation products of carbon capture and storage (CCS) solutions. In this work, we confirm the existence of the two dense polymorphs of the hydrated magnesium carbonate MgCO3·3H2O nesquehonite mineral previously reported, and we characterize their structures using synchrotron single-crystal X-ray diffraction at 3.1 and 11.6 GPa. Phase transitions entail the distortion and atomic rearrangement of the Mg-centered polyhedra and the tilting of the [CO3] carbonate units. In particular, the Mg coordination number increases from 6 in nesquehonite to 7 in the second high-pressure phase, while maintaining a topology based on complex MgCO3(H2O)2 chains. We also studied their vibrational behavior upon compression using Raman spectroscopy and complemented the experimental results with density-functional theory (DFT) calculations. The role played by hydrogen bonds in the compressibility and the polymorphism of this hydrated carbonate is also discussed.

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OBJECTIVES: Food protein-induced enterocolitis syndrome (FPIES) is a severe type of non-IgE (immunoglobulin E)-mediated (NIM) food allergy, with cow's milk (CM) being the most common offending food. The relationship between the gut microbiota and its metabolites with the inflammatory process in infants with CM FPIES is unknown, although evidence suggests a microbial dysbiosis in NIM patients. This study was performed to contribute to the knowledge of the interaction between the gut microbiota and its derived metabolites with the local immune system in feces of infants with CM FPIES at diagnosis. METHODS: Twelve infants with CM FPIES and a matched healthy control group were recruited and the gut microbiota was investigated by 16S amplicon and shotgun sequencing. Fatty acids (FAs) were measured by gas chromatography, while immune factors were determined by enzyme-linked immunosorbent assay and Luminex technology. RESULTS: A specific pattern of microbiota in the gut of CM FPIES patients was found, characterized by a high abundance of enterobacteria. Also, an intense excretion of FAs in the feces of these infants was observed. Furthermore, correlations were found between fecal bifidobacteria and immune factors. CONCLUSION: These fecal determinations may be useful to gain insight into the pathophysiology of this syndrome and should be taken in consideration for future studies of FPIES patients.

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Notch signaling regulates cell fate decisions and has context-dependent tumorigenic or tumor suppressor functions. Although several Notch inhibitors are under development as cancer therapies, the mechanical force requirement for Notch receptor activation has hindered attempts to generate soluble agonists. To address this problem, we engineered synthetic Notch agonist (SNAG) proteins that mimic the tension-generating mechanism of endogenous ligands. SNAGs were designed by fusing a high-affinity variant of the Notch ligand Delta-like 4 (DLL4) to antibody fragments that induce target internalization. This bispecific format enables the SNAG-bound biomarkers to "pull" on Notch receptors, triggering Notch activation in mixed populations of biomarker-expressing and non-expressing cells. SNAGs targeting the immune checkpoint PDL1 potently activated Notch in co-cultures of Notch1- and PDL1-expressing cells, but not in monocultures of Notch1-expressing cells alone. Additional SNAGs targeting the tumor antigens CD19 and HER2 also activated Notch in mixed cell populations, indicating that the SNAG design concept is adaptable to multiple biomarkers. SNAG-mediated Notch activation was blocked by a dynamin inhibitor, and efficacy increased dramatically when SNAGs were dimerized via fusion to antibody Fc domains, suggesting that endocytosis and multimerization are important for optimal SNAG function. These insights will greatly expand our ability to modulate Notch signaling for applications in immunotherapy and regenerative medicine.

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BACKGROUND: The purpose of this study is to analyze the long-term evolution of patients with small choroidal melanocytic tumors (SCMTs) undergoing observation, and to assess their rate of transformation into melanomas and survival. METHODS: A retrospective single-cohort study of patients with SCMTs (1-3 mm in height and 5-10 mm in base) diagnosed from January 1992 to February 2023 was carried out, with observation as the initial treatment. The main criterion for a transformation into melanoma is considered to be an increase in size of more than 1 mm in height and/or more than 1 mm in base measured on an ultrasound/retinography, recorded in two consecutive visits separated by one to three months. RESULTS: 243 patients were included with a mean age of 65.3 years and a mean follow-up of 7.9 years (6 months-27.9 years); 27 patients showed tumor growth. The probabilities of growth at 5, 10, and 15 years are 10%, 14%, and 17%, respectively. Regarding survival, 22 patients died and only 3 deaths were due to melanoma metastasis. Survival rates at 5 and 10 years are 99% and 97%. CONCLUSIONS: Observation is a viable therapeutic option for SCMTs, avoiding the side effects of treatment, considering the majority of these tumors do not progress to melanoma. With close monitoring, patients can be treated promptly upon detecting a transformation. Additionally, the findings confirm that small melanocytic tumors can lead to metastatic disease, albeit at a low rate.

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AIM: To describe the latest scientific evidence regarding community-based interventions performed on patients in need of palliative care worldwide. INTRODUCTION AND BACKGROUND: Given the rise of chronic diseases, their complexities and the fragility of patients, we are facing around 56.8 million people in need of palliative care. Community-based healthcare, particularly palliative care, can address social inequalities and improve the biopsychosocial health of disadvantaged populations. Therefore, primary care, as the main health referent in the community, has a central role in the care of these patients. METHODS: This is an integrative review from January 2017 to June 2022 that follows the PRISMA statement and has been registered in PROSPERO. PubMed, Cuiden, the Web of Science (WoS), Cochrane and LILACS were the five databases searched. The scientific quality assessment of the articles was carried out following the CASPe methodology. Study selection was carried out by two researchers, A.V.L. and J.M.C.T., using the inclusion and exclusion criteria mentioned below. In cases of doubt or discrepancy, a third author (J.R.S.) was consulted. RESULTS: The interventions mentioned in the 16 articles analysed were classified under the following categories: music therapy, laughter therapy, spiritual and cognitive interventions, aromatherapy, interdisciplinary and community-based teams, advance care planning and community, volunteering, telemedicine and care mapping. EXAMPLE: Educating people to talk about different ethical issues could improve their quality of life and help develop more compassionate cities. CONCLUSIONS: We have identified interventions that are easily accessible (laughter therapy, telemedicine or music therapy), simple enough to be carried out at the community level and do not incur high costs. This is why they are recommended for people with palliative care needs in order to improve their quality of life.

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BACKGROUND: Unknown cardioembolic sources are frequent causes of cryptogenic stroke. We analyzed the risk of atrial fibrillation (AF) or high burden of ectopic atrial activity (HBEA) in patients with cryptogenic stroke, assessing atrial function and 1-year outcomes. METHODS AND RESULTS: The ARIES (Atrial Imaging and Cardiac Rhythm in Cryptogenic Embolic Stroke) study is an observational study including patients with cryptogenic stroke. We analyzed the frequency of AF and HBEA (>3000 atrial ectopic beats/day or >2 bursts or atrial tachycardia between 3 beats and ≤30 seconds) in two 30-day Holter-ECGs, comparing advanced echocardiography signs of left atrial (LA) dysfunction according to rhythm: AF, HBEA, and normal sinus rhythm. We also evaluated 1-year stroke recurrence and mortality. The study included 109 patients; 35 (32.1%) patients had AF, 27 (24.8%) HBEA, and 47 (43.1%) normal sinus rhythm. Compared with those with normal sinus rhythm, patients with AF presented higher 2-dimensional and 3-dimensional LA indexed volumes (38.8±11.2 versus 27.3±11.8 mL/m2, and 50.6±17.2 versus 34.0±15.4 mL/m2, respectively, P<0.001), lower 3-dimensional LA ejection fraction (50±14.6 versus 62.7±11.8, P=0.001), LA reservoir strain (22.0±8.6 versus 30.4±10.5, P<0.001), and LA contraction strain (10.5±8.18 versus 17.1±7.5, P<0.001), remaining significant in multivariate analysis. Patients with HBEA showed higher LA indexed volumes and lower LA reservoir strain than patients with normal sinus rhythm only in univariate analysis. There were no differences in ischemic recurrence or mortality among the groups. CONCLUSIONS: Patients with cryptogenic stroke showed a high incidence of AF and HBEA. AF is strongly related to LA volume, LA function, and LA reservoir and contraction strain, whereas HBEA showed milder structural changes. Advanced LA echocardiography could help patient selection for long-term ECG monitoring in suspected cardiac sources.

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Fibrilación Atrial , Función del Atrio Izquierdo , Electrocardiografía Ambulatoria , Accidente Cerebrovascular Embólico , Recurrencia , Humanos , Masculino , Femenino , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/diagnóstico , Anciano , Persona de Mediana Edad , Accidente Cerebrovascular Embólico/etiología , Accidente Cerebrovascular Embólico/fisiopatología , Función del Atrio Izquierdo/fisiología , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/fisiopatología , Frecuencia Cardíaca/fisiología , Factores de Riesgo , Complejos Atriales Prematuros/fisiopatología , Complejos Atriales Prematuros/diagnóstico , Complejos Atriales Prematuros/complicaciones , Complejos Atriales Prematuros/epidemiología , Ecocardiografía/métodos , Factores de Tiempo , Medición de Riesgo/métodos

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Implants made from titanium are used as prostheses because of their biocompatibility and their mechanical properties close to those of human bone. However, the risk of bacterial infection is always a major concern during surgery, and the development of biofilm can make these infections difficult to treat. A promising strategy to mitigate against bacterial infections is the use of antifouling and antimicrobial coatings, where bioresorbable polymers can play an important role due to their controlled degradability and sustained drug release, as well as excellent biocompatibility. In the present study, poly(d,l-lactide) (PDLLA) and poly[d,l-lactide-co-methyl ether poly(ethylene glycol)] (PDLLA-PEG) were studied, varying the PEG content (20-40% w/w) to analyze the effectiveness of PEG as an antifouling molecule. In addition, silver sulfadiazine (AgSD) was used as an additional antimicrobial agent with a concentration ≤5% w/w and incorporated into the PEGylated polymers to create a polymer with both antifouling and antimicrobial properties. Polymers synthesized were applied using spin coating to obtain homogeneous coatings to protect samples made from titanium/aluminum/vanadium (Ti6Al4V). The polymer coatings had a smoothing effect in comparison to that of the uncoated material, decreasing the contact area available for bacterial colonization. It was also noted that PEG addition into the polymeric chain developed amphiphilic materials with a decrease in contact angle from the most hydrophobic (Ti6Al4V) to the most hydrophilic PDLLA-PEG (60/40), highlighting the increase in water uptake contributing to the hydration layer formation, which confers the antifouling effect on the coating. This study demonstrated that the addition of PEG above 20% w/w and AgSD above 1% w/v into the formulation was able to decrease bacterial adherence against clinically relevant biofilm former strains Staphylococcus aureus and Pseudomonas aeruginosa.

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Aleaciones , Antibacterianos , Biopelículas , Materiales Biocompatibles Revestidos , Ensayo de Materiales , Poliésteres , Staphylococcus aureus , Titanio , Biopelículas/efectos de los fármacos , Titanio/química , Titanio/farmacología , Aleaciones/química , Aleaciones/farmacología , Poliésteres/química , Poliésteres/farmacología , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Staphylococcus aureus/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Humanos , Tamaño de la Partícula , Polietilenglicoles/química , Polietilenglicoles/farmacología , Propiedades de Superficie , Prótesis e Implantes

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BACKGROUND: Brain imaging studies investigating grey matter in functional neurological disorder (FND) have used univariate approaches to report group-level differences compared with healthy controls (HCs). However, these findings have limited translatability because they do not differentiate patients from controls at the individual-level. METHODS: 183 participants were prospectively recruited across three groups: 61 patients with mixed FND (FND-mixed), 61 age-matched and sex-matched HCs and 61 age, sex, depression and anxiety-matched psychiatric controls (PCs). Radial basis function support vector machine classifiers with cross-validation were used to distinguish individuals with FND from HCs and PCs using 134 FreeSurfer-derived grey matter MRI features. RESULTS: Patients with FND-mixed were differentiated from HCs with an accuracy of 0.66 (p=0.005; area under the receiving operating characteristic (AUROC)=0.74); this sample was also distinguished from PCs with an accuracy of 0.60 (p=0.038; AUROC=0.56). When focusing on the functional motor disorder subtype (FND-motor, n=46), a classifier robustly differentiated these patients from HCs (accuracy=0.72; p=0.002; AUROC=0.80). FND-motor could not be distinguished from PCs, and the functional seizures subtype (n=23) could not be classified against either control group. Important regions contributing to statistically significant multivariate classifications included the cingulate gyrus, hippocampal subfields and amygdalar nuclei. Correctly versus incorrectly classified participants did not differ across a range of tested psychometric variables. CONCLUSIONS: These findings underscore the interconnection of brain structure and function in the pathophysiology of FND and demonstrate the feasibility of using structural MRI to classify the disorder. Out-of-sample replication and larger-scale classifier efforts incorporating psychiatric and neurological controls are needed.

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Objective: In patients with iron deficiency anaemia (IDA), the diagnostic yield of gastroscopy and colonoscopy (bidirectional endoscopy) in detecting neoplastic lesions is low. This study aimed to develop and validate a faecal immunochemical test (FIT)-based model to optimise the work-up of patients with IDA. Methods: Outpatients with IDA were enrolled in a prospective, multicentre study from April 2016 to October 2019. One FIT was performed before bidirectional endoscopy. Significant gastrointestinal lesions were recorded and a combined model developed with variables that were independently associated with significant colorectal lesions in the multivariate analysis. The model cut-off was selected to provide a sensitivity of at least 95% for colorectal cancer (CRC) detection, and its performance was compared to different FIT cut-offs. The data set was randomly split into two groups (developed and validation cohorts). An online calculator was developed for clinical application. Results: The development and validation cohorts included 373 and 160 patients, respectively. The developed model included FIT value, age, and sex. In the development and validation cohorts, a model cut-off of 0.1375 provided a negative predictive value of 98.1 and 96.7% for CRC and 90.7 and 88.3% for significant colorectal lesions, respectively. This combined model reduced the rate of missed significant colorectal lesions compared to FIT alone and could have avoided more than one-fourth of colonoscopies. Conclusion: The FIT-based combined model developed in this study may serve as a useful diagnostic tool to triage IDA patients for early endoscopic referral, resulting in considerable reduction of unnecessary colonoscopies.

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OBJECTIVE: To establish the construct validity of the Spanish version of the BARRIERS scale. METHOD: Methodological study of validation of a measurement instrument based on data from previously published studies. The study population consisted of nurses from the Basque Health Service and the Canary Health Service. The following variables were extracted and unified: Years of professional experience, possession of a specialist nursing degree, possession of a doctorate, type of activity performed by the professional and field of work. For construct validation, a confirmatory factor analysis (CFA) was performed based on the initial model proposed for the scale and RASCH analysis. A polychoric correlation matrix, factor extraction by unweighted least squares and PROMIN oblique rotation were used. For the RASCH analysis, the Joint Maximun Likelihood estimation (JMLE) method was used; the fit of the items and persons were estimated by means of outfit - Unweighted Mean Square fit statistic (UMS) and infit -Weighted Mean Square Fit Statistic (WMS), as well as the reliability and separation of items and persons. RESULTS: A total of 1200 nurses and midwives made up the final validation sample (n = 1200), with a mean professional experience of 21.22 ± 9.26 years. The CFA presented a good fit to the data (KMO = 0.935 [95% CI: 0.921-0.945]), changing the factorial assignment in 6 items, while 5 items received factorial scores in more than one factor. The fit values for the 4-factor solution were RMSEA = 0.026 [95% CI: 0.026-0.027] and GFI = 0.991 [95% CI: 0.986-0.991]. In the RASCH analysis most items presented infit-WMS and outfit-UMS values with a good fit. CONCLUSIONS: The Spanish version of the BARRIERS scale has adequate construct validity although there are changes in the assignment of items to the dimensions compared to the original model. The RASCH analysis indicates adequate fit for both persons and items.

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Autoinforme , Humanos , Reproducibilidad de los Resultados , España , Adulto , Femenino , Masculino , Persona de Mediana Edad

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Favipiravir is a ribonucleoside analogue that has been explored as a therapeutic for the treatment of Ebola Virus Disease (EVD). Promising data from rodent models has informed nonhuman primate trials, as well as evaluation in patients during the 2013-2016 West African EVD outbreak of favipiravir treatment. However, mixed results from these studies hindered regulatory approval of favipiravir for the indication of EVD. This study examined the influence of route of administration, duration of treatment, and treatment schedule of favipiravir in immune competent mouse and guinea pig models using rodent-adapted Zaire ebolavirus (EBOV). A dose of 300 mg/kg/day of favipiravir with an 8-day treatment was found to be fully effective at preventing lethal EVD-like disease in BALB/c mice regardless of route of administration (oral, intraperitoneal, or subcutaneous) or whether it was provided as a once-daily dose or a twice-daily split dose. Preclinical data generated in guinea pigs demonstrates that an 8-day treatment of 300 mg/kg/day of favipiravir reduces mortality following EBOV challenge regardless of route of treatment or duration of treatments for 8, 11, or 15 days. This work supports the future translational development of favipiravir as an EVD therapeutic.

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Amidas , Antivirales , Modelos Animales de Enfermedad , Ebolavirus , Fiebre Hemorrágica Ebola , Ratones Endogámicos BALB C , Pirazinas , Animales , Amidas/uso terapéutico , Amidas/administración & dosificación , Amidas/farmacología , Cobayas , Pirazinas/administración & dosificación , Pirazinas/uso terapéutico , Fiebre Hemorrágica Ebola/tratamiento farmacológico , Ratones , Ebolavirus/efectos de los fármacos , Antivirales/administración & dosificación , Antivirales/uso terapéutico , Femenino , Vías de Administración de Medicamentos , Esquema de Medicación

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The primary aim of this literature review is to delineate the key inflammatory cytokines involved in the pathophysiology of pulp inflammation. By elucidating the roles of these cytokines, a deeper comprehension of the distinct stages of inflamed pulp can be attained, thereby facilitating more accurate diagnostic strategies in endodontics. The PRISMA statement and Cochrane handbook were used for the search strategy. The keywords were created based on the review question using the PICO framework. The relevant studies were meticulously assessed according to predefined inclusion and exclusion criteria for this systematic review. A rigorous quality checklist was implemented to evaluate each included study, ensuring scrutiny for both quality and risk-of-bias assessments. The initial pilot search conducted on PubMed, Scopus, Cochrane, and WoS databases yielded 9 pertinent articles. Within these articles, multiple cytokines were identified and discussed as potential candidates for use in endodontic diagnosis, notably including IL-8, IL-6, TNF-α, and IL-2. These cytokines have been highlighted due to their significant roles in the inflammatory processes associated with pulp pathology. The identification of specific inflammatory cytokines holds promise for enhancing endodontic diagnostic procedures and exploring diverse treatment modalities. However, the current body of research in this area remains limited. Further comprehensive studies are warranted to fully elucidate the potential of cytokines in refining diagnostic techniques in endodontics.

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Eosinophils are myeloid effector cells whose main homing is the gastrointestinal tract. There, they take part in type I and type II immune responses. They also contribute to other non-immunological homeostatic functions like mucus production, tissue regeneration, and angiogenesis. In colorectal cancer (CRC), eosinophils locate in the center of the tumor and in the front of invasion and play an anti-tumoral role. They directly kill tumor cells by releasing cytotoxic compounds and eosinophil extracellular traps or indirectly by activating other immune cells via cytokines. As CRC progresses, the number of infiltrating eosinophils decreases. Although this phenomenon is not fully understood, it is known that some changes in the microenvironmental milieu and microbiome can affect eosinophil infiltration. Importantly, a high number of intratumoral eosinophils is a favorable prognostic factor independent from the tumor stage. Moreover, after immunotherapy, responding patients usually display eosinophilia, so eosinophils could be a good biomarker candidate to monitor treatment outcomes. Finally, even though eosinophils seem to play an interesting anti-tumoral role in CRC, much more research is needed to fully understand their interactions in the CRC microenvironment. This review explores the multifaceted roles of eosinophils in colorectal cancer, highlighting their anti-tumoral effects, prognostic significance, and potential as a biomarker for treatment outcomes.

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Neoplasias Colorrectales , Eosinófilos , Microambiente Tumoral , Humanos , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Eosinófilos/inmunología , Eosinófilos/metabolismo , Microambiente Tumoral/inmunología , Pronóstico , Animales , Inmunoterapia/métodos , Biomarcadores de Tumor/metabolismo

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Background and aims Patients’ perception of their bowel cleansing quality may guide rescue cleansing strategies before colonoscopy. The main aim of this study was to train and validate a convolutional neural network (CNN) for classifying rectal effluent during bowel preparation intake as “adequate” or “inadequate” cleansing before colonoscopy.Patients and methodsPatients referred for outpatient colonoscopy were asked to provide images of their rectal effluent during the bowel preparation process. The images were categorized as adequate or inadequate cleansing based on a predefined 4-picture quality scale. A total of 1203 images were collected from 660 patients. The initial dataset (799 images), was split into a training set (80%) and a validation set (20%). The second dataset (404 images) was used to develop a second test of the CNN accuracy. Afterward, CNN prediction was prospectively compared with the Boston Bowel Preparation Scale (BBPS) in 200 additional patients who provided a picture of their last rectal effluent.ResultsOn the initial dataset, a global accuracy of 97.49%, a sensitivity of 98.17% and a specificity of 96.66% were obtained using the CNN model. On the second dataset, an accuracy of 95%, a sensitivity of 99.60% and a specificity of 87.41% were obtained. The results from the CNN model were significantly associated with those from the BBPS (P<0.001), and 77.78% of the patients with poor bowel preparation were correctly classified.ConclusionThe designed CNN is capable of classifying “adequate cleansing” and “inadequate cleansing” images with high accuracy. (AU)

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Antecedentes y objetivos La percepción de los pacientes sobre la calidad de su limpieza intestinal puede guiar las estrategias de limpieza de rescate antes de una colonoscopia. El objetivo principal de este estudio fue entrenar y validar una red neuronal convolucional (CNN) para clasificar el efluente rectal durante la preparación intestinal como «adecuado» o «inadecuado».Pacientes y métodosPacientes no seleccionados proporcionaron imágenes del efluente rectal durante el proceso de preparación intestinal. Las imágenes fueron categorizadas como una limpieza adecuada o inadecuada según una escala de calidad de 4 imágenes predefinida. Se recopilaron un total de 1.203 imágenes de 660 pacientes. El conjunto de datos inicial (799 imágenes) se dividió en un conjunto de entrenamiento (80%) y un conjunto de validación (20%). Un segundo conjunto de datos (404 imágenes) se utilizó para evaluar la precisión de la CNN. Posteriormente, la predicción de la CNN se comparó prospectivamente con la escala de preparación colónica de Boston (BBPS) en 200 pacientes que proporcionaron una imagen de su último efluente rectal.ResultadosEn el conjunto de datos inicial, la precisión global fue del 97,49%, la sensibilidad del 98,17% y la especificidad del 96,66%. En el segundo conjunto de datos, se obtuvo una precisión del 95%, una sensibilidad del 99,60% y una especificidad del 87,41%. Los resultados del modelo de CNN se asociaron significativamente con la escala de preparación colónica de Boston (p<0,001), y el 77,78% de los pacientes con una preparación intestinal deficiente fueron clasificados correctamente.ConclusiónLa CNN diseñada es capaz de clasificar imágenes de «limpieza adecuada» y «limpieza inadecuada» con alta precisión. (AU)

Asunto(s)

Humanos , Inteligencia Artificial , Colonoscopía