Withdrawal of drug therapy in responders to cardiac resynchronization therapy: rationale and design of the REMOVE trial.

Introduction and objectives Cardiac resynchronization therapy (CRT) is an effective treatment for patients with nonischemic dilated cardiomyopathy associated with left bundle branch block (LBBB). In these patients, the device can normalize left ventricular ejection fraction (LVEF). Nevertheless, it remains unclear whether CRT responders still require neurohormonal blockers. The aim of this study is to determine the long-term safety of withdrawing drug therapy in these patients. Methods The REMOVE trial (NCT05151861) is a prospective, multicenter, open-label and randomized 1:1 study designed to assess the effect of withdrawing neurohormonal blockers in patients with nonischemic dilated cardiomyopathy associated with left bundle branch block who recovered LVEF after CRT. The study will include a 12-month follow-up with the option to continue into the follow-up extension phase for up to 24 months. The primary endpoint is the recurrence of cardiomyopathy defined as any of the following criteria: a) a reduction in LVEF > 10% (provided the LVEF is < 50%); b) a reduction in LVEF > 10% accompanied by an increase > 15% in the indexed end-systolic volume relative to the previous value and in a range higher than the normal values, or c) decompensated heart failure requiring intravenous diuretic administration. In patients meeting the primary endpoint, drug therapy will be restarted. Conclusions The results of this study will help to enhance our understanding of CRT superresponders, a specific group of patients.

N-terminal pro-B-type natriuretic peptide post-discharge monitoring in the management of patients with heart failure and preserved ejection fraction - a randomized trial: The NICE study.

AIMS: There is a lack of specific studies assessing the impact of natriuretic peptide monitoring in the post-discharge management of patients with heart failure (HF) and preserved ejection fraction (HFpEF), throughout the vulnerable phase following acute HF hospitalization. The NICE study aims to assess the clinical benefit of incorporating N-terminal pro-B-type natriuretic peptide (NT-proBNP) into the post-discharge management of HFpEF patients. METHODS AND RESULTS: Individuals admitted with HFpEF (left ventricular ejection fraction >50%) were included in a multicentre randomized controlled study employing an open-label design with event blinding (NCT02807168). Upon discharge, 157 patients were randomly allocated to either NT-proBNP monitoring (n = 79) or no access to NT-proBNP (control group, n = 78) during pre-scheduled visits at 2, 4 and 12 weeks. Clinical endpoints were evaluated at 6 months. The primary endpoint of HF rehospitalizations occurred in 12.1% patients, without significant differences observed between the NT-proBNP monitoring group (12.8%) and the control group (11.4%) (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.47-2.81, p = 0.760). Regarding secondary endpoints, the NT-proBNP monitoring group demonstrated a significantly lower risk of death (1.3% vs. 10.1%; HR 0.12, 95% CI 0.02-0.09), whereas non-HF hospitalizations (12.8% vs. 19.0%, p = 0.171) and any adverse clinical event (26.9% vs. 36.7%, p = 0.17) did not reach statistical significance. Awareness of NT-proBNP levels were associated with higher doses of diuretics and renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers) in the NT-proBNP monitoring group. CONCLUSIONS: Post-discharge monitoring of NT-proBNP in HFpEF patients did not exhibit an association with reduced rates of HF hospitalization in this study. Nonetheless, it appears to enhance global clinical management by optimizing medical therapies and contributing to improved overall survival.

Value of increased soluble suppressor tumorigenicity biomarker 2 (sST2) on admission as an indicator of severity in patients with COVID-19 / Valor del aumento del biomarcador supresor soluble de tumorigenicidad 2 (sST2) al ingreso como indicador de gravedad en pacientes con COVID-19

Background Soluble suppressor of tumorigenicity-2 (sST2) is a biomarker for heart failure and pulmonary injury. We hypothesize that sST2 could help predict severity of SARS-CoV-2 infections. Methods sST2 was analyzed in patients consecutively admitted for SARS-CoV-2 pneumonia. Other prognostic markers were also measured. In-hospital complications were registered, including death, ICU admission, and respiratory support requirements. Results 495 patients were studied (53% male, age: 57.6±17.6). At admission, median sST2 concentrations was 48.5ng/mL [IQR, 30.6–83.1ng/mL] and correlated with male gender, older age, comorbidities, other severity biomarkers, and respiratory support requirements. sST2 levels were higher in patients who died (n=45, 9.1%) (45.6 [28.0, 75.9]ng/mL vs. 144 [82.6, 319] ng/mL, p<0.001) and those admitted to ICU (n=46, 9.3%) (44.7 [27.5, 71.3] ng/mL vs. 125 [69.0, 262]ng/mL, p<0.001). sST2 levels>210ng/mL were a strong predictor of complicated in-hospital courses, with higher risk of death (OR, 39.3, CI95% 15.9, 103) and death/ICU (OR 38.3, CI95% 16.3–97.5) after adjusting for all other risk factors. The addition of sST2 enhanced the predictive capacity of mortality risk models. Conclusions sST2 represents a robust severity predictor in COVID-19 and could be an important tool for identifying at-risk patients who may benefit from closer follow-up and specific therapies (AU)

Antecedentes El supresor soluble de tumorigenicidad 2 (sST2) es un biomarcador de insuficiencia cardiaca y daño pulmonar. Nuestra hipótesis es que la determinación de sST2 al ingreso podría ayudar a predecir la gravedad de la infección por SARS-CoV-2. Métodos Se analizó la concentración de sST2 en pacientes ingresados por neumonía por SARS-CoV-2, junto con otros biomarcadores pronósticos conocidos. Asimismo, se registraron las complicaciones durante la estancia hospitalaria, incluidas la muerte, el ingreso en Unidad de Cuidados Intensivos (UCI) y los requerimientos de soporte respiratorio. Resultados Se estudiaron 495 pacientes (53% hombres, edad 57,6 ± 17,6). Al ingreso, la mediana de la concentración de sST2 fue 48,5 ng/mL (índice intercuartílico [IQR] 30,6-83,1 ng/mL) y correlacionó con el género masculino, una mayor edad, comorbilidades, otros biomarcadores de gravedad, así como necesidad de soporte respiratorio. Los niveles de sST2 fueron mayores en pacientes que fallecieron (n = 45, 9,1%) (45,6 [28,0, 75,9] ng/mL vs. 144 [82,6, 319] ng/mL, p < 0,001) y aquellos que requirieron ingreso en UCI (n = 46, 9,3%) (44,7 [27,5, 71,3] ng/mL vs. 125 [69,0, 262] ng/mL, p < 0,001). Así, los valores de sST2 > 210 ng/mL se han demostrado como un fuerte predictor de complicaciones, con un mayor riesgo de fallecimiento (odds ratio [OR], 39,3, intervalo de confianza [IC] 95% 15,9, 103) y fallecimiento o ingreso en UCI (OR 38,3, IC 95% 16,3-97,5), tras el ajuste por todos los demás factores de riesgo. La adición de la determinación de los niveles de sST2 mejoró la potencia predictiva de los modelos de riesgo desarrollados. Conclusiones El sST2 representa un predictor robusto de la gravedad en pacientes con COVID-19 y podría convertirse en una herramienta importante para la identificación de pacientes en riesgo que podrían beneficiarse de un mayor seguimiento y terapias específicas (AU)

Increased risk of hospitalization and death in Mexican children and adolescents with COVID-19 and comorbidities.

BACKGROUND: Although COVID-19 (coronavirus disease 2019) in children is usually mild, they need hospitalization and intensive care in exceptional cases. Adverse outcomes have been observed mainly among children with comorbidities, justifying their vaccination. This study aimed to assess the risk of hospitalization and death in Mexican children and adolescents with COVID-19 and comorbidities. METHODS: A cross-sectional study was performed on 366,542 confirmed COVID-19 cases under 18 years, reported by the Mexican Ministry of Health up to July 9, 2022. Logistic regression models were performed. RESULTS: The mean age was 10.98 years, 50.6% were male, and 7.3% reported at least one comorbidity. The percentage of hospitalization and death in COVID-19 patients with and without comorbidities was 3.52%, and 0.20%, respectively; children with comorbidities presented a higher percentage of hospitalization (14.0%) and death (1.9%). The probability of hospitalization was 5.6 times greater in pediatric patients with COVID-19 and comorbidities, and the comorbidities that showed the greatest risk were immunosuppression (odds ratio (OR) 22.06), chronic kidney disease (CKD) (11.36), and cardiovascular diseases (5.66). The probability of death in patients with comorbidities was 11.01 times higher than in those without diseases, and the highest risk was observed in those with CKD (OR 12.57), cardiovascular diseases (6.87), and diabetes (5.83). CONCLUSIONS: Pediatric patients with comorbidities presented a higher risk of severe COVID-19. It is suggested that vaccination should be promoted with greater emphasis on pediatric patients with comorbidities.

INTRODUCCIÓN: Aunque COVID-19 (enfermedad por coronavirus 2019) en niños es usualmente leve, en casos excepcionales requieren hospitalización y cuidados intensivos. Los resultados adversos han sido observados principalmente en los niños con comorbilidades, justificando su vacunación. El objetivo de este estudio fue evaluar el riesgo de hospitalización y muerte en niños y adolescentes mexicanos con COVID-19 y comorbilidades. MÉTODOS: Estudio transversal en 366,542 casos de COVID-19 confirmados, menores de 18 años y reportados por la Secretaría de Salud de México, hasta el 9 de julio del 2022. Se ejecutaron modelos multivariados de regresión logística. RESULTADOS: El promedio de edad fue de 10.98 años, 50.6% de sexo masculino, y 7.3% reportaron al menos una comorbilidad. El porcentaje de hospitalización y muerte en pacientes con COVID-19 sin comorbilidades fue 3.52% y 0.20%, respectivamente; mientras que los pacientes con comorbilidades presentaron más elevados porcentajes de hospitalización (14.0%) y muerte (1.9%). La probabilidad de hospitalización fue 5.6 veces más en los pacientes con COVID-19 y comorbilidades, comparando con aquellos sin comorbilidades. Las comorbilidades que mostraron más riesgo fueron inmunosupresión (razón de momios (RM) 22.06), enfermedad renal crónica (ERC) (RM 11.36) y enfermedades cardiovasculares (RM 5.66). La probabilidad de muerte en los pacientes con comorbilidades fue 11.01 veces más que en aquellos sin enfermedades, y fue más elevado en aquellos con ERC (RM 12.57), enfermedades cardiovasculares (RM 6.87) y diabetes (RM 5.83). CONCLUSIONES: Los pacientes pediátricos con comorbilidades presentaron mayor riesgo de COVID-19 severo, por lo que se sugiere promover con mayor énfasis la vacunación en ellos.

Value of increased soluble suppressor tumorigenicity biomarker 2 (sST2) on admission as an indicator of severity in patients with COVID-19.

BACKGROUND: Soluble suppressor of tumorigenicity-2 (sST2) is a biomarker for heart failure and pulmonary injury. We hypothesize that sST2 could help predict severity of SARS-CoV-2 infections. METHODS: sST2 was analyzed in patients consecutively admitted for SARS-CoV-2 pneumonia. Other prognostic markers were also measured. In-hospital complications were registered, including death, ICU admission, and respiratory support requirements. RESULTS: 495 patients were studied (53% male, age: 57.6±17.6). At admission, median sST2 concentrations was 48.5ng/mL [IQR, 30.6-83.1ng/mL] and correlated with male gender, older age, comorbidities, other severity biomarkers, and respiratory support requirements. sST2 levels were higher in patients who died (n=45, 9.1%) (45.6 [28.0, 75.9]ng/mL vs. 144 [82.6, 319] ng/mL, p<0.001) and those admitted to ICU (n=46, 9.3%) (44.7 [27.5, 71.3] ng/mL vs. 125 [69.0, 262]ng/mL, p<0.001). sST2 levels>210ng/mL were a strong predictor of complicated in-hospital courses, with higher risk of death (OR, 39.3, CI95% 15.9, 103) and death/ICU (OR 38.3, CI95% 16.3-97.5) after adjusting for all other risk factors. The addition of sST2 enhanced the predictive capacity of mortality risk models. CONCLUSIONS: sST2 represents a robust severity predictor in COVID-19 and could be an important tool for identifying at-risk patients who may benefit from closer follow-up and specific therapies.

Increased risk of hospitalization and death in Mexican children and adolescents with COVID-19 and comorbidities / Riesgo incrementado de hospitalización y muerte en niños y adolescentes mexicanos con COVID-19 y comorbilidad

Abstract Background: Although COVID-19 (coronavirus disease 2019) in children is usually mild, they need hospitalization and intensive care in exceptional cases. Adverse outcomes have been observed mainly among children with comorbidities, justifying their vaccination. This study aimed to assess the risk of hospitalization and death in Mexican children and adolescents with COVID-19 and comorbidities. Methods: A cross-sectional study was performed on 366,542 confirmed COVID-19 cases under 18 years, reported by the Mexican Ministry of Health up to July 9, 2022. Logistic regression models were performed. Results: The mean age was 10.98 years, 50.6% were male, and 7.3% reported at least one comorbidity. The percentage of hospitalization and death in COVID-19 patients with and without comorbidities was 3.52%, and 0.20%, respectively; children with comorbidities presented a higher percentage of hospitalization (14.0%) and death (1.9%). The probability of hospitalization was 5.6 times greater in pediatric patients with COVID-19 and comorbidities, and the comorbidities that showed the greatest risk were immunosuppression (odds ratio (OR) 22.06), chronic kidney disease (CKD) (11.36), and cardiovascular diseases (5.66). The probability of death in patients with comorbidities was 11.01 times higher than in those without diseases, and the highest risk was observed in those with CKD (OR 12.57), cardiovascular diseases (6.87), and diabetes (5.83). Conclusions: Pediatric patients with comorbidities presented a higher risk of severe COVID-19. It is suggested that vaccination should be promoted with greater emphasis on pediatric patients with comorbidities.

Resumen Introducción: Aunque COVID-19 (enfermedad por coronavirus 2019) en niños es usualmente leve, en casos excepcionales requieren hospitalización y cuidados intensivos. Los resultados adversos han sido observados principalmente en los niños con comorbilidades, justificando su vacunación. El objetivo de este estudio fue evaluar el riesgo de hospitalización y muerte en niños y adolescentes mexicanos con COVID-19 y comorbilidades. Métodos: Estudio transversal en 366,542 casos de COVID-19 confirmados, menores de 18 años y reportados por la Secretaría de Salud de México, hasta el 9 de julio del 2022. Se ejecutaron modelos multivariados de regresión logística. Resultados: El promedio de edad fue de 10.98 años, 50.6% de sexo masculino, y 7.3% reportaron al menos una comorbilidad. El porcentaje de hospitalización y muerte en pacientes con COVID-19 sin comorbilidades fue 3.52% y 0.20%, respectivamente; mientras que los pacientes con comorbilidades presentaron más elevados porcentajes de hospitalización (14.0%) y muerte (1.9%). La probabilidad de hospitalización fue 5.6 veces más en los pacientes con COVID-19 y comorbilidades, comparando con aquellos sin comorbilidades. Las comorbilidades que mostraron más riesgo fueron inmunosupresión (razón de momios (RM) 22.06), enfermedad renal crónica (ERC) (RM 11.36) y enfermedades cardiovasculares (RM 5.66). La probabilidad de muerte en los pacientes con comorbilidades fue 11.01 veces más que en aquellos sin enfermedades, y fue más elevado en aquellos con ERC (RM 12.57), enfermedades cardiovasculares (RM 6.87) y diabetes (RM 5.83). Conclusiones: Los pacientes pediátricos con comorbilidades presentaron mayor riesgo de COVID-19 severo, por lo que se sugiere promover con mayor énfasis la vacunación en ellos.

Refractory anorexia nervosa in adulthood and nucleus accumbens deep brain stimulation.

Background: Anorexia Nervosa is a life-threatening mental illness with numerous consequences. Some cases are chronic and refractory to multiple treatments. Consequently, there is great interest in therapeutic alternatives that may improve severe patients. We present an adult patient with anorexia nervosa that underwent to bilateral nucleus accumbens deep brain stimulation (NAc-DBS). Case description: The patient was a healthy 46-year-old woman with higher education and an adequate premorbid socio-labour situation. Her disease had a late onset (25 years). The patient never presented clinical remission or weight stability. In recent years, the patient's body mass index (BMI) was 13.16 (32kg). The case was evaluated with multiple neuropsychological tests as well as the BMI before and after surgery. The clinical follow-up was 50 months. After bilateral NAc-DBS the patient experienced an important clinical benefit and significant improvement in neuropsychological tests and weight (BMI 17.28, 42 kg; 50th month) Programming: 4,5V, 130Hz, 210 µs. Conclusion: Despite the patient´s age and the long duration of the disease, our results suggest that bilateral nucleus accumbens stimulation may be a useful and effective therapeutic strategy for cases such as the one presented. Additionally, this case presents a surgical midlife patient with both the latest disease onset and the longest follow-up after treatment in the literature.

Carbapenemase-Encoding Genes and Colistin Resistance in Gram-Negative Bacteria During the COVID-19 Pandemic in Mexico: Results from the Invifar Network.

In this study, we report the carbapenemase-encoding genes and colistin resistance in Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa in the second year of the COVID-19 pandemic. Clinical isolates included carbapenem-resistant K. pneumoniae, carbapenem-resistant E. coli, carbapenem-resistant A. baumannii, and carbapenem-resistant P. aeruginosa. Carbapenemase-encoding genes were detected by PCR. Carbapenem-resistant K. pneumoniae and carbapenem-resistant E. coli isolates were analyzed using the Rapid Polymyxin NP assay. mcr genes were screened by PCR. Pulsed-field gel electrophoresis and whole-genome sequencing were performed on representative isolates. A total of 80 carbapenem-resistant E. coli, 103 carbapenem-resistant K. pneumoniae, 284 carbapenem-resistant A. baumannii, and 129 carbapenem-resistant P. aeruginosa isolates were recovered. All carbapenem-resistant E. coli and carbapenem-resistant K. pneumoniae isolates were included for further analysis. A selection of carbapenem-resistant A. baumannii and carbapenem-resistant P. aeruginosa strains was further analyzed (86 carbapenem-resistant A. baumannii and 82 carbapenem-resistant P. aeruginosa). Among carbapenem-resistant K. pneumoniae and carbapenem-resistant E. coli isolates, the most frequent gene was blaNDM (86/103 [83.5%] and 72/80 [90%], respectively). For carbapenem-resistant A. baumannii, the most frequently detected gene was blaOXA-40 (52/86, 60.5%), and for carbapenem-resistant P. aeruginosa, was blaVIM (19/82, 23.2%). For carbapenem-resistant A. baumannii, five indistinguishable pulsotypes were detected. Circulation of K. pneumoniae New Delhi metallo-ß-lactamase (NDM) and E. coli NDM was detected in Mexico. High virulence sequence types (STs), such as K. pneumoniae ST307, E. coli ST167, P. aeruginosa ST111, and A. baumannii ST2, were detected. Among K. pneumoniae isolates, 18/101 (17.8%) were positive for the Polymyxin NP test (two, 11.0% positive for the mcr-1 gene, and one, 5.6% with disruption of the mgrB gene). All E. coli isolates were negative for the Polymyxin NP test. In conclusion, K. pneumoniae NDM and E. coli NDM were detected in Mexico, with the circulation of highly virulent STs. These results are relevant in clinical practice to guide antibiotic therapies considering the molecular mechanisms of resistance to carbapenems.

Multidecadal fluctuations in green turtle hatchling production related to climate variability.

The state of Campeche, Mexico, harbors one of the largest green turtle (Chelonia mydas) rookeries of the Wider Caribbean Region. Since the 1970s, harvesting of this population was common practice, but it has since ceased, and the population is rebounding as a consequence. In this rookery, during the past 37 years (1984-2020), the positive relationship between the annual number of nesting females and the number of hatchlings they produce has revealed a long-term population signal that we postulate could be related to environmental factors. To investigate this relationship more deeply, we adopt a stock-recruitment (SR) approach, which is commonly used in fisheries. Regression analysis methods for the SR relationship, including a dynamic version of the model that incorporates the effect of sea surface temperature, show that the number of recruits produced and the number of hatchlings per unit nester were significantly and inversely correlated with a 26-year cycle of the Atlantic Multidecadal Oscillation (AMO) with a three year lag. A possible explanation for this finding is that environmental conditions during warming periods of the 26-year AMO cycle may negatively affect hatchling production by altering the nest moisture content during the incubation period, and increasing embryonic mortality, while the annual female abundance at nesting beaches may decrease due to trophic effects. The time series of abundance corresponding to other population units of green turtles as well as other species of sea turtles in the Gulf of Mexico present a similar behavior to that evaluated here, suggesting a basin-wide environmental effect.

Trends in Reproductive Indicators of Green and Hawksbill Sea Turtles over a 30-Year Monitoring Period in the Southern Gulf of Mexico and Their Conservation Implications.

Long-term monitoring programs of species at risk are efficacious tools to assess population changes, evaluate conservation strategies, and improve management practices to ensure populations reach levels at which they can fulfill their ecological roles. For sea turtles, annual nesting beach surveys are the most accessible method to estimating the population abundance and reproductive output, especially when these are done in primary nesting sites. However, little data exist on the long-term assessment of these parameters. Here, we present the trends of the nest abundance, female size, hatching, and emergence success of hawksbill (Eretmochelys imbricata) and green (Chelonia mydas) turtles at key nesting beaches in the southern Gulf of Mexico over 31 years (from 1990 to 2021). The nest abundance showed an increasing trend in both species as a result of the sustained protection and conservation effort, but there was no significant temporal trend in the annual female size, clutch size, hatching, and emergence success. However, these indicators showed decreasing mean values over the last decade and should be closely monitored. We suggest these decreases link to the combined effects of ocean warming and anthropogenic pressures affecting the sea turtle foraging grounds. Aside from protecting key nesting sites, protecting and restoring crucial foraging habitats should be an immediate priority requiring international cooperation.

Induction immunosuppression and outcome in kidney transplant recipients with early COVID-19 after transplantation.

Coronavirus disease 2019 (COVID-19) in kidney transplant recipients has a high risk of complications and mortality, especially in older recipients diagnosed during the early period after transplantation. Management of immunosuppression has been challenging during the pandemic. We investigated the impact of induction immunosuppression, either basiliximab or thymoglobulin, on the clinical evolution of kidney transplant recipients developing COVID-19 during the early period after transplantation. We included kidney transplant recipients with ˂6 months with a functioning graft diagnosed with COVID-19 from the initial pandemic outbreak (March 2020) until 31 July 2021 from different Spanish centres participating in a nationwide registry. A total of 127 patients from 17 Spanish centres developed COVID-19 during the first 6 months after transplantation; 73 (57.5%) received basiliximab and 54 (42.5%) thymoglobulin. Demographics were not different between groups but patients receiving thymoglobulin were more sensitized [calculated panel reactive antibodies (cPRAs) 32.7 ± 40.8% versus 5.6 ± 18.5%] and were more frequently retransplants (30% versus 4%). Recipients ˃65 years of age treated with thymoglobulin showed the highest rate of acute respiratory distress syndrome [64.7% versus 37.1% for older recipients receiving thymoglobulin and basiliximab (P < .05), respectively, and 23.7% and 18.9% for young recipients receiving basiliximab and thymoglobulin (P > .05)], respectively, and the poorest survival [mortality rate 64.7% and 42.9% for older recipients treated with thymoglobulin and basiliximab, respectively (P < .05) and 8.1% and 10.5% for young recipients treated with thymoglobulin and basiliximab (P > .05), respectively]. Older recipients treated with thymoglobulin showed the poorest survival in the Cox regression model adjusted for comorbidities. Thus thymoglobulin should be used with caution in older recipients during the present pandemic era.

Chemical characterization and microencapsulation of extracellular fungal pigments.

In this work, extracellular colored metabolites obtained from the filamentous fungi Talaromyces australis and Penicillium murcianum, isolated in the Andean-Patagonian native forests of Chile, were studied as prospect compounds to increase the sustainability of cosmetic products. The chemical and antioxidant properties of these natural pigments were characterized and strategies for their microencapsulation were also studied. UHPLC/MS-MS analyses indicated that the predominant metabolites detected in the cultures of P. murcianum were monascin (m/z = 411.15) and monashexenone (m/z = 319.10), while athrorosin H (m/z = 458.20) and damnacanthal (m/z = 281.05) were detected in cultures of T. australis. ORAC tests revealed that P. murcianum's metabolites had the greatest antioxidant properties with values higher than 2000 µmol of trolox equivalents/g. The fungal metabolites were successfully microencapsulated by ionic gelation into structures made of 1.3% sodium alginate, 0.2% chitosan, and 0.07% hyaluronic acid. The microencapsulation process generated structures of 543.57 ± 0.13 µm of mean diameter (d50) with an efficiency of 30% for P. murcianum, and 329.59 ± 0.15 µm of mean diameter (d50) and 40% efficiency, for T. australis. The chemical and biological characterization show the biotechnological potential of these fungal species to obtain pigments with antioxidant activity that could be useful in the cosmetic industry. The encapsulation process enables the production of easy-to-handle dry powder from the fungal metabolites, which could be potentially marketed as a functional cosmetic ingredient. KEY POINTS: • The predominant fungal pigments were of azaphilone and anthraquinoid classes. • The fungal pigments showed high antioxidant activity by ORAC assay. • Fungal pigment microcapsules obtained by ionic gelation were characterized.

Physical Activity in Centenarians beyond Cut-Point-Based Accelerometer Metrics.

This study described and compared physical activity (PA) characteristics at the end of the human lifespan using conventional cut-point-based versus cut-point-free accelerometer metrics. Eighteen institutionalized centenarians (101.5 ± 2.1 years, 72.2% female, 89% frail) wore the wrist GENEActiv accelerometer for 7 days. Conventional metrics, such as time spent in light-intensity PA (LiPA) and moderate-to-vigorous intensity PA (MVPA) were calculated according to published cut-points for adults and older adults. The following cut-point-free metrics were evaluated: average acceleration, intensity gradient and Mx metrics. Depending on the cut-point, centenarians accumulated a median of 15-132 min/day of LiPA and 3-15 min/day of MVPA. The average acceleration was 9.2 mg [Q1: 6.7 mg-Q3: 12.6 mg] and the intensity gradient was -3.19 [-3.34--3.12]. The distribution of Z-values revealed positive skew for MVPA, indicating a potential floor effect, whereas the skew magnitude was attenuated for cut-point-free metrics such as intensity gradient or M5. However, both cut-point-based and cut-point-free metrics were similarly positively associated with functional independence, cognitive and physical capacities. This is the first time that PA has been described in centenarians using cut-point-free metrics. Our results suggest that new analytical approaches could overcome cut-point limitations when studying the oldest-old. Future studies using these new cut-point-free PA metrics are warranted to provide more complete and comparable information across groups and populations.

Creencias, actitudes y sentimientos de estudiantes y docentes de enfermería ante la pandemia de covid-19 / Believes, attituds and feelings in nursing students and proffesors facing the covid-19 pandemic

Resumen: Objetivo: Identificar las creencias, actitudes y sentimientos de estudiantes y docentes de la Licenciatura en Enfermería y Obstetricia de la Facultad de Ciencias de la Salud de la Universidad Autónoma de Tlaxcala frente a la pandemia del Covid-19. Materiales y métodos: Estudio descriptivo y trasversal, realizando un muestreo por conveniencia de estudiantes y docentes de enfermería, a quienes se les envió un cuestionario vía internet, previamente validado que valora las creencias, actitudes y sentimientos ante una alerta epidemiológica. Se realizó un análisis descriptivo de los resultados en el programa estadístico SPSS v27. Resultados: El principal temor estudiantes y docentes durante una pandemia son infectar a su familia, la muerte de alguien cercano, no contar con la orientación y medidas de prevención otorgadas por las instituciones donde laboran, pero están conscientes del riesgo y responsabilidad que implica atender a los pacientes, dar o recibir clases presenciales, y es muy bajo el sentimiento de ser discriminados al ser sujetos de alto riesgo de trasmitir la enfermedad. Conclusiones: El temor a infectarse e infectar a los familiares, genera un sentimiento de culpabilidad por el riesgo de morir. Estudiantes y docentes están conscientes del riesgo y por eso exigen la orientación y las medidas de protección en las instituciones.

Abstract: Objective: To identify what believes, attitudes and feelings are in nursing students and professors in the Health Sciences Faculty at the Universidad Autonoma de Tlaxcala, facing the Covid-19 pandemic. Material and Methods: A descriptive and transversal study using a convenient sample population of students and professors in nursing, to whom a questionnaire was sent via internet, previously validated to determine beliefs, attitudes and feelings facing an epidemiologic alert. A descriptive analysis was done in the statistic program SPSS v27. Results: The most common feeling found are: being afraid of infecting a family member or a close friend, the death of a family member or a close friend, not getting appropriate orientation or training by the institution where they work or study to prevent an infection; Though they are conscious of the risk working with infected patients, and also by the responsibilities when attending classes or teaching in a classroom. The feeling for being discriminated by the people is low, thus because they are in risk of infecting other persons. Conclusions: Being afraid of being contagious or widespread the infection within the family members, suffering feelings of guilt over infecting students and professors. Both of them, are conscious of the risk to be infected, and all them claim the institution for protection and orientation programs to avoid the infection by Covid-19.

La profesionalización en el contexto de las ciencias médicas en Cuba: una mirada desde los artículos científicos publicados por autores cubanos / Professionalization in the context of medical sciences in Cuba: a view from scientific articles published by Cuban authors

RESUMEN Introducción: en la actualidad los estudios sobre profesionalización son un campo abierto a nuevas áreas y a los más diversos abordajes. Fenómeno que se manifiesta de igual manera en el campo de las ciencias de la salud. Objetivo: realizar una revisión sistemática sobre la profesionalización en el contexto de las ciencias médicas en Cuba. Métodos: se realizó una investigación descriptiva de corte transaccional. Se emplearon dos criterios de búsquedas, la base de datos de cada una de las revistas de las ciencias médicas del país y la búsqueda abierta en varios motores de búsquedas y bases de datos. Como instrumento básico de recogida de datos se diseñó una matriz de adyacencia formada por filas y columnas. Resultados: la búsqueda realizada permitió identificar 24 artículos científicos sometidos a la revisión por pares. El comportamiento de las publicaciones en los años registrados reveló de manera general que es muy reducido el número de artículos que sobre el tema se han publicado. Se observó que la centralidad de la red gira en torno a cuatro nodos que tienen la mayor cantidad de concurrencia: profesionalización, profesionalización pedagógica, profesionalización docente y profesionalización científica Conclusiones: se concluye que la profesionalización es una categoría usada en el contexto de las ciencias médicas en Cuba y en la gestión de los diferentes procesos que se llevan a cabo. No obstante, la socialización de artículos científicos no está adecuadamente respaldada dada la totalidad de prácticas que en este campo se realizan.

ABSTRACT Introduction: at present, studies on professionalization continue to be a field open to new areas and to the most diverse approaches. This phenomenon is equally visible in the field of health sciences. Objective: to carry out a systematic review on professionalization in the context of medical sciences in Cuba. Methods: a descriptive-transactional-type research was carried out. Two search criteria were used: the database of each one of the medical sciences journals in the country and the open search in several search engines and databases. An adjacent matrix formed by rows and columns was designed as a basic data collection instrument. Results: the search made it possible to identify 24 scientific articles submitted to peer-review. The behavior of the publications in the years recorded revealed in general that the number of articles published on the subject is very small. It was observed that the centrality of the network revolves around four nodes that have the highest number of concurrence: professionalization, pedagogical professionalization, teaching professionalization and scientific professionalization. Conclusions: it is concluded that professionalization is a category used in the context of medical sciences in Cuba and in the management of the different processes conducted. However, the socialization of scientific articles is not adequately supported given the totality of practices carried out in this field.

A real-world evidence study of nabiximols in multiple sclerosis patients with resistant spasticity: Analysis in relation to the newly described 'spasticity-plus syndrome'.

BACKGROUND AND PURPOSE: Nabiximols is a therapeutic option for patients with multiple sclerosis (MS) spasticity whose symptoms are poorly controlled by conventional oral first-line medications. This study aimed to assess the relationship between changes in spasticity severity (measured on the 0-10 numeric rating scale [NRS]) and the presence of associated symptoms in patients treated with nabiximols, and to investigate the presence of the newly described 'spasticity-plus syndrome'. METHODS: We analyzed real-world data from the Italian Medicines Agency e-Registry on 1138 patients with MS spasticity who began treatment with nabiximols. Evaluation time points were baseline, 4 weeks, and 3, 6, 12 and 18 months after treatment start. RESULTS: Common symptoms associated with MS spasticity in this cohort were pain (38.4% at baseline), sleep disturbances (32.7%), and spasms/cramps (28.5%). Pain was frequently clustered with sleep disturbances (57.2% of pain cases) and spasms/cramps (43.9%). Approximately one-third of patients with data at all evaluation time points maintained treatment at 18 months. Nabiximols reduced the baseline mean spasticity 0-10 NRS score by 24.6% at Week 4, and by 33.9% at 18 months in treatment continuers. Nabiximols resolved a range of MS spasticity-associated symptoms at Week 4, and after 18 months in treatment continuers. CONCLUSION: This real-world analysis supports the concept of a spasticity-plus syndrome and suggests that nabiximols can favorably impact a range of spasticity-associated symptoms.

CA 15-3 prognostic biomarker in SARS-CoV-2 pneumonia.

The severity of lung involvement is the main prognostic factor in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Carbohydrate antigen 15-3 (CA 15-3), a marker of lung damage and fibrosis, could help predict the prognosis of SARS-CoV-2 pneumonia. This was a retrospective and observational study. CA 15-3 was analyzed in the blood samples of patients consecutively admitted for SARS-CoV-2 pneumonia and whose blood samples were available in the biobank. Other prognostic markers were also measured (interleukin 6 [IL6], C-reactive protein [CRP], D-dimer, troponin T, and NT-ProBNP). The occurrence of in-hospital complications was registered, including death, the need for medical intensive care, and oxygen therapy at discharge. In this study, 539 patients were recruited (54.9% men, mean age: 59.6 ± 16.4 years). At admission, the mean concentrations of CA 15-3 was 20.5 ± 15.8 U/mL, and the concentration was correlated with male sex, older age, and other severity markers of coronavirus disease of 2019 (COVID-19) (IL6, CRP, D-dimer, troponine T, and NT-ProBNP). CA 15-3 levels were higher in patients who died (n = 56, 10.4%) (35.33 ± 30.45 vs. 18.8 ± 12.11, p < 0.001), who required intensive medical support (n = 78, 14.4%; 31.17 ± 27.83 vs. 18.68 ± 11.83; p < 0.001), and who were discharged with supplemental oxygen (n = 64, 13.3%; 22.65 ± 14.41 vs. 18.2 ± 11.7; p = 0.011). Elevated CA 15-3 levels (above 34.5 U/mL) were a strong predictor of a complicated in-hospital course, in terms of a higher risk of death (adjusted odds ratio [OR] 3.74, 95% confidence interval [CI]: 1.22-11.9, p = 0.022) and need for intensive care (adjusted OR 4.56, 95% CI: 1.37-15.8) after adjusting for all other risk factors. The degree of lung damage and fibrosis evaluated in terms of CA 15-3 concentrations may allow early identification of the increased risk of complications in patients with SARS-CoV-2 pneumonia.

Critical warm ischemia time point for cardiac donation after circulatory death.

Donation after circulatory death (DCD) represents a promising opportunity to overcome the relative shortage of donors for heart transplantation. However, the necessary period of warm ischemia is a concern. This study aims to determine the critical warm ischemia time based on in vivo biochemical changes. Sixteen DCD non-cardiac donors, without cardiovascular disease, underwent serial endomyocardial biopsies immediately before withdrawal of life-sustaining therapy (WLST), at circulatory arrest (CA) and every 2 min thereafter. Samples were processed into representative pools to assess calcium homeostasis, mitochondrial function and cellular viability. Compared to baseline, no significant deterioration was observed in any studied parameter at the time of CA (median: 9 min; IQR: 7-13 min; range: 4-19 min). Ten min after CA, phosphorylation of cAMP-dependent protein kinase-A on Thr197 and SERCA2 decreased markedly; and parallelly, mitochondrial complex II and IV activities decreased, and caspase 3/7 activity raised significantly. These results did not differ when donors with higher WLST to CA times (≥9 min) were analyzed separately. In human cardiomyocytes, the period from WLST to CA and the first 10 min after CA were not associated with a significant compromise in cellular function or viability. These findings may help to incorporate DCD into heart transplant programs.

Role of cytomegalovirus infection after kidney transplantation on the subsequent risk of atherosclerotic and thrombotic events.

Background and aims: Whether cytomegalovirus (CMV) infection increases the risk of cardiovascular complications after kidney transplantation (KT) through different indirect effects remains controversial. Methods: We analyzed the incidence of post-transplant atherosclerotic (PAEs) and thrombotic events (PTEs) in 465 KT recipients according to the previous exposure to any level or high-level (≥1,000 IU/mL) CMV viremia (either asymptomatic or clinical disease) by means of landmark analysis beyond days 30, 180 and 360 after transplantation. Proportional hazards models were constructed with death and graft loss as competing risks. Results: After a median of 722 days, the cumulative incidences of PAE and PTE were 6.0% each. Most PAEs (53.6%) occurred beyond post-transplant day 360, whereas most PTEs (60.7%) were diagnosed between days 30-180.The incidence of PAE beyond day 180 was higher among patients with previous CMV viremia compared to those without (two-year rates: 4.7% versus 0.4%; P-value = 0.035). This difference was more pronounced in recipients developing high-level viremia (6.3% versus 0.7%, respectively; P-value = 0.013). After multivariate adjustment for age, pre-transplant cardiovascular risk, antiplatelet and statin therapy and graft function, however, associations were not maintained either for any-level (hazard ratio [HR]: 1.84; 95% confidence interval [CI]: 0.48-7.05) or high-level CMV viremia (HR: 2.84; 95% CI: 0.78-10.36). No significant differences were found in the remaining landmark analyses (days 30 or 360) or for the outcome of PTE either. Conclusions: Our study does not support that CMV infection independently contributes to the risk of PAE or PTE after KT.