Targeting the protein folding transition state by mutation: Large scale (un)folding rate accelerations without altering native stability.

Proteins are constantly undergoing folding and unfolding transitions, with rates that determine their homeostasis in vivo and modulate their biological function. The ability to optimize these rates without affecting overall native stability is hence highly desirable for protein engineering and design. The great challenge is, however, that mutations generally affect folding and unfolding rates with inversely complementary fractions of the net free energy change they inflict on the native state. Here we address this challenge by targeting the folding transition state (FTS) of chymotrypsin inhibitor 2 (CI2), a very slow and stable two-state folding protein with an FTS known to be refractory to change by mutation. We first discovered that the CI2's FTS is energetically taxed by the desolvation of several, highly conserved, charges that form a buried salt bridge network in the native structure. Based on these findings, we designed a CI2 variant that bears just four mutations and aims to selectively stabilize the FTS. This variant has >250-fold faster rates in both directions and hence identical native stability, demonstrating the success of our FTS-centric design strategy. With an optimized FTS, CI2 also becomes 250-fold more sensitive to proteolytic degradation by its natural substrate chymotrypsin, and completely loses its activity as inhibitor. These results indicate that CI2 has been selected through evolution to have a very unstable FTS in order to attain the kinetic stability needed to effectively function as protease inhibitor. Moreover, the CI2 case showcases that protein (un)folding rates can critically pivot around a few key residues-interactions, which can strongly modify the general effects of known structural factors such as domain size and fold topology. From a practical standpoint, our results suggest that future efforts should perhaps focus on identifying such critical residues-interactions in proteins as best strategy to significantly improve our ability to predict and engineer protein (un)folding rates.

Effectiveness of a Prostacyclin IP Receptor Agonist in Patients With Pulmonary Arterial Hypertension in the Real-world Andalusian Setting: The RAMPHA Study.

PURPOSE: The pillar for therapeutic decisions in the evolution of pulmonary arterial hypertension (PAH) is the patients' prognostic stratification. METHODS: A retrospective cohort study was conducted in a Spanish real-world setting to assess the clinical improvement of PAH patients treated with selexipag measured as changes in the risk profile. Secondary objectives were to describe their baseline characteristics, initial risk status, and variables used to assess patient survival and adverse events. FINDINGS: Total 42 patients (mean age 52.36 [SD: 15.09] years) were included. All had received initial endothelin receptor antagonist treatment and 95.2% dual therapy with phosphodiesterase-5 inhibitor or riociguat. At 6 to 12 months from baseline, patients risk stratification tripled the percentage of patients with low risk, and a trend towards improved risk stratification (P = 0.122). World Health Organization functional class changed, with more patients in milder classes (P = 0.003), and symptom progression slowed down (P < 0.0001). At 3-years, survival was 85.7% and the estimated median survival time was 2.73 years (SD: 1.351; 95% CI: 2.51-2.95). IMPLICATIONS: Selexipag did not achieve a significant improvement in risk profile, although it did show an excellent survival rate, effectively improved functional class, and delayed symptom progression in real life. Selexipag was well tolerated and showed a favorable safety profile, supporting a clinical benefit for PAH patients.

Elevated Troponins after COVID-19 Hospitalization and Long-Term COVID-19 Symptoms: Incidence, Prognosis, and Clinical Outcomes-Results from a Multi-Center International Prospective Registry (HOPE-2).

Background: Acute cardiac injury (ACI) after COVID-19 has been linked with unfavorable clinical outcomes, but data on the clinical impact of elevated cardiac troponin on discharge during follow-up are scarce. Our objective is to elucidate the clinical outcome of patients with elevated troponin on discharge after surviving a COVID-19 hospitalization. Methods: We conducted an analysis in the prospective registry HOPE-2 (NCT04778020). Only patients discharged alive were selected for analysis, and all-cause death on follow-up was considered as the primary endpoint. As a secondary endpoint, we established any long-term COVID-19 symptoms. HOPE-2 stopped enrolling patients on 31 December 2021, with 9299 patients hospitalized with COVID-19, of which 1805 were deceased during the acute phase. Finally, 2382 patients alive on discharge underwent propensity score matching by relevant baseline variables in a 1:3 fashion, from 56 centers in 8 countries. Results: Patients with elevated troponin experienced significantly higher all-cause death during follow-up (log-rank = 27.23, p < 0.001), and had a higher chance of experiencing long-term COVID-19 cardiovascular symptoms. Specifically, fatigue and dyspnea (57.7% and 62.8%, with p-values of 0.009 and <0.001, respectively) are among the most common. Conclusions: After surviving the acute phase, patients with elevated troponin on discharge present increased mortality and long-term COVID-19 symptoms over time, which is clinically relevant in follow-up visits.

Risk prediction of major cardiac adverse events and all-cause death following covid-19 hospitalization at one year follow-up: The HOPE-2 score.

BACKGROUND: Long-term consequences of COVID-19 are still partly known. AIM OF THE STUDY: To derive a clinical score for risk prediction of long-term major cardiac adverse events (MACE) and all cause death in COVID-19 hospitalized patients. METHODS: 2573 consecutive patients were enrolled in a multicenter, international registry (HOPE-2) from January 2020 to April 2021 and identified as the derivation cohort. Five hundred and twenty-six patients from the Cardio-Covid-Italy registry were considered as external validation cohort. A long-term prognostic risk score for MACE and all cause death was derived from a multivariable regression model. RESULTS: Out of 2573 patients enrolled in the HOPE-2 registry, 1481 (58 %) were male, with mean age of 60±16 years. At long-term follow-up, the overall rate of patients affected by MACE and/or all cause death was 7.8 %. After multivariable regression analysis, independent predictors of MACE and all cause death were identified. The HOPE-2 prognostic score was therefore calculated by giving: 1-4 points for age class (<65 years, 65-74, 75-84, ≥85), 3 points for history of cardiovascular disease, 1 point for hypertension, 3 points for increased troponin serum levels at admission and 2 points for acute renal failure during hospitalization. Score accuracy at ROC curve analysis was 0.79 (0.74 at external validation). Stratification into 3 risk groups (<3, 3-6, >6 points) classified patients into low, intermediate and high risk. The observed MACE and all-cause death rates were 1.9 %, 9.4 % and 26.3 % for low- intermediate and high-risk patients, respectively (Log-rank test p < 0.01). CONCLUSIONS: The HOPE-2 prognostic score may be useful for long-term risk stratification in patients with previous COVID-19 hospitalization. High-risk patients may require a strict follow-up.

Slipping rib syndrome in childhood. A case series. / Síndrome de la costilla deslizante en la edad pediátrica. Serie de casos.

Among the causes of chest pain, slipping rib has a low prevalence, usually with a history of trauma, and its management is controversial. Slipping rib syndrome should be included in the differential diagnosis of causes of chest pain in children. When not associated with previous trauma and cartilage deformity, it is necessary to consider an alteration in rib development, regardless of the typical traumatic etiology in adults. Here we describe a series of pediatric patients with slipping rib seen at a referral hospital between 2001 and 2022. Nine patients aged 11 to 16 years were included. Only 2 had a history of trauma. All patients described a sudden onset of severe thoracic abdominal pain. The patients underwent open resection of the affected costal cartilages, with resolution of pain.

Entre las causas de dolor torácico, la costilla deslizante presenta baja prevalencia, antecedentes traumáticos y manejo controvertido. Este síndrome merece ser incluido en el diagnóstico diferencial de causas de dolor torácico en niños. Al no asociarse a traumatismos previos y la deformidad de cartílagos, nos induce a pensar en una alteración en el desarrollo costal, al margen de la etiología traumática típica en adultos. Se presenta una serie de pacientes pediátricos intervenidos por costilla deslizante en un centro de referencia entre 2001 y 2022. Se incluyeron nueve pacientes, con un rango de edades de 11 a 16 años. Solo dos casos describen traumatismo previo. Todos presentan un inicio súbito de dolor toracoabdominal intenso. Los pacientes fueron intervenidos mediante resección abierta de cartílagos costales afectos, con resolución del dolor.

Classic and Atypical Late Infantile Neuronal Ceroid Lipofuscinosis in Latin America: Clinical and Genetic Aspects, and Treatment Outcome with Cerliponase Alfa.

Introduction: Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), is a neurodegenerative autosomal recessive disease caused by TPP1 gene variants, with a spectrum of classic and atypical phenotypes. The aim of treatment is to slow functional decline as early as possible in an attempt to improve quality of life and survival. This study describes the clinical characteristics as well as the response to treatment with cerliponase alfa. Materials and methods: A retrospective study was conducted in five Latin-American countries, using clinical records from patients with CLN2. Clinical follow-up and treatment variables are described. A descriptive and bivariate statistical analysis was performed. Results: A total of 36 patients were observed (range of follow-up of 61-110 weeks post-treatment). At presentation, patients with the classic phenotype (n = 16) exhibited regression in language (90%), while seizures were the predominant symptom (87%) in patients with the atypical phenotype (n = 20). Median age of symptom onset and time to first specialized consultation was 3 (classical) and 7 (atypical) years, while the median time interval between onset of symptoms and treatment initiation was 4 years (classical) and 7.5 (atypical). The most frequent variant was c.827 A > T in 17/72 alleles, followed by c.622C > T in 6/72 alleles. All patients were treated with cerliponase alfa, and either remained functionally stable or had a loss of 1 point on the CLN2 scale, or up to 2 points on the Wells Cornel and Hamburg scales, when compared to pretreatment values. Discussion and conclusion: This study reports the largest number of patients with CLN2 currently on treatment with cerliponase alfa in the world. Data show a higher frequency of patients with atypical phenotypes and a high allelic proportion of intron variants in our region. There was evidence of long intervals until first specialized consultation, diagnosis, and enzyme replacement therapy. Follow-up after the initiation of cerliponase alfa showed slower progression or stabilization of the disease, associated with adequate clinical outcomes and stable functional scores. These improvements were consistent in both clinical phenotypes.

The importance of data in Pulmonary Arterial Hypertension: from international registries to Machine Learning. / La importancia de los datos en la hipertensión arterial pulmonar: de los registros internacionales al machine learning.

Real-world registries have been critical to building the scientific knowledge of rare diseases, including Pulmonary Arterial Hypertension (PAH). In the past 4 decades, a considerable number of registries on this condition have allowed to improve the pathology and its subgroups definition, to advance in the understanding of its pathophysiology, to elaborate prognostic scales and to check the transferability of the results from clinical trials to clinical practice. However, in a moment where a huge amount of data from multiple sources is available, they are not always taken into account by the registries. For that reason, Machine Learning (ML) offer a unique opportunity to manage all these data and, finally, to obtain tools that may help to get an earlier diagnose, to help to deduce the prognosis and, in the end, to advance in Personalized Medicine. Thus, we present a narrative revision with the aims of, in one hand, summing up the aspects in which data extraction is important in rare diseases -focusing on the knowledge gained from PAH real-world registries- and, on the other hand, describing some of the achievements and the potential use of the ML techniques on PAH.

ADAM: a robotic companion for enhanced quality of life in aging populations.

One of the major problems of today's society is the rapid aging of its population. Life expectancy is increasing, but the quality of life is not. Faced with the growing number of people who require cognitive or physical assistance, new technological tools are emerging to help them. In this article, we present the ADAM robot, a new robot designed for domestic physical assistance. It mainly consists of a mobile base, two arms with grippers and vision systems. All this allows the performance of physical tasks that require navigation and manipulation of the environment. Among ADAM's features are its modularity, its adaptability to indoor environments and its versatility to function as an experimental platform and for service applications. In addition, it is designed to work respecting the user's personal space and is collaborative, so it can learn from experiences taught by them. We present the design of the robot as well as examples of use in domestic environments both alone and in collaboration with other domestic platforms, demonstrating its potential.

Index and Repeat Ablation for Atrial Fibrillation in Older versus Younger Patients: A Propensity-Score Matching Analysis.

Catheter ablation is a well-established rhythm control therapy in atrial fibrillation (AF). Although the prevalence of AF increases dramatically with age, the prognosis and safety profile of index and repeat ablation procedures remain unclear in the older population. The primary endpoint of this study was to assess the arrhythmia recurrence, reablation and complication rates in older patients. Secondary endpoints were the identification of independent predictors of arrhythmia recurrence and reablation, including information on pulmonary vein (PV) reconnection and other atrial foci. Older (n=129, ≥70 years) and younger (n=129, <70 years) patients were compared using a propensity-score matching analysis based on age, gender, obesity, hypertension, dyslipidemia, diabetes mellitus, dilated left atrium, severe obstructive sleep apnea, cardiac disease, left systolic ventricular function, AF pattern and ablation technique. Arrhythmia recurrence and reablation were evaluated in both groups using a Cox regression analysis in order to identify predictors. During a 30-month follow-up period, there were no significant differences between older and younger patients in the arrhythmia-free survival (65.1% and 59.7%; log-rank test p=0.403) and complication (10.1% and 10.9%; p>0.999) rates after the index ablation. However, the reablation rate was significantly different (46.7% and 69.2%; p<0.05, respectively). In those patients who underwent reablation procedure (redo subgroups), there were no differences in the incidence of PV reconnection (38.1% redo-older and 27.8% redo-younger patients; p=0.556). However, the redo-older patients had lower reconnected PVs per patient (p<0.01) and lower atrial foci (2.3 and 3.7; p<0.01) than the redo-younger patients. A further important finding was that age was not an independent predictor of arrhythmia recurrence or reablation. Our data reveal that the AF index ablation in older patients had a similar efficacy and safety profile to younger patients. Therefore, age alone must not be considered a prognostic factor for AF ablation but the presence of limiting factors such as frailty and multiple comorbidities.

Molecular simulations integrated with experiments for probing the interaction dynamics and binding mechanisms of intrinsically disordered proteins.

Intrinsically disordered proteins (IDPs) exploit their plasticity to deploy a rich panoply of soft interactions and binding phenomena. Advances in tailoring molecular simulations for IDPs combined with experimental cross-validation offer an atomistic view of the mechanisms that control IDP binding, function, and dysfunction. The emerging theme is that unbound IDPs autonomously form transient local structures and self-interactions that determine their binding behavior. Recent results have shed light on whether and how IDPs fold, stay disordered or drive condensation upon binding; how they achieve binding specificity and select among competing partners. The disorder-binding paradigm is now being proactively used by researchers to target IDPs for rational drug design and engineer molecular responsive elements for biosensing applications.

Efectos del Entrenamiento de Fuerza sobre el perfil lipídico en niños y adolescentes con sobrepeso y obesidad. Una revisión sistemática / Effects of Resistance Training on lipid profile in overweight and obese children and adolescents. A systematic review

El desarrollo de enfermedades cardiovasculares (ECV) ateroscleróticas comienza en edades tempranas y está influenciado por factores genéticos y ambientales. La literatura actual propone el entrenamiento de fuerza (EF) como un medio para reducir el riesgo de ECV y mejorar el perfil lipídico en niños y adolescentes con sobrepeso y obesidad. Con el objetivo de examinar los efectos de un programa de EF en este grupo de población, se realizó una revisión sistemática utilizando el protocolo PRISMA y se buscaron estudios en cinco bases de datos (Pubmed, Scopus, the Cochrane Library, Embase y Web of Science). Un total de 11 estudios cumplieron los criterios finales de inclusión. Los resultados de esta revisión indicaron que las intervenciones de EF supervisadas y realizadas al menos 3 días a la semana con una duración de 8 semanas, mejoraron significativamente los parámetros lipídicos del colesterol (CT) y las lipoproteínas de baja densidad (LDL). Los programas de EF pueden ser considerados como un tratamiento no farmacológico adecuado para mejorar el perfil lipídico y la salud cardiovascular de niños y adolescentes con sobrepeso y obesidad (AU)

The development of atherosclerotic cardiovascular disease (CVD) begins early in life and is influenced by genetic and environmental factors. Resistance training (RT) is proposed as a means to reduce CVD risk and improve lipid profile in overweight and obese children and adolescents. In order to examine the effects of an RT programme in this population group, a systematic review was conducted using the PRISMA and protocol and using a total of five databases (Pubmed, Scopus, the Cochrane Library, Embase and Web of Science). A total of 11 studies met the final inclusion criteria. The results of these studies indicated that supervised PE interventions performed at least 3 days per week with lasting 8 weeks significantly improved lipid parameters of cholesterol (TC) and low-density lipoprotein (LDL). Consequently, it was concluded that RT programmes can be considered as a suitable non-pharmacological treatment to improve the lipid profile and cardiovascular health of overweight and obese children and adolescents (AU)

The Nß motif of NaTrxh directs secretion as an endoplasmic reticulum transit peptide and variations might result in different cellular targeting.

Soluble secretory proteins with a signal peptide reach the extracellular space through the endoplasmic reticulum-Golgi conventional pathway. During translation, the signal peptide is recognised by the signal recognition particle and results in a co-translational translocation to the endoplasmic reticulum to continue the secretory pathway. However, soluble secretory proteins lacking a signal peptide are also abundant, and several unconventional (endoplasmic reticulum/Golgi independent) pathways have been proposed and some demonstrated. This work describes new features of the secretion signal called Nß, originally identified in NaTrxh, a plant extracellular thioredoxin, that does not possess an orthodox signal peptide. We provide evidence that other proteins, including thioredoxins type h, with similar sequences are also signal peptide-lacking secretory proteins. To be a secretion signal, positions 5, 8 and 9 must contain neutral residues in plant proteins-a negative residue in position 8 is suggested in animal proteins-to maintain the Nß motif negatively charged and a hydrophilic profile. Moreover, our results suggest that the NaTrxh translocation to the endoplasmic reticulum occurs as a post-translational event. Finally, the Nß motif sequence at the N- or C-terminus could be a feature that may help to predict protein localisation, mainly in plant and animal proteins.

Seven Additional Patients with SOX17 Related Pulmonary Arterial Hypertension and Review of the Literature.

Pulmonary arterial hypertension (PAH) is an infrequent disorder characterized by high blood pressure in the pulmonary arteries. It may lead to premature death or the requirement for lung and/or heart transplantation. Genetics plays an important and increasing role in the diagnosis of PAH. Here, we report seven additional patients with variants in SOX17 and a review of sixty previously described patients in the literature. Patients described in this study suffered with additional conditions including large septal defects, as described by other groups. Collectively, sixty-seven PAH patients have been reported so far with variants in SOX17, including missense and loss-of-function (LoF) variants. The majority of the loss-of-function variants found in SOX17 were detected in the last exon of the gene. Meanwhile, most missense variants were located within exon one, suggesting a probable tolerated change at the amino terminal part of the protein. In addition, we reported two idiopathic PAH patients presenting with the same variant previously detected in five patients by other studies, suggesting a possible hot spot. Research conducted on PAH associated with congenital heart disease (CHD) indicated that variants in SOX17 might be particularly prevalent in this subgroup, as two out of our seven additional patients presented with CHD. Further research is still necessary to clarify the precise association between the biological pathway of SOX17 and the development of PAH.

Analysis of the role of motivating operations in the therapeutic verbal interaction / Análisis del rol de las operaciones motivadoras en la interacción verbal terapéutica

El concepto de operación motivadora (OM) ayuda a suplir los problemas de la noción tradicional de motivación en el estudio del proceso terapéutico. En este trabajo, se analizó el rol de tres tipos de verbalizaciones del terapeuta con una función de OM y se comprobó su relación con el comportamiento verbal de los clientes. Para tal propósito, se observaron grabaciones de 40 sesiones de terapia pertenecientes a 9 casos diferentes. El Sistema ACOVEO fue el sistema de categorías empleado para identificar las categorías OM con información clínica, OM con consecuencias y OM con emparejamiento. El SISC-CVC fue aquel utilizado para identificar las verbalizaciones de las clientes codificadas como Acuerdo y Desacuerdo. Se llevaron a cabo análisis secuenciales para comprobar la relación entre las diferentes OMs entre ellas y con el acuerdo del cliente. Los resultados mostraron que las diferentes OMs fueron emitidas en bloque y que cuando la categoría OM con información clínica se emitía con OM con consecuencias o con OM con emparejamiento se encontraba una mayor asociación con la categoría de Acuerdo (r = 2.47; r = 1.86) que con la de Desacuerdo (r = -.53; r = -.36). Estos resultados destacan la importancia de la emisión de OMs que asocian de manera directa el comportamiento del cliente con eventos con un componente elicitador, ofreciendo estrategias más eficaces para los terapeutas.(AU)

The concept of motivating operation(MO) helps to overcome both theoretical and practical problems of the traditional notion of motivation in the study of the therapeutic process. In this research, the role of three types of therapists’ verbalizations with an MO functionwas analyzed, in addition to their association with clients’ verbal behavior. For this purpose, recordings of 40 clinical sessions belonging to 9 different cases were ob-served. The ACOVEO System was the observational category system used to identify the therapists’ verbal MOs coded as MO with clinical information, MO with consequences, andMO with pairings. The SISC-CVC was the one used to identify clients’ verbalizations coded as Agreementand Disagreement. Se-quential analyses were performed to test the relation between the three dif-ferent types of MOs with themselves, as well as with clients’ concurrence. Results showed that the different MOs were emitted in chunks and when MO with clinical information was uttered either with MO with consequences or MO with pairingsthere was a greater association with Agreement(r = 2.47; r = 1.86) rather than with Disagreement (r = -.53;r = -.36). These findings high-light the importance of the emission of MOs that associate directly events with an eliciting component with clients’ behavior, giving more efficacious strategies to the therapists.(AU)

Factores determinantes sobre la calificación en la fase de oposición de Educación Física en Educación Primaria / Determining factors on the qualification in the competitive examinations for Physical Education in Primary Education

El concurso-oposición de Educación Física en Educación Primaria en España ha sido escasamente estudiado en la literatura científica, pese a que todos los docentes en la enseñanza pública deben realizarlo. El objetivo de esta investigación fue determinar si había una asociación entre la experiencia docente, el número de veces presentado al concurso-oposición, el modo de preparación, los hábitos de los opositores y el método de estudio con respecto al resultado final obtenido en la fase de oposición de Educación Física en 2022. Los 166 opositores participantes realizaron un cuestionario y cuatro de ellos fueron entrevistados. Se calcularon los estadísticos descriptivos y el coeficiente Alfa de Cronbach para medir la fiabilidad de las respuestas proporcionadas por la muestra en el cuestionario, se obtuvieron las correlaciones bivariadas de todas las dimensiones respecto a la nota obtenida y se realizó un análisis de regresión lineal. Los resultados determinaron relaciones estadísticamente significativas entre la nota final y la mayoría de las variables del método de estudio y entre la nota y el hábito de estudio. El 18% de la varianza de la nota final vino explicada por los predictores de práctica de la unidad didáctica, literatura de temas y elaboración de la unidad didáctica. Además, el 4% de la varianza de la nota final tuvo como predictor la variable de hábito de estudio. Los resultados permiten concluir que los factores influyentes en la calificación tienen que ver con el método de estudio y no con la experiencia o el número de veces presentado al concurso-oposición. (AU)

Competitive examinations in primary Physical Education in Spain have been little studied in the scientific literature, although every teacher in state schools has to do them. The aim of this study was to determine whether there is a relationship between teachers' experience, the number of times they have taken competitive examinations, the type of preparation, candidates’ habits, and study methods in relation to the qualifications obtained in competitive examinations in Physical Education in 2022. The 166 participating candidates completed a questionnaire and four of them were interviewed. Descriptive statistics and Cronbach's alpha coefficient were calculated to measure the reliability of the answers given by the sample in the questionnaire, bivariate correlations were obtained for all the dimensions in relation to the mark obtained, and linear regression analysis was carried out. The results showed statistically significant relationships between the final qualification of the competitive examinations and most of the variables of the study method and between the mark and the study habits. 18% of the variance of the final mark was explained by the predictors of the practice of the didactic unit, the literature of the syllabus and the elaboration of the didactic unit. In addition, 4% of the variance in the final mark was explained by the variable study habits.These results allow us to conclude that the factors influencing qualification are related to the method of study and not to experience or the number of times the candidate has taken the competitive examination. (AU)

Multi-Omics Approach Reveals Prebiotic and Potential Antioxidant Effects of Essential Oils from the Mediterranean Diet on Cardiometabolic Disorder Using Humanized Gnotobiotic Mice.

Essential oils sourced from herbs commonly used in the Mediterranean diet have demonstrated advantageous attributes as nutraceuticals and prebiotics within a model of severe cardiometabolic disorder. The primary objective of this study was to assess the influences exerted by essential oils derived from thyme (Thymus vulgaris) and oregano (Origanum vulgare) via a comprehensive multi-omics approach within a gnotobiotic murine model featuring colonic microbiota acquired from patients diagnosed with coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM). Our findings demonstrated prebiotic and potential antioxidant effects elicited by these essential oils. We observed a substantial increase in the relative abundance of the Lactobacillus genus in the gut microbiota, accompanied by higher levels of short-chain fatty acids and a reduction in trimethylamine N-oxide levels and protein oxidation in the plasma. Moreover, functional enrichment analysis of the cardiac tissue proteome unveiled an over-representation of pathways related to mitochondrial function, oxidative stress, and cardiac contraction. These findings provide compelling evidence of the prebiotic and antioxidant actions of thyme- and oregano-derived essential oils, which extend to cardiac function. These results encourage further investigation into the promising utility of essential oils derived from herbs commonly used in the Mediterranean diet as potential nutraceutical interventions for mitigating chronic diseases linked to CAD and T2DM.

Clinical Profile and Determinants of Mortality in Patients with Interstitial Lung Disease Admitted for COVID-19.

BACKGROUND: Concern has risen about the effects of COVID-19 in interstitial lung disease (ILD) patients. The aim of our study was to determine clinical characteristics and prognostic factors of ILD patients admitted for COVID-19. METHODS: Ancillary analysis of an international, multicenter COVID-19 registry (HOPE: Health Outcome Predictive Evaluation) was performed. The subgroup of ILD patients was selected and compared with the rest of the cohort. RESULTS: A total of 114 patients with ILDs were evaluated. Mean ± SD age was 72.4 ± 13.6 years, and 65.8% were men. ILD patients were older, had more comorbidities, received more home oxygen therapy and more frequently had respiratory failure upon admission than non-ILD patients (all p < 0.05). In laboratory findings, ILD patients more frequently had elevated LDH, C-reactive protein, and D-dimer levels (all p < 0.05). A multivariate analysis showed that chronic kidney disease and respiratory insufficiency on admission were predictors of ventilatory support, and that older age, kidney disease and elevated LDH were predictors of death. CONCLUSIONS: Our data show that ILD patients admitted for COVID-19 are older, have more comorbidities, more frequently require ventilatory support and have higher mortality than those without ILDs. Older age, kidney disease and LDH were independent predictors of mortality in this population.

Post-COVID-19 syndrome and diabetes mellitus: a propensity-matched analysis of the International HOPE-II COVID-19 Registry.

Background: Diabetes mellitus (DM) is one of the most frequent comorbidities in patients suffering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a higher rate of severe course of coronavirus disease (COVID-19). However, data about post-COVID-19 syndrome (PCS) in patients with DM are limited. Methods: This multicenter, propensity score-matched study compared long-term follow-up data about cardiovascular, neuropsychiatric, respiratory, gastrointestinal, and other symptoms in 8,719 patients with DM to those without DM. The 1:1 propensity score matching (PSM) according to age and sex resulted in 1,548 matched pairs. Results: Diabetics and nondiabetics had a mean age of 72.6 ± 12.7 years old. At follow-up, cardiovascular symptoms such as dyspnea and increased resting heart rate occurred less in patients with DM (13.2% vs. 16.4%; p = 0.01) than those without DM (2.8% vs. 5.6%; p = 0.05), respectively. The incidence of newly diagnosed arterial hypertension was slightly lower in DM patients as compared to non-DM patients (0.5% vs. 1.6%; p = 0.18). Abnormal spirometry was observed more in patients with DM than those without DM (18.8% vs. 13; p = 0.24). Paranoia was diagnosed more frequently in patients with DM than in non-DM patients at follow-up time (4% vs. 1.2%; p = 0.009). The incidence of newly diagnosed renal insufficiency was higher in patients suffering from DM as compared to patients without DM (4.8% vs. 2.6%; p = 0.09). The rate of readmission was comparable in patients with and without DM (19.7% vs. 18.3%; p = 0.61). The reinfection rate with COVID-19 was comparable in both groups (2.9% in diabetics vs. 2.3% in nondiabetics; p = 0.55). Long-term mortality was higher in DM patients than in non-DM patients (33.9% vs. 29.1%; p = 0.005). Conclusions: The mortality rate was higher in patients with DM type II as compared to those without DM. Readmission and reinfection rates with COVID-19 were comparable in both groups. The incidence of cardiovascular symptoms was higher in patients without DM.