Shedding Light on Dark Chemical Matter: The Discovery of a SARS-CoV-2 Mpro Main Protease Inhibitor through Intensive Virtual Screening and In Vitro Evaluation.

The development of specific antiviral therapies targeting SARS-CoV-2 remains fundamental because of the continued high incidence of COVID-19 and limited accessibility to antivirals in some countries. In this context, dark chemical matter (DCM), a set of drug-like compounds with outstanding selectivity profiles that have never shown bioactivity despite being extensively assayed, appears to be an excellent starting point for drug development. Accordingly, in this study, we performed a high-throughput screening to identify inhibitors of the SARS-CoV-2 main protease (Mpro) using DCM compounds as ligands. Multiple receptors and two different docking scoring functions were employed to identify the best molecular docking poses. The selected structures were subjected to extensive conventional and Gaussian accelerated molecular dynamics. From the results, four compounds with the best molecular behavior and binding energy were selected for experimental testing, one of which presented inhibitory activity with a Ki value of 48 ± 5 µM. Through virtual screening, we identified a significant starting point for drug development, shedding new light on DCM compounds.

Hospitalizations for food-induced anaphylaxis in Spain (2016-2021): A population-based epidemiologic study.

BACKGROUND: Food-induced anaphylaxis (FIA) is a major public health problem resulting in serious clinical complications, emergency department visits, hospitalization, and death. OBJECTIVE: The objectives of this investigation were to assess the epidemiology and the trends in hospitalizations because of FIA in Spain between 2016 and 2021. METHODS: An observational descriptive study was conducted using data from the Spanish National hospital discharge database. Information is coded based on the International Classification of Diseases, Tenth Revision. The study population was analyzed by sex and age group and according to food triggers, clinical characteristics, admission to the intensive care unit (ICU), severity, and in-hospital mortality (IHM). The annual incidence of hospitalizations because of FIA per 100,000 person-years was estimated and analyzed using Poisson regression models. Multivariable logistic regression models were constructed to identify which variables were associated with severe FIA. RESULTS: A total of 2161 hospital admissions for FIA in were recorded in Spain from 2016 to 2021. The overall incidence rate was 0.77 cases per 100,000 person-years. The highest incidence was found in the <15-year age group (3.68), with lower figures among those aged 15-59 years (0.25) and ≥60 years (0.29). Poisson regression showed a significant increase in incidence from 2016 to 2021 only among children (3.78 per 100,000 vs. 5.02 per 100,000 person-years; p=.047). The most frequent food triggers were ""Milk and dairy products" (419/2161, 19.4% of cases) and "Peanuts and tree nuts and seeds" (409/2161, 18.9%). Overall, 256 of 2161 (11.9%) patients hospitalized because of FIA required admission to the ICU, and 11 patients (0.5%) died in hospital. Among children, the most severe cases of FIA appeared in patients aged 0 to 4 years (40/99, 40.4%). Among adults, 69.4% (111/160) of cases occurred in those aged 15 to 59 years. Multivariable logistic regression showed the variables associated with severe FIA to be age 15-59 years (OR, 5.1; 95% CI, 3.11-8.36), age ≥60 years (OR, 3.87; 95% CI, 1.99-7.53), and asthma. CONCLUSIONS: In Spain, the incidence of hospitalization because of FIA increased slightly, although the only significant increase was among children. Even if IHM remains low and stable, the proportion of severe cases is high and has not improved from 2016 to 2021, with older age and asthma being risk factors for severity. Surveillance must be improved, and preventive strategies implemented to reduce the burden of FIA.

Model predictive manipulation of compliant objects with multi-objective optimizer and adversarial network for occlusion compensation.

BACKGROUND: The manipulation of compliant objects by robotic systems remains a challenging task, largely due to their variable shapes and the complex, high-dimensional nature of their interaction dynamics. Traditional robotic manipulation strategies struggle with the accurate modeling and control necessary to handle such materials, especially in the presence of visual occlusions that frequently occur in dynamic environments. Meanwhile, for most unstructured environments, robots are required to have autonomous interactions with their surroundings. METHODS: To solve the shape manipulation of compliant objects in an unstructured environment, we begin by exploring the regression-based algorithm of representing the high-dimensional configuration space of deformable objects in a compressed form that enables efficient and effective manipulation. Simultaneously, we address the issue of visual occlusions by proposing the integration of an adversarial network, enabling guiding the shaping task even with partial observations of the object. Afterwards, we propose a receding-time estimator to coordinate the robot action with the computed shape features while satisfying various performance criteria. Finally, model predictive controller is utilized to compute the robot's shaping motions subject to safety constraints. Detailed experiments are presented to evaluate the proposed manipulation framework. SIGNIFICANT FINDINGS: Our MPC framework utilizes the compressed representation and occlusion-compensated information to predict the object's behavior, while the multi-objective optimizer ensures that the resulting control actions meet multiple performance criteria. Through rigorous experimental validation, our approach demonstrates superior manipulation capabilities in scenarios with visual obstructions, outperforming existing methods in terms of precision and operational reliability. The findings highlight the potential of our integrated approach to significantly enhance the manipulation of compliant objects in real-world robotic applications.

Detrimental Impact of Atrial Fibrillation among Patients Hospitalized for Acute Exacerbation of COPD: Results of a Population-Based Study in Spain from 2016 to 2021.

Background/Objectives: To analyze changes in the prevalence of atrial fibrillation (AF) in patients hospitalized for acute exacerbation of chronic obstructive pulmonary disease (AE-COPD); to evaluate hospital outcomes according to AF status, assessing sex differences; to identify factors associated with AF presence; and to analyze variables associated with in-hospital mortality (IHM) in AE-COPD patients with AF. Methods: We used data from the Registry of Specialized Care Activity-Basic Minimum Data Set (RAE-CMBD) to select patients aged ≥40 years with COPD in Spain (2016-2021). We stratified the study population according to AF presence and sex. The propensity score matching (PSM) methodology was employed to create comparable groups based on age, admission year, and comorbidities at the time of hospitalization. Results: We identified 399,196 hospitalizations that met the inclusion criteria. Among them, 20.58% had AF. The prevalence of AF rose from 2016 to 2021 (18.26% to 20.95%), though the increase was only significant in men. The median length of hospital stay (LOHS) and IHM were significantly higher in patients with AF than in those without AF. After PSM, IHM remained significantly higher for man and women with AF. Older age, male sex, and several comorbidities were factors associated with AF. Additionally, older age, male sex, different comorbidities including COVID-19, hospitalization in the year 2020, mechanical ventilation, and intensive care unit (ICU) admission were associated with higher IHM in patients with AE-COPD and AF. Conclusions: AF prevalence was high in patients hospitalized for AE-COPD, was higher in men than in women, and increased over time. AF presence was associated with worse outcomes. The variables associated with IHM in hospitalized AE-COPD patients with AF were older age, male sex, different comorbidities including COVID-19 presence, hospitalization in the year 2020, need of mechanical ventilation, and ICU admission.

Influence of diabetes and other risk factors on in-hospital mortality following kidney transplantation: an analysis of the Spanish National Hospital Discharge Database from 2016 to 2020.

INTRODUCTION: To assess time trends in incidence, clinical characteristics, complications, and hospital outcomes among patients with type 1 diabetes (T1D), with type 2 diabetes (T2D), and patients without diabetes who underwent kidney transplant (KT); to identify variables associated with in-hospital mortality (IHM); and to determine the impact of the COVID-19 pandemic. RESEARCH DESIGN AND METHODS: We used a nationwide discharge database to select KT recipients admitted to Spanish hospitals from 2016 to 2020. We stratified patients according to diabetes status. We used multivariable logistic regression to identify the variables associated with IHM. RESULTS: A total of 14 594 KTs were performed in Spain (T2D, 22.28%; T1D, 3.72%). The number of KTs rose between 2016 and 2019 and and decreased from 2019 to 2020 in all groups. In patients with T2D, the frequency of KT complications increased from 21.08% in 2016 to 34.17% in 2020 (p<0.001). Patients with T2D had significantly more comorbidity than patients with T1D and patients without diabetes (p<0.001). Patients with T1D experienced KT rejection significantly more frequently (8.09%) than patients with T2D (5.57%).COVID-19 was recorded in 26 out of the 2444 KTs performed in 2020, being found in 6 of the 39 patients deceased that year (15.38%) and in 0.83% of the survivors.The variables associated with IHM were comorbidity and complications of KT. The presence of T1D was associated with IHM (OR 2.6; 95% CI 1.36 to 5.16) when patients without diabetes were the reference category. However, T2D was not associated with a higher IHM (OR 0.86; 95% CI 0.61 to 1.2). CONCLUSIONS: The COVID-19 pandemic led to a decrease in the number of transplants. Patients with T1D have more rejection of the transplanted organ than patients with T2D. Fewer women with T2D undergo KT. The presence of T1D is a risk factor for IHM.

Cognitive Reserve and Frontotemporal Disorders: Exploring the Relationship Between Education, Physical Activity, and Cognitive Dysfunction in Older Adults.

In this study we investigated the relationship between cognitive reserve (CR) proxies, such as education, physical activity (PA), and cognitive dysfunction (CD) in the presence or absence of frontotemporal disorders (FTD). Previous research has suggested that education and PA may delay the onset of CD and reduce the risk of developing dementia. However, it remains unclear whether these CR proxies can protect against CD when FTD is present. We aimed to explore this relationship and determine whether sustained CR may be evident regardless of FTD. We recruited 149 older adults (aged 65-99 years) from community centers where they were voluntarily participating in leisure activities. We used bioelectrical impedance to measure their body composition, and we administered the International PA Questionnaire and the Mini-Mental State Examination to measure their PA and cognitive function, respectively. We used the Frontal Assessment Battery to screen for frontotemporal dementia. Our results showed that people with FTD were older, had lower education, and engaged in less PA, relative to other participants. Regression models revealed that age, education, and PA were significant predictors of FTD. More specifically, FTD was negatively associated with cognitive functioning, and there were significant interaction effects between FTD and education and PA. PA and education were significant predictors of cognitive functioning, and, when values for PA and education were high, they offset the effects of FTD on cognitive function. These findings support impressions that PA and years of education provide an insulating or compensatory effect on cognitive functioning in older adults with executive dysfunction or frontotemporal dementia, highlighting the importance of encouraging both pursuits.

Extending MeCP2 interactome: canonical nucleosomal histones interact with MeCP2.

MeCP2 is a general regulator of transcription involved in the repression/activation of genes depending on the local epigenetic context. It acts as a chromatin regulator and binds with exquisite specificity to gene promoters. The set of epigenetic marks recognized by MeCP2 has been already established (mainly, cytosine modifications in CpG and CpA), as well as many of the constituents of its interactome. We unveil a new set of interactions for MeCP2 with the four canonical nucleosomal histones. MeCP2 interacts with high affinity with H2A, H2B, H3 and H4. In addition, Rett syndrome associated mutations in MeCP2 and histone epigenetic marks modulate these interactions. Given the abundance and the structural/functional relevance of histones and their involvement in epigenetic regulation, this new set of interactions and its modulating elements provide a new addition to the 'alphabet' for this epigenetic reader.

Association between Asthma and Lower Levels of Physical Activity: Results of a Population-Based Case-Control Study in Spain.

(1) Background: Our aim was to determine changes in the prevalence of physical activity (PA) in adults with asthma between 2014 and 2020 in Spain, investigate sex differences and the effect of other variables on adherence to PA, and compare the prevalence of PA between individuals with and without asthma. (2) Methods: This study was a cross-sectional, population-based, matched, case-control study using European Health Interview Surveys for Spain (EHISS) for 2014 and 2020. (3) Results: We identified 1262 and 1103 patients with asthma in the 2014 and 2020 EHISS, respectively. The prevalence of PA remained stable (57.2% vs. 55.7%, respectively), while the percentage of persons who reported walking continuously for at least 2 days a week increased from 73.9% to 82.2% (p < 0.001). Male sex, younger age, better self-rated health, and lower body mass index (BMI) were significantly associated with greater PA. From 2014 to 2020, the number of walking days ≥2 increased by 64% (OR1.64 95%CI 1.34-2.00). Asthma was associated with less PA (OR0.87 95%CI 0.47-0.72) and a lower number of walking days ≥2 (OR0.84 95%0.72-0.97). (4) Conclusions: Walking frequency improved over time among people with asthma. Differences in PA were detected by age, sex, self-rated health status, and BMI. Asthma was associated with less LTPA and a lower number of walking days ≥2.

Trends and sex differences in atrial fibrillation among patients hospitalized due to asthma: Insights from a nationwide population-based discharge database in Spain, 2016-2021.

AIMS: To analyze changes in the prevalence of atrial fibrillation (AF) in patients hospitalized due to asthma; to compare hospital outcomes in asthma patients with and without AF, assessing sex differences; to identify variables associated with the presence of AF; and to analyze the factors associated with in-hospital mortality (IHM) among asthma patients with AF. METHODS: We used data from the Registry of Specialized Care Activity-Basic Minimum Data Set to select all patients aged ≥40 years with an asthma diagnosis in Spain, from 2016 to 2021. We stratified the study population according to the presence of AF and sex. RESULTS: We identified 65,233 hospitalizations that met the inclusion criteria (14.85 % with AF). The prevalence of AF significantly increased over time, with the male sex being a protective factor for its presentation. IHM were significantly higher in patients with AF. Older age, being a woman, congestive heart failure, renal disease, obstructive sleep apnea, hypertension, and hyperthyroidism were associated with the presence of AF. Advanced age and the presence of cancer and COVID-19 were factors associated with a higher IHM, as well as admission to an intensive care unit and the use of invasive mechanical ventilation. There were no association of sex with the IHM. CONCLUSIONS: AF is highly prevalent among subjects hospitalized due to asthma, with this prevalence having increased significantly in Spain over time. The presence of AF in patients with asthma was associated significantly with a higher LOHS and IHM. Sex was not associated with IHM in these patients.

Trends in Anaphylaxis Hospitalizations among Adults in Spain and Their Relationship with Asthma-Analysis of Hospital Discharge data from 2016 to 2021.

(1) Background: Anaphylaxis is a rapid-onset, life-threatening hypersensitivity reaction. This study explores the epidemiological trends and clinical outcomes of adult patients with and without asthma hospitalized for anaphylaxis in Spain from 2016 to 2021. (2) Methods: Data from the Spanish National Hospital Discharge Database (RAE-CMBD) were analyzed. We stratified patients with anaphylaxis based on their asthma diagnosis and evaluated various comorbidities and clinical outcomes. Propensity score matching was used to match confounders. (3) Results: The total number of hospitalizations for anaphylaxis remained stable, with a decrease in 2020 probably due to the COVID-19 pandemic. Drug-induced anaphylaxis increased, in addition to being the main triggering factor. Asthma prevalence among those admitted for anaphylaxis emerged from 7.63% to 10.69%, with a higher frequency of respiratory failure and need for mechanical ventilation in this group; despite this, ICU admissions and in-hospital mortality did not differ significantly between asthmatics and non-asthmatics. Asthma was also not a risk factor for severe anaphylaxis. Multivariable analysis identified advanced age, ischemic heart disease, acute respiratory failure, and invasive mechanical ventilation as factors associated with severe anaphylaxis. (4) Conclusions: This study provides valuable information on the complexity of anaphylaxis, its relationship with asthma, and factors influencing its severity. Overall, clinical outcomes did not differ significantly in asthmatic patients compared to non-asthmatic patients, although asthmatic patients had more respiratory complications. Further research is necessary to delve deeper into the multifactorial nature of anaphylaxis and its implications in clinical practice.

Physical activity among adults with chronic obstructive pulmonary disease in Spain (2014-2020): Temporal trends, sex differences, and associated factors.

OBJECTIVES: To evaluate trends in the prevalence of physical activity (PA) from 2014 to 2020; to identify sex differences and sociodemographic and health-related factors associated with PA in individuals with chronic obstructive pulmonary disease (COPD); and to compare PA between individuals with and without COPD. METHODS: Cross-sectional and case-control study. SOURCE: European Health Interview Surveys for Spain (EHISS) conducted in 2014 and 2020. We included sociodemographic and health-related covariates. We compared individuals with and without COPD after matching for age and sex. RESULTS: The number of adults with COPD was 1086 and 910 in EHISS2014 and EHISS2020, respectively. In this population, self-reported "Medium or high frequency of PA" remained stable (42.9% in 2014 and 43.5% in 2020; p = 0.779). However, the percentage who walked on two or more days per week rose significantly over time (63.4%-69.9%; p = 0.004). Men with COPD reported more PA than women with COPD in both surveys. After matching, significantly lower levels of PA were recorded in COPD patients than in adults without COPD. Multivariable logistic regression confirmed this trend in COPD patients and showed that male sex, younger age, higher educational level, very good/good self-perceived health, and absence of comorbidities, obesity, and smoking were associated with more frequent PA. CONCLUSIONS: The temporal trend in PA among Spanish adults with COPD is favorable, although there is much room for improvement. Insufficient PA is more prevalent in these patients than in the general population. Sex differences were found, with significantly more frequent PA among males with COPD.

Observational Study of the Association between Atrial Fibrillation and In-Hospital Mortality during Hospitalization for Solid Organ Transplants in Spain from 2004 to 2021.

(1) Background: We analyzed the association between atrial fibrillation or atrial flutter (AF) and in-hospital mortality (IHM) among patients who underwent solid organ transplants in Spain from 2004 to 2021. (2) Methods: We gathered information from all hospital admissions for lung, liver, kidney, and heart transplants. (3) Results: A total of 71,827 transplants were analyzed (4598 lung transplants; 18,127 liver transplants; 45,262 kidney transplants; and 4734 heart transplants). One third of these were for women. Overall, the prevalence of AF was 6.8% and increased from 5.3% in 2004-2009 to 8.6% in 2016-2021. The highest prevalence of AF was found for heart transplants (24.0%), followed by lung transplants (14.7%). The rates for kidney and liver transplants were 5.3% and 4.1%, respectively. The AF code increased over time for all of the transplants analyzed (p < 0.001). The patients' IHM decreased significantly from 2004-2009 to 2016-2021 for all types of transplants. AF was associated with a higher IHM for all of the types of transplants analyzed, except for heart transplants. (4) Conclusions: The prevalence of AF among patients admitted for solid organ transplants was highest for those who underwent heart transplants. The mortality rate during the patients' admission for lung, liver, kidney, or heart transplants decreased over time. AF was independently associated with a higher risk of dying in the hospital for those who underwent lung, liver, or kidney transplants.

Trends and Hospital Outcomes in HOSPITAL Admissions for Anaphylaxis in Children with and without Asthma in Spain (2016-2021).

(1) Background: To assess and compare the temporal trends in the incidence, characteristics and hospital outcomes among children with and without asthma who were hospitalized with anaphylaxis in Spain from 2016 to 2021, and identify the variables associated with severe anaphylaxis among children with asthma. (2) Methods: An observational, retrospective study was conducted using a population-based database. The study population included pediatric patients with anaphylaxis. This population was stratified based on whether they had asthma. (3) Results: The number of hospital admissions was stable from 2016 to 2019, dropping in 2020 and raising to the highest number in 2021. A total of 60.63% of hospitalizations occurred in boys and the most common anaphylactic reactions were due to food consumption (67.28%), increasing over time. The in-hospital mortality (IHM) remained stable and under 1% in all the years studied. The incidence of anaphylaxis was 2.14 times higher in children with asthma than in those without asthma (IRR 2.14; 95% CI 1.87-2.44). Furthermore, it was 1.79 times higher in boys with asthma than in those without asthma (IRR 1.79; 95% CI 1.06-2.45) and 2.68 times higher in girls with asthma than in those without asthma (IRR 2.68; 95% CI 2.23-3.12). Asthma was not associated with severe anaphylaxis (OR 1.31; 95% CI 0.88-1.96). (4) Conclusions: The number of hospitalizations for anaphylaxis in children remained stable from 2016 to 2019, dropping in 2020 and recovering in 2021. IHM was low and remained stable during the study period. The incidence of hospitalizations for anaphylaxis was higher in asthmatic children than in non-asthmatics, but there were no differences in the occurrence of severe anaphylaxis among them.

Association between Hospital-Acquired Pneumonia and In-Hospital Mortality in Solid Organ Transplant Admissions: An Observational Analysis in Spain, 2004-2021.

(1) Background: To analyze the association between hospital-acquired pneumonia (HAP) and in-hospital mortality (IHM) during hospital admission for solid organ transplant in Spain during 2004-2021. (2) Methods: We used national hospital discharge data to select all hospital admissions for kidney, liver, heart, and lung transplants. We stratified the data according to HAP status. To examine time trends, we grouped data into three consecutive 6-year periods (2004-2009; 2010-2015; and 2016-2021). We assessed in-hospital mortality (IHM) in logistic regression analyses and obtained odds ratios (ORs) with their 95% confidence intervals (CIs). (3) Results: We identified a total of 71,827 transplants (45,262, kidney; 18,127, liver; 4734, heart; and 4598, lung). Two thirds of the patients were men. Overall, the rate of HAP during admission was 2.6% and decreased from 3.0% during 2004-2009 to 2.4% during 2016-2021. The highest rate of HAP corresponded to lung transplant (9.4%), whereas we found the lowest rate for kidney transplant (1.1%). Rates of HAP for liver and heart transplants were 3.8% and 6.3%, respectively. IHM was significantly lower during 2016-2021 compared to 2004-2009 for all types of transplants (ORs (CIs) = 0.65 (0.53-0.79) for kidney; 0.73 (0.63-0.84) for liver; 0.72 (0.59-0.87) for heart; and 0.39 (0.31-0.47) for lung). HAP was associated with IHM for all types of transplants (ORs (CIs) = 4.47 (2.85-9.08) for kidney; 2.96 (2.34-3.75) for liver; 1.86 (1.34-2.57) for heart; and 2.97 (2.24-3.94) for lung). (4) Conclusions: Rates of HAP during admission for solid organ transplant differ depending on the type of transplant. Although IHM during admission for solid organ transplant has decreased over time in our country, HAP persists and is associated with a higher IHM after accounting for potential confounding variables.

Temporal trends and outcomes of heart transplantation in Spain (2002-2021): propensity score matching analysis to compare patients with and without type 2 diabetes.

BACKGROUND: The impact of Type 2 Diabetes (T2D) on the outcomes of heart transplantation (HT) has not yet been clearly established. The objectives of this study were to examine the trends in the prevalence of T2D among individuals who underwent a HT in Spain from 2002 to 2021, and to compare the clinical characteristics and hospitalization outcomes between HT recipients with and without T2D. METHODS: We used the national hospital discharge database to select HT recipients aged 35 and older. The International Classification of Diseases, Ninth and Tenth Revisions (ICD-9 and ICD-10) were used to identify patients with and without T2D. We also recorded comorbidities, complications of HT, and procedures. Propensity score matching (PSM) and Cox regression were used to analyze the effect of T2D on in-hospital mortality (IHM). RESULTS: Between 2002 and 2021, a total of 4429 HTs (T2D, 19.14%) were performed in Spain. The number of HTs in patients with T2D decreased from 2002 to 2005 (n = 171) to 2014-2017 (n = 154), then rose during 2018-2021 (n = 186). Complications of HT increased in patients with and without T2D over the study period (26.9% and 31.31% in 2002-2005 vs. 42.47% and 45.01% in 2018-2021, respectively). The results of the PSM showed that pneumonia and Gram-negative bacterial infections were less frequent in patients with T2D and that these patients less frequently required hemodialysis, extracorporeal membrane oxygenation (ECMO), and tracheostomy. They also had a shorter hospital stay and lower IHM than patients without diabetes. The variables associated with IHM in patients with T2D were hemodialysis and ECMO. IHM decreased over time in people with and without T2D. The Cox regression analysis showed that T2D was associated with lower IHM (HR 0.77; 95% CI 0.63-0.98). CONCLUSIONS: The number of HTs increased in the period 2018-2021 compared with 2002-2005 in patients with and without T2D. Over time, complications of HT increased in both groups studied, whereas IHM decreased. The presence of T2D is associated with lower IHM.

Clinical Characteristics and Outcomes of Patients Hospitalized with Epidermolysis Bullosa: A Retrospective Population-Based Observational Study in Spain (2016-2021).

(1) Background: Epidermolysis bullosa (EB) comprises a group of rare skin diseases. We assessed diagnostic procedures, comorbidity profiles, length of hospital stay (LOHS), costs, and in-hospital mortality (IHM) associated with EB. (2) Methods: A retrospective, population-based observational study was performed using the Spanish National Hospital Discharge Database. Hospitalized patients with EB in Spain were identified for the period 2016 to 2021. (3) Results: A total of 677 hospitalizations were identified among 342 patients with a diagnosis of EB. Fifty percent of patients had at least one readmission during the 6-year follow-up. Notably, rehospitalizations were more common among patients aged 2-17 years. The most prevalent comorbidity was digestive disorders, which were associated with the frequency of esophageal dilatation procedures and percutaneous endoscopic gastrostomy. The longest LOHS was recorded for the 0- to 1-year age group. IHM increased with age, and the difference was statistically significant. The prevalence of malignant neoplasm was 36.88%, with cutaneous squamous cell carcinoma being the most frequent. The overall cost per hospitalized patient was estimated to be EUR 10,895.22 (SD EUR 13,394.81), with significant variations between age groups. (4) Conclusions: Readmissions are very frequent among people with EB. We observed a higher LOHS in the 0- to 1-year age group, while the highest rates of IHM were observed in patients older than 50 years. There was a substantial prevalence of comorbidities, namely, digestive disorders, infectious diseases, and especially cancer.

Psychological impact after treatment in patients with head and neck cancer

Background: Cancer is the second cause of death all over the world and it causes considerable morbidity, disability, and treatment sequela, which often lead to post-treatment pain and disfigurement. This study aims to evaluate such physical sequelae, and their psychological, (cognitive and emotional), impact, in a cohort of patients treated for Head and Neck (HNC) cancer, in search for methods to help such patients deal effectively with the psychological effects of their cancer treatments adverse consequences. Material and methods: The sample consists of 56 subjects, 47 men and 9 women, ranging from 47 years to 86 years of age, who were treated for head and neck cancers at Spanish Public General Hospital in the Otolaryngology Unit, Surgery Section. Two types of questionnaires were used in the study: the Questionnaire of Sequelae after Treatment of head and neck carcinoma and the State-Trait Anxiety Inventory (STAI-E and R). Results: With respect to anxiety, the study found high levels of state anxiety which was significantly associated with the degree of perception of social stigma but was not associated with the post-treatment sequelae themselves nor with the level of discomfort that such symptomatic sequelae produced. The presence of a post-surgical stoma with cannula, increased patient's stigma (both components: external rejection and self-rejection) and state anxiety ratings, while there was no difference in state anxiety between cannulated and non-cannulated patients. There are few differences between men and women in terms of the presence of anxiety and their responses are similar in terms of the after-effects of surgery. Conclusions: Our study confirmed that current treatments for Head and Neck carcinoma generate adverse symptomatic sequela that impose significant psychological and physical burden for these patients. We will discuss the various pathways for preventive intervention that these findings open up. (AU)

Compartmentalized primary cultures of dorsal root ganglion neurons to model peripheral pathophysiological conditions.

Neurosensory disorders such as pain and pruritus remain a major health problem greatly impacting the quality of life, and often increasing the risk of mortality. Current pre-clinical models to investigate dysfunction of sensory neurons have shown a limited clinical translation, in part, by failing to mimic the compartmentalized nociceptor anatomy that exhibits a central compartment containing the soma and a peripheral one harboring the axon endings with distinct molecular and cellular environmental composition. Thus, there is a need to validate compartmentalized preclinical neurosensory models for investigating the pathophysiology of peripheral sensory disorders and to test drug candidates. Here, we have addressed this issue and developed a microfluidic-based preclinical nociceptor model and validated it for investigating inflammatory and neuropathic peripheral disorders. We show that this model reproduces the peripheral sensitization and resolution produced by an inflammatory soup and by the chemotherapeutic drug paclitaxel. Furthermore, compartmentalized nociceptor primary cultures were amenable to co-culture with keratinocytes in the axonal compartment. Interaction of axonal endings with keratinocytes modulated neuronal responses, consistent with a crosstalk between both cell types. These findings pave the way towards translational pre-clinical sensory models for skin pathophysiological research and drug development.

Trends and Outcomes in Lung Transplantation in Patients with and without Idiopathic Pulmonary Fibrosis in Spain during the Period 2016-2020.

(1) Background: This paper aims to assess temporal trends (2016-2020) in incidence, patient's characteristics, complications, length of hospital stay (LOHS) and in-hospital mortality (IHM) among patients with and without idiopathic pulmonary fibrosis (IPF) undergoing lung transplantation (LTx). We also analyse the effect of the COVID-19 pandemic on LTx in these populations. (2) Methods: A retrospective, population-based observational study was conducted using the Spanish National Hospital Discharge Database. Multivariable adjustment was conducted with logistic regression to analyse the IHM. (3) Results: We identified 1777 admissions for LTx during the study period, of which 573 (32.2%) were performed in patients with IPF. The number of hospital admissions for LTx rose from 2016 to 2020, both in patients with and without IPF, but a marked reduction was observed from year 2019 to year 2020. Over time, the proportion of single LTx decreased and bilateral LTx increased significantly in both groups. The incidence of LTx complications increased significantly over time along with the increase in the incidence of IPF. No significant differences in the incidence of complications or in the IHM between patients with and without IPF were found. Suffering any complication of the LTx and pulmonary hypertension were conditions positively associated with IHM in patients with and without IPF. The IHM remained stable from 2016 to 2020 in both study populations and was not affected by the COVID pandemic. (4) Conclusions: Patients with IPF account for almost a third of all lung transplants. The number of LTx increased over time in patients with and without IPF, but a marked reduction was observed from 2019 to 2020. Although the proportion of LTx complications increased significantly over time in both groups, the IHM did not change. IPF was not associated with increased complications or IHM after LTx.

Autochthonous Peruvian Natural Plants as Potential SARS-CoV-2 Mpro Main Protease Inhibitors.

Over 750 million cases of COVID-19, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), have been reported since the onset of the global outbreak. The need for effective treatments has spurred intensive research for therapeutic agents based on pharmaceutical repositioning or natural products. In light of prior studies asserting the bioactivity of natural compounds of the autochthonous Peruvian flora, the present study focuses on the identification SARS-CoV-2 Mpro main protease dimer inhibitors. To this end, a target-based virtual screening was performed over a representative set of Peruvian flora-derived natural compounds. The best poses obtained from the ensemble molecular docking process were selected. These structures were subjected to extensive molecular dynamics steps for the computation of binding free energies along the trajectory and evaluation of the stability of the complexes. The compounds exhibiting the best free energy behaviors were selected for in vitro testing, confirming the inhibitory activity of Hyperoside against Mpro, with a Ki value lower than 20 µM, presumably through allosteric modulation.