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The biotechnological development of monoclonal antibodies and their immunotherapeutic use in oncology have grown exponentially in the last decade, becoming the first-line therapy for some types of cancer. Their mechanism of action is based on the ability to regulate the immune system or by interacting with targets that are either overexpressed in tumor cells, released into the extracellular milieu or involved in processes that favor tumor growth. In addition, the intrinsic characteristics of each subclass of antibodies provide specific effector functions against the tumor by activating antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis, among other mechanisms. The rational design and engineering of monoclonal antibodies have improved their pharmacokinetic and pharmacodynamic features, thus optimizing the therapeutic regimens administered to cancer patients and improving their clinical outcomes. The selection of the immunoglobulin G subclass, modifications to its crystallizable region (Fc), and conjugation of radioactive substances or antineoplastic drugs may all improve the antitumor effects of therapeutic antibodies. This review aims to provide insights into the immunological and pharmacological aspects of therapeutic antibodies used in oncology, with a rational approach at molecular modifications that can be introduced into these biological tools, improving their efficacy in the treatment of cancer., (© 2024. The Author(s).)

Background: Retrospective studies and randomized controlled trials support the safety of laparoscopic complete mesocolic excision (CME) for the treatment of right-sided colon cancer (RSCC). Few studies, however, examine the learning curve of this operation and its impact on safety during an implementation period. We aim to evaluate the learning curve and safety of the implementation of laparoscopic CME with intracorporeal anastomosis for RSCC., Methods: Consecutive patients undergoing a laparoscopic right colectomy with intracorporeal anastomosis for RSCC between January 2016 and June 2023 were included. Clinical, perioperative, and histopathological variables were collected. Correlation and cumulative sum (CUSUM) analyses between the operating time and case number were performed. Breakpoints of the learning curve were estimated using the broken-line model. CME and conventional laparoscopic right colectomy outcomes were compared after propensity score matching (PSM)., Results: Two hundred and ninety patients underwent laparoscopic right colectomy during study period. One hundred and eight met inclusion criteria. After PSM, 56 non-CME and 28 CME patients were compared. CME group had a non-statistically significant tendency to a longer operating time (201 versus 195 min; p = 0.657) and a shorter hospital stay (3 versus 4 days; p = 0.279). No significant differences were found in total complication rates or their profile. Correlation analysis identified a significant trend toward operating time reduction with increasing case numbers (Pearson correlation coefficient =  - 0.624; p = 0.001). According to the CUSUM analysis, an institutional learning curve was deemed completed after 13 cases and the broken-line model identified three phases: learning (1-6 cases), consolidation (7-13 cases), and mastery (after 13 cases)., Conclusion: The learning curve of laparoscopic CME for RSCC can be achieved after 13 cases in centers with experience in advanced laparoscopic surgery and surgeons with familiarity with this technique. Its implementation within this setting seems to be as safe as performing a conventional right colectomy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Approximately 1 million scorpion stings are recorded annually worldwide, resulting in 3000 deaths. Scorpion venom has various effects on the human body, with neurological complications occurring in about 2% of cases. Among these complications, stroke-whether ischemic or hemorrhagic-is particularly significant. A systematic literature review was conducted through a bibliographic search using key terms in the PubMed, Scopus, Scielo, Latin American and Caribbean Literature in Health Sciences (LILACS) and Google Schoolar databases without date restrictions. Articles related to stroke due to scorpion stings in Spanish, English, and Portuguese were included. Our protocol was registered in PROSPERO. A total of 24 articles met the inclusion criteria for this review. The primary neurological symptoms caused by scorpion stings include hemiplegia, hemiparesis, seizures, and limb weakness. Stroke should be suspected in the presence of these symptoms, as scorpion stings can lead to both hemorrhagic and ischemic strokes in both adults and pediatric populations. While stroke is a rare complication of scorpion stings, it is crucial to consider this diagnosis in patients presenting with neurological symptoms, necessitating the use of computed tomography or magnetic resonance imaging if stroke is suspected., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Patients recovering from COVID-19 commonly exhibit cognitive and brain alterations, yet the specific neuropathological mechanisms and risk factors underlying these alterations remain elusive. Given the significant global incidence of COVID-19, identifying factors that can distinguish individuals at risk of developing brain alterations is crucial for prioritizing follow-up care. Here, we report findings from a sample of patients consisting of 73 adults with a mild to moderate SARS-CoV-2 infection without signs of respiratory failure and 27 with infections attributed to other agents and no history of COVID-19. The participants underwent cognitive screening, a decision-making task, and MRI evaluations. We assessed for the presence of anosmia and the requirement for hospitalization. Groups did not differ in age or cognitive performance. Patients who presented with anosmia exhibited more impulsive alternative changes after a shift in probabilities (r =  - 0.26, p = 0.001), while patients who required hospitalization showed more perseverative choices (r = 0.25, p = 0.003). Anosmia correlated with brain measures, including decreased functional activity during the decision-making task, thinning of cortical thickness in parietal regions, and loss of white matter integrity. Hence, anosmia could be a factor to be considered when identifying at-risk populations for follow-up., (© 2024. The Author(s).)

Introduction: This systematic review identified qualitative and mixed-methods empirical studies on psychotherapy from dialogical and narrative approaches, aiming to address the following questions: (1) How are subjectivity and intersubjectivity qualitatively understood in dialogical and/or narrative psychotherapies studied using dialogical and narrative approaches? (2) How do therapeutic changes occur, including their facilitators and barriers? (3) What psychotherapeutic resources are available for psychotherapists in these types of studies?, Method: The articles were selected according to the Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the eligibility criteria proposed by the PICOS strategy (participants, interventions, comparators, outcomes, and study design) from 163 records identified in the Web of Science Core Collection databases., Results: The systematic review process allowed the selection of 16 articles. The results provided insights into the understanding of subjectivity, intersubjectivity, change in psychotherapy, its facilitators, and barriers from these perspectives. It also offered some therapeutic interventions that can be implemented in psychotherapies, integrating dialogical and/or narrative aspects., Discussion: The centrality of dialogical exploration of patient/client resources, therapists as interlocutors fostering client agency, polyphony serving as scaffolding for change, and interconnection with the sociocultural environment are discussed. The integration of this latter topic has been a challenge for these types of studies, considering the active construction of shared meanings. The dialogical and narrative approaches focus psychotherapy on transforming meanings through dialogue and re-authoring stories, evolving within cultural and historical contexts. Thus, this study highlights the relevance of these perspectives in contemporary psychotherapy, emphasizing dialogue in co-creation within an intersubjective framework., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mellado, del Río, Andreucci-Annunziata and Molina.)

Purpose: The current research aimed to determine the prevalence and the relationships between perceived stress, burnout, and job satisfaction among practicing speech-language pathologists (SLPs) in Spain. In addition, their perspectives and experiences related to their job were explored., Method: A mixed methods research design was used with cross-sectional quantitative and qualitative methodology. Four hundred and thirty-eight SLPs completed the Perceived Stress Scale, the Maslach Burnout Inventory, and the Font Roja Job Satisfaction Questionnaire in order to report perceived stress, burnout, and job satisfaction, respectively. Ten SLPs participated in semi-structured interviews., Result: With respect to stress, 61.6% of SLPs reported a moderate level of stress and 18.7% reported a high level of stress. With respect to burnout, only 7.56% of the participants met the criteria commonly used for its diagnosis. However, 45.2% of SLPs reported a high level of emotional exhaustion, and 52.7% expressed a low degree of personal accomplishment. Job satisfaction was average for 94% of SLPs and high for just 1% of participants. The level of job satisfaction was significantly related to job stress, emotional exhaustion, and depersonalisation. Qualitative content analyses produced themes and subthemes regarding work recognition, relationships with people in the workplace, work conditions, and job control., Conclusion: A noteworthy percentage of SLPs reported emotional exhaustion and reduced personal achievement. Findings suggest that strengthening job control and social support might become protective factors to avoid the full development of burnout, which should impact positively on an individual's wellbeing and, in turn, the quality of the services provided.

Introduction: Exposure to gases and particulate matter released during volcanic eruptions can prove harmful to population health. This paper reports the preliminary results of the ASHES study, aimed at ascertaining the respiratory health effects of the 2021 volcanic eruption in La Palma Island (Spain) on the adult population without previous respiratory disease., Methods: Ambispective cohort study on the healthy adult population. Three exposure groups were considered: Group 1, high exposure; Group 2, moderate exposure; and Group 3, minor or no exposure. We carried out a descriptive analysis of symptoms during and after the eruption, as well as measure lung function after the eruption (through forced spirometry and diffusing capacity of carbon monoxide)., Results: The analysis included 474 subjects: 54 in Group 1, 335 in Group 2, and 85 in Group 3. A significant increase in most symptoms was observed for subjects in the groups exposed during the eruption. After the eruption, this increase remained for some symptoms. There seems to be a dose-response relationship, such that the higher the exposure, the higher the odds ratio. A prebronchodilator FEV 1 /FVC ratio<70% was observed in 13.0% of subjects in Group 1, 8.6% of subjects in Group 2, and 7.1% of subjects in Group 3., Conclusions: This study is the first to report a dose-response relationship between exposure to volcanic eruptions and the presence of symptoms in adults. Furthermore, there is a tendency toward obstructive impairment in individuals with higher exposure., (Copyright © 2024 The Author(s). Published by Elsevier España, S.L.U. All rights reserved.)

Background: Fibrotic interstitial lung diseases (fILDs) are a heterogeneous group of lung diseases associated with significant morbidity and mortality. Despite a large increase in the number of clinical trials in the last 10 years, current regulatory-approved management approaches are limited to two therapies that prevent the progression of fibrosis. The drug development pipeline is long and there is an urgent need to accelerate this process. This manuscript introduces the concept and design of an innovative research approach to drug development in fILD: a global Randomised Embedded Multifactorial Adaptive Platform in fILD (REMAP-ILD)., Methods: Description of the REMAP-ILD concept and design: the specific terminology, design characteristics (multifactorial, adaptive features, statistical approach), target population, interventions, outcomes, mission and values, and organisational structure., Results: The target population will be adult patients with fILD, and the primary outcome will be a disease progression model incorporating forced vital capacity and mortality over 12 months. Responsive adaptive randomisation, prespecified thresholds for success and futility will be used to assess the effectiveness and safety of interventions. REMAP-ILD embraces the core values of diversity, equity, and inclusion for patients and researchers, and prioritises an open-science approach to data sharing and dissemination of results., Conclusion: By using an innovative and efficient adaptive multi-interventional trial platform design, we aim to accelerate and improve care for patients with fILD. Through worldwide collaboration, novel analytical methodology and pragmatic trial delivery, REMAP-ILD aims to overcome major limitations associated with conventional randomised controlled trial approaches to rapidly improve the care of people living with fILD., Competing Interests: Competing interests: LK-D—research grants from Boehringer Ingelheim and Bristol-Myers-Squibb, research grant from the Brazilian Ministry of Health (PROADI-SUS), non-financial research support from Fisher & Paykel; personal fees from Sarava and Boehringer Ingelheim. TK—personal fees from Boehringer Ingelheim, United Therapeutics, Puretech and Veracyte. CJR—research grant from Boehringer Ingelheim; personal fees from Boehringer Ingelheim, Pliant Therapeutics, AstraZeneca, Trevi Therapeutics, Hoffmann La Roche and Cipla. PR-O—research grants from Boehringer Ingelheim, Hoffmann La Roche, CSL Behring, FibroGen, Vicore Pharma, Gilead, Galecto and Chiesi; personal fees from Boehringer Ingelheim, Hoffmann La Roche, Cipla, Tecnofarma, Respiratory Effectiveness Group and The Limbic. NC—personal fees from Boehringer Ingelheim, Liminal Biosciences, Vicor Pharma, Bridge Biotherapeutics and Transcrip. MF-C—research grants from CSL Behring, Boehringer Ingelheim and Roche; personal fees from Boehringer Ingelheim, MSD, AstraZeneca and GSK. A-MH-V—research grants from Boehringer Ingelheim and Janssen; personal fees from ARXX, Boehringer Ingelheim, Janssen, Medscape, Roche, Genentech, Bayer, Lilly and Merck Sharp & Dohme. KAJ—research grants from University Hospital Foundation and Three Lakes Foundation; personal fees from Boehringer Ingelheim, Pliant, Thyron, Brainomix and Hoffman La Roche. YHK—research grants from NHMRC, MRFF, Air Liquide Healthcare, Austin Medical Research Foundation, Lung Foundation Australia/Thoracic Society of Australia and New Zealand, and RACP. SBM—research grants from Three Lakes Foundation, NIH/NHLBI, Merck, Boehringer Ingelheim, Pliant Therapeutics, American Thoracic Society, and National Scleroderma Foundation; personal fees from Wolters Kluwer, Roche, DevPro Biopharma, Gilead, Accendatech, Cowen and APIE Therapeutics. LP—research grants from Janssen and Ferrer; personal fees from Janssen, Ferrer, United Therapeutics, MSD and Liquidia. HP—research grants from Boehringer Ingelheim, AstraZeneca and Siemens; personal fees from Boehringer Ingelheim, Sanofi, Janssen, MSD, AstraZeneca and Chiesi. MM-M—research grants from Boehringer Ingelheim and Roche; personal fees from Boehringer Ingelheim, Ferrer and Chiesi. JST—research grant from Boehringer Ingelheim; personal fees from Boehringer Ingelheim and Aflofarm. SR—personal fees from Cipla and Boehringer Ingelheim. JJ—research grants from Gilead, Microsoft research and GSK; personal fees from Boehringer Ingelheim, Roche, GSK and Takeda. DR—research grants from NIHR; personal fees from OMass Therapeutics, Sosei Heptares and GSK. LGS—personal fees from Daiichi Sankyo and Chiesi. MK—research grants from Boehringer Ingelheim and Roche; personal fees from Nichtraucherhelden/Sanero, Boehringer Ingelheim and Roche. NK—research grants from Veracyte, Boehringer Ingelheim, BMS and non-financial support from AstraZeneca; scientific founder at Thyron; personal fees from Boehringer Ingelheim, Pliant, AstraZeneca, RohBar, Veracyte, Augmanity, CSL Behring, Splisense, Galapagos, Fibrogen, GSK, Merck and Thyron; and reports Equity in Pliant and Thyron. RL—senior consultant for Berry Consultants. WA—personal fees from Boehringer Ingelheim. GJ—research grants from AstraZeneca, Biogen, Galecto, GSK, Nordic Biosciences, RedX and Pliant; personal fees from Apollo Therapeutics, AstraZeneca, Brainomix, Bristol-Myers-Squibb, Chiesi, Cohbar, Daewoong, Veracyte, GSK, Resolution Therapeutics, Pliant, Hoffmann La Roche, PatientMPower, Pinsent Masons, Galapagos and Vicore Pharma. BGB, IB-V, BW, TJ, MQ and VC have no conflicts to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This paper investigates the effect of nozzle temperature, from 180 to 260 °C, on properties of polylactic acid (PLA) samples manufactured by fused deposition modeling (FDM) technology. The main objective of this research is to determinate an optimum nozzle temperature relative to tensile, flexural and compressive properties of printed specimens. After manufacturing, the samples exhibit an amorphous structure, without crystallization effects, independently of the fabrication temperature. In order to determine the influence of printing temperature on mechanical properties, uniaxial tensile, three-point flexural and compression strength tests were carried out. The obtained results suggest that a relative low printing temperature could reduce the material flow and decrease the density of the final prototype, with a negative effect on both the quality and the mechanical properties of the pieces. If temperature increases up to 260 °C, an excess of material can be deposited, but with no significant negative effect on mechanical parameters. There is an optimum nozzle temperature interval, depending on the considered piece and test, for which mechanical values can be optimized. Taking into account all tests, a recommended extruder temperature interval may be identified as 220-240 °C. This range encompasses all mechanical parameters, avoiding the highest temperature where an excess of material was observed. For this printing temperature interval, no significant mechanical variations were appreciated, which corresponds to a stable behavior of the manufactured specimens.

Introduction: Sleep-disordered breathing (SDB) is a major comorbidity in idiopathic pulmonary fibrosis (IPF) and is associated with a poor outcome. There is a lack of knowledge regarding the impact of SDB treatment on IPF. We assessed at one year: (1) the effect of CPAP and/or nocturnal oxygen therapy on IPF regarding lung function, blood mediators, and quality of life; (2) adherence to SDB treatment and SDB changes., Methodology: This is a prospective study of consecutive newly diagnosed IPF patients initiating anti-fibrotic treatment. Lung function, polysomnography, blood tests and quality of life questionnaires were performed at inclusion and after one year. Patients were classified as obstructive sleep apnoea (OSA), central sleep apnoea (CSA), and sleep-sustained hypoxemia (SSH). SDB therapy (CPAP and/or nocturnal oxygen therapy) was initiated if needed., Results: Fifty patients were enrolled (36% had OSA, 22% CSA, and 12% SSH). CPAP was started in 54% of patients and nocturnal oxygen therapy in 16%. At one-year, polysomnography found improved parameters, though 17% of patients had to add nocturnal oxygen therapy or CPAP, while 33% presented SDB onset at this second polysomnography. CPAP compliance at one year was 6.74 h/night (SD 0.74). After one year, matrix metalloproteinase-1 decreased in OSA and CSA (p = 0.029; p = 0.027), C-reactive protein in OSA (p = 0.045), and surfactant protein D in CSA group (p = 0.074). There was no significant change in lung function., Conclusions: Treatment of SBD with CPAP and NOT can be well tolerated with a high compliance. IPF patients may exhibit SDB progression and require periodic re-assessment. Further studies to evaluate the impact of SDB treatment on lung function and serological mediators are needed., (© 2024. The Author(s).)

Objective: To assess the real-world, long-term effectiveness of rituximab (RTX) as a rescue therapy in patients with antisynthetase syndrome and progressive interstitial lung disease (ASS-ILD)., Methods: Multicentre observational retrospective longitudinal study of a cohort of patients with ASS-ILD that started treatment with RTX due to recurrent or ongoing progressive ILD despite therapy with glucocorticoids and immunosuppressants., Results: Twenty-eight patients were analyzed. Examining the entire study population, before treatment with RTX the mean decline in %pFVC and %pDLCO from the ASS-ILD diagnosis to the initiation of RTX treatment (T0) was -6.44% and -14.85%, respectively. After six months of treatment, RTX reversed the decline in pulmonary function test (PFT) parameters: ∆%pFVC +6.29% (95% CI: -10.07 to 2.51; p=0.002 compared to T0) and ∆%pDLCO +6.15% (95% CI: -10.86 to -1.43; p=0.013). Twenty-four patients completed one year of therapy and 22 two years, maintaining the response in PFT: ∆%pFVC: +9.93% (95% CI: -15.61 to -4.25; p=0.002) and ∆%pDLCO: +7.66% (95% CI: -11.67 to -3.65; p<0.001). In addition, there was a significant reduction in the median dose of prednisone, and it could be suspended in 18% of cases. In 33% of patients who required oxygen therapy at the start of treatment, it could be discontinued. The frequency of adverse events reached 28.5% of cases., Conclusion: Based on our results, RTX appears to be effective as rescue therapy in most patients with recurrent or progressive ASS-ILD unresponsive to conventional treatment. The use of RTX was well tolerated in the majority of patients., (© 2024. The Author(s).)

Purpose: Ascending aorta (AAo) acute pathology still has an open-surgery indication with a high mortality rate associated to cardiopulmonary bypass and circulatory arrest. In these cases, the endovascular aortic approach could be an excellent option. The aim of the present study is to detail an optimized technique for the endovascular treatment of AAo diseases, based on thoracic endovascular aortic repair (TEVAR) and transcatheter aortic valve implantation (TAVI) procedures., Technique: The procedure implies the usual preparation for TEVAR and TAVI implants. A transient pacemaker lead is necessary to deliver the prosthesis under "rapid pacing." As in the TAVI technique, a final high-support guidewire is placed at the left ventricle. The proximal landing zone is the sinotubular junction (zone 0B). Transesophageal echocardiography is essential to ensure aortic valve function and patency in coronary arteries during the delivery. To assess a potential occlusion of the brachiocephalic artery, a guidewire is positioned in the descending aorta from the axillary artery. Finally, a noncovered stent is implanted to stabilize the AAo prosthesis., Conclusion: The technique presented here can standardize a safe and reproducible procedure to endovascular repair of AAo diseases. However, new devices specifically designed for the AAo could facilitate the transcatheter approach., Clinical Impact: Ascending aorta acute pathology still has an open-surgery indication with high mortality rate associated to cardiopulmonary bypass and circulatory arrest. Moreover, near 30% of patients are not considered suitable for surgery because of age, critical situation or the presence of severe comorbidities. The present study provides a detailed and optimized technique for the endovascular treatment of ascending aorta disease, based on TEVAR and TAVI procedures., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

ATP citrate lyase (ACLY) inhibitors have the potential of modulating central processes in protein, carbohydrate, and lipid metabolism, which can have relevant physiological consequences in aging and age-related diseases. Here, we show that hepatic phospho-active ACLY correlates with overweight and Model for End-stage Liver Disease score in humans. Wild-type mice treated chronically with the ACLY inhibitor potassium hydroxycitrate exhibited delayed early mortality. In AML12 hepatocyte cultures, the ACLY inhibitors potassium hydroxycitrate, SB-204990, and bempedoic acid fostered lipid accumulation, which was also observed in the liver of healthy-fed mice treated with potassium hydroxycitrate. Analysis of soleus tissue indicated that potassium hydroxycitrate produced the modulation of wound healing processes. In vivo, potassium hydroxycitrate modulated locomotor function toward increased wire hang performance and reduced rotarod performance in healthy-fed mice, and improved locomotion in mice exposed to cardiotoxin-induced muscle atrophy. Our findings implicate ACLY and ACLY inhibitors in different aspects of aging and muscle regeneration., (© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Objective: The objective of the study was to analyze the diagnostic process and the time until the start of treatment of patients with idiopathic pulmonary fibrosis in relation to the publication of successive clinical practice guide., Material and Methods: Multicenter, observational, ambispective study, in which patients includes in the idiopathic pulmonary fibrosis registry of the Spanish Society of Pulmonologist and Thoracic Surgery were analyzed. An electronic data collection notebook was enabled on the society's website. Sociodemographic and clinical variables were collected at diagnosis and follow-up of the patients., Results: From January 2012 to december 2019, 1064 patients were included in the registry, with 929 finally analyzed. The diagnosis process varied depending on the year in which it was performed, and the radiological pattern observed in the high-resolution computed tomography. Up to 26.3% of the cases (244) were diagnosed with chest high-resolution computed tomography and clinical evaluation. Surgical biopsy was used up to 50.2% of cases diagnosed before 2011, while it has been used in 14.2% since 2018. The median time from the onset of symptoms to diagnosis was 360 days (IQR 120-720), taking more than 2 years in the 21.0% of patients. A percentage of 79.4 of patients received antifibrotic treatment. The average time from diagnosis to the antifibrotic treatment has been 309 ± 596.5 days, with a median of 49 (IQR 0-307)., Conclusions: The diagnostic process, including the time until diagnosis and the type of test used, has changed from 2011 to 2019, probably due to advances in clinical research and the publication of diagnostic-therapeutic consensus guidelines., (© 2024 Sociedad Española de Neumología y Cirugía Torácica (SEPAR). Published by Elsevier España, S.L.U.)

Background: Small bowel tumors (SBT) are infrequent and represent a small proportion of digestive neoplasms. There is scarce information about SBT in Latin America., Aim: To describe the epidemiology, clinical characteristics, diagnostic methods, and survival of malignant SBTs., Methods: Retrospective observational study of adult patients with histopathological diagnosis of SBT between 2007 and 2021 in a university hospital in Chile., Results: A total of 104 patients [51.9% men; mean age 57 years] with SBT. Histological type: neuroendocrine tumor (NET) (43.7%, n=38), gastrointestinal stromal tumors (GIST) (21.8%, n=19), lymphoma (17.2%, n=15) and adenocarcinoma (AC) (11.5%, n=10). GIST was more frequent in duodenum (50%; n=12) and NET in the ileum (65.8%; n=25). Metastasis was observed in 17 cases, most commonly from colon and melanoma. Nausea and vomiting were significantly more often observed in AC (p=0.035), as well as gastrointestinal bleeding in GIST (p=0.007). The most common diagnostic tools were CT and CT enteroclysis with an elevated diagnostic yield (86% and 94% respectively). The 5-year survival of GIST, NET, lymphoma and AC were 94.7% (95%CI: 68.1-99.2), 82.2% (95%CI: 57.6-93.3), 40.0% (95%CI: 16.5-82.8) and 25.9% (95%CI: 4.5-55.7%), respectively. NET (HR 6.1; 95%CI: 2.1-17.2) and GIST (HR 24.4; 95%CI: 3.0-19.8) were independently associated with higher survival compared to AC, adjusted for age and sex., Conclusions: Malignant SBT are rare conditions and NETs are the most common histological subtype. Clinical presentation at diagnosis, location or complications may suggest a more probable diagnosis. GIST and NET are associated with better survival compared to other malignant subtypes., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Background: Disease penetrance in genotype-positive (G+) relatives of families with dilated cardiomyopathy (DCM) and the characteristics associated with DCM onset in these individuals are unknown., Objectives: This study sought to determine the penetrance of new DCM diagnosis in G+ relatives and to identify factors associated with DCM development., Methods: The authors evaluated 779 G+ patients (age 35.8 ± 17.3 years; 459 [59%] females; 367 [47%] with variants in TTN) without DCM followed at 25 Spanish centers., Results: After a median follow-up of 37.1 months (Q1-Q3: 16.3-63.8 months), 85 individuals (10.9%) developed DCM (incidence rate of 2.9 per 100 person-years; 95% CI: 2.3-3.5 per 100 person-years). DCM penetrance and age at DCM onset was different according to underlying gene group (log-rank P = 0.015 and P <0.01, respectively). In a multivariable model excluding CMR parameters, independent predictors of DCM development were: older age (HR per 1-year increase: 1.02; 95% CI: 1.0-1.04), an abnormal electrocardiogram (HR: 2.13; 95% CI: 1.38-3.29); presence of variants in motor sarcomeric genes (HR: 1.92; 95% CI: 1.05-3.50); lower left ventricular ejection fraction (HR per 1% increase: 0.86; 95% CI: 0.82-0.90) and larger left ventricular end-diastolic diameter (HR per 1-mm increase: 1.10; 95% CI: 1.06-1.13). Multivariable analysis in individuals with cardiac magnetic resonance and late gadolinium enhancement assessment (n = 360, 45%) identified late gadolinium enhancement as an additional independent predictor of DCM development (HR: 2.52; 95% CI: 1.43-4.45)., Conclusions: Following a first negative screening, approximately 11% of G+ relatives developed DCM during a median follow-up of 3 years. Older age, an abnormal electrocardiogram, lower left ventricular ejection fraction, increased left ventricular end-diastolic diameter, motor sarcomeric genetic variants, and late gadolinium enhancement are associated with a higher risk of developing DCM., Competing Interests: Funding Support and Author Disclosures This study was funded by the Spanish Society of Cardiology (Grant in Inherited Cardiac Diseases 2022) and the Instituto de Salud Carlos III through the projects “PI18/0004, PI20/0320” (Co-funded by European Regional Development Fund/European Social Fund “A way to make Europe”/“Investing in your future”). The CNIC is supported by the ISCIII, MCIN, the Pro-CNIC Foundation, and the Severo Ochoa Centers of Excellence program (CEX2020-001041-S). The Hospital Universitario Puerta de Hierro, Hospital Clínic, Hospital Vall Hebron, Hospital Virgen del Rocío, Hospital Universitario Gregorio Marañon, and the Hospital Universitario Virgen de la Arrixaca are members of the European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart: ERN GUARD-Heart. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Lymphangioleiomyomatosis (LAM) is a rare disease that affects women almost exclusively. We aimed to determine the psychological profile in patients with LAM, and their potential association with sociodemographic and clinical features, and to know their role in coping with the disease., Material and Methods: Cross-sectional and descriptive study in collaboration with the Spanish Association of LAM (AELAM). The variables measured were: socio-demographic, psychological (anxiety, depression, demoralization, spirituality, resilience, social support), clinical (treatment) and health-related quality of life., Results: We studied 87 LAM patients, with a mean (SD) age of 47.7 (7.7) years, and time since diagnose was 10.1 (5.4) years. 75.9% of patients were receiving sirolimus or everolimus, and oxygen therapy was required in 34.5% of patients. Anxiety was found in 46% of patients, depression in 55%, while only 2% presented demoralization and 14% deficit in spirituality. Social support and resilience were adequate. The "non-severe" group (without oxygen therapy) presented worse results in anxiety. A structural equation model to explore association between variables, showed very adequate fit indices: χ 2 (14) = 29.743 ( p  = .074); CFI = .983; TLI = .967; SRMR = .058; RMSEA = .075[.000-.128]. The model identifies resilience, spirituality and social support as "protective factors" from anxiety, depression, and demoralization., Conclusions: This study performed on a large series of women with LAM describes their psychological profile, in addition to showing how they cope with the disease. We have found that other psychological constructs, such as perceived social support and resilience, are protective factors. Early psychological evaluation and intervention is necessary to reduce comorbidities and prevent mental health problems in women with LAM., (© 2024 Sociedad Española de Neumología y Cirugía Torácica (SEPAR). Published by Elsevier España, S.L.U.)

Background: Exercise training in patients with HCM has evidenced benefits on functional capacity, cardiac function, and a reversion of adverse cardiac remodeling. The objective of this study was to assess the effect of a concurrent resistance and cardiorespiratory training program on functional capacity, biochemical parameters, and echocardiographic variables in a pilot group. Methods: Two HCM patients were evaluated before and after 12 weeks of individualized concurrent training with two sessions/week. Pre- and post-training data were compared for each patient. Evaluations included a cardiopulmonary exercise test (CPET), body composition, echocardiography, electrocardiography, and blood analysis. Results: Training promoted an increase in functional capacity (+4 mL·kg -1 ·min -1 ), ventilatory thresholds, and other CPET-derived variables associated with a better prognosis and long-term survival. Muscular mass was augmented (0.8 and 1.2 kg), along with a mean increase of 62% in upper and lower body strength. Echocardiographic features demonstrated the maintenance of cardiac function with signs of positive left ventricular remodeling and an improvement in diastolic function. Blood analyses, including cardiac troponins and NT-proBNP, displayed uneven changes in each patient, but the values fell into normal ranges in both cases. Conclusions: The available data suggest a positive effect of concurrent resistance and cardiorespiratory training on patients' functional capacity and cardiac function that may improve their functional class, quality of life, and long-term prognosis. The replication of this protocol in a larger cohort of patients is warranted to confirm these preliminary results.

Plant viral nanoparticles (VNPs) are attractive to nanomedicine researchers because of their safety, ease of production, resistance, and straightforward functionalization. In this paper, we developed and successfully purified a VNP derived from turnip mosaic virus (TuMV), a well-known plant pathogen, that exhibits a high affinity for immunoglobulins G (IgG) thanks to its functionalization with the Z domain of staphylococcal Protein A via gene fusion. We selected cetuximab as a model IgG to demonstrate the versatility of this novel TuMV VNP by developing a fluorescent nanoplatform to mark tumoral cells from the Cal33 line of a tongue squamous cell carcinoma. Using confocal microscopy, we observed that fluorescent VNP-cetuximab bound selectively to Cal33 and was internalized, revealing the potential of this nanotool in cancer research.

The aim of this study was to evaluate and compare the effects on biochemical parameters and organosomatic indices in the freshwater bivalve Diplodon chilensis exposed to a glyphosate-based formulation under direct and dietary exposures (4 mg a.p./L). After 1, 7, and 14 days of exposure, reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) levels and the activities of glutathione-S- transferase (GST), superoxide dismutase (SOD), and catalase (CAT) were evaluated in the gills and digestive gland. The hepatosomatic (HSI) and branchiosomatic (BSI) indices were also analyzed. Direct and dietary glyphosate-based formulation exposure altered the redox homeostasis in the gills and digestive gland throughout the experimental time, inducing the detoxification response (GST), the antioxidant defenses (SOD, CAT, GSH), and causing lipid peroxidation. After 14 days of exposure, the HSI and BSI increased significantly (43% and 157%, respectively) only in the bivalves under direct exposure. Greater changes in the biochemical parameters were induced by the dietary exposure than by the direct exposure. Furthermore, the gills presented an earlier response compared to the digestive gland. These results suggested that direct and dietary exposure to a glyphosate-based formulation induced oxidative stress in the gills and digestive glands of D. chilensis. Thus, the presence of glyphosate-based formulations in aquatic ecosystems could represent a risk for filter-feeding organisms like bivalves., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: In modern societies, motorcycle accidents have become a great problem for health systems worldwide. In Spain, the size and the power of the engine of 2-wheel vehicles determine the type of driving license and the age at which these vehicles can be used (mopeds and motorcycles, which at the same time can have a small or large engine capacity). The objective of the present study was to analyze and characterize low- and high-power motorcycle accidents in Spain, between 2014 and 2020, both included and compared these categories with each other., Methods: Retrospective, descriptive, and observational study of motorcycle and moped accidents in Spain between 2014 and 2020, both included., Results: The mortality of motorcycle accident riders in Spain is associated with males aged between 30 and 40 years old, with a high-power motorcycle, and an A or A1 driver's license, who is 6.7 times more likely to die in crossings and highways than a moped, while wearing a helmet, and if not, this increases to 4.89 times. During the COVID-19 pandemic, an increase in death at 24 h after a high-power motorcycle accident was observed, as compared with a large reduction in the total medical assistance provided in 2019-2020., Conclusions: High-power motorcycles had higher scores in mortality and morbity rates than low-power ones, with a significant increase in mortality during the pandemic, even though number of accidents and medical assistance provided were drastically reduced., (© 2023. The Author(s).)

(1) Background: Clinical simulation is an educational approach that aims to replicate real-life scenarios. Its primary goal is to help nursing students acquire the necessary knowledge and skills to perform effectively in clinical settings. This study focuses on the relationship between communication skills, evidence-based practice (EBP), and clinical simulation. We aimed to assess how communication skills and EBP competencies affect nursing students' performance in simulated clinical scenarios. (2) Methods: We conducted an observational, cross-sectional study with 180 third-year nursing students at the University of Murcia. We used validated instruments to evaluate the students' EBP competencies, communication skills, non-technical skills, and nursing interventions in simulated scenarios. (3) Results: The results showed that the students had varying competencies in EBP and communication skills. However, there was a positive and statistically significant correlation ( p < 0.001) between these variables, non-technical skills, and the simulated clinical scenario nursing interventions. Our regression models revealed that communication skills and EBP competence significantly influenced the performance of the student nurses regarding their clinical and non-technical skills in the simulated scenarios. (4) Conclusions: Communication skills and EBP competencies predict performance in simulated scenarios for nursing students.

Purpose: MELAS syndrome is a genetic disorder caused by mitochondrial DNA mutations. We previously described that MELAS patients had increased CSF glutamate and decreased CSF glutamine levels and that oral glutamine supplementation restores these values. Proton magnetic resonance spectroscopy ( 1 H-MRS) allows the in vivo evaluation of brain metabolism. We aimed to compare 1 H-MRS of MELAS patients with controls, the 1 H-MRS after glutamine supplementation in the MELAS group, and investigate the association between 1 H-MRS and CSF lactate, glutamate, and glutamine levels., Methods: We conducted an observational case-control study and an open-label, single-cohort study with single-voxel MRS (TE 144/35 ms). We assessed the brain metabolism changes in the prefrontal (PFC) and parieto-occipital) cortex (POC) after oral glutamine supplementation in MELAS patients. MR spectra were analyzed with jMRUI software., Results: Nine patients with MELAS syndrome (35.8 ± 3.2 years) and nine sex- and age-matched controls were recruited. Lactate/creatine levels were increased in MELAS patients in both PFC and POC (0.40 ± 0.05 vs. 0, p < 0.001; 0.32 ± 0.03 vs. 0, p < 0.001, respectively). No differences were observed between groups in glutamate and glutamine (Glx/creatine), either in PFC (p = 0.930) or POC (p = 0.310). No differences were observed after glutamine supplementation. A positive correlation was found between CSF lactate and lactate/creatine only in POC (0.85, p = 0.003)., Conclusion: No significant metabolite changes were observed in the brains of MELAS patients after glutamine supplementation. While we found a positive correlation between lactate levels in CSF and 1 H-MRS in MELAS patients, we could not monitor treatment response over short periods with this tool., Trial Registration: ClinicalTrials.gov Identifier: NCT04948138; initial release 24/06/2021; first patient enrolled on 1/07/2021. https://clinicaltrials.gov/ct2/show/NCT04948138., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Fibrotic hypersensitivity pneumonitis (fHP) is an immune-mediated interstitial lung disease caused by sensitisation to chronic allergen inhalation. This study aimed to determine prognostic indicators of progression and mortality in fHP., Methods: This was a retrospective, multicentre, observational, cross-sectional cohort study of consecutive patients diagnosed with fHP from 1 January 2012 to 31 December 2021. Multivariate Cox regression analyses were used to calculate hazard ratios (HRs) with 95% confidence intervals for predictors of progression and survival., Results: A total of 403 patients were diagnosed with fHP: median (interquartile range) age 66.5 (14.0) years, 51.9% females and 55.1% never-smokers. The cause of fHP was mainly fungal (39.7%) or avian (41.4%). Lung biopsy was performed in 269 cases (66.7%). In the whole cohort the variables that were related to mortality or lung transplant were older age (HR 1.08; p<0.001), percentage predicted forced vital capacity (HR 0.96; p=0.001), lymphocytosis in bronchoalveolar lavage (BAL) (HR 0.93; p=0.001), presence of acute exacerbation during follow-up (HR 3.04; p=0.001) and GAP (gender, age and lung physiology) index (HR 1.96; p<0.01). In the group of biopsied patients, the presence of fibroblastic foci at biopsy (HR 8.39; p<0.001) stands out in multivariate Cox regression analyses as a highly significant predictor for increased mortality or lung transplant. GAP index (HR 1.26; p=0.009), lymphocytosis in BAL (HR 0.97; p=0.018) and age (HR 1.03; p=0.018) are also predictors of progression., Conclusions: The study identified several prognostic factors for progression and/or survival in fHP. The presence of fibroblastic foci at biopsy was a consistent predictor for increased mortality and the presence of lymphocytosis in BAL was inversely related to mortality., Competing Interests: Conflict of interest: E. Cano-Jiménez has received grants and fees for research purposes or speaking from Roche, Bristol Myers and Boehringer Ingelheim. Conflict of interest: A. Villar Gómez has received travel grants, consulting fees, speaking fees or research grants from Boehringer Ingelheim, Roche, Glaxo and Chiesi. Conflict of interest: M. Aburto Barrenechea reports lecture fees and support for attending meetings from Boehringer Ingelheim in the last 36 months, outside the submitted work. Conflict of interest: J. Sellarés Torres has received funding from Boehringer and Roche, outside the submitted work. Conflict of interest: D. Castillo Villegas reports personal fees and nonfinancial support from Roche; grants, personal fees and nonfinancial support from Boehringer Ingelheim; grants from Fujirebio; and personal fees from Veracyte, outside the submitted work. Conflict of interest: C. González Fernández has participated in conferences, scientific meetings, consulting, research and scientific dissemination activities funded by AstraZeneca, Chiesi, Teva, Sanofi, Novartis, GlaxoSmithKline, Boehringer Ingelheim, Bristol Myers Squibb and Roche. Conflict of interest: M. Molina-Molina has received grants and fees for research purposes and scientific advice from Ferrer, Boehringer Ingelheim, Roche, Esteve-Teijin, Chiesi and Janssen. Conflict of interest: E. Velez Segovia, J. Francesqui, O. Acosta Fernández, J. Bordas-Martinez, K. Portillo Carroz, A.J. Solis Solis, A.B. Llanos Gonzáles, E. Cabrera Cesar, E. Balcells Vilarnau, A. Reyes Pardessus, M. García Moyano, A. Urrutia Gajate and A. Blanco Hortas have no conflicts of interest to report., (Copyright ©The authors 2024.)

Zeolitic imidazolate frameworks (ZIFs) are widely used MOFs because of certain characteristics, but also because they can be prepared at room temperature using water as the unique solvent. However, these a priori sustainable conditions inevitably entail a huge and somehow unusable excess of linker. Here, we present the formation of ZIFs at room temperature in water, starting from mixtures with a linker/metal ratio of two, that is, coinciding with the stoichiometry found in the final MOFs, in the presence of amines. ZIF-8 can be prepared with triethylamine (TEA), giving a yield of Zn of 96.6%. Other bases, like NaOH, tetraethylammonium hydroxide or ammonium hydroxide, do not lead to ZIF-8 under the same conditions. The so-obtained ZIF-8 contains TEA inside its cavities, making it less porous than its conventionally prepared counterparts. Amine can be removed by mild thermal treatments (200-250 °C). Such thermal treatments induce the generation of g-C 3 N 4 -like species which could give added value to these materials as potential photocatalysts, increasing their affinity to CO 2 , as proved in this work. This methodology can be successfully extended to other amines, like N,N-dicyclohexylmethylamine, as well as to other prepared ZIFs, like Co-based ZIF-67, isostructural to ZIF-8.

Purpose: To evaluate the effect of different whole-corneal and whole-eye higher order aberrations (HOAs) on levels of axis discrepancy., Methods: This was a retrospective study including healthy candidates for refractive surgery, with one eye being randomly selected. A total of 360 eyes were included. Whole-corneal and whole-eye HOAs were measured twice with a Pentacam AXL Wave (Oculus Optikgeräte GmbH), and subjective manifest refraction was obtained. Axis discrepancy was defined as the absolute difference between Total Corneal Refractive Power flat keratometry axis and manifest refractive axis. Two multiple linear regression models that sought to explore the effect of HOAs in predicting axis discrepancy while adjusting for corneal and refractive confounders were built., Results: Mean age was 29.1 ± 5.8 years and 63.9% of the patients were women. Mean manifest sphere and cylinder were -3.09 ± 2.36 and -1.45 ± 1.37 diopters (D), respectively. Mean cylinder axis discrepancy was 14.4 ± 14.5°. On multiple linear regression, the only variables significantly associated with axis discrepancy were corneal cylinder and corneal lower order aberrations [ F (5,339) = 29.746; P < .001; adjusted R 2 = 0.295]. Lower levels of corneal cylinder are by far the main contributor to astigmatism axis mismatch (ß = -1.164). There was not a single HOA, either corneal or ocular, that significantly loaded into any models., Conclusions: Astigmatism axis mismatch decreases rapidly with increasing levels of corneal astigmatism. Corneal and whole-eye HOAs have no role in astigmatism axis mismatch in healthy candidates for refractive surgery. [ J Refract Surg . 2024;40(2):e89-e97.] .

The Ecuadorian Amazon rainforest stands out as one of the world's most biodiverse regions, yet faces significant threats due to oil extraction activities dating back to the 1970s in the northeastern provinces. This research investigates the environmental and societal consequences of prolonged petroleum exploitation and oil spills in Ecuador's Amazon. Conducted in June 2015, the study involved a comprehensive analysis of freshwater sediment samples from 24 locations in the Rio Aguarico and Napo basins. Parameters such as water and air temperature, conductivity, soil pH, and hydrocarbon concentrations were examined. Total petroleum hydrocarbon (TPH) concentrations ranged from 9.4 to 847.4 mg kg -1 , with polycyclic aromatic hydrocarbon (PAH) levels varying from 10.15 to 711.1 mg kg -1 . The pristane/phytane ratio indicated historic hydrocarbon pollution in 8 of the 15 chemically analyzed sediments. Using non-culturable techniques (Illumina), bacterial analyses identified over 350 ASV, with prominent families including Comamonadaceae , Chitinophagaceae , Anaeromyxobacteraceae , Sphingomonadaceae , and Xanthobacteraceae . Bacterial diversity, assessed in eight samples, exhibited a positive correlation with PAH concentrations. The study provides insights into how microbial communities respond to varying levels of hydrocarbon pollution, shedding light on the enduring impact of oil exploitation in the Amazonian region. Its objective is to deepen our understanding of the environmental and human well-being in the affected area, underscoring the pressing need for remedial actions in the face of ongoing ecological challenges.

Humans often face the challenge of making decisions between ambiguous options. The level of ambiguity in decision-making has been linked to activity in the parietal cortex, but its exact computational role remains elusive. To test the hypothesis that the parietal cortex plays a causal role in computing ambiguous probabilities, we conducted consecutive fMRI and TMS-EEG studies. We found that participants assigned unknown probabilities to objective probabilities, elevating the uncertainty of their decisions. Parietal cortex activity correlated with the objective degree of ambiguity and with a process that underestimates the uncertainty during decision-making. Conversely, the midcingulate cortex (MCC) encodes prediction errors and increases its connectivity with the parietal cortex during outcome processing. Disruption of the parietal activity increased the uncertainty evaluation of the options, decreasing cingulate cortex oscillations during outcome evaluation and lateral frontal oscillations related to value ambiguous probability. These results provide evidence for a causal role of the parietal cortex in computing uncertainty during ambiguous decisions made by humans., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Valdebenito-Oyarzo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Apoptosis supports tissue homeostasis and prevents immune disorders by removing damaged and functionally aberrant cells. Here, Ou et al. utilized genetic, pharmacological, and proteomic approaches focused on sulfur amino acid catabolism to discover that hydrogen sulfide (H 2 S) release during apoptosis suppresses Th17 cell differentiation, thus providing therapeutic targets for autoimmune diseases., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Chronic obstructive pulmonary disease (COPD) has been associated with worse clinical evolution/survival during a hospitalization for SARS-CoV2 (COVID-19). The objective of this study was to learn the situation of these patients at discharge as well as the risk of re-admission/mortality in the following 12 months., Methods: We carried out a subanalysis of the RECOVID registry. A multicenter, observational study that retrospectively collected data on severe acute COVID-19 episodes and follow-up visits for up to a year in survivors. The data collection protocol includes general demographic data, smoking, comorbidities, pharmacological treatment, infection severity, complications during hospitalization and required treatment. At discharge, resting oxygen saturation (SpO2), dyspnea according to the mMRC (modified Medical Research Council) scale and long-term oxygen therapy prescription were recorded. The follow-up database included the clinical management visits at 6 and 12 months, where re-admission and mortality were recorded., Results: A total of 2047 patients were included (5.6% had a COPD diagnosis). At discharge, patients with COPD had greater dyspnea and a greater need for prescription home oxygen. After adjusting for age, sex and Charlson comorbidity index, patients with COPD had a greater risk of hospital re-admission due to respiratory causes (HR 2.57 [1.35-4.89], p = 0.004), with no significant differences in survival., Conclusion: Patients with COPD who overcome a serious SARS-CoV2 infection show a worse clinical situation at discharge and a greater risk of re-admission for respiratory causes., Competing Interests: Dr Pedro Pablo España reports personal fees from Glaxo, grants from Pfizer, outside the submitted work. Drs Nuria Toledo-Pons reports personal fees from GSK, Chiesi; non-financial support from FAES and Sanofi, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2023 Figueira‐Gonçalves et al.)

Cistus ladanifer L. (rockrose) is a widespread shrub species of the Mediterranean region with products highly valued by the perfume and cosmetics industry. In this research, the variability in yield, chemical composition and phytotoxic activity of C. ladanifer essential oils collected from 12 plots belonging to four natural populations and settled on two different types of edaphic substrates were evaluated. The essential oils were analyzed by GC-MS. The essential oil content ranged from 0.19 to 0.42 mL/100 g. The volatile profiles were found to be rich in oxygenated sesquiterpenes and oxygenated monoterpenes. PCA analysis clustered the samples into two groups that were mainly attributed to the type of substrate on which the plants grow. Furthermore, CCA and correlation analysis revealed that soil organic matter was the most effective edaphoclimatic driver accounting for these high levels of variation in essential oil yield and composition. Finally, C. ladanifer essential oils showed strong phytotoxic activity on R. sativus seedlings, indicating its potential use as a natural bio-herbicide in agriculture. The results showed that the effect associated to local edaphoclimatic conditions not only impacted on the quality and quantity of the essential oil, but also on the industrial uses derived from its biological activities., (© 2023 The Authors. Chemistry & Biodiversity published by Wiley-VHCA AG, Zurich, Switzerland.)

Introduction: There are no data on the association of type of pneumonia and long-term mortality by the type of pneumonia (COVID-19 or community-acquired pneumonia [CAP]) on long-term mortality after an adjustment for potential confounding variables. We aimed to assess the type of pneumonia and risk factors for long-term mortality in patients who were hospitalized in conventional ward and later discharged., Methods: Retrospective analysis of two prospective and multicentre cohorts of hospitalized patients with COVID-19 and CAP. The main outcome under study was 1-year mortality in hospitalized patients in conventional ward and later discharged. We adjusted a Bayesian logistic regression model to assess associations between the type of pneumonia and 1-year mortality controlling for confounders., Results: The study included a total of 1,693 and 2,374 discharged patients in the COVID-19 and CAP cohorts, respectively. Of these, 1,525 (90.1%) and 2,249 (95%) patients underwent analysis. Until 1-year follow-up, 69 (4.5%) and 148 (6.6%) patients from the COVID-19 and CAP cohorts, respectively, died ( p  = 0.008). However, the Bayesian model showed a low probability of effect (PE) of finding relevant differences in long-term mortality between CAP and COVID-19 (odds ratio 1.127, 95% credibility interval 0.862-1.591; PE = 0.774)., Conclusion: COVID-19 and CAP have similar long-term mortality after adjusting for potential confounders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Méndez, González-Jiménez, Latorre, Mengot, Zalacain, Ruiz, Serrano, España, Uranga, Cillóniz, Hervás, Torres, Menéndez, NEUMONAC and RECOVID.)

Background: The role of the immune system in the pathobiology of Idiopathic Pulmonary Fibrosis (IPF) is controversial., Methods: To investigate it, we calculated immune signatures with Gene Set Variation Analysis (GSVA) and applied them to the lung transcriptome followed by unbiased cluster analysis of GSVA immune-enrichment scores, in 109 IPF patients from the Lung Tissue Research Consortium (LTRC). Results were validated experimentally using cell-based methods (flow cytometry) in lung tissue of IPF patients from the University of Pittsburgh (n = 26). Finally, differential gene expression and hypergeometric test were used to explore non-immune differences between clusters., Results: We identified two clusters (C#1 and C#2) of IPF patients of similar size in the LTRC dataset. C#1 included 58 patients (53%) with enrichment in GSVA immune signatures, particularly cytotoxic and memory T cells signatures, whereas C#2 included 51 patients (47%) with an overall lower expression of GSVA immune signatures (results were validated by flow cytometry with similar unbiased clustering generation). Differential gene expression between clusters identified differences in cilium, epithelial and secretory cell genes, all of them showing an inverse correlation with the immune response signatures. Notably, both clusters showed distinct features despite clinical similarities., Conclusions: In end-stage IPF lung tissue, we identified two clusters of patients with very different levels of immune signatures and gene expression but with similar clinical characteristics. Weather these immune clusters differentiate diverse disease trajectories remains unexplored., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Mild cognitive impairment (CI) has an exponential increase in its prevalence and causes functional deficits and dependence. Its early detection allows for timely treatment and greater therapeutic efficacy. However, mild cognitive impairment (MCI) is currently underdiagnosed. Although recent decades have seen a rise in computerized instruments for the detection and early diagnosis of MCI, showing numerous advantages over the classic paper-and-pencil methods, such as standardized stimulus presentation. However, their limitations include the use of self-administered application without professional supervision. Few of these instruments have Spanish-adapted versions., Objective: To translate, adapt, and validate the computerized Information Processing Assessment Battery (COGNITO) battery in the Spanish population and to develop a portable administration system that facilitates its application in different settings. COGNITO was then administered to 232 Spanish participants (18-89 years) without cognitive impairment, after which preliminary normative data were obtained., Results: Strong positive correlations were found between the main cognitive domains assessed by COGNITO and the variables of age, educational level, and MEC score. The gender variable only correlated with visuospatial skills, with men outperforming women. The test-retest correlations conducted after 4 weeks with 89 participants revealed adequate reliability coefficients ranging between.63 and.66 (visuospatial skills = 0.35). Internal consistency coefficients were satisfactory in Attention-Executive Functions and Memory domains., Conclusions: The Spanish adaptation of COGNITO shows adequate psychometric characteristics of validity and reliability. The preliminary normative data provided may contribute to the early detection of cognitive impairments associated with both normal aging and various types of neurological pathology. This tool has great utility and versatility for neuropsychological practice., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Out-of-hospital cardiac arrest is considered a global problem. In the last few years, there has been a growing interest in telephone-cardiopulmonary resuscitation guided by a telecommunicator. Indeed, several studies have demonstrated that it increases the chances of survival rate. This study focuses on the key points the operator should follow when performing telephone-cardiopulmonary resuscitation. The main objective of this paper is to design an algorithm to improve the telephone-cardiopulmonary resuscitation response protocol., Methods: The available evidence and the areas of uncertainty that have not been previously mentioned in the literature are discussed. All the information has been analyzed by two discussion groups. Later, a consensus was reached among all members. Finally, a response algorithm was designed and implemented in clinical simulation., Results: All the witnesses were able to recognize the OHCA, call for emergency assistance, follow all the operator's instructions, move the victim, and place their hands in the correct position to perform CPR., Discussion: The results of the pilot study provide us a basis for further experimental studies using randomization and experimental and control groups., Conclusions: No standardized recommendations exist for the operator to perform telephone-guided CPR. For this reason, a response algorithm was designed.

Colostrum performs nutritional, anti-inflammatory and anti-infective functions and promotes immune system formation and organ development. The new coronavirus, SARS-CoV-2, has generated concerns about viral transmission through human milk, with a lack of evidence about human milk's protective effects against the infection. This study aimed at analyzing presence of the virus and at identifying the protein expression profile of human colostrum in active and COVID-19-recovered patients. Colostrum samples were collected from women with COVID-19 ( n = 3), women recently recovered from the infection ( n = 4), and non-infected women ( n = 5). The samples were analyzed by means of RT-qPCR to determine presence of the virus and using SWATH-MS for proteomic analysis. Proteomic results were then analyzed using bioinformatic methods. The viral tests were negative for SARS-CoV-2 in the colostrum from COVID-19 patients. The proteomic analysis identified 301 common proteins in all samples analyzed. Nineteen proteins were upregulated and 7 were downregulated in the COVID-19 group versus the control samples, whereas 18 were upregulated and 7 were downregulated when comparing the COVID-19 group to the recovered group. Eleven proteins were biomarkers of active COVID-19 infection. Ten were upregulated: ACTN1, CD36, FAM3B, GPRC5B, IGHA2, IGK, PLTP, RAC1, SDCBP and SERPINF1, and one was downregulated: PSAP. These proteins are mainly related to immunity, inflammatory response and protein transport. In conclusion, the results of this study suggest that colostrum is not a vehicle for mother-to-child SARS-CoV-2 transmission. Moreover, the colostrum's proteome of active and recuperated patients indicate that it could provide immune benefits to infants.

Wild edible fruits, neglected by the development of commercial agriculture, have recently aroused as a good source of natural colorants and bioactive compounds. These novel uses could cover the recent demand for healthier foods with functional properties. Prunus avium, Fragaria vesca and Vaccinium myrtillus wild fruits were characterized by individual anthocyanin profile and color CIELAB parameters, as well as phenolic fraction. In addition, some bioactivities were evaluated. In P. avium cyanidin-O-deoxyhexosyl-pentoside was the representative anthocyanin, in F. vesca pelargonidin-3-O-glucoside and in V. myrtillus delphinidin-O-hexoside. The three wild edible fruits showed interesting antioxidant activity especially in OxHLIA assays. V. myrtillus was the fruit with the best results for the bacterial growth inhibition, while F. vesca with better fungal growth inhibition. These results evidenced the richness of these wild fruits in bioactive compounds and pigments with antioxidant capacity, therefore, their potential use as natural colorants for healthier food products design., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To identify prognostic models which estimate the risk of critical COVID-19 in hospitalized patients and to assess their validation properties., Study Design and Setting: We conducted a systematic review in Medline (up to January 2021) of studies developing or updating a model that estimated the risk of critical COVID-19, defined as death, admission to intensive care unit, and/or use of mechanical ventilation during admission. Models were validated in two datasets with different backgrounds (HM [private Spanish hospital network], n = 1,753, and ICS [public Catalan health system], n = 1,104), by assessing discrimination (area under the curve [AUC]) and calibration (plots)., Results: We validated 18 prognostic models. Discrimination was good in nine of them (AUCs ≥ 80%) and higher in those predicting mortality (AUCs 65%-87%) than those predicting intensive care unit admission or a composite outcome (AUCs 53%-78%). Calibration was poor in all models providing outcome's probabilities and good in four models providing a point-based score. These four models used mortality as outcome and included age, oxygen saturation, and C-reactive protein among their predictors., Conclusion: The validity of models predicting critical COVID-19 by using only routinely collected predictors is variable. Four models showed good discrimination and calibration when externally validated and are recommended for their use., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: After severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia, patients may show lung sequelae on radiology and functional impairment at the 1-year follow-up. We aimed to describe the persistence of symptoms, radiological alterations, or reduced diffusing capacity of the lung for carbon monoxide (D LCO ) at 1-year follow-up in patients from the Spanish Registry RECOVID., Methods: RECOVID collected symptom and radiological and functional lung tests data on hospitalized patients with coronavirus disease 2019 during the acute phase and at the 6- and 12-month follow-up visits., Results: Of the 2500 enrolled survivors (90% admitted to the ward), 1874 had follow-up visits for up to a year. Of these, 42% continued to present with symptoms, 27% had radiological sequelae and 31% had reduced D LCO . Independently associated factors included female sex, asthma and the requirement for invasive or non-invasive mechanical ventilation. Complete radiological resolution was 72.2% at 12 months; associated factors with incomplete recovery were age, male sex, oxygen or respiratory support, corticosteroids and an initial SpO 2 /FiO 2 <450 or CURB-65 ≥2. Reduced D LCO was observed in 31% of patients at 12 months; associated factors were older age, female sex, smoking habit, SpO 2 /FiO 2 <450 and CURB-65 ≥2 and the requirement of respiratory support.At 12 months, a proportion of the asymptomatic patients showed reduced D LCO (9.5%), radiological findings (25%) or both (11%)., Conclusions: The factors associated with symptom persistence, incomplete radiological resolution and D LCO <80% differed according to age, sex, comorbidities and respiratory support. The burden of symptoms, reduced D LCO and incomplete radiological resolution were considerable in patients with SARS-CoV-2 pneumonia at the 1-year follow-up after hospitalisation., (© 2023 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Introduction: SARS CoV2 infection has had a major impact on renal transplant patients with a high mortality in the first months of the pandemic. Intentional reduction of immunosuppressive therapy has been postulated as one of the cornerstone in the management of the infection in the absence of targeted antiviral treatment. This has been modified according to the patient`s clinical situation and its effect on renal function or anti-HLA antibodies in the medium term has not been evaluated., Objectives: Evaluate the management of immunosuppressive therapy made during SARS-CoV2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID19 diagnosis., Material and Methods: Retrospective, national multicentre, retrospective study (30 centres) of kidney transplant recipients with COVID19 from 01/02/20 to 31/12/20. Clinical variables were collected from medical records and included in an anonymised database. SPSS statistical software was used for data analysis., Results: renal transplant recipients with COVID19 were included (62.6% male), with a mean age of 57.5 years. The predominant immunosuppressive treatment prior to COVID19 was triple therapy with prednisone, tacrolimus and mycophenolic acid (54.6%) followed by m-TOR inhibitor regimens (18.6%). After diagnosis of infection, mycophenolic acid was discontinued in 73.8% of patients, m-TOR inhibitor in 41.4%, tacrolimus in 10.5% and cyclosporin A in 10%. In turn, 26.9% received dexamethasone and 50.9% were started on or had their baseline prednisone dose increased. Mean creatinine before diagnosis of COVID19, at diagnosis and at 6 months was: 1.7 ± 0.8, 2.1 ± 1.2 and 1.8 ± 1 mg/dl respectively (p < 0.001). 56.9% of the patients (N = 350) were monitored for anti-HLA antibodies. 94% (N = 329) had no anti-HLA changes, while 6% (N = 21) had positive anti-HLA antibodies. Among the patients with donor-specific antibodies post-COVID19 (N = 9), 7 patients (3.1%) had one immunosuppressant discontinued (5 patients had mycophenolic acid and 2 had tacrolimus), 1 patient had both immunosuppressants discontinued (3.4%) and 1 patient had no change in immunosuppression (1.1%), these differences were not significant., Conclusions: The management of immunosuppressive therapy after diagnosis of COVID19 was primarily based on discontinuation of mycophenolic acid with very discrete reductions or discontinuations of calcineurin inhibitors. This immunosuppression management did not influence renal function or changes in anti-HLA antibodies 6 months after diagnosis., (Copyright © 2022 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Mitogen-activated protein kinase (MAPK) pathways regulate essential processes in eukaryotes. However, since uncontrolled activation of these cascades has deleterious effects, precise negative regulation of signaling flow through them, mainly executed by protein phosphatases, is crucial. Previous studies showed that the absence of Ptc1 protein phosphatase results in the upregulation of the MAPK of the cell wall integrity (CWI) pathway, Slt2, and numerous functional defects in Saccharomyces cerevisiae, including a failure to undergo cell separation under heat stress. In this study, we demonstrate that multibudded ptc1 Δ cells also exhibit impaired mitochondrial inheritance and that excessive Slt2 kinase activity is responsible for their growth deficiency and daughter-specific G 1 cell cycle arrest, as well as other physiological alterations, namely, mitochondrial hyperpolarization and reactive oxygen species (ROS) accumulation. We bring to light the fact that sustained Slt2 kinase activity inhibits signaling through the Sch9 branch of the TORC1 pathway in ptc1 Δ cells, leading to increased autophagy. After cytokinesis, septin rings asymmetrically disassembled in ptc1 Δ multibudded cells, abnormally remaining at the daughter cell side and eventually relocalizing at the daughter cell periphery, where they occasionally colocalized with the autophagic protein Atg9. Finally, we show that the inability of ptc1 Δ cells to undergo cell separation is not due to a failure in the regulation of Ace2 and morphogenesis (RAM) pathway, since the transcription factor Ace2 correctly enters the daughter cell nuclei. However, the Ace2-regulated endochitinase Cts1 did not localize to the septum, preventing the proper degradation of this structure. IMPORTANCE This study provides further evidence that the cell cycle is regulated by complex signaling networks whose purpose is to guarantee a robust response to environmental threats. Using the S. cerevisiae eukaryotic model, we show that, under the stress conditions that activate the CWI MAPK pathway, the absence of the protein phosphatase Ptc1 renders Slt2 hyperactive, leading to numerous physiological alterations, including perturbed mitochondrial inheritance, oxidative stress, changes in septin dynamics, increased autophagy, TORC1-Sch9 inhibition, and ultimately cell cycle arrest and the failure of daughter cells to separate, likely due to the absence of key degradative enzymes at the septum. These results imply novel roles for the CWI pathway and unravel new cell cycle-regulatory controls that operate beyond the RAM pathway, arresting buds in G 1 without compromising further division rounds in the mother cell., Competing Interests: The authors declare no conflict of interest.

Materials such as wood, textiles, or plastics that are part of the exhibition system in museums are known to emit pollutants such as organic acids. Scientific and technical objects that include these materials in their composition can themselves be a potential source of emissions, which, together with inappropriate humidity and temperature conditions, can lead to corrosion of the metallic parts. In this work, we have studied the corrosivity of different locations in two venues of the Spanish National Museum of Science and Technology (MUNCYT). Coupons of the most representative metals from the collection were placed in different showcases and rooms for 9 months. The corrosion of the coupons has been evaluated in terms of the rate of mass gain, colour changes and characterisation of the corrosion products. The results were correlated to the relative humidity and concentration of gaseous pollutants to determine which metals are most susceptible to corrosion. The results show that metal artefacts exposed in showcases have a higher risk of corrosion than those exposed directly in the room, and that some pollutants are emitted by the artefacts. The corrosivity of the museum environment is low for copper, brass, and aluminium in most locations; however, some placements present a higher aggressivity for steel and lead, due to the high humidity and the presence of organic acids.

Child exposure to maltreatment and neglect constitutes a significant public health problem throughout Latin American and Caribbean (LAC) countries. Although evidence-based parent training (PT) interventions constitute an empirically demonstrated alternative to prevent child maltreatment and neglect, multiple implementation barriers have prevented the large-scale dissemination of evidence-based PT interventions across LAC countries. This selective prevention study consisted of an exploratory quasi-experimental design implemented in Chile, aimed at examining the initial impact of a culturally adapted version of the evidence-based PT intervention known as GenerationPMTO©. The parenting intervention was adapted in a previous pilot study, according to a rigorous model of cultural adaptation. Based on self-reports completed by 281 caregivers, when compared to baseline measurements, significant improvements at intervention completion were observed in the majority of caregivers' parenting practices, as well as child internalizing and externalizing problematic behaviors. This study provides promising initial empirical evidence that efficacious PT interventions developed in the US can be transported to Latin American contexts, as long as they are thoroughly adapted to achieve high contextual and cultural relevance. The rates of child maltreatment across LAC countries constitute an urgent and permanent call for strongly promoting this line of prevention research., (© 2023 Family Process Institute.)

Background: Congenital myasthenic syndromes (CMSs) and primary mitochondrial myopathies (PMMs) can present with ptosis, external ophthalmoplegia, and limb weakness., Methods: Our method involved the description of three cases of CMS that were initially characterized as probable PMM., Results: All patients were male and presented with ptosis and/or external ophthalmoplegia at birth, with proximal muscle weakness and fatigue on physical exertion. After normal repetitive nerve stimulation (RNS) studies performed on facial muscles, a muscle biopsy (at a median age of 9) was performed to rule out congenital myopathies. In all three cases, the biopsy findings (COX-negative fibers or respiratory chain defects) pointed to PMM. They were referred to our neuromuscular unit in adulthood to establish a genetic diagnosis. However, at this time, fatigability was evident in the physical exams and RNS in the spinal accessory nerve showed a decremental response in all cases. Targeted genetic studies revealed pathogenic variants in the MUSK , DOK7 , and RAPSN genes. The median diagnostic delay was 29 years. Treatment resulted in functional improvement in all cases., Conclusions: Early identification of CMS is essential as medical treatment can provide clear benefits. Its diagnosis can be challenging due to phenotypic overlap with other debilitating disorders. Thus, a high index of suspicion is necessary to guide the diagnostic strategy.