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Objective: to determine the prevalence of Helicobacter pylori infection in patients having undergone gastrectomy for non-neoplastic disease who later developed gastric stump cancer. Material and methods: retrospective study of all patients with partial gastrectomy for non-malignant peptic disease who were submitted to an endoscopic exploration between 1995 and 2001. A comparison was made of major clinical and histological characteristics, and the presence of Helicobacter pylori among patients with and without gastric cancer in the stomach remnant. Results: a total of 73 patients were studied in this period. Fifteen patients (20.5%) had remnant-stump gastric cancer. All but one were adenocarcinomas (71% intestinal and 29% diffuse, respectively). The average time between diagnosis of gastric cancer and previous gastrectomy was 32 (14-48) years. There was a higher detection rate of Helicobacter pylori in patients with cancer in the gastric remnant (100 vs. 81.5%, respectively, p < 0.07). No relationship was seen between type of gastric reconstruction (Billroth I or II) and rate of Helicobacter pylori detection. Conclusions: Helicobacter pylori infection is frequent in patients with previous gastrectomy for non-neoplastic disease. The results of the study suggest that Helicobacter pylori infection may play a role in gastric stump cancer.Objetivo: determinar la prevalencia de la infección por Helicobacter pylori en pacientes gastrectomizados por enfermedad no neoplásica, y que han desarrollado posteriormente cáncer gástrico. Material y métodos: estudio retrospectivo con reclutamiento de todos los pacientes con gastrectomía parcial por enfermedad péptica benigna que han sido sometidos a una exploración endoscópica entre 1995-2001. Se ha realizado una comparación de las principales características clínicas e histológicas y de la presencia de Helicobacter pylori en los pacientes con y sin cáncer del remanente gástrico. Resultados: se han estudiado un total de 73 pacientes en este periodo. Se han encontrado 15 pacientes (20,5%) con cáncer en el remanente gástrico, 14 adenocarcinomas (71% tipo intestinal y 29% tipo difuso) y un linfoma. El tiempo transcurrido entre el diagnóstico de cáncer gástrico y la gastrectomía previa ha sido de 32 (14-48) años. Se ha detectado un alto porcentaje de infección por Helicobacter pylori (100% en los pacientes con cáncer vs. 81,5% en los pacientes sin cáncer, p < 0,07). No se ha observado relación entre el tipo de reconstrucción gástrica (Billroth I o II) y el porcentaje de infección por Helicobacter pylori. Conclusiones: la infección por Helicobacter pylori es frecuente en pacientes gastrectomizados por patología benigna. Los resultados de este estudio sugieren que la infección por Helicobacter pylori podría jugar un papel en el cáncer gástrico.

Treadmilling protein filaments perform essential cellular functions by growing from one end while shrinking from the other, driven by nucleotide hydrolysis. Bacterial cell division relies on the primitive tubulin homolog FtsZ, a target for antibiotic discovery that assembles into single treadmilling filaments that hydrolyse GTP at an active site formed upon subunit association. We determined high-resolution filament structures of FtsZ from the pathogen Staphylococcus aureus in complex with different nucleotide analogs and cations, including mimetics of the ground and transition states of catalysis. Together with mutational and biochemical analyses, our structures reveal interactions made by the GTP γ-phosphate and Mg2+ at the subunit interface, a K+ ion stabilizing loop T7 for co-catalysis, new roles of key residues at the active site and a nearby crosstalk area, and rearrangements of a dynamic water shell bridging adjacent subunits upon GTP hydrolysis. We propose a mechanistic model that integrates nucleotide hydrolysis signaling with assembly-associated conformational changes and filament treadmilling. Equivalent assembly mechanisms may apply to more complex tubulin and actin cytomotive filaments that share analogous features with FtsZ.

The global spread of bacterial antimicrobial resistance is associated to millions of deaths from bacterial infections per year, many of which were previously treatable. This, combined with slow antibiotic deployment, has created an urgent need for developing new antibiotics. A still clinically unexploited mode of action consists in suppressing bacterial cell division. FtsZ, an assembling GTPase, is the key protein organizing division in most bacteria and an attractive target for antibiotic discovery. Nevertheless, developing effective antibacterial inhibitors targeting FtsZ has proven challenging. Here we review our decade-long multidisciplinary research on small molecule inhibitors of bacterial division, in the context of global efforts to discover FtsZ-targeting antibiotics. We focus on methods to characterize synthetic inhibitors that either replace bound GTP from the FtsZ nucleotide binding pocket conserved across diverse bacteria or selectively bind into the allosteric site at the interdomain cleft of FtsZ from Bacillus subtilis and the pathogen Staphylococcus aureus. These approaches include phenotype screening combined with fluorescence polarization screens for ligands binding into each site, followed by detailed cytological profiling, and biochemical and structural studies. The results are analyzed to design an optimized workflow to identify effective FtsZ inhibitors, and new approaches for the discovery of FtsZ-targeting antibiotics are discussed.

BackgroundThe NAQ (Negative Acts Questionnaire) has been widely used in more than 40 countries to measure the mobbing phenomenon. This research aims to present a psychometric study based on the Spanish version of the NAQ-R carried out by González-Trijueque and Graña (2013). As opposed to the original scale, this sample contains 23 items and a three-dimension model (personal bullying, work-related bullying, and physically intimidating forms of bullying).MethodsWe used a heterogeneous occupational sample of 2,538 Spanish employees to analyze internal consistency and concurrent validity. In addition, a Confirmatory Factor Analysis was carried out based on the GLS (generalized least squares) method.ResultsResults showed high internal reliability (Cronbach’s alpha = 0.91) and high correlations containing clinical symptoms, burn-out indicators, and coping resources. The Confirmatory Factor Analysis developed upon the heterogeneous occupational sample validates the three-dimension structure in the Spanish version of the NAQ-R aimed to measure harassment behaviors at the workplace.ConclusionThe NAQ-R reaffirms its validity and reliability as a measure for mobbing-related behaviors. Hence, the scale may become a useful tool in research and forensic practice.

En el presente trabajo se realiza una revisión de diferentes aportaciones teóricas y empíricas que abordan la relación entre las conductas agresivas y antisociales en la adolescencia y un conjunto de procesos cognitivos distorsionados que interfieren en la percepción y comprensión de los eventos o experiencias sociales. A partir de las diferentes aproximaciones teóricas, en esta revisión se sugiere la necesidad de contar con una perspectiva más integradora que permita una mejor conceptualización y tipificación de estos procesos cognitivos distorsionados, a fin de clarificar la naturaleza y la función específica que cada uno de ellos desempeña en la explicación del comportamiento agresivo y antisocial en adolescentes.

Cell division protein FtsZ is the organizer of the cytokinetic ring in almost all bacteria and a target for the discovery of new antibacterial agents that are needed to counter widespread antibiotic resistance. Bacterial cytological profiling, using quantitative microscopy, is a powerful approach for identifying the mechanism of action of antibacterial molecules affecting different cellular pathways. We have determined the cytological profile on Bacillus subtilis cells of a selection of small molecule inhibitors targeting FtsZ on different binding sites. FtsZ inhibitors lead to long undivided cells, impair the normal assembly of FtsZ into the midcell Z-rings, induce aberrant ring distributions, punctate FtsZ foci, membrane spots and also modify nucleoid length. Quantitative analysis of cell and nucleoid length combined, or the Z-ring distribution, allows categorizing FtsZ inhibitors and to distinguish them from antibiotics with other mechanisms of action, which should be useful for identifying new antibacterial FtsZ inhibitors. Biochemical assays of FtsZ polymerization and GTPase activity combined explain the cellular effects of the FtsZ polymer stabilizing agent PC190723 and its fragments. MciZ is a 40-aminoacid endogenous inhibitor of cell division normally expressed during sporulation in B. subtilis. Using FtsZ cytological profiling we have determined that exogenous synthetic MciZ is an effective inhibitor of B. subtilis cell division, Z-ring formation and localization. This finding supports our cell-based approach to screen for FtsZ inhibitors and opens new possibilities for peptide inhibitors of bacterial cell division.

Background:Entry of nutrients into the small intestine activates neuro-hormonal signals that regulate food intake through induction of satiation.Objective:To evaluate whether caloric intake can be decreased by pharmacologically accelerating gastric emptying (GE) of nutrients into the small intestine.Methods:Subjects were tested in 2 days, at baseline (day1) and after randomly receiving, in a double-blind manner, a 1 h infusion of erythromycin (3 mg Kg−1, to accelerate GE) or placebo (day 2). Ad libitum caloric intake and postprandial gastrointestinal symptoms were evaluated using a validated nutrient drink test, simultaneously measuring gastric by scintigraphy. Plasma levels of satiation factors were also measured to evaluate their role in the modification of caloric intake and postprandial symptoms. Acceleration of GE was assessed as the difference in percentage emptied between day 2 and day 1 (DGE). The effects of DGE on caloric intake and symptoms were evaluated using multiple (lineal) regression.Results:Among 30 overweight/obese subjects (24F and 6 M), 15 received erythromycin and 15 placebo. The overall median age was 36 years (IQR: 30-42) and body mass index was 30 Kg m−2 (IQR: 27-36). Subjects receiving erythromycin on day 2 presented accelerated GE as compared with placebo (P=0.0002). DGE at 15 min after initiating eating had a significant effect on prospective caloric intake (P=0.004). From the best-fitted regression model (R 2=81%, P<0.0001), a 10% increase in GE at 15 min induced on an average a 135±43.5 Kcal decrease in caloric intake. Postprandial increase in cholecystokinin (CCK) (P=0.03) and insulin (P=0.02) was associated with decreased caloric intake. Acceleration of GE at 60 min after initiating eating increased postprandial symptom scores measured 30 min after the completion of food consumption (P=0.01). Postprandial increase in CCK (P=0.002) and PP (P=0.02) was associated with postprandial symptoms.Conclusion:Meal size can be reduced in overweight/obese subjects by pharmacologically accelerating GE. This may be a reasonable target in obesity management. [ABSTRACT FROM AUTHOR]

Ten commercial composts were evaluated on the basis of chemical, physical and biological characteristics and compared with a compost produced by a safe matrix in controlled conditions. FT-IR spectra, 13C CP-MAS NMR spectra and molecular weights were also assayed on humic acids extracted from the composts. The results show that the origin of the starting materials affects the quality of the end products especially for their heavy metal content and genotoxic effect. The presence of a high percentage of low molecular weight fractions generally recorded in the humic acids from commercial composts could be due to uncorrected composting process. FT-IR and 13C CP-MAS NMR spectra agree with functional group assignments, characterising the level of humification. The results show that commercial composts can display harmful properties probably due to the origin of the starting material, therefore a regulation about both compost production and characterisation should be suitable. [ABSTRACT FROM AUTHOR]

El presente estudio investiga la relación entre la psicopatía y la reincidencia, así como el tipo de agresión (instrumental y/o expresiva) más característico de la psicopatía. Los resultados han sido obtenidos del análisis de datos recogidos de una muestra de 285 internos en centros penitenciarios de la Comunidad de Madrid, mostrando la relación existente entre la psicopatía y el riesgo de reincidencia, siendo este mayor en aquellos grupos que presentan una puntuación moderada o elevada en aquella. Además, nuestros resultados indican que la agresión relacionada con la psicopatía puede ser tanto expresiva como instrumental, sin que una de ellas sea más característica que la otra, aunque su relación más significativa se da en los niveles moderados y altos de psicopatía.

El presente trabajo profundiza en el estudio de la agresión en menores infractores. El objetivo principal fue comprobar si la reiteración delictiva y la desadaptación institucional al centro de reforma variaban en distintos grupos configurados según diferentes patrones de agresión. Se analizó el historial delictivo y las faltas disciplinarias en el periodo inicial del internamiento, y se aplicó el Cuestionario de Agresión Reactivo-Proactiva en una muestra de 184 menores infractores de entre 14 y 20 años de edad, que cumplían medidas de internamiento en un centro de ejecución de medidas judiciales en la Comunidad de Madrid. Los resultados indicaron que los sujetos agresivos proactivos presentaron un número mayor de delitos y los sujetos con baja agresión incurrieron en menos faltas disciplinarias. Se discuten los resultados señalando la importancia que tiene determinar el tipo de agresión de cara a la intervención y la valoración del riesgo de violencia.

Objectives: The present study performed a systematic review of the scientific literature that deals with the academic performance of university students with ADHD, collecting the research conducted between 2018 and 2024. Likewise, we aimed to know the factors that influence on academic performance and evaluate the tools used in the collection of ADHD symptoms and educational data., Methods: The electronic databases PubMed, PsycInfo, and Scopus were used to search studies using PRISMA guidelines. Quantitative studies selected had to discuss about academic performance in college students with ADHD. For each study, quality of evidence was examined using the Quality Assessment Tool of the National Heart Lung and Blood Institute., Results: Fifteen studies with good-fair quality were included in the review. These studies demonstrated that an ADHD diagnosis or significant ADHD symptoms are associated with lower academic performance in college students, particularly those with inattention symptoms. Additionally, factors such as executive functions, medication use, and study strategies also influence the academic performance of these students. The most commonly used instruments for the assessment of ADHD were the screening measures ADHD Self-Report Scale and the ADHD Rating Scale-Self Report Version. To assess academic performance half of the studies collected the Grade Point Average directly from university records, while in other studies, students were asked directly for their grades., Conclusion: Overall, ADHD has a relevant impact on the academic performance of university students, but the evaluation methodology used has some differences with respect to child's evaluations procedures. Therefore, studies in this population must include not only self-reported symptomatology, but also assessments from clinicians specialized in adult ADHD., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.C. has received fees from Takeda and Laboratorios Rubió for participating in psychiatric meetings. The remaining authors declare no conflict of interest.

Objective: To estimate rates and time to reach emergence of consciousness from vegetative state/unresponsive wakefulness syndrome (VS/UWS), and explore factors associated with improved recovery in children and adolescents with disorders of consciousness (DoC) following severe traumatic and non-traumatic brain injury., Methods: Analytical, retrospective, cohort study. Clinical records of consecutively referred patients admitted in VS/UWS to a neurological rehabilitation institute in Argentina, between 2005 and 2021 were reviewed. Seventy children and adolescents were included in the analysis. A specialized 12-week rehabilitation program was administered, and emergence was defined by scores ≥44 points on the Western Neuro Sensory Stimulation Profile (WNSSP), sustained for at least 3 weeks on consecutive weekly evaluations., Results: Emergence from VS/UWS to consciousness occurred within 5.4 (SD 2.6) weeks in almost one-third of patients. Multivariate Cox regression analysis showed emergence was significantly lower in patients with hypoxic ischemic encephalopathy compared to patients with other non-traumatic etiologies [HRadj 0.23 (95% CI 0.06-0.89); p  = 0.03)]., Conclusions: Our findings reinforce growing evidence on the impact of etiology on DoC recovery in pediatric populations, ultimately influencing treatment and family-related decisions in child neurorehabilitation.

WHAT IS KNOWN ON THE SUBJECT?: Quitlines are known to be effective in helping people quit smoking, including those with mental health conditions. It is particularly important to address smoking in this population as the prevalence of smoking ranges from 40% to 75%. However, professionals working in quitlines often face barriers due to their limited training and resources to effectively support these smokers quit, especially if they are not mental health professionals. Therefore, training programmes should be developed to enhance their knowledge and skills in providing smoking cessation support to this vulnerable population. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: The '061 QUIT-MENTAL study' evaluated the efficacy of a proactive telephone-based intervention for smoking cessation among smokers with severe mental health disorders. Conducted through a quitline service in Catalonia, Spain, the study focused on training non-mental health specialized nurses and other health professionals to provide evidence-based interventions for promoting smoking cessation among individuals with mental health disorders. The objective of this study is to assess the changes in nurses' knowledge and readiness to treat smokers with mental health conditions, while also capturing their insights and perceptions regarding the facilitators and barriers to providing smoking cessation interventions. The training and insights of the nurses were integral to conducting this research and providing valuable information for the future sustainability of such interventions. This is particularly important as quitlines hold the potential to offer cessation support to these patients at the community level. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: While the training programme was successful in improving non-mental health specialized nurses' knowledge and motivation skills to help patients with mental health disorders quit smoking, they encountered obstacles in delivering this intervention over the phone. These difficulties were mainly due to challenges in reaching participants and delivering the intervention as detailed in the protocol. The study highlights the need of reducing barriers for providers in attending to these patients, particularly if they are non-mental health specialized professionals. By minimizing the stigmatization associated with caring for mentally ill individuals and promoting coordination with specialists, innovative approaches may be introduced to alleviate the burden of tobacco-related diseases among this population. ABSTRACT: Introduction The viewpoint of those who implement a programme for the first time is crucial for understanding its impact and ensuring its long-term viability. The 061 QUIT-MENTAL study was a pragmatic randomized controlled trial evaluating a proactive telephone-based intervention addressed to mental health patients conducted by non-psychiatric specialized nurses. Aim We assessed nurses' knowledge of smoking cessation interventions addressed to this population before and after receiving training and their insights after delivering the intervention. Method Mixed methods study: (1) Pre-post evaluation to assess self-reported knowledge, self-efficacy and opinions about smoking cessation. (2) In-depth interviews with key nurses to ascertain their perceptions regarding the impact of the training received in delivering the study intervention. Results The training enhanced nurses' knowledge of psychological and pharmacological resources to aid these patients, as well as their ability to increase their motivation to quit. However, nurses reported difficulties in delivering population-based interventions to individuals with mental health disorders. These challenges primarily arose from participants being hard to reach, exhibiting low motivation to quit, struggling to comprehend instructions or follow recommendations, and nurses feeling unsure about their capacity to assist individuals with mental illnesses in quitting, despite the training they received. Discussion Despite the training and protocol designed to facilitate the delivery of the intervention, nurses faced difficulties in providing population-based interventions to individuals with mental health disorders. Implications for Practice Future quitline programmes aimed at the population with mental health disorders should strive to reduce barriers for providers in attending to these patients, particularly if they are non-mental health specialized professionals. By minimizing the stigmatization associated with caring for mentally ill individuals and promoting coordination with specialists, innovative approaches may be introduced to alleviate the burden of tobacco-related diseases among this population., (© 2024 John Wiley & Sons Ltd.)

Background: The aim of this study is to determine the prevalence of nocturnal enuresis (NE) in children with obstructive sleep apnea (OSA), the effect of adenotonsillectomy (AT) and the width of the arches, and to compare them with control children without respiratory problems., Methods: Children from 2 to 12 years old were divided into three groups: children with OSA and NE (n = 51), children with OSA without NE (n = 79), and the control group (n = 168). NE was defined as at least one bedwetting incident per month. Arch widths were measured at the baseline and one year after. OSA was diagnosed by means of polysomnography, and the apnea-hypopnea index (AHI) was obtained. Parents completed the Pediatric Sleep Questionnaire (PSQ) to classify their children into those with and without NE., Results: NE was present in 39.2% of children with OSA compared to 28% in the control group ( p = 0.04). After AT, 49% of the children with OSA and NE significantly improved. Both OSA groups had narrower arch widths than the control group ( p = 0.012), with the NE group having the narrowest widths. NE is more prevalent in children with OSA and should be considered one of the first signs of breathing disorders. Adenotonsillectomy reduces NE in about half of the affected children. Both arch widths are narrower in children with OSA, particularly in those with NE.

Background: Approximately 1 in 6 cannabis users develop a cannabis use disorder (CUD) and the odds increase to 1 in 2 for daily users., Objective: The Dual use of Cannabis and Tobacco Monitoreing through a Gamified Web app (DuCATA&#95;GAM-CaT) project aims to identify cannabis-tobacco patterns of use and withdrawal symptoms among individuals with CUD who are attending substance abuse programs., Methods: The project uses a mixed methods approach consisting of 3 studies. First, a participatory qualitative study involves focus groups comprising individuals with CUD, clinicians, project researchers, and an expert gamification company to co-design a gamified web app. Second, a longitudinal prospective study to follow up individuals over 6 weeks with CUD attending substance abuse programs . Participants report their cannabis-tobacco usage patterns, type and frequency of tobacco use, nicotine dependence, withdrawal symptoms, psychoemotional factors, and motivation to quit both substances. Predictive analysis techniques are used to analyze clinical, demographic, psychological, and environmental data to predict the probability of achieving abstinence. Third, homogeneous focus groups to explore participants' experiences during their CUD treatment., Results: By June 2024, the project had completed the first study, defining eligible cannabis user profiles, developed the initial web app prototype, and initiated recruitment across 10 centers, with 74 participants enrolled, aiming to reach 150 participants in total., Conclusions: All participants are required to provide informed consent, and their information is kept confidential and anonymized following confidentiality rules. The research team is committed to disseminating the results obtained to professional and patient groups, as well as informing public health agents, to positively influence political and social decision makers and design programmers. Additionally, we aim to prioritize the publication of the results in high-impact journals specialized in drug abuse, public health, and health care services research., Trial Registration: ClinicalTrials.gov NCT05512091; https://clinicaltrials.gov/study/NCT05512091., International Registered Report Identifier (irrid): DERR1-10.2196/58335., (©Judith Saura, Ariadna Feliu, Marta Enríquez-Mestre, Marcela Fu, Montse Ballbè, Yolanda Castellano, Margarida Pla, Nathalia Rosa, Petia Radeva, Elena Maestre-González, Carmen Cabezas, Joan Colom, Josep M Suelves, Silvia Mondon, Pablo Barrio, Magalí Andreu, Antònia Raich, Jordi Bernabeu, Jordi Vilaplana, Xavier Roca Tutusaus, Joseph Guydish, Esteve Fernández, Cristina Martínez. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 19.09.2024.)

The rapid dynamic responses of predictive control algorithms are widely acknowledged. However, achieving accurate steady-state reference tracking hinges not just on a precise mathematical model of the system but also on its parameters. This document presents a predictive control scheme augmented with integral state feedback tailored to a photovoltaic (PV) application. In scenarios with uncertain system parameters, steady-state errors can particularly impact reactive power regulation, where the absence of an integral term in the loop exacerbates this issue. The robustness and sensitivity of both predictive control and the proposed enhanced predictive controller are thoroughly examined. Simulation and experimental results are included to validate the effectiveness of this approach.

Objectives: Addressing substance use in psychiatric care encounters significant barriers, but the emergence of specialized services offers an opportunity to advance and scale up the integration of addiction services within psychiatric settings. However, research gaps still exist in this field, particularly in understanding the substance relapse rates of people with co-occurring disorders after a psychiatric hospitalization. This study aimed to investigate and compare the relapse rates of patients under inpatient care with exclusively addiction-related issues and those with co-occurring disorders after a hospitalization in a psychiatric ward and gain insights into differences in outcomes for these two patient groups., Methods: This retrospective analysis examined electronic medical records of patients admitted to the Acute Psychiatry Ward of the Hospital Clinic of Barcelona with a substance use disorder diagnosis between January 2019 and February 2021. Cox regression was used to identify variables independently associated with the first relapse episode., Results: From a total of 318 admissions (79.2% with psychiatric comorbidity), 76.1% relapsed during the study follow-up, with a median survival time of 54 days. Younger age, female gender, voluntary admission, and outpatient follow-up were independently associated with relapse. The presence of a co-occurring disorder was not associated with relapse., Conclusion: This study highlights the need for interventions aimed at improving post-discharge abstinence rates for addiction-related hospitalizations. It also challenges the notion that co-occurring disorders automatically imply a worsened prognosis and emphasizes the importance of addressing addiction and psychiatric comorbidity in a comprehensive, integrated, and specialized manner.

The properties of single microtubules within the microtubule network can be modulated through post-translational modifications (PTMs), including acetylation within the lumen of microtubules. To access the lumen, the enzymes could enter through the microtubule ends and at damage sites along the microtubule shaft. Here we show that the acetylation profile depends on damage sites, which can be caused by the motor protein kinesin-1. Indeed, the entry of the deacetylase HDAC6 into the microtubule lumen can be modulated by kinesin-1-induced damage sites. In contrast, activity of the microtubule acetylase αTAT1 is independent of kinesin-1-caused shaft damage. On a cellular level, our results show that microtubule acetylation distributes in an exponential gradient. This gradient results from tight regulation of microtubule (de)acetylation and scales with the size of the cells. The control of shaft damage represents a mechanism to regulate PTMs inside the microtubule by giving access to the lumen., (© 2024. The Author(s).)

Objective: To describe the epidemiology and CT findings for nontuberculous mycobacterial lung infections and outcomes depending on the treatment., Material and Methods: We retrospectively studied 131 consecutive patients with positive cultures for nontuberculous mycobacteria between 2005 and 2016. We selected those who met the criteria for nontuberculous mycobacterial lung infection. We analysed the epidemiologic data; clinical, microbiological, and radiological findings; treatment; and outcome according to treatment., Results: We included 34 patients (mean age, 55 y; 67.6% men); 50% were immunodepressed (58.8% of these were HIV+), 20.6% had COPD, 5.9% had known tumors, 5.9% had cystic fibrosis, and 29.4% had no comorbidities. We found that 20.6% had a history of tuberculosis and 20.6% were also infected with other microorganisms. Mycobacterium avium complex was the most frequently isolated germ (52.9%); 7 (20.6%) were also infected with other organisms. The most common CT findings were nodules (64.7%), tree-in-bud pattern (61.8%), centrilobular nodules (44.1 %), consolidations (41.2%), bronchiectasis (35.3%), and cavities (32.4%). We compared findings between men and women and between immunodepressed and immunocompetent patients. Treatment was antituberculosis drugs in 67.6% of patients (72% of whom showed improvement) and conventional antibiotics in 20.6% (all of whom showed radiologic improvement)., Conclusion: The diagnosis of nontuberculous mycobacterial lung infections is complex. The clinical and radiologic findings are nonspecific and a significant percentage of pateints can have other, concomitant infections., (Copyright © 2021 SERAM. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The RALPH (Recognizing and Addressing Limited PHarmaceutical Literacy) interview guide makes it possible to identify patients with limited pharmaceutical knowledge and to assess their skills in the functional, communicative, and critical health literacy domains., Objective: (s): To perform a cross-cultural validation of the RALPH interview guide in Spanish population; to conduct a descriptive analysis based on patients' responses., Methods: A cross-sectional study of patients' pharmaceutical literacy skills was conducted in three stages: systematic translation, administration of the interview and analysis of psychometric properties. The target population included adult patients (≥18 years) who attend one of the participating community pharmacies in Barcelona (Spain). Content validity was evaluated by an expert committee. Viability was assessed in the pilot test, and reliability was assessed using internal consistency and intertemporal stability. Construct validity was assessed by factor analysis., Results: A total of 103 patients were interviewed at 20 pharmacies. Cronbach's alpha values based on standardized items ranged between 0.720 and 0.764. For the longitudinal component, the ICC test-retest reliability was 0.924. The factor analysis was verified by KMO (0.619) and Bartlett's test of sphericity (P-value <0.05). The definitive RALPH guide translated into Spanish maintains the same structure as the original. Some expressions were simplified, and the questions on the comprehension of warnings or specific instructions for use, contradictory information and shared decision-making were reformulated. Pharmaceutical literacy skills were seen to be most limited with regard to the critical domain. The responses of the Spanish patients were in agreement with the original results of the RALPH interview guide., Conclusions: The RALPH interview guide in Spanish complies with the requirements viability, validity, and reliability. This tool may be able to identify the low pharmaceutical literacy skills of patients coming to community pharmacies in Spain, and its use may also be extended to other Spanish-speaking countries., Competing Interests: Declaration of competing interest The authors report no conflicts of interest for this work., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Traumatic brain injury (TBI) often results in long-lasting patterns of neurological deficits including motor, sensory, and cognitive abnormalities. Cranial gunshot survivors are among the most disabled TBI patients and face a lifetime of disability with no approved strategies to protect or repair the brain after injury. Recent studies using a model of penetrating TBI (pTBI) have reported that human neural stem cells (hNSCs) transplantation can lead to dose and location-dependent neuroprotection. Evidence for regional patterns of microglial activation has also been reported after pTBI with evidence for microglial cell death by pyroptosis. Because of the importance of injury-induced microglial activation in the pathogenesis of TBI, we tested the hypothesis that dose-dependent hNSC mediated neuroprotection after pTBI was associated with reduced microglial activation in pericontusional cortical areas. To test this hypothesis, quantitative microglial/macrophage Iba1 immunohistochemistry and Sholl analysis was conducted to investigate the arborization patterns using four experimental groups including, (i) Sham operated (no injury) + low dose (0.16 million cells/rat), (ii) pTBI + vehicle (no cells), (iii) pTBI + low dose hNSCs (0.16 million/rat), and (iv) pTBI + high dose hNSCs (1.6 million cells/rat). At 3 months post-transplantation (transplants at one week after pTBI), the total number of intersections was significantly reduced in vehicle treated pTBI animals versus sham operated controls indicating increased microglia/macrophage activation. In contrast, hNSC transplantation led to a dose-dependent increase in the number of intersections compared to pTBI vehicle indicating less microglia/macrophage activation. The peak of Sholl intersections at 1 μm from the center of the microglia/macrophages ranged from ~6,500-14,000 intersections for sham operated, ~250-500 intersections for pTBI vehicle, ~550-1,000 intersections for pTBI low dose, and ~2,500-7,500 intersections for pTBI high dose. Plotting data along the rostrocaudal axis also showed that pericontusional cortical areas protected by hNSC transplantation had increased intersections compared to nontreated pTBI animals. These studies using a non-biased Sholl analysis demonstrated a dose-dependent reduction in inflammatory cell activation that may be associated with a neuroprotective effect driven by the cellular transplant in perilesional regions after pTBI., Competing Interests: HMB and WDD are co-founders and managing members of InflamaCORE, LLC and have licensed patents on inflammasome proteins as biomarkers of injury and disease as well as on targeting inflammasome proteins for therapeutic purposes. HMB and WDD are Scientific Advisory Board Members of ZyVersa Therapeutics. MLA, NM, YS, SG declare no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Computer-assisted diagnosis (CAD) algorithms have shown its usefulness for the identification of pulmonary nodules in chest x-rays, but its capability to diagnose lung cancer (LC) is unknown. A CAD algorithm for the identification of pulmonary nodules was created and used on a retrospective cohort of patients with x-rays performed in 2008 and not examined by a radiologist when obtained. X-rays were sorted according to the probability of pulmonary nodule, read by a radiologist and the evolution for the following three years was assessed. The CAD algorithm sorted 20,303 x-rays and defined four subgroups with 250 images each (percentiles ≥ 98, 66, 33 and 0). Fifty-eight pulmonary nodules were identified in the ≥ 98 percentile (23,2%), while only 64 were found in lower percentiles (8,5%) (p < 0.001). A pulmonary nodule was confirmed by the radiologist in 39 out of 173 patients in the high-probability group who had follow-up information (22.5%), and in 5 of them a LC was diagnosed with a delay of 11 months (12.8%). In one quarter of the chest x-rays considered as high-probability for pulmonary nodule by a CAD algorithm, the finding is confirmed and corresponds to an undiagnosed LC in one tenth of the cases., (© 2023. The Author(s).)

Penetrating traumatic brain injury (pTBI) is increasingly survivable, but permanently disabling as adult mammalian nervous system does not regenerate. Recently, our group demonstrated transplant location-dependent neuroprotection and safety of clinical trial-grade human neural stem cell (hNSC) transplantation in a rodent model of acute pTBI. To evaluate whether longer injury-transplantation intervals marked by chronic inflammation impede engraftment, 60 male Sprague-Dawley rats were randomized to three sets. Each set was divided equally into two groups: 1) with no injury (sham) or 2) pTBI. After either 1 week (groups 1 and 2), 2 weeks (groups 3 and 4), or 4 weeks after injury (groups 5 and 6), each animal received 0.5 million hNSCs perilesionally. A seventh group of pTBI animals treated with vehicle served as the negative control. All animals were allowed to survive 12 weeks with standard chemical immunosuppression. Motor capacity was assessed pre-transplant to establish injury-induced deficit and followed by testing at 8 and 12 weeks after transplantation. Animals were euthanized, perfused, and examined for lesion size, axonal degeneration, and engraftment. Compared to vehicle, transplanted groups showed a trend for reduced lesion size and axonal injury across intervals. Remote secondary axonal injury was significantly reduced in groups 2 and 4, but not in group 6. The majority of animals showed robust engraftment independent of the injury-transplant time interval. Modest amelioration of motor deficit paralleled the axonal injury trend. In aggregate, pTBI-induced remote secondary axonal injury was resolved by early, but not delayed, hNSC transplantation., Competing Interests: The human neural stem cells (GFP labeled NSI-566 RSC) were provided by Dr. Karl Johe and Dr. Thomas G. Hazel, employees of NeuralStem Inc. (Germantown, MD). Dr. Gajavelli is an employee of Lacerta Therapeutics, a company developing viral vector-based gene therapies for central nervous system disorders., (© MaryLourdes Andreu et al., 2023; Published by Mary Ann Liebert, Inc.)

The disease caused by Sars-Cov-2 (Covid-19) has become a worldwide pandemic and consequently a public health problem. Multiple complications associated with Covid-19 have been described, including coagulation abnormalities. Although the infection is known to induce a prothrombotic state, hemorrhagic complications have also been reported in patients with Covid-19, especially in anticoagulated patients. We present two cases of spontaneous pulmonary hematoma in patients with Covid-19 undergoing anticoagulant treatment. We aim to describe this complication, which although uncommon, should be taken into account in anticoagulated patients with Covid-19., (Copyright © 2021 SERAM. Published by Elsevier España, S.L.U. All rights reserved.)

Control of microtubule abundance, stability, and length is crucial to regulate intracellular transport as well as cell polarity and division. How microtubule stability depends on tubulin addition or removal at the dynamic ends is well studied. However, microtubule rescue, the event when a microtubule switches from shrinking to growing, occurs at tubulin exchange sites along the shaft. Molecular motors have recently been shown to promote such exchanges. Using a stochastic theoretical description, we study how microtubule stability and length depend on motor-induced tubulin exchange and thus rescue. Our theoretical description matches our in vitro experiments on microtubule dynamics in the presence of kinesin-1 molecular motors. Although the overall dynamics of a population of microtubules can be captured by an effective rescue rate, by assigning rescue to exchange sites, we reveal that the dynamics of individual microtubules within the population differ dramatically. Furthermore, we study in detail a transition from bounded to unbounded microtubule growth. Our results provide novel insights into how molecular motors imprint information of microtubule stability on the microtubule network., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Nonlinear systems are not susceptible to research with a reductionist approach. In this sense, the complexity theory provides an alternative approach to quantify the importance of contextual factors in patients with musculoskeletal pain. The use of positive (placebo) or negative (nocebo) contextual factors in the therapeutic setting could largely account for the non-specific component of treatment efficacy, directly affecting the quality of patients’ health-related outcomes (e.g., pain, disability, or satisfaction). In recent years, there has been a better understanding of the effects of contextual factors. However, the knowledge and awareness of them is limited and heterogeneous among physical therapists, reducing their translational value in the field of physiotherapy. The purpose of this essay is to describe the management of patients with musculoskeletal pain from the complexity theory perspective.

Background: Approximately 80% of people with a substance use disorder (SUD) are smokers. Starting SUD treatment offers the opportunity to also quit smoking. The ACT-ATAC project aims to identify the predictors associated with smoking cessation among persons treated for alcohol and/or cannabis use disorder in Barcelona. This manuscript reports its methodology and the experience of carrying it out during the COVID-19 pandemic., Methods: Mixed methods project with three substudies. Substudy 1 (S1) comprises heterogeneous discussion groups among clinicians. S2 has two prospective cohorts composed of smokers under treatment for alcohol and/or cannabis use disorder and the clinicians in charge of these patients. Participating smokers will be followed for 12 months and interviewed about their substance use and the tobacco cessation services received using the Spanish version of the users' Knowledge, Attitudes, and Services (S-KAS) scale. The clinicians will be asked about their self-reported practices in smoking cessation using the Knowledge, Attitudes, and Practices (S-KAP) scale. S3 comprises heterogeneous discussion groups with smokers. Data will be triangulated using qualitative and quantitative analyses. To facilitate the recruitment process, the researchers have introduced several strategies (design clear protocols, set monthly online meetings, extend the project, provide gift cards, etc.)., Discussion: The results of S1 were used to develop the questionnaires. S2 required some adjustments due to the COVID-19 pandemic, particularly the follow-up interviews being conducted by phone instead of face-to-face, and the recruitment rhythm was lower than expected. Recruitment will last until reaching at least 200-250 users. The fieldwork could not have been possible without the collaboration of the ACT-ATAC team and the introduction of several strategies. Trial registration The ACT-ATAC project has been successfully registered at Clinicaltrials.gov [NCT04841655]., (© 2022. The Author(s).)

Carnosic acid (CA) is a phenolic diterpene characterized by its high antioxidant activity; it is used in industrial, cosmetic, and nutritional applications. We evaluated the radioprotective capacity of CA on cells directly exposed to X-rays and non-irradiated cells that received signals from X-ray treated cells (radiation induced bystander effect, RIBE). The genoprotective capacity was studied by in vivo and in vitro micronucleus assays. Radioprotective capacity was evaluated by clonogenic cell survival, MTT, apoptosis and intracellular glutathione assays comparing radiosensitive cells (human prostate epithelium, PNT2) with radioresistant cells (murine metastatic melanoma, B16F10). CA was found to exhibit a genoprotective capacity in cells exposed to radiation (p < 0.001) and in RIBE (p < 0.01). In PNT2 cells, considered as normal cells in our study, CA achieved 97% cell survival after exposure to 20 Gy of X-rays, eliminating 67% of radiation-induced cell death (p < 0.001), decreasing apoptosis (p < 0.001), and increasing the GSH/GSSH ratio (p < 0.01). However, the administration of CA to B16F10 cells decreased cell survival by 32%, increased cell death by 200% (p < 0.001) compared to irradiated cells, and increased cell death by 100% (p < 0.001) in RIBE bystander cells (p < 0.01). Furthermore, it increased apoptosis (p < 0.001) and decreased the GSH/GSSG ratio (p < 0.01), expressing a paradoxical radiosensitizing effect in these cells. Knowing the potential mechanisms of action of substances such as CA could help to create new applications that would protect healthy cells and exclusively damage neoplastic cells, thus presenting a new desirable strategy for cancer patients in need of radiotherapy.

Traumatic brain injuries (TBI) often produce disability in survivors due to unresolved inflammation and progressive neurodegeneration. The central nervous system in mammals is incapable of self-repair. Two decades of preclinical studies and clinical trials have provided insights into TBI pathophysiology that could be utilized to develop clinically relevant therapy. Our laboratory recently reported efficacy of clinical trial grade fetal human neural stem cells (hNSCs) in immunosuppressed rats with penetrating traumatic brain injury (pTBI). Next, in compliance with the United States Food and Drug Administration (USFDA) guidance, this study explores safety by assessing the tumorigenicity potential of intracranial hNSC transplants in athymic rats with pTBI. First, the maximum tolerated dose (MTD) was determined. Then, forty athymic pTBI rats were randomized to either: Group A. pTBI + vehicle or Group B. pTBI + hNSCs at MTD one week after injury with 6-months survival, sufficient time to uncover transplant associated tumorigenicity. A board-certified Pathologist examined hematoxylin-eosin (H&E), Ki67 immunostained brain and spinal cord, serial sections along with several abnormal peripheral masses for evidence of lesion, transplant, and oncogenesis. There was no evidence of transplant derived tumors or oncogenic tissue necrosis. Consistent with athymic literature, the lesion remained unchanged even after robust hNSC engraftment. This safety study supports the conclusion that hNSCs are safe for transplantation in pTBI. The differences in lesion expansion between immunosuppressed and athymic rats in the presence of hNSCs suggests an unexpected role for thymus derived cells in resolution of trauma induced inflammation., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Vedolizumab is a humanized monoclonal antibody targeting the α 4 β 7 integrin used for the treatment of ulcerative colitis. Few biomarkers related to vedolizumab response have been identified. The aim of this work was to assess whether baseline circulating CD4 + and CD8 + memory T-lymphocyte subpopulations could help to identify patients with response to vedolizumab treatment in ulcerative colitis., Methods: Prospective pilot study in 15 patients with active ulcerative colitis and previous failure to anti-TNFα starting vedolizumab treatment. Peripheral blood samples were obtained before the first dose of vedolizumab and at week 6 and 14 of treatment. Clinical remission was defined as a Mayo Clinic partial score of ≤2 points without any concomitant dose of steroids. Biochemical remission or endoscopic improvement was defined as fecal calprotectin <250 mcg/g or Mayo endoscopic subscore ≤1., Results: At week 14, nine patients achieved clinical remission and eight patients achieved biochemical remission or endoscopic improvement. Patients in clinical remission presented higher baseline CD8 α 4 β 7 + memory T cells concentration when compared with patients with no remission. In addition, patients with biochemical remission or endoscopic improvement at week 14 presented higher baseline concentration of CD8 α 4 β 7 + memory T cells. No differences were identified according to flare severity, extent of disease or type of anti-TNFα failure. There were no significant differences regarding changes in T cell subsets during vedolizumab induction., Conclusion: CD8 + α 4 β 7 + memory T cells before starting vedolizumab therapy could be an early predictor of remission in ulcerative colitis patients and therefore help to select a subset of responders., Competing Interests: The study funding was part of the Investigator Initiated Sponsored Research Program by Takeda. Design, recruitment, data analysis, and manuscript were performed independently by researchers at Hospital del Mar. Takeda Pharmaceuticals and associated employees did not intervene in any part of the process and did not have access to any of the data. 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 © 2022 Gonzalez-Vivo, Lund Tiirikainen, Andreu, Fernandez-Clotet, López-García, Murciano Gonzalo, Abril Rodriguez, de Jesús-Gil, Ruiz-Romeu, Sans-de San Nicolàs, Santamaria-Babí and Márquez-Mosquera.)

Objectives: Exposure to different types of injuries in rugby union is common. It is important to know about the injury epidemiology for medical teams care in order to optimize players´ performance and the treatment of common injuries, but there is limited specific information related to amateur rugby union. The purpose of this study is to determine the incidence, prevalence, injury burden, severity, nature of injuries sustained by senior amateur male rugby players from three clubs in Argentina during a given season., Methods: An observational, analytical, prospective, multicenter study was developed. Data collection was conducted from 15 March 2019 to 2 November 2019, during a complete season under the applicable standards of the Rugby Injury Consensus Group according to the Orchard Sports Injury and Illness Classification System.Incidence (injuries/1000 player-match-hours), prevalence (%), severity (time loss), injury burden (days lost/1000 player-match-hours), injured location and type of injury (%) were estimated., Results: 250 players and 180 injuries were assessed. Injury prevalence was 52.4%. Incidence rate per match and training was 30.9/1000 player-match-hours, and 0.77/1000 player-training-hours, respectively.The median injury severity score was 23 (IQR 12.7-52) days lost accounting for an injury burden of 97.3/1000 player-hours. Of the total, 113 (62.8%) injuries were contact injuries. The lower limbs were the most commonly affected (58.9%). Hamstring strain injury had the highest incidence and anterior cruciate ligament tear was the most severe injury., Conclusion: The prevalence, incidence, and injury burden reported in this study are unprecedented and would add knowledge for the amateur rugby union community. Trainers, physicians, and physical therapists, should consider it to improve their clinical practice.

Objectives: We assessed the rate of false-positive diagnoses of MDCT-pulmonary angiography (MDCT-A) in patients with single isolated subsegmental pulmonary embolism (SISSPE)., Methods: All patients who underwent MDCT-A between 2006 and 2017 for ruling out acute pulmonary embolism (PE) and received an initial diagnosis of SISSPE were included. The MDCT-A of these patients were reviewed retrospectively by four experienced thoracic radiologists, who applied radiological criteria recommended by the American College of Chest Physicians Antithrombotic Guidelines (ACCP 2016) for the diagnosis of SISSPE. Data extracted from medical records were history of venous thromboembolism (VTE), alternative diagnoses, other diagnostic studies for VTE, anticoagulation, bleeding complications, and VTE over the following 3 months., Results: Of 3839 patients undergoing MDCT-A, PE was found in 1021 (26.6%) and SISSPE in 59 (1.5% overall and 5.8% of all patients with PE). An alternative diagnosis to PE was made on the basis of CT in 33 (55.9%) patients. Forty-one (69.5%) patients received anticoagulants, and major life-threatening bleeding complications occurred in 2, with one death. Recurrent PE was not documented in any patient with SISSPE. In the retrospective assessment of the 59 cases of SISSPE, 21 were negative for PE, with a false-positive rate of 35.6% (21/59); so the percentage of SISSPE cases after the revision was 3.7% of all patients with PE; 11 of these 21 patients received anticoagulation., Conclusions: Radiologists should be aware of the high rate of false-positives when making the diagnosis of SISSPE on MDCT-A without using strict diagnostic criteria. Misdiagnosis exposes patients to unnecessary anticoagulation., Key Points: • Radiologist should be aware of the high rate of false-positive diagnoses of single isolated subsegmental pulmonary embolism (SISSPE) in MDCT-pulmonary angiography (MDCT-A) performed for ruling out pulmonary embolism. • Misdiagnosis of SISSPE in MDCT-A can be reduced by using strict diagnostic radiological criteria recommended by the American College of Chest Physicians Antithrombotic Guidelines. • Unnecessary anticoagulation therapy with potential severe bleeding complications may result from misdiagnosis of SISSPE., (© 2021. The Author(s), under exclusive licence to European Society of Radiology.)