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Aim: to study a sample of patients with morbid obesity who are on the waiting list for a surgical intervention, to establish various scores of surgical risk (Possum and severity score), and to assess potential criteria for list prioritization. Design: we calculated physiological and surgical Possum scores for every patient, and analysed comorbidities and other associated factors to calculate the severity score. Likewise, we calculated the predictive rates of morbimortality. Differences between associated comorbidities in body mass index (BMI) were also analyzed. The correlation between Possum score, prediction rates, and severity score were analyzed. Patients: fifty-two patients on the surgical waiting list in our institution (San Juan University Hospital, Reus) from 26/4/02 to 5/03/04. Results: the mean qualitative score is significantly higher in the female sex. Invalidating arthropathy and socio-occupational and/or psychiatric criteria are significantly higher in women. There is a significant correlation between the severity score and Possum score. Age does not correlate with any of the variables studied. Conclusions: possum scores are significantly related to BMI, particularly in terms of morbidity rates. The degree of correlation between the Possum score and the qualitative score tells how useful the latter is to cover other determinant factors in the severity of this condition. Socio-occupational and psychiatric criteria, and invalidating arthropathy are the main variables to be taken into account for postsurgical prediction, and are directly related to BMI degree.Objetivo: estudio de una muestra de pacientes afectos de obesidad mórbida y en lista de espera para intervención quirúrgica, determinar el riesgo quirúrgico según diferentes scores (Possum y score de gravedad) y valorar los posibles criterios en la priorización de dicha lista. Diseño: cálculo del Possum fisiológico y quirúrgico para cada paciente y análisis de las comorbilidades y otros factores asociados para el cálculo del score de gravedad. Cálculo de los ratios predictivos de morbi-mortalidad. Análisis de las diferencias observadas, según el índice de masa corporal (IMC), de las comorbilidades asociadas. Análisis del grado de correlación entre el Possum, los ratios de predicción y el score de gravedad. Pacientes: Cincuenta y dos pacientes incluidos en la lista de espera quirúrgica de nuestro centro (Hospital Universitario San Joan de Reus) durante el periodo del 26/4/02 al 5/03/04. Resultados: el score cualitativo tiene una media superior significativa en el sexo masculino. La artropatía invalidante y los criterios socio-laborales y/o psiquiátricos son significativamente superiores en el sexo femenino. Existe una correlación significativa entre el score de gravedad y el Possum. La edad no se correlaciona en nuestra serie con ninguna de las variables estudiadas. Conclusiones: los valores del Possum están relacionados significativamente con el IMC, en especial en base al ratio de morbilidad. El grado de correlación entre el Possum y el score cualitativo nos indica la utilidad de este para cubrir otros factores determinantes en la gravedad de esta patología. Los criterios socio-laborales y psiquiátricos y la artropatía invalidante, son las principales variables a tener en cuenta en la predicción postquirúrgica, estando directamente relacionados con el grado de IMC.

The development of reduced models provide efficient methods that can be used to perform short term experimental data analysis or narrow down the parametric range of more sophisticated numerical approaches. Reduced models are derived by simplifying the physics description with the goal of retaining only the essential ingredients required to reproduce the phenomena under study. This is the role of the gyro-fluid code FAR3d, dedicated to analyze the linear and nonlinear stability of Alfvén Eigenmodes (AE), Energetic Particle Modes (EPM) and magnetic-hydrodynamic modes as pressure gradient driven mode (PGDM) and current driven modes (CDM) in nuclear fusion devices. Such analysis is valuable for improving the plasma heating efficiency and confinement; this can enhance the overall device performance. The present review is dedicated to a description of the most important contributions of the FAR3d code in the field of energetic particles (EP) and AE/EPM stability. FAR3d is used to model and characterize the AE/EPM activity measured in fusion devices as LHD, JET, DIII-D, EAST, TJ-II and Heliotron J. In addition, the computational efficiency of FAR3d facilitates performing massive parametric studies leading to the identification of optimization trends with respect to the AE/EPM stability. This can aid in identifying operational regimes where AE/EPM activity is avoided or minimized. This technique is applied to the analysis of optimized configurations with respect to the thermal plasma parameters, magnetic field configuration, external actuators and the effect of multiple EP populations. In addition, the AE/EPM saturation phase is analyzed, taking into account both steady-state phases and bursting activity observed in LHD and DIII-D devices. The nonlinear calculations provide: the induced EP transport, the generation of zonal structures as well as the energy transfer towards the thermal plasma and between different toroidal/helical families. Finally, FAR3d is used to forecast the AE/EPM stability in operational scenarios of future devices as ITER, CFETR, JT60SA and CFQS as well as possible approaches to optimization with respect to variations in the most important plasma parameters.

Recent developments and tools integrated into the TAPaS code are presented, enabling realistic scenario simulations of particle dynamics within experimental tokamak magnetic equilibria. In particular, the enhanced capabilities of TAPaS enable seamless coupling with external simulations, provided the metric and equilibrium magnetic field of the external code are known. Coupling TAPaS with the gyro-fluid code FAR3d, the transport and losses of energetic particles in the presence Alfvén eigenmodes (AEs) in DIII-D plasma discharge $\#159243$ were investigated. Detailed analyses of prompt losses with and without collisions were performed. Then, further analysis was performed in the presence of electromagnetic perturbations resulting from AEs activity. The results indicate that, for the energies and the initial conditions considered here, the presence of AEs enhances the particle losses.

Current profile reconstructions are obtained for high current ( $I_p \simeq 550$ kA) post-disruption runaway electron (RE) plateau plasmas in DIII-D. Two novel methods of measuring the RE current profile in high-current RE plateaus are introduced and compared: localization of the q = 2 rational surface using visible synchrotron emission (SE) imaging and the measurement of the polarization angle of line-integrated Ar-II line emission. The two methods are found to be consistent with each other within the data uncertainties. Different simulations of the RE current profile are compared with the measurements: the toroidal fluid RE model is found to best fit the data, within the measurement uncertainties. In addition to introducing two novel methods to measure the RE current profile and validating present simulation capabilities, this work demonstrates that instabilities can grow at q = 2 and q = 1 surfaces without necessarily causing a RE final loss instability. Numerical simulations are also presented to elucidate the role of these instabilities on synchrotron emission.

Subcritical energetic electrons (SEEs) produced by the runaway electron (RE) avalanche source at energies below the runaway threshold are found to be the primary contributor to surface heating of plasma-facing components (PFCs) during final loss events. This finding is supported by theoretical analysis, computational modeling with the Kinetic Orbit Runaway electrons Code (KORC), and qualitative agreement with DIII-D experimental observations. The avalanche source generates significantly more secondary electrons below the runaway threshold, which thermalize rapidly when well-confined. However, during a final loss event, the RE beam impacts the first wall, and SEEs are deconfined before they can thermalize. Additionally, because the energy deposition length decreases faster than energy, the deposited energy density, and thus the maximum PFC surface temperature change, is larger for SEEs than REs. KORC simulations employ an analytic first wall to model particle deconfinement onto a non-axisymmetric wall composed of individual tiles. PFC surface heating is calculated using a 1D model extended to include an energy-dependent deposition length scale. Simulations of DIII-D qualitatively agree with infrared (IR) imaging only when SEEs from the avalanche source are included. These results demonstrate that SEEs are the dominant contributor to PFC surface heating and indicate that the avalanche source plays a critical role in the PFC damage caused during final loss events. The prominence of SEEs also has important implications for interpreting IR imaging, one of the primary diagnostics for RE-wall interaction diagnosis, despite REs dominating the energy and current density. This result improves predictions of wall damage due to post-disruption REs to estimate material lifetime and design RE mitigation systems for ITER and future reactors.

Diabetes mellitus (DM) is a public health problem with a prevalence of 345 million people worldwide that it may double by the year 2030 and have a high costs and mortality. Gastrointestinal surgery is accepted as a form of treatment that was already suggested for obese in 1987 by Pories, confirmed for obese patients by the meta-analysis of Buchwald and the direct comparison of gastric bypass with medical treatment in the study of Schauer that demonstrate a 4 fold greater resolution rate of DM with surgery. Improvement occurs immediately after surgery, before the patients lose weight in with BMI > 35; but there is doubt if the existent evidence is enough to extrapolate these results to patients with BMI < 35 and especially with BMI < 30, in spite that four reviews in patients with this BMI and DM2 demonstrated the same results when stomach, duodenum and part of jejunum is bypassed as happen gastric bypass (better results with this of one anastomosis than of two anastomosis, Rouxen-Y) BPD. For patients with a BMI between 30 and 35 restrictive techniques: LAGB and SGL are good but not better than the mixed: RYGB, BAGUA, or SG-DJB with remission from 60 to 100%, minor in the derivative: BPD and above on the IID with a 81% of remission. There are no differences in the metabolic control in comparison to the obese, It is progressively better with DJB, SDS, IID and BAGUA especially in patients who do not require insulin, have less time with disease, have normal C peptide levels, and not so much relation with the initial BMI that is only important to decide the degree of restriction. Although several mechanisms has been suggesed for explaining these results such as caloric intake, hormonal changes, bypass of the anterior or early stimulation of posterior intestine, fundectomy, intestinal gluconeogenesis and others, new ones will appear in the near future.

La búsqueda de nuevas alternativas para estabilizar suelos con desechos motivó la realización de esta investigación exploratoria para evaluar en forma preliminar las propiedades geotécnicas de un suelo fino de subrasante mezclado con diferentes porcentajes (4 %, 8 %, 12 % y 16 %) de Aceite de Motor Usado (AMU). En el desarrollo de esta investigación se realizaron ensayos de límites de Atterberg, coeficiente de permeabilidad (k), compresión inconfinada (qu), y relación humedad-densidad de un suelo clasificado como MH. Los ensayos se realizaron tanto para el suelo sin estabilizar como para el suelo estabilizado con AMU. Los resultados muestran que los limites líquido y plástico tienden a disminuir con el incremento de AMU, la densidad seca máxima se incrementa ligeramente, el contenido de humedad optima disminuye significativamente, la resistencia a la compresión inconfinada (qu) se mantiene constante para contenidos de AMU hasta el 8 % y la permeabilidad (k) no muestra variación significativa.

Human-robot interaction has been going stronger and stronger, up to find a notorious level on brain-machines interfaces. This assistive technology offers a great hope for patients suffering severe neuromuscular disorders. Starting from the current limitations hindering its extensive application outside the research laboratories, this paper reviews findings and prospects on functional magnetic resonance imaging showing how fMRI can help to overcome those limitations, while playing a key role on improving the development of brain-machine interfaces based on electroencephalography. The different types of derived benefits for this interfaces, as well as the different kinds of impact on their components, are presented under a field classification that reveals the distinctive roles that fMRI can play on the present context. The review concludes that fMRI provides complementary knowledge of immediate application, and that a greater profit could be obtained from the own EEG signal by integrating both neuroimaging modalities.

Resumen: Las Interfaces Cerebro-Computador proporcionan un canal para enviar órdenes al mundo exterior haciendo uso de medidas electrofisiológicas de la actividad cerebral. En este artículo se presenta la combinación de un método de selección de características y un algoritmo de clasificación probabilístico para construir el modelo predictivo de la intención anticipada de movimiento voluntario de pacientes con temblor a partir de un solo ensayo. Los resultados obtenidos muestran una potencial de discriminación del 70%, una tasa de error aceptable (6.6%) y una rápida respuesta (cada 250 ms), lo que indica que esta combinación es una buena base para la construcción de ICCs que no requieran entrenamiento del usuario de forma personalizada, asíncrona y adaptativa. Palabras clave: Interfaz Cerebro-Computador (ICC) asíncrona, señal electroencefalográfica, personalización, ritmos sensorimotores, minería de datos, adaptación, clasificación

A review of non-diffusive transport in fluids and plasmas is presented. In the fluid context, non-diffusive chaotic transport by Rossby waves in zonal flows is studied following a Lagrangian approach. In the plasma physics context the problem of interest is test particle transport in pressure-gradient-driven plasma turbulence. In both systems the probability density function (PDF) of particle displacements is strongly non-Gaussian and the statistical moments exhibit super-diffusive anomalous scaling. Fractional diffusion models are proposed and tested in the quantitative description of the non-diffusive Lagrangian statistics of the fluid and plasma problems. Also, fractional diffusion operators are used to construct non-local transport models exhibiting up-hill transport, multivalued flux-gradient relations, fast pulse propagation phenomena, and "tunneling" of perturbations across transport barriers.

Background: Gastrointestinal stromal tumours (GISTs) are rare. Few cases of such tumours are reported in the literature. Until recently, they were only treated surgically but, nowadays, for high grade tumours, we can consider wide excision, not only as a palliative measure, but also to enable subsequent treatment with Imatinib mesylate. Methods: We describe the case of a patient with a high-grade GIST, who, two years after undergoing surgery and medical treatment, is still in remission. Computerised axial tomography (CT) of the abdomen detected the presence of multiple heterogeneous solid masses of various sizes but no localised retroperitoneal adenopathies. Main findings: Median laparotomy was performed and revealed multiple intraperitoneal tumours. The larger masses were excised and the smaller residual implants are currently being treated with Imatinib mesylate. The patient had visceral, parietal and peritoneal dissemination. One of them, located in the supramesocolic area, had a maximal diameter of 20cm. Another one, at the level of the retro-gastric space, had a diameter of 22cm. The other tumours were smaller and spread over the parietal and visceral peritoneum, mainly between the loops of the small intestine and pelvis. Two years after cytoreduction surgery, the patient is well and free of obvious disease and has shown a good tolerance to pharmacological treatment. Conclusions: Imatinib mesylate has revolutionised the treatment of GIST and offers good palliation and prolongation of overall survival. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal stromal tumours (GISTs) are rare. Few cases of such tumours are reported in the literature. Until recently, they were only treated surgically but, nowadays, for high grade tumours, we can consider wide excision, not only as a palliative measure, but also to enable subsequent treatment with Imatinib mesylate.Methods: We describe the case of a patient with a high-grade GIST, who, two years after undergoing surgery and medical treatment, is still in remission. Computerised axial tomography (CT) of the abdomen detected the presence of multiple heterogeneous solid masses of various sizes but no localised retroperitoneal adenopathies.Main Findings: Median laparotomy was performed and revealed multiple intraperitoneal tumours. The larger masses were excised and the smaller residual implants are currently being treated with Imatinib mesylate. The patient had visceral, parietal and peritoneal dissemination. One of them, located in the supramesocolic area, had a maximal diameter of 20cm. Another one, at the level of the retro-gastric space, had a diameter of 22cm. The other tumours were smaller and spread over the parietal and visceral peritoneum, mainly between the loops of the small intestine and pelvis. Two years after cytoreduction surgery, the patient is well and free of obvious disease and has shown a good tolerance to pharmacological treatment.Conclusions: Imatinib mesylate has revolutionised the treatment of GIST and offers good palliation and prolongation of overall survival. [ABSTRACT FROM AUTHOR]

Novel measurements and modeling of runaway electron (RE) dynamics in DIII-D have resolved experimental discrepancies and validated predictions for ITER, improving confidence that RE avoidance and mitigation can be predictably achieved. Considering RE formation, first experimental assessments of the RE seed current demonstrates that present hot-tail theories are not yet accurate and require improved treatment of the pellet dynamics. Novel measurements of kinetic instabilities in the MHz-range have been made in the RE formation phase, with the intensity of these modes correlated with previously unexplained empirical thresholds for RE generation. Controlled RE dissipation experiments in quiescent regimes have validated RE distribution function dependencies on collisional and synchrotron damping, both in terms of distribution function shape and dissipation rates. Measurements of RE bremsstrahlung and synchrotron emission are now used in tandem to resolve energy and pitch-angle effects. A resolution to long-standing dissipation anomalies in the quiescent regime is offered by taking into account kinetic instability effects on RE phase-space dynamics. Kinetic instabilities in the 100–200 MHz range are directly observed, though modeling finds the largest dissipation arises from GHz range instabilities that are beyond the reach of existing diagnostics. Kinetic instabilities are also observed in the mature post-disruption RE plateau phase, so long as the collisional damping rate is reduced with low-Z injection. Experiments with high-Z injection find that the dissipation rate saturates with injection quantity, likely due to neutral diffusion rates being slower than vertical instability rates in DIII-D. Considering the final loss, a 0D model for first-wall Joule heating is found to be in agreement with experiment, and controlled access to RE equilibria with edge safety factor of two identifies novel dynamics brought about by large-scale kink instabilities. These dynamics are typified by fast (tens of microseconds) RE loss rates without RE beam regeneration. The above measurements and comparison with theory represent significant advances in the understanding of RE dynamics and indicate possible new opportunities for RE avoidance or mitigation via kinetic instabilities. [ABSTRACT FROM AUTHOR]

The transport of particles in the presence of energetic geodesic acoustic modes (EGAMs) is analysed by means of full-f global gyro-kinetic simulations, using the multi-species version of the code and a test particle tracking post-treatment, which solves the equations of motion of passive gyro-centres embedded in the self-consistent EGAM potential obtained from the simulations. It is found that EGAMs induce the transport of particles, which eventually results in counter-passing particle losses modulated at the EGAM frequency. A detailed analysis of the trajectories of the test gyro-centres is performed and evidence of the interaction between the EGAM island and the region of magnetically trapped particles (trapping cone) is provided. In particular, we report for the first time on the complex interaction between the stochastic separatrix of the EGAM island and the X-point of the trapping cone, creating a channel for the transport of particles from the to the regions. Therefore, for the cases analysed in this work, the co-injection of energetic particles might lead to a significant reduction of EGAM-induced losses. This result opens up new perspectives for further studies of the selection of energetic particle injection in order to minimize the losses due to EGAMs. [ABSTRACT FROM AUTHOR]

Developing avoidance or mitigation strategies of runaway electrons (REs) in magnetic confinement fusion (MCF) plasmas is of crucial importance for the safe operation of ITER. In order to develop these strategies, an accurate diagnostic capability that allows good estimates of the RE distribution function in these plasmas is needed. Synchrotron radiation (SR) of RE in MCF, besides of being one of the main damping mechanisms for RE in the high energy relativistic regime, is routinely used in current MCF experiments to infer the parameters of RE energy and pitch angle distribution functions. In the present paper we address the long standing question about what are the relationships between different REs distribution functions and their corresponding synchrotron emission simultaneously including: full-orbit effects, information of the spectral and angular distribution of SR of each electron, and basic geometric optics of a camera. We study the spatial distribution of the SR on the poloidal plane, and the statistical properties of the expected value of the synchrotron spectra of REs. We observe a strong dependence of the synchrotron emission measured by the camera on the pitch angle distribution of runaways, namely we find that crescent shapes of the spatial distribution of the SR as measured by the camera relate to RE distributions with small pitch angles, while ellipse shapes relate to distributions of runaways with larger the pitch angles. A weak dependence of the synchrotron emission measured by the camera with the RE energy, value of the q-profile at the edge, and the chosen range of wavelengths is observed. Furthermore, we find that oversimplifying the angular dependence of the SR changes the shape of the synchrotron spectra, and overestimates its amplitude by approximately 20 times for avalanching runaways and by approximately 60 times for mono-energetic distributions of runaways1. [ABSTRACT FROM AUTHOR]

Multi-filter images from the solar corona are used to obtain temperature maps that are analyzed using techniques based on proper orthogonal decomposition (POD) in order to extract dynamical and structural information at various scales. Exploring active regions before and after a solar flare and comparing them with quiet regions, we show that the multi-scale behavior presents distinct statistical properties for each case that can be used to characterize the level of activity in a region. Information about the nature of heat transport is also to be extracted from the analysis.

Background: Coronary artery dissection is managed primarily conservatively with serial imaging or percutaneous coronary intervention (PCI). Exposure to contrast in either modality could potentially result in acute tubular necrosis (ATN). However, no data compares ATN incidence in these management strategies. This study compares the incidence of ATN and associated mortality of PCI and conservative management of coronary artery dissection., Methods: A retrospective analysis was performed using data from the National Inpatient Sample database, including patients with coronary artery dissection between 2016 through 2020. We analyzed the incidence of ATN and associated mortality of PCI and conservative management of coronary artery dissection., Results: We found that the odds of developing ATN were 22% lower in patients managed with PCI than those managed conservatively. There was no difference in the in-hospital mortality or hospital length of stay between the two groups but the mortality rate in patients with ATN was double that of those who did not develop ATN in both PCI and conservatively managed groups., Conclusions: The higher incidents of ATN in patients with coronary dissection being managed with conservative measures compared to PCI suggest that the use of CTA may be harmful. Additionally, persons who developed ATN may have higher mortality. Therefore, more studies in the management of coronary artery dissection need to be done which would allow further steps to be taken to reduce this harm., Competing Interests: Declaration of competing interest No disclosures/conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Individuals with nephrotic syndrome (NS) are thought to have elevated cardiovascular risk because of a known association with hyperlipidemia. Unfortunately, no studies have compared the cardiovascular risk profiles of individual nephrotic syndromes. This study explores the prevalence and patterns of coronary artery disease (CAD) in patients with different types of NS, which may aid in developing risk reduction strategies., Methods: This retrospective study queried data from the National Inpatient Sample database spanning 2016-2020 and included patients over the age of 18 years with minimal change disease (MCD), membranous nephropathy (MN), and focal segmental glomerulosclerosis (FSGS). We analyzed the prevalence and trends of hyperlipidemia and CAD in the study population., Results: Of the 15,025 cohort, there were 3625 (24.1%) MCD, 4160 (27.7%) MN, and 7315 (48.7%) FSGS. Patients with MN were found to be older with a higher prevalence of hyperlipidemia and CAD compared to other groups. The odds of developing CAD when adjusting for confounding factors were increased in FSGS (adjusted odds [aOR] 1.570, 95% CI 1.406-1.753, p < 0.001) while reduced in MCD (aOR 0.671, 95% CI 0.580-0.777, p < 0.001) and MN (aOR 0.782, 95% CI 0.698-0.876, p < 0.001)., Conclusions: The divergent results of the different NS types highlight the need for targeted research to better understand and characterize the distinct cardiovascular risk profiles inherent in each type of nephrotic disease for risk stratification., Competing Interests: Declaration of competing interest No disclosures/conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: The burden of multimorbidity is recognised increasingly in low- and middle-income countries (LMICs), creating a strong emphasis on the need for effective evidence-based interventions. Core outcome sets (COS) appropriate for the study of multimorbidity in LMICs do not presently exist. These are required to standardise reporting and contribute to a consistent and cohesive evidence-base to inform policy and practice. We describe the development of two COS for intervention trials aimed at preventing and treating multimorbidity in adults in LMICs., Methods: To generate a comprehensive list of relevant prevention and treatment outcomes, we conducted a systematic review and qualitative interviews with people with multimorbidity and their caregivers living in LMICs. We then used a modified two-round Delphi process to identify outcomes most important to four stakeholder groups (people with multimorbidity/caregivers, multimorbidity researchers, healthcare professionals and policymakers) with representation from 33 countries. Consensus meetings were used to reach agreement on the two final COS., Registration: https://www.comet-initiative.org/Studies/Details/1580., Results: The systematic review and qualitative interviews identified 24 outcomes for prevention and 49 for treatment of multimorbidity. An additional 12 prevention and 6 treatment outcomes were added from Delphi round 1. Delphi round 2 surveys were completed by 95 of 132 round 1 participants (72.0%) for prevention and 95 of 133 (71.4%) participants for treatment outcomes. Consensus meetings agreed four outcomes for the prevention COS: (1) adverse events, (2) development of new comorbidity, (3) health risk behaviour and (4) quality of life; and four for the treatment COS: (1) adherence to treatment, (2) adverse events, (3) out-of-pocket expenditure and (4) quality of life., Conclusion: Following established guidelines, we developed two COS for trials of interventions for multimorbidity prevention and treatment, specific to adults in LMIC contexts. We recommend their inclusion in future trials to meaningfully advance the field of multimorbidity research in LMICs., Prospero Registration Number: CRD42020197293., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Known for their distinct antigen-sampling abilities, microfold cells, or M cells, have been well characterized in the gut and other mucosa including the lungs and nasal-associated lymphoid tissue (NALT). More recently, however, they have been identified in tissues where they were not initially suspected to reside, which raises the following question: what external and internal factors dictate differentiation toward this specific role? In this discussion, we will focus on murine studies to determine how these cells are identified (e.g., markers and function) and ask the broader question of factors triggering M-cell localization and patterning. Then, through the consideration of unconventional M cells, which include villous M cells, Type II taste cells, and medullary thymic epithelial M cells (microfold mTECs), we will establish the M cell as not just a player in mucosal immunity but as a versatile niche cell that adapts to its home tissue. To this end, we will consider the lymphoid structure relationship and apical stimuli to better discuss how the differing cellular programming and the physical environment within each tissue yield these cells and their unique organization. Thus, by exploring this constellation of M cells, we hope to better understand the multifaceted nature of this cell in its different anatomical locales., 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 Del Castillo and Lo.)

Artisanal and small-scale gold mining (ASGM) in the Amazon has degraded tropical forests and escalated mercury (Hg) pollution, affecting biodiversity, ecological processes and rural livelihoods. In the Peruvian Amazon, ASGM annually releases some 181 tons of Hg into the environment. Despite some recent advances in understanding the spatial distribution of Hg within gold mine spoils and the surrounding landscape, temporal dynamics in Hg movement are not well understood. We aimed to reveal spatio-temporal trends of soil Hg in areas degraded by ASGM.,. We analyzed soil and sediment samples during the dry and rainy seasons across 14 ha of potentially contaminated sites and natural forests, in the vicinities of the Native community of San Jacinto in Madre de Dios, Peru. Soil Hg levels of areas impacted by ASGM (0.02 ± 0.02 mg kg -1 ) were generally below soil environmental quality standards (6.60 mg kg -1 ). However, they showed high variability, mainly explained by the type of natural cover vegetation, soil organic matter (SOM), clay and sand particles. Temporal trends in Hg levels in soils between seasons differed between landscape units distinguished in the mine spoils. During the rainy season, Hg levels decreased up to 45.5% in uncovered soils, while in artificial pond sediments Hg increased by up to 961%. During the dry season, uncovered degraded soils were more prone to lose Hg than sites covered by vegetation, mainly due to higher soil temperatures and concomitantly increasing volatilization. Soils from natural forests and degraded soil covered by regenerating vegetation showed a high capacity to retain Hg mainly due to the higher plant biomass, higher SOM, and increasing concentrations of clay particles. Disturbingly, our findings suggest high Hg mobility from gold mine spoil to close by sedimentary materials, mainly in artificial ponds through alluvial deposition and pluvial lixiviation. Thus, further research is needed on monitoring, and remediation of sediments in artificial to design sustainable land use strategies., 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 Elsevier Inc. All rights reserved.)

SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17 years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6 years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials., Competing Interests: AG-C has received honoraria for research support and lectures from PTC Therapeutics, she has received honoraria for lectures from Biomarin, Immedica and Recordati Rare Diseases Foundation, and is a co-founder of the Hospital Sant Joan de Déu start-up “Neuroprotect Life Sciences”. The remaining 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 Ribeiro-Constante, Tristán-Noguero, Martínez Calvo, Ibañez-Mico, Peña Segura, Ramos-Fernández, Moyano Chicano, Camino León, Soto Insuga, González Alguacil, Valera Dávila, Fernández-Jaén, Plans, Camacho, Visa-Reñé, Martin-Tamayo Blázquez, Paredes-Carmona, Marti-Carrera, Hernández-Fabián, Tomas Davi, Sanchez, Herraiz, Pita, Gonzalez, O'Callaghan, Iglesias Santa Polonia, Cazorla, Ferrando Lucas, González-Meneses, Sala-Coromina, Macaya, Lasa-Aranzasti, Cueto-González, Valera Párraga, Campistol Plana, Serrano, Alonso, Del Castillo-Berges, Schwartz-Palleja, Illescas, Ramírez Camacho, Sans Capdevila, García-Cazorla, Bayés and Alonso-Colmenero.)

Background: Preterm birth has been associated with increased risk of hypertension and cardiovascular disease later in adulthood, attributed to cardiovascular and metabolic alterations in early life. However, there is paucity of evidence from low- and middle-income countries (LMICs)., Methods: We investigated the differences between preterm (<37 weeks gestational age) and term-born individuals in birth length and weight as well as adult (18 and 20 years) height, weight and blood pressure in the Brazilian 1993 Pelotas birth cohort using linear regressions. Analyses were adjusted for the maternal weight at the beginning of pregnancy and maternal education and family income at childbirth. Additional models were adjusted for body mass index (BMI) and birthweight. Separate analyses were run for males and females. The complete sample was analysed with an interaction term for sex., Results: Of the 3585 babies included at birth, 3010 were followed up in adulthood at 22 years. Preterm participants had lower length and weight at birth. This difference remained for male participants in adulthood, but female participants were no shorter than their term counterparts by 18 years of age. At 22 years, females born preterm had lower blood pressures (systolic blood pressure -1.00 mmHg, 95%CI -2.7, 0.7 mmHg; diastolic blood pressure -1.1 mmHg, 95%CI -2.4, 0.3 mmHg) than females born at term. These differences were not found in male participants., Conclusions: In this Brazilian cohort we found contrasting results regarding the association of preterm birth with blood pressure in young adulthood, which may be unique to an LMIC., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Development of immunocompetent T cells in the thymus is required for effective defence against all types of pathogens, including viruses, bacteria and fungi. To this end, T cells undergo a very strict educational program in the thymus, during which both non-functional and self-reactive T cell clones are eliminated by means of positive and negative selection 1 .Thymic epithelial cells (TECs) have an indispensable role in these processes, and previous studies have shown the notable heterogeneity of these cells 2-7 . Here, using multiomic analysis, we provide further insights into the functional and developmental diversity of TECs in mice, and reveal a detailed atlas of the TEC compartment according to cell transcriptional states and chromatin landscapes. Our analysis highlights unconventional TEC subsets that are similar to functionally well-defined parenchymal populations, including endocrine cells, microfold cells and myocytes. By focusing on the endocrine and microfold TEC populations, we show that endocrine TECs require Insm1 for their development and are crucial to maintaining thymus cellularity in a ghrelin-dependent manner; by contrast, microfold TECs require Spib for their development and are essential for the generation of thymic IgA + plasma cells. Collectively, our study reveals that medullary TECs have the potential to differentiate into various types of molecularly distinct and functionally defined cells, which not only contribute to the induction of central tolerance, but also regulate the homeostasis of other thymus-resident populations., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The biosorption and recovery of ionic gadolinium (Gd) from contaminated water by the free-floating duckweed Lemna gibba was studied. The highest non-toxic concentration range was determined as (6.7 mg L -1 ). The concentration of Gd in the medium and in the plant biomass was monitored and a mass balance was established. Tissue Gd concentration of Lemna increased with increasing Gd concentration of the medium. The bioconcentration factor was up to 1134 and in nontoxic concentrations up to 2.5 g kg -1 Gd tissue concentration was reached. Lemna ash contained 23.2 g Gd kg -1 . Gd removal efficiency from the medium was 95%, however, only 17-37% of the initial Gd content of the medium accumulated in Lemna biomass, an average of 5% remained in the water, and 60-79% was calculated as a precipitate. Gadolinium-exposed Lemna plants released ionic Gd into the nutrient solution when they were transferred to a Gd-free medium. The experimental results revealed that in constructed wetlands, L. gibba is able to remove ionic Gd from the water and can be suitable for bioremediation and recovery purposes., 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 Authors. Published by Elsevier B.V. All rights reserved.)

Obesity is a chronic and complex disease, with an increasing incidence worldwide that is associated with metabolic disorders such as type 2 diabetes mellitus (T2DM). Thus, it is important to determine the differences between metabolically healthy obese individuals and those with metabolic disorders. The aim of this study was to perform an untargeted metabolomics assay in women with morbid obesity (MO) compared to a normal weight group, and to differentiate the metabolome of these women with MO who present with T2DM. We carried out a liquid chromatography-mass spectrometry-based untargeted metabolomics assay using serum samples of 209 Caucasian women: 73 with normal weight and 136 with MO, of which 71 had T2DM. First, we found increased levels of choline and acylglycerols and lower levels of bile acids, steroids, ceramides, glycosphingolipids, lysophosphatidylcholines, and lysophosphatidylethanolamines in MO women than in the control group. Then, in MO women with T2DM, we found increased levels of glutamate, propionyl-carnitine, bile acids, ceramides, lysophosphatidylcholine 14:0, phosphatidylinositols and phosphoethanolamines, and lower levels of Phe-Ile/Leu. Thus, we found metabolites with opposite trends of concentration in the two metabolomic analyses. These metabolites could be considered possible new factors of study in the pathogenesis of MO and associated T2DM in women.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic hepatic disease. Although mostly benign, this disease can evolve into nonalcoholic steatohepatitis (NASH). The stimulator of interferon genes (STING) plays an important role in the immune response against stressed cells, but this protein may also be involved in liver lipogenesis and microbiota composition. In this study, the role of STING in NAFLD was evaluated by RT-qPCR to analyze STING mRNA abundance and by immunohistochemical analysis to evaluate protein expression in liver biopsies from a cohort composed of 69 women with morbid obesity classified according to their liver involvement (normal liver, n = 27; simple steatosis (SS), n = 26; NASH, n = 16). The results showed that STING mRNA expression in the liver increases with the occurrence of NAFLD, specifically in the SS stage in which the degree of steatosis is mild or moderate. Protein analysis corroborated these results. Positive correlations were observed among hepatic STING mRNA abundance and gamma-glutamyl transferase and alkaline phosphatase levels, hepatic Toll-like receptor 9 expression and some circulating microbiota-derived bile acids. In conclusion, STING may be involved in the outcome and progression of NAFLD and may be related to hepatic lipid metabolism. However, further studies are needed to confirm these findings.

Objectives: Substantial levels of residual renal clearance and urine output may occur in patients treated with hemodialysis or hemodiafiltration. However, the relationships among residual renal urea, creatinine, and phosphate clearances, respectively, and between clearances and urine volume have not been well described., Methods: We performed a prospective, cross-sectional study which enrolled hemodialysis and hemodiafiltration patients with a urine volume of >100 mL/day, in whom at least 2 residual renal clearances were obtained over a 6-month observation period. Urine was collected for 24 hours prior to the midweek treatment session and concentrations of urea, creatinine, and phosphate were measured., Results: Thirty-eight patients (24 men, 14 women) with a mean age of 70.4 ± 12.4 (SD) years were included in this analysis. All patients were dialyzed 3 times per week with mean treatment duration of 243 ± 7.89 minutes. Twenty patients were undergoing hemodiafiltration and 18 patients high-flux hemodialysis. In total, 102 dialysis sessions, of which 52 were hemodiafiltration, and urine collections were analyzed. Mean urine volume was 457 ± 254 mL per 24 hours. Residual renal clearance rates of urea (Kr Urea), creatinine (Kr Cr), and phosphate (Kr Phos) were 1.60 ± 0.979, 4.69 ± 3.79, and 1.98 ± 1.36 mL/minute, respectively. Mean ratios of Kr Cr/Kr Urea, Kr Phos/Kr Urea, and Kr Phos/Kr Cr were 2.83 ± 1.21, 1.23 ± 0.387, and 0.477 ± 0.185, respectively. There was a modest correlation between Kr Phos and daily urine volume (r = 0.605, P = .001)., Conclusions: In maintenance hemodialysis and hemodiafiltration patients, residual renal phosphate clearance is approximately 23% higher than residual renal urea clearance. Urine volume is a modestly accurate surrogate for estimating residual renal phosphate clearance, but only when urine volume is <300 mL/day., (Copyright © 2022 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: A high incidence of asthma is prevalent among residents near the Salton Sea, a large inland terminal lake in southern California. This arid region has high levels of ambient particulate matter (PM); yet while high PM levels are often associated with asthma in many environments, it is possible that the rapidly retreating lake, and exposed playa or lakebed, may contribute components with a specific role in promoting asthma symptoms., Objectives: Our hypothesis is that asthma may be higher in residents closest to the Salton Sea due to chronic exposures to playa dust. Playa emissions may be concentrating dissolved material from the lake, with microbial components capable of inducing pulmonary innate immune responses. To test this hypothesis, we used a mouse model of aerosol exposures to assess the effects of playa dust., Methods: From dust collected around the Salton Sea region, aqueous extracts were used to generate aerosols, which were injected into an environmental chamber for mouse exposure studies. We compared the effects of exposure to Salton Sea aerosols, as well as to known immunostimulatory reference materials. Acute 48-h and chronic 7-day exposures were compared, with lungs analyzed for inflammatory cell recruitment and gene expression., Results: Dust from sites nearest to the Salton Sea triggered lung neutrophil inflammation that was stronger at 48-h but reduced at 7-days. This acute inflammatory profile and kinetics resembled the response to innate immune ligands LTA and LPS while distinct from the classic allergic response to Alternaria., Conclusion: Lung inflammatory responses to Salton Sea dusts are similar to acute innate immune responses, raising the possibility that microbial components are entrained in the dust, promoting inflammation. This effect highlights the health risks at drying terminal lakes from inflammatory components in dust emissions from exposed lakebed., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Given that obesity is a major medical problem associated with non-alcoholic fatty liver disease and the lack of studies on postsurgery weight loss according to hepatic histology, we aimed to analyse weight loss indicators according to non-alcoholic steatohepatitis (NASH) presence one and 2 years postsurgery., Materials and Methods: The weight loss pattern of 410 women with severe obesity (SO) was analysed after sleeve gastrectomy (SG, n = 191) and Roux-en-Y gastric bypass (RYGB, n = 219) according to NASH presence at baseline and at 12 and 24 months postsurgery. Weight loss indicators: expected BMI (eBMI), excess BMI loss percentage (%EBMIL), total weight loss percentage (%TWL) and alterable weight loss percentage (%AWL)., Results: Unlike RYGB, after SG, a higher percentage of NASH patients do not reach the eBMI 2 years postsurgery. %TWL and %AWL presented no differences after RYGB despite the presence of NASH. After SG, there is a worse ponderal evolution of all indicators analysed in the presence of NASH. Unlike SG, diabetic patients lose less weight than non-diabetic patients after RYGB. The presence of NASH in diabetics had no impact on weight loss indicators, but in non-diabetics, it had an impact, particularly in the SG group., Conclusion: The presence of NASH suggests a worse weight loss pattern through all the analysed indicators one and 2 years after SG in women. The presence of T2DM appears to result in less weight loss after RYGB, but only non-diabetic women presenting NASH lose less weight that non-diabetic women in the absence of NASH after SG., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Crohn's disease is a debilitating chronic inflammatory disorder of the mammalian gastrointestinal tract. Current interventions using anti-tumour necrosis factor [anti-TNF] biologics show long-term benefit in only half of patients. This study focused on the role of the TNF receptor 1 [TNFR1] in pathogenesis in a TNF-driven model of ileitis., Methods: We studied TNFΔAU-rich element [ARE]/+ [TNFdARE] mice, which develop progressive ileitis similar to Crohn's ileitis. Histopathological analysis and gene expression profiling were used to characterize disease progression from 5 to 16 weeks. Mice with TNFR1 hemizygosity [TNFdARE/R1het] allowed us to assess gene dosage effects. Transcriptional profiling established inflection points in disease progression; inflammatory gene expression increased at 8 weeks with a plateau by 10 weeks, so these were selected as endpoints of treatment using the TNF biologic infliximab and the TNFR1-specific XPro1595. Differences in recruitment of cells in the lamina propria were assessed using flow cytometry., Results: TNFdARE/R1het mice displayed stable long-term protection from disease, associated with decreased recruitment of CD11bhiF4/80lo monocytes and CD11bhiLy6Ghi neutrophils, suggesting an important role of TNFR1 signalling in pathogenesis, and indicating potential benefit from TNFR1-specific intervention. Treatment with infliximab and XPro1595 both showed a similar impact on disease in TNFdARE mice. Importantly, these beneficial effects were greatly surpassed by hemizygosity at the TNFR1 locus., Conclusions: Treatment with either infliximab or XPro1595 produced moderate protection from ileitis in TNFdARE mice. However, hemizygosity at the TNFR1 locus in TNFdARE mice showed far better protection, implicating TNFR1 signalling as a key mediator of TNF-driven disease., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: Major concerns years after the sleeve gastrectomy (SG) include weight regain, development of hiatal hernia (HH) and gastroesophageal reflux disease, with esophagitis and Barrett's esophagus (BE). Both problems could be related, and the incidence of asymptomatic patients is troubling., Objective: To study the incidence of reflux symptoms, esophagitis, BE, HH, and asymptomatic pathology and their relationship with weight regain in patients 5 years after undergoing SG at different bariatric centers in Spain., Setting: Public and private hospitals with bariatric surgery units., Methods: Prospective, multicenter, nonrandomized study involving 13 Spanish hospitals with a cumulative experience of 4,500 patients having undergone the SG procedure and patients who had been subjected to the procedure at least 5 years previously along with preoperative gastroscopy. The clinical history, preoperative gastroscopy, and technical details of the SG were recorded. A specific clinical questionnaire was given that recorded the intake volume, perception of satiety, and gastroesophageal reflux (GER) symptoms. Gastroscopy, pH-metry, and manometry studies were carried out, and the data were analyzed statistically. The study has been authorized by the official Spanish ethics committee CEI/CEIm Hospital Universitario Gran Canaria Dr Negrín (code 2019-216-1)., Results: One hundred and five patients who underwent SG and who had with at least 5 years of follow-up were included. All procedures were performed laparoscopically. The mean age of patients was 51.1 years, and 70.5% were women. The mean characteristics of the SG procedure were a 37.2F probe, at 4.6 cm from the pylorus, and a crura closure was performed in 5 cases. There were no major complications (Clavien-Dindo grade >3) or deaths. The average preoperative body mass index was 46.3 kg/m 2 , the minimum reached was 20.6 kg/m 2 , whereas the average after 5 years was of 34.5 kg/m 2 . GER, HH, and esophagitis symptoms went from 17.1%, 28.6%, and 5.7%, respectively, before the SG to 76%, 30.5%, and 31.4%, respectively, 5 years after the procedure. Symptoms persisted over the years in 37.1% of cases and presented de novo in 52.8% of cases. Fifty-three percent of manometries (n = 27, total 51) and 64% of pH-metries (n = 32, total 53; DeMeester average score was 65) were pathologic 5 years after the procedure. Concerning gastroscopies, 5 years after the procedure, HH was found in 33 patients (30.5% of total) and esophagitis in 32 patients (31.4% of total). Eighty patients (76%) had GER symptoms, and 25 patients (24%) were asymptomatic. Only 1 patient (.9%) developed BE., Conclusions: Our study has confirmed a high rate of both persistent and de novo esophagitis and hiatal hernia, many of which were asymptomatic, 5 years after SG had been performed. Weight regain and a striking increase in gastric capacity are risk factors indicative of esophagitis, even when patients are asymptomatic. We consider a control gastroscopy and the preventive use of proton pump inhibitors necessary in these cases regardless of symptoms. We recommend that a control gastroscopy should be performed in all cases regardless of symptoms 5 years after SG. Further studies are needed to validate these recommendations., (Copyright © 2021 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Nonalcoholic steatohepatitis (NASH) is frequently associated with severe obesity. The liver is the principal storage repository for iron, and the excessive accumulation of this metal may promote hepatic inflammation. Laparoscopic sleeve gastrectomy (LSG) results in weight loss and improvement in comorbidities such as NASH. The aim of this study was to assess the specific NASH-related changes in iron metabolism and to investigate whether these changes are reversed by LSG. We included 150 patients with morbid obesity who provided 12-h fasting blood samples immediately before LSG together with an intraoperative wedge-liver biopsy. Thirty-eight patients with NASH underwent a second blood extraction 12 months postsurgery. Serum samples were collected from a control group comprising 50 healthy volunteers. We found significantly higher serum iron and transferrin concentrations in patients with NASH along with the highest degrees of steatosis, fibrosis, hepatocellular ballooning, and lobular inflammation. However, we did not find any significant accumulation of iron in the hepatic biopsies. Presurgery serum iron concentrations were lower in the patient group than in the control group and increased 1 year postsurgery. Serum ferritin levels showed changes in the opposite direction. We did not observe any significant change in serum transferrin concentrations. These changes were reversed by LSG. We conclude that alterations in serum iron-related variables are related to the severity of NASH in patients with morbid obesity, and these alterations are reversed by LSG. We also found that severe forms of NASH can be found in the absence of increased iron stores., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Background: Engineered stone silicosis is an emerging disease in many countries worldwide produced by the inhalation of respirable dust of engineered stone. This silicosis has a high incidence among young workers, with a short latency period and greater aggressiveness than silicosis caused by natural materials. Although the silica content is very high and this is the key factor, it has been postulated that other constituents in engineered stones can influence the aggressiveness of the disease. Different samples of engineered stone countertops (fabricated by workers during the years prior to their diagnoses), as well as seven lung samples from exposed patients, were analyzed by multiple techniques., Results: The different countertops were composed of SiO 2 in percentages between 87.9 and 99.6%, with variable relationships of quartz and cristobalite depending on the sample. The most abundant metals were Al, Na, Fe, Ca and Ti. The most frequent volatile organic compounds were styrene, toluene and m-xylene, and among the polycyclic aromatic hydrocarbons, phenanthrene and naphthalene were detected in all samples. Patients were all males, between 26 and 46 years-old (average age: 36) at the moment of the diagnosis. They were exposed to the engineered stone an average time of 14 years. At diagnosis, only one patient had progressive massive fibrosis. After a follow-up period of 8 ± 3 years, four patients presented progressive massive fibrosis. Samples obtained from lung biopsies most frequently showed well or ill-defined nodules, composed of histiocytic cells and fibroblasts without central hyalinization. All tissue samples showed high proportion of Si and Al at the center of the nodules, becoming sparser at the periphery. Al to Si content ratios turned out to be higher than 1 in two of the studied cases. Correlation between Si and Al was very high (r = 0.93)., Conclusion: Some of the volatile organic compounds, polycyclic aromatic hydrocarbons and metals detected in the studied countertop samples have been described as causative of lung inflammation and respiratory disease. Among inorganic constituents, aluminum has been a relevant component within the silicotic nodule, reaching atomic concentrations even higher than silicon in some cases. Such concentrations, both for silicon and aluminum showed a decreasing tendency from the center of the nodule towards its frontier., (© 2021. The Author(s).)

Cancer stem cells, in contrast to their more differentiated daughter cells, can endure genotoxic insults, escape apoptosis, and cause tumor recurrence. Understanding how normal adult stem cells survive and go to quiescence may help identify druggable pathways that cancer stem cells have co-opted. In this study, we utilize a genetically tractable model for stem cell survival in the Drosophila gonad to screen drug candidates and probe chemical-genetic interactions. Our study employs three levels of small molecule screening: (1) a medium-throughput primary screen in male germline stem cells (GSCs), (2) a secondary screen with irradiation and protein-constrained food in female GSCs, and (3) a tertiary screen in breast cancer organoids in vitro. Herein, we uncover a series of small molecule drug candidates that may sensitize cancer stem cells to apoptosis. Further, we have assessed these small molecules for chemical-genetic interactions in the germline and identified the NF-κB pathway as an essential and druggable pathway in GSC quiescence and viability. Our study demonstrates the power of the Drosophila stem cell niche as a model system for targeted drug discovery.

This study focuses on the development of a new hybrid biological material to be applied in the production of electrical energy. These organo-metallic cells are constituted by cyanobacteria ( Fischerella muscicola ) and silver nanoparticles (AgNPs). AgNPs were obtained by green synthesis using the extract of the fruit of the Berberis hallii plant as reducing agent with two different concentrations of silver nitrate (AgNO 3 ), 1 and 10 mM. The morphology, physicochemical and electrical properties of the cyanobacteria with and without AgNPs were evaluated. To verify the efficacy of this new material, and the effect of the medium used, Nitrofoska or BG-11, the growth kinetics was evaluated by UV-vis up to t = 63 d with and without renewal of the culture medium and O 2 /CO 2 exchange. Through morphological characterizations of Fischerella muscicola it was possible to identify the presence of an associated bacterium identified using molecular techniques as Pseudomona guguanensi that could act as a supporting organism in the growth of this cyanobacteria. The studies carried out did not shown cell toxicity for the cultures that have AgNPs and on the other hand, it was observed that the hybrid cells (Cy-AgNPs) are electron carriers recording an increase of up to 57% and 18% in their electrical potential with BG-11 and Nitrofoska culture media, respectively and an increase in the anodic current peak of 6.5% of Cy-AgNPs respect to only F. musicola., (© 2021 IOP Publishing Ltd.)

Nutrient sensing plays important roles in promoting satiety and maintaining good homeostatic control. Taste receptors (TAS) are located through the gastrointestinal tract, and recent studies have shown they have a relationship with metabolic disorders. The aim of this study was to analyze the jejunal expression of TAS1R2, TAS1R3, TAS2R14 and TAS2R38 in women with morbid obesity, first classified according to metabolic syndrome presence (MetS; n = 24) or absence (non-MetS; n = 45) and then classified according to hepatic histology as normal liver ( n = 28) or nonalcoholic fatty liver disease ( n = 41). Regarding MetS, we found decreased expression of TAS2R14 in MetS patients. However, when we subclassified patients according to liver histology, we did not find differences between groups. We found negative correlations between glucose levels, triglycerides and MetS with TAS1R3 expression. Moreover, TAS2R14 jejunal expression correlated negatively with the presence of MetS and ghrelin levels and positively with the jejunal Toll-like receptor (TLR)4, peroxisome proliferator-activated receptor (PPAR)-γ, and interleukin (IL)-10 levels. Furthermore, TAS2R38 expression correlated negatively with TLR9 jejunal expression and IL-6 levels and positively with TLR4 levels. Our findings suggest that metabolic dysfunctions such as MetS trigger downregulation of the intestinal TASs. Therefore, taste receptors modulation could be a possible therapeutic target for metabolic disorders.

A 77-year-old male presented to the Emergency Department due to a clinical and radiological pattern of intestinal obstruction. An abdominal computed tomography (CT) scan revealed a dilatation of the jejunum loops with a change in bowel caliber in the proximal ileum and segmental edema of the intestinal wall. An urgent laparotomy was performed which revealed adhesions between intestinal loops and an intraluminal mass in the proximal ileum with a change in the bowel caliber. The affected segment of the proximal ileum measuring 20 cm was resected and a small-bowel manual termino-terminal anastomosis was performed. The patient was discharged seven days following the surgery.

Secreted frizzled-related protein 5 (SFRP5), an antagonist of the noncanonical WNT pathway, has a controversial role in liver disease. The aim of this study was to analyze the role of SFRP5 and the noncanonical WNT pathway in nonalcoholic fatty liver disease (NAFLD). Plasma SFRP5 levels were determined by ELISA in women with normal weight (NW; n = 20) and morbid obesity (MO; n = 69). Women with MO were subclassified according to hepatic histology into normal liver (NL; n = 28), NAFLD ( n = 41) (simple steatosis (SS; n = 24), and nonalcoholic steatohepatitis (NASH; n = 17)). We used RT-qPCR to evaluate the hepatic mRNA expression of SFRP5, WNT5A, and JNK in women with MO. SFRP5 levels were lower in NW than in MO patients who underwent a very low-calorie diet before surgery. Hepatic SFRP5 mRNA expression was higher in SS than in NL or NASH; additionally, patients with hepatic inflammation or ballooning presented lower SFRP5 abundance. WNT5A and JNK expression was enhanced in NAFLD compared with NL. In conclusion, circulating SFRP5 levels depend on the diet, and hepatic SFRP5 seems to have a protective role in the first steps of NAFLD; however, SFRP5 could be deregulated in an advanced stage while WNT5A and JNK are activated, promoting liver damage.

Recent studies suggest a link between pro-neurotensin (pro-NT) and nonalcoholic fatty liver disease (NAFLD), but the published data are conflicting. Thus, we aimed to analyze pro-NT levels in women with morbid obesity (MO) and NAFLD to investigate if this molecule is involved in NAFLD and liver lipid metabolism. Plasma levels of pro-NT were determined in 56 subjects with MO and 18 with normal weight (NW). All patients with MO were subclassified according to their liver histology into the normal liver (NL, n = 20) and NAFLD ( n = 36) groups. The NAFLD group had 17 subjects with simple steatosis (SS) and 19 with nonalcoholic steatohepatitis (NASH). We used a chemiluminescence sandwich immunoassay to quantify pro-NT in plasma and RT-qPCR to evaluate the hepatic mRNA levels of several lipid metabolism-related genes. We reported that pro-NT levels were significantly higher in MO with NAFLD than in MO without NAFLD. Additionally, pro-NT levels were higher in NASH patients than in NL. The hepatic expression of lipid metabolism-related genes was found to be altered in NAFLD, as previously reported. Additionally, although pro-NT levels correlated with LDL, there was no association with the main lipid metabolism-related genes. These findings suggest that pro-NT could be related to NAFLD progression.

The pathogenic mechanisms underlying nonalcoholic fatty liver disease (NAFLD) are beginning to be understood. RUNX1 is involved in angiogenesis, which is crucial in inflammation, but its role in nonalcoholic steatohepatitis (NASH) remains unclear. The aim of this study was to analyze RUNX1 mRNA hepatic and jejunal abundance in women with morbid obesity (MO) and NAFLD. RUNX1, lipid metabolism-related genes, and TLRs in women with MO and normal liver (NL, n = 28), NAFLD ( n = 41) (simple steatosis (SS, n = 24), or NASH ( n = 17)) were analyzed by RT-qPCR. The RUNX1 hepatic expression was higher in SS than in NL or NASH, as likewise confirmed by immunohistochemistry. An increased expression of hepatic FAS was found in NAFLD. Hepatic RUNX1 correlated positively with FAS. There were no significant differences in the jejunum RUNX1 expressions in the different groups. Jejunal FXR expression was lower in NASH than in NL, while the TLR9 expression increased as NAFLD progressed. Jejunal RUNX1 correlated positively with jejunal PPARγ, TLR4, and TLR5. In summary, the hepatic expression of RUNX1 seems to be involved in the first steps of the NAFLD process; however, in NASH, it seems to be downregulated. Our findings provide important insights into the role of RUNX1 in the context of NAFLD/NASH, suggesting a protective role.

Background & Aims: A holistic insight on the relationship between obesity and metabolic dysfunction-associated fatty liver disease is an unmet clinical need. Omics investigations can be used to investigate the multifaceted role of altered mitochondrial pathways to promote nonalcoholic steatohepatitis, a major risk factor for liver disease-associated death. There are no specific treatments but remission via surgery might offer an opportunity to examine the signaling processes that govern the complex spectrum of chronic liver diseases observed in extreme obesity. We aim to assess the emerging relationship between metabolism, methylation and liver disease., Methods: We tailed the flow of information, before and after steatohepatitis remission, from biochemical, histological, and multi-omics analyses in liver biopsies from patients with extreme obesity and successful bariatric surgery. Functional studies were performed in HepG2 cells and primary hepatocytes., Results: The reversal of hepatic mitochondrial dysfunction and the control of oxidative stress and inflammatory responses revealed the regulatory role of mitogen-activated protein kinases. The reversible metabolic rearrangements leading to steatohepatitis increased the glutaminolysis-induced production of α-ketoglutarate and the hyperactivation of mammalian target of rapamycin complex 1. These changes were crucial for the adenosine monophosphate-activated protein kinase/mammalian target of rapamycin-driven pathways that modulated hepatocyte survival by coordinating apoptosis and autophagy. The signaling activity of α-ketoglutarate and the associated metabolites also affected methylation-related epigenomic remodeling enzymes. Integrative analysis of hepatic transcriptome signatures and differentially methylated genomic regions distinguished patients with and without steatohepatitis., Conclusion: We provide evidence supporting the multifaceted potential of the increased glutaminolysis-induced α-ketoglutarate production and the mammalian target of rapamycin complex 1 dysregulation as a conceivable source of the inefficient adaptive responses leading to steatohepatitis., Lay Summary: Steatohepatitis is a frequent and threatening complication of extreme obesity without specific treatment. Omics technologies can be used to identify therapeutic targets. We highlight increased glutaminolysis-induced α-ketoglutarate production as a potential source of signals promoting and exacerbating steatohepatitis., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Glucagon-like peptide-2 (GLP-2) is a gastrointestinal hormone released in response to nutritional intake that exerts a wide range of effects by activating GLP-2 receptors. In addition to its intestinotrophic effects, GLP-2 also positively influences glucose metabolism under conditions of obesity, but the mechanisms behind this remain unclear. Here, we have investigated the molecular role of the GLP-2/GLP-2 receptor axis in energetic metabolism, focusing on its potential modulatory effects on adipose tissue., Experimental Approach: Physiological measurements (body weight, food intake, locomotor activity, and energy expenditure) and metabolic studies (glucose and insulin tolerance tests) were performed on lean and obese mice treated with the protease-resistant GLP-2 analogue teduglutide., Key Results: Acute but not chronic centrally administered teduglutide decreased food intake and weight-gain. By contrast, chronic activation of peripheral GLP-2 receptors increased body weight-independent glucose tolerance and had anti-inflammatory effects on visceral adipose tissue. Using a gene silencing approach, we found that adipose tissue is necessary for these beneficial effects of teduglutide. Finally, teduglutide regulates the inflammatory state and acts as an anabolic signal in human adipocytes., Conclusion and Implications: Overall, our data identify adipose tissue as a new, clinically relevant, site of action for GLP-2 activity in obesity., Linked Articles: This article is part of a themed issue on Cellular metabolism and diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.10/issuetoc., (© 2020 The British Pharmacological Society.)

Background: Most relative weight-loss metrics follow the formula "Weight loss(%) = 100 · (Initial BMI - Final BMI) / (Initial BMI-a)," where a is the reference point that defines the metric. The percentage of total weight loss (%TWL, a = 0) and percentage of excess weight loss (%EWL, a = 25) are influenced by a patient's initial weight. Recently, the percentage of alterable weight loss metric (%AWL, a = 13) has been reported to produce initial-weight-independent outcomes., Objectives: This study aimed to replicate the methodology used for %AWL determination in a Mediterranean cohort of bariatric patients., Settings: Multicenter study in 10 large hospitals in Spain., Methods: Two large prospective databases were retrospectively searched for all primary laparoscopic gastric bypass patients with 2 years of follow-up. Outcomes at nadir were expressed and analyzed with 26 different metrics (a from 0 to 25), looking for the metric whose outcomes produced (1) the lowest coefficient of variation, (2) no differences between initially lighter and heavier patients, and (3) no correlation with patients' initial BMI., Results: A cohort of 1793 patients was stratified into 4 gender-age groups: younger women (YW, n = 733), older women (OW, n = 674), younger men (YM, n = 197), and older men (OM, n = 189). The calculations suggested an optimal reference point of 18 kg/m 2 , defining a new metric (percentage of Mediterranean alterable weight loss, %MAWL). When %TWL, %EWL, %AWL, and %MAWL were tested on the whole sample, only %MAWL produced initial-weight-independent results., Conclusions: In our Mediterranean cohort of patients, a reference point of 18 (and not 13) yielded initial-weight-independent outcomes.