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Abstract Introduction We aimed to describe the risk profile of respiratory syncytial virus (RSV) infections among adults ≥ 60 years in Valladolid from January 2010 to August 2022, and to compare them with influenza and COVID-19 controls. Methods This was a retrospective cohort study of all laboratory-confirmed RSV infections identified in centralized microbiology database during a 12-year period. We analyzed risk factors for RSV hospitalization and severity (length of stay, intensive care unit admission, in-hospital death or readmission

Introducción: La disfagia es una condición que afecta la eficiencia de la deglución de los alimentos. Mundialmente, una tercera parte de los ancianos padece de algún grado de disfagia, representando un alto riesgo de malnutrición debido a que las carentes opciones alimenticias destinadas a este público no satisfacensus requerimientos nutricionales. Objetivo: Esta investigación tuvo como objetivo desarrollar formulaciones de almuerzos con textura modificada para pacientes con disfagia, a partir de materias primas típicas dominicanas. Materiales y métodos: Se realizaron dos almuerzos de diferentes composiciones [sancocho (S) y arroz con habichuelas y carnes (AHC)] y viscosidades (néctar: 51-350 mPa.s; miel: 351-1,750 mPa.s y pudín: 1,751- 2,500 mPa.s), a los cuales se les evaluó el análisis químico aproximado y la aceptación sensorial. Se utilizó un diseño completamente al azar, bajo arreglo factorial (2 x 3). Resultados: Se evidenciaron diferencias entre las medias de los tratamientos (p

Abstract To evaluate the prognostic value of biomarkers from peripheral blood obtained as routine laboratory assessment for overall survival in a cohort of stage III non-small cell lung cancer (NSCLC) patients treated with definitive radiochemotherapy at a high-volume cancer center. Seven blood biomarkers from 160 patients treated with definitive radiochemotherapy for stage III NSCLC were analyzed throughout the course treatment. Parameters were preselected using univariable and multivariable proportional hazards analysis and were assessed for internal validity using leave-one-out cross validation. Cross validated classifiers including biomarkers in addition to important clinical parameters were compared with classifiers containing the clinical parameters alone. An increased C-reactive protein (CRP) value in the final week of radiotherapy was found as a prognostic factor for overall survival, both as a continuous (HR 1.099 (1.038–1.164), p

Methane (CH4) and carbon dioxide (CO2) emissions from tropical freshwater ecosystems have been understudied, particularly in terms of their interaction with limnological dynamics, their cycling, and the emission mechanisms of CH4. To help reduce that knowledge gap, this study addressed these processes in Valle de Bravo (VB), a tropical (19° 11. 65′ N) reservoir lake, that provides water supply to Mexico City metropolitan area. CH4 and CO2 concentrations and emissions from VB were measured during four field campaigns distributed along the annual limnological cycle of the reservoir. Dissolved CH4 concentration varied over four orders of magnitude (0.015–176.808 μmol L−1), and dissolved CO2 varied from below atmospheric saturation (15.062 μmol L−1) to 10 times that concentration (219.505 μmol L−1). CH4 fluxes ranged from 23.25 to 1220.80 μmol m−2 day−1, while CO2 fluxes ranged from −60.11 to 254.99 mmol m−2 day−1. Seasonal monitoring also allowed the assessment of the annual emissions as well as the greenhouse gas (GHG) storage during thermal stratification, which accounted for >58% of the total GHG annual emissions from VB. Overall, VB is a source of GHG, and its major contribution is the CH4 released during the autumn overturn. HIGHLIGHTS The limnological dynamics of freshwater bodies have important effects on their GHG emissions.; Because of this, CH4 emissions from VB varied seasonally by two orders of magnitude (23.25–1,220.80 μmol m−2 day−1).; Overall, VB was a net source of CH4 and CO2, but during stratification, it was a net sink of both GHGs.; Most of the emissions were associated with the storage during the stratification period.;

Abstract Background The COVID-19 pandemic disrupted daily life, economies, and health, prompting strict government measures, including nationwide lockdowns and school closures in Uganda, resulting in significant academic setbacks for adolescents. The coping strategies employed by school-going adolescents in Uganda amidst the COVID-19 pandemic remain inadequately understood. This study aimed to assess the coping strategies adopted by school-going adolescents (early, middle and late adolescents) in the Manafwa watershed, recognized as one of Uganda’s most vulnerable regions, during the COVID-19 pandemic. Methods A cross sectional study design was conducted from I5th May, 2023 to 30th June, 2023 on 762 school going adolescents from government-aided secondary schools within the Manafwa watershed area. The adolescent version of the KidCope tool was used to evaluate adolescents’ coping strategies. Factor analysis identified correlations among adolescents’ coping strategies. Independent Samples t-Test and One-Way Variance of Analysis (ANOVA) was used for comparing the mean score differences of the coping strategies among the gender and adolescents’ stages respectively. Results Majority (n = 141, 36.2%) of the participants employed adaptive coping followed by negative-emotion coping (n = 127, 32.6%) and avoidant coping (n = 122, 31.3%). Females employed statistically higher resignation as a coping strategy compared to males, (mean of 1.2 vs. 1.0, respectively; P = 0.026). A higher proportion (n = 88, 69.3%) of middle age adolescents employed negative-emotion regulation (P-value = 0.040). However, those in early adolescence significantly utilized distraction as a coping strategy more than those in middle adolescence (mean difference = 0.36, p = 0.013). Conclusion During the pandemic, majority of school-going adolescents employed adaptive coping mechanisms, including positive emotional regulation and social support. However, compared to males, females employed resignation more frequently. Moreover, middle-aged adolescents had a greater propensity for negative emotion copying. Findings from this study contribute valuable information for the development of targeted interventions and support mechanisms for adolescents facing unprecedented challenges.

Abstract Background Targeting mucosal immunity of the gut, which is known to provide antigen processing, while avoiding excessive or unnecessary inflammation, was tested as a way to modulate COVID-19 severity. Methods Randomized open-label trial in 204 adults hospitalized with non-critical COVID-19 who received for 14 days in addition to standard of care (SOC) degalactosylated bovine glycoproteins formulations of either MAF capsules (MAF group) or M capsules (M group) or SOC only (control group). Results Median recovery time when patients did not require supplemental oxygen was 6 days in both study groups compared to 9 days in the control (MAF vs. control; P = 0.020 and M vs. control; P = 0.004). A greater reduction in mortality was seen in the MAF group compared to the control by day 14 (8.3% vs. 1.6%; P = 0.121) and by day 29 (15.3% vs. 3.2%; P = 0.020), and similarly in the M group by day 14 (8.3% vs. 2.9%; P = 0.276) and by day 29 (15.3% vs. 2.9%; P = 0.017). The proportion of those who had baseline absolute lymphocyte count (ALC) lower than 0.8 × 109/L was 13/63 (20.6%), 17/69 (24.6%), and 18/72 (25.0%) of patients in MAF, M, and control group respectively. Day 29 mortality among these lymphopenic patients was three times higher than for the intent-to-treat population (21% vs. 7%) and consisted in above subgroups: 2/13 (15%), 2/17 (12%), and 6/18 (33%) of patients. The decreased mortality in both study subgroups correlated with greater ALC restoration above 0.8 × 109/L level seen on day 14 in 91% (11/12) and 87.5% (14/16) of survivors in MAF and M subgroups respectively compared to 53.3% (8/15) of survivors in control subgroup. Incidences of any ALC decrease below the baseline level on day 14 occurred in 25.4% of patients in the MAF group and 29.0% of patients in the M group compared to 45.8% in control and ALC depletion by ≥ 50% from the baseline level consisted of 7.9%, 5.8%, and 15.3% of cases in these groups respectively. Conclusion This study showed that both study agents prevented ALC depletion and accelerated its restoration, which is believed to be one of the mechanisms of improved crucial clinical outcomes in hospitalized COVID-19 patients. Trial registration The trial was registered after the trial start in ClinicalTrials.gov NCT04762628, registered 21/02/2021, https://www.clinicaltrials.gov/ct2/show/NCT04762628 .

Abstract Magnetic resonance (MR) acquisitions of the torso are frequently affected by respiratory motion with detrimental effects on signal quality. The motion of organs inside the body is typically decoupled from surface motion and is best captured using rapid MR imaging (MRI). We propose a pipeline for prospective motion correction of the target organ using MR image navigators providing absolute motion estimates in millimeters. Our method is designed to feature multi-nuclear interleaving for non-proton MR acquisitions and to tolerate local transmit coils with inhomogeneous field and sensitivity distributions. OpenCV object tracking was introduced for rapid estimation of in-plane displacements in 2D MR images. A full three-dimensional translation vector was derived by combining displacements from slices of multiple and arbitrary orientations. The pipeline was implemented on 3 T and 7 T MR scanners and tested in phantoms and volunteers. Fast motion handling was achieved with low-resolution 2D MR image navigators and direct implementation of OpenCV into the MR scanner’s reconstruction pipeline. Motion-phantom measurements demonstrate high tracking precision and accuracy with minor processing latency. The feasibility of the pipeline for reliable in-vivo motion extraction was shown on heart and kidney data. Organ motion was manually assessed by independent operators to quantify tracking performance. Object tracking performed convincingly on 7774 navigator images from phantom scans and different organs in volunteers. In particular the kernelized correlation filter (KCF) achieved similar accuracy (74%) as scored from inter-operator comparison (82%) while processing at a rate of over 100 frames per second. We conclude that fast 2D MR navigator images and computer vision object tracking can be used for accurate and rapid prospective motion correction. This and the modular structure of the pipeline allows for the proposed method to be used in imaging of moving organs and in challenging applications like cardiac magnetic resonance spectroscopy (MRS) or magnetic resonance imaging (MRI) guided radiotherapy.

IntroductionCytomegaloviruses (CMVs) extensively reorganize the membrane system of the cell and establish a new structure as large as the cell nucleus called the assembly compartment (AC). Our previous studies on murine CMV (MCMV)-infected fibroblasts indicated that the inner part of the AC contains rearranged early endosomes, recycling endosomes, endosomal recycling compartments and trans-Golgi membrane structures that are extensively tubulated, including the expansion and retention of tubular Rab10 elements. An essential process that initiates Rab10-associated tubulation is cargo sorting and retrieval mediated by SNX27, Retromer, and ESCPE-1 (endosomal SNX-BAR sorting complex for promoting exit 1) complexes.ObjectiveThe aim of this study was to investigate the role of SNX27:Retromer:ESCPE-1 complexes in the biogenesis of pre-AC in MCMV-infected cells and subsequently their role in secondary envelopment and release of infectious virions.ResultsHere we show that SNX27:Retromer:ESCPE1-mediated tubulation is essential for the establishment of a Rab10-decorated subset of membranes within the pre-AC, a function that requires an intact F3 subdomain of the SNX27 FERM domain. Suppression of SNX27-mediated functions resulted in an almost tenfold decrease in the release of infectious virions. However, these effects cannot be directly linked to the contribution of SNX27:Retromer:ESCPE-1-dependent tubulation to the secondary envelopment, as suppression of these components, including the F3-FERM domain, led to a decrease in MCMV protein expression and inhibited the progression of the replication cycle.ConclusionThis study demonstrates a novel and important function of membrane tubulation within the pre-AC associated with the control of viral protein expression.

IntroductionRespiratory viral infections (RVIs) are a major global contributor to morbidity and mortality. The susceptibility and outcome of RVIs are strongly age-dependent and show considerable inter-population differences, pointing to genetically and/or environmentally driven developmental variability. The factors determining the age-dependency and shaping the age-related changes of human anti-RVI immunity after birth are still elusive. MethodsWe are conducting a prospective birth cohort study aiming at identifying endogenous and environmental factors associated with the susceptibility to RVIs and their impact on cellular and humoral immune responses against the influenza A virus (IAV), respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The MIAI birth cohort enrolls healthy, full-term neonates born at the University Hospital Würzburg, Germany, with follow-up at four defined time-points during the first year of life. At each study visit, clinical metadata including diet, lifestyle, sociodemographic information, and physical examinations, are collected along with extensive biomaterial sampling. Biomaterials are used to generate comprehensive, integrated multi-omics datasets including transcriptomic, epigenomic, proteomic, metabolomic and microbiomic methods. DiscussionThe results are expected to capture a holistic picture of the variability of immune trajectories with a focus on cellular and humoral key players involved in the defense of RVIs and the impact of host and environmental factors thereon. Thereby, MIAI aims at providing insights that allow unraveling molecular mechanisms that can be targeted to promote the development of competent anti-RVI immunity in early life and prevent severe RVIs.Clinical trial registrationhttps://drks.de/search/de/trial/, identifier DRKS00034278.

Understanding how corruption affects the relationship between natural resources and growth has profound implications for sustainable development goals in Sub-Saharan Africa (SSA). This study investigates the nexus between natural resources, economic growth, and corruption in SSA from 1985 to 2022, by employing a Panel Smooth Transition Regression model. Results indicate that corruption distorts natural resources and lowers economic growth. The magnitude of the effect of corruption depends on the type of corruption. The impact of political corruption is more relevant than the others form of corruption. In a low corruption regime, mineral, oil, and forest resources do not affect growth; (b) in a high corruption regime, oil and forest resources hinder growth whereas mineral resources lead to higher economic growth. The analysis highlights the need for policy measures that encourage sustainable economic development and promoting reinforcement of institutional quality.

Pathogenic variants in the leucine zipper-like transcriptional regulator 1 gene (LZTR1) have been identified in schwannomatosis and Noonan syndrome. Here, we expand the phenotype spectrum of LZTR1 variants. We identified four loss-of-function heterozygous LZTR1 variants in five children with multiple café au lait macules and one adult with multiple café au lait macules and axillar freckling, by applying gene panel analysis in four families. The three LZTR1 variants, namely, c.184del/p.Glu62Serfs*39, c.1927C T/ p.Arg340* had been previously reported in a patient with schwannomatosis. Similar to what is known from other LZTR1-associated conditions, penetrance of the skin manifestations was reduced in two carriers of the familial variants. Our study expands the LZTR1 phenotype to the presence of isolated café au lait macules with or without freckling. Thus, variants in the LZTR1 gene should be considered in patients with multiple café au lait macules.

The countries of the Middle East and North Africa (MENA) have only recently discovered their modern industrial heritage as an object of conservation and future development. Through an in-depth analysis of four industrial sites in Egypt and Iran, testifying to a designated modern era, this article documents the complex historical process of industrialization and its political and economic background. Building on fieldwork, archive studies, workshops, and interviews, the article explores how built structures of modern industrial sites signify the multi-facetted, symbiotic, and exploitative international exchange behind the modernization of economies in the region. In the face of many obstacles to the conservation of this heritage, ranging from incomplete listings and ineffectual policies to high development pressures on urban land, this article aims to transcend the current Eurocentrism in industrial heritage research and practice, and encourage regional claims on this significant heritage.

Abstract Background Low and middle-income countries remain disproportionately affected by high rates of child mortality. Clinical practice guidelines are essential clinical tools supporting implementation of effective, safe, and cost-effective healthcare. High-quality evidence-based guidelines play a key role in improving clinical management to impact child mortality. We aimed to identify and assess the quality of guidelines for newborn and child health published in South Africa, Nigeria and Malawi in the last 5 years (2017–2022). Methods We searched relevant websites (June–July 2022), for publicly available national and subnational de novo or adapted guidelines, addressing newborn and child health in the three countries. Pairs of reviewers independently extracted information from eligible guidelines (scope, topic, target population and users, responsible developers, stakeholder consultation process, adaptation description, assessment of evidence certainty). We appraised guideline quality using the Appraisal of Guidelines for Research & Evaluation (AGREE II) instrument. Results We identified 40-guidelines from the three countries. Of these, 8/40 reported being adopted from a parent guideline. More guidelines (n = 19) provided guidance on communicable diseases than on non-communicable diseases (n = 8). Guidelines were most often developed by national health ministries (n = 30) and professional societies (n = 14). Eighteen guidelines reported on stakeholder consultation; with Nigeria (10/11) and Malawi (3/6) faring better than South Africa (5/23) in reporting this activity. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used in 1/7 guidelines that reported assessing certainty of evidence. Overall guidelines scored well on two AGREE II domains: scope and purpose median (IQR) score 68% (IQR 47–83), and clarity of presentation 81% (67–94). Domains critical for ensuring credible guidance scored below 20%: rigour of development 11% (4–32) and editorial independence 6% (0–27). Conclusion National ministries and professional societies drive guideline activities in Malawi, Nigeria and South Arica. However, the methods and reporting do not adhere to global standards. We found low AGREE II scores for rigour of guideline development and editorial independence and limited use of GRADE or adaptation methods. This undermines the credibility of available guidelines to support evidence-informed care. Our findings highlight the importance of ongoing efforts to strengthen partnerships, capacity, and support for guideline development.

Abstract Acetylcarnitine is an essential metabolite for maintaining metabolic flexibility and glucose homeostasis. The in vivo behavior of muscle acetylcarnitine content during exercise has not been shown with magnetic resonance spectroscopy. Therefore, this study aimed to explore the behavior of skeletal muscle acetylcarnitine during rest, plantar flexion exercise, and recovery in the human gastrocnemius muscle under aerobic conditions. Ten lean volunteers and nine overweight volunteers participated in the study. A 7 T whole-body MR system with a double-tuned surface coil was used to acquire spectra from the gastrocnemius medialis. An MR-compatible ergometer was used for the plantar flexion exercise. Semi-LASER-localized 1H MR spectra and slab-localized 31P MR spectra were acquired simultaneously in one interleaved exercise/recovery session. The time-resolved interleaved 1H/31P MRS acquisition yielded excellent data quality. A between-group difference in acetylcarnitine metabolism over time was detected. Significantly slower τPCr recovery, τPCr on-kinetics, and lower Qmax in the overweight group, compared to the lean group was found. Linear relations between τPCr on-kinetics, τPCr recovery, VO2max and acetylcarnitine content were identified. In conclusion, we are the first to show in vivo changes of skeletal muscle acetylcarnitine during acute exercise and immediate exercise recovery with a submaximal aerobic workload using interleaved 1H/31P MRS at 7 T.

Abstract Human cytomegalovirus (HCMV) is a widespread pathogen that in immunocompromised hosts can cause life-threatening disease. Studying HCMV-exposed monocyte-derived dendritic cells by single-cell RNA sequencing, we observe that most cells are entered by the virus, whereas less than 30% of them initiate viral gene expression. Increased viral gene expression is associated with activation of the stimulator of interferon genes (STING) that usually induces anti-viral interferon responses, and with the induction of several pro- (RHOB, HSP1A1, DNAJB1) and anti-viral (RNF213, TNFSF10, IFI16) genes. Upon progression of infection, interferon-beta but not interferon-lambda transcription is inhibited. Similarly, interferon-stimulated gene expression is initially induced and then shut off, thus further promoting productive infection. Monocyte-derived dendritic cells are composed of 3 subsets, with one being especially susceptible to HCMV. In conclusion, HCMV permissiveness of monocyte-derived dendritic cells depends on complex interactions between virus sensing, regulation of the interferon response, and viral gene expression.

Abstract Atopic dermatitis (AD) is a chronic, relapsing immunoinflammatory skin condition characterized by sensations such as pruritis, pain, and neuronal hypersensitivity. The mechanisms underlying these sensations are multifactorial and involve complex crosstalk among several cutaneous components. This review explores the role these components play in the pathophysiology of atopic dermatitis. In the skin intercellular spaces, sensory nerves interact with keratinocytes and immune cells via myriad mediators and receptors. These interactions generate action potentials that transmit pruritis and pain signals from the peripheral nervous system to the brain. Keratinocytes, the most abundant cell type in the epidermis, are key effector cells, triggering crosstalk with immune cells and sensory neurons to elicit pruritis, pain, and inflammation. Filaggrin expression by keratinocytes is reduced in atopic dermatitis, causing a weakened skin barrier and elevated skin pH. Fibroblasts are the main cell type in the dermis and, in atopic dermatitis, appear to reduce keratinocyte differentiation, further weakening the skin barrier. Fibroblasts and mast cells promote inflammation while dermal dendritic cells appear to attenuate inflammation. Inflammatory cytokines and chemokines play a major role in AD pathogenesis. Type 2 immune responses typically generate pruritis, and the type 1 and type 3 responses generate pain. Type 2 responses and increased skin pH contribute to barrier dysfunction and promote dysbiosis of the skin microbiome, causing the proliferation of Staphyloccocus aureus. In conclusion, understanding the dynamic interactions between cutaneous components in AD could drive the development of therapies to improve the quality of life for patients with AD.

Common variable immunodeficiency is a heterogeneous symptomatic group of inborn errors of immunity that mainly affects antibodies production and/or function, predisposing patients to recurrent and severe infections. More than half of them usually develop autoimmunity, lymphoproliferation, enteropathy, and malignancies. Among these conditions, chronic lung disease such as granulomatous–lymphocytic interstitial lung disease is one of the leading causes of death in these patients. Recently, many genes that play a key role in B and T cells’ development, maintenance, and/or cytokines signaling pathways have been implicated in the pathogenesis of the disease. Here, we describe the first Argentinian patient presenting with common variable immunodeficiency and granulomatous–lymphocytic interstitial lung disease, harboring two in cis heterozygous variants in the SOCS1 gene.

Background: The technological applications of radiofrequency electromagnetic fields (RF-EMF) have been steadily increasing since the 1950s exposing large proportions of the population. The World Health Organization (WHO) is assessing the potential health effects of exposure to RF-EMF. Objectives: To systematically assess the effects of exposure to RF-EMF on self-reported non-specific symptoms in human subjects and to assess the accuracy of perceptions of presence or absence of RF-EMF exposure. Methods: Eligibility criteria: experimental studies carried out in the general population and in individuals with idiopathic environmental intolerance attributed to EMF (IEI-EMF), in any language.Information sources: Medline, Web of Science, PsycInfo, Cochrane Library, Epistemonikos, Embase and EMF portal, searched till April 2022.Risk of Bias (ROB): we used the RoB tool developed by OHAT adapted to the topic of this review.Synthesis of results: we synthesized studies using random effects meta-analysis and sensitivity analyses, where appropriate. Results: Included studies: 41 studies were included, mostly cross over trials and from Europe, with a total of 2,874 participants.Synthesis of results: considering the primary outcomes, we carried out meta-analyses of 10 exposure-outcomes pairs. All evidence suggested no or small non-significant effects of exposure on symptoms with high (three comparisons), moderate (four comparisons), low (one comparison) and very low (two comparisons) certainty of evidence. The effects (standard mean difference, where positive values indicate presence of symptom being exposed) in the general population for head exposure were (95% confidence intervals) 0.08 (−0.07 to 0.22) for headache, −0.01 (−0.22 to 0.20) for sleeping disturbances and 0.13 (−0.51 to 0.76) for composite symptoms; and for whole-body exposure: 0.09 (−0.35 to 0.54), 0.00 (−0.15 to 0.15) for sleeping disturbances and −0.05 (−0.17 to 0.07) for composite symptoms. For IEI-EMF individuals SMD ranged from −0.19 to 0.11, all of them with confidence intervals crossing the value of zero.Further, the available evidence suggested that study volunteers could not perceive the EMF exposure status better than what is expected by chance and that IEI-EMF individuals could not determine EMF conditions better than the general population. Discussion: Limitations of evidence: experimental conditions are substantially different from real-life situations in the duration, frequency, distance and position of the exposure. Most studies were conducted in young, healthy volunteers, who might be more resilient to RF-EMF than the general population. The outcomes of interest in this systematic review were symptoms, which are self-reported. The available information did not allow to assess the potential effects of exposures beyond acute exposure and in elderly or in chronically ill people. It cannot be ruled out that a real EMF effect in IEI-EMF groups is masked by a mix with insensitive subjects. However, studies on symptoms reporting and/or field perceptions did not find any evidence that there were particularly vulnerable individuals in the IEI-EMF group, although in open provocation studies, when volunteers were informed about the presence or absence of EMF exposure, such differences were consistently observed.Interpretation: available evidence suggests that acute RF-EMF below regulatory limits does not cause symptoms and corresponding claims in the everyday life are related to perceived and not to real EMF exposure status.

Introduction: Patients with metastatic NSCLC (mNSCLC) treated with immune checkpoint inhibitors in clinical practice may often not meet the strict inclusion criteria of clinical trials. Our aim was to assess the trial eligibility of patients with mNSCLC treated with pembrolizumab monotherapy in real-world and to compare the outcome of “trial-ineligible” and “potentially trial-eligible” patients. Methods: Data from the prospective, clinical research platform CRISP were used to compare patient characteristics, treatment, and outcome of patients with programmed cell death-ligand 1 tumor proportion score greater than or equal to 50% tumors treated with pembrolizumab monotherapy who are deemed either “potentially trial-eligible” or “trial-ineligible” according to inclusion and exclusion criteria of the registrational studies (KEYNOTE-024 and -042). Results: Of 746 patients included, 343 patients (46.0%) were classified as “trial-ineligible” and had significantly worse outcomes compared with “potentially trial-eligible” patients (n = 403, 54.0%): median progression-free survival: 6.2 (95% confidence interval [CI]: 5.2–8.4) versus 10.3 (95% CI: 8.4–13.8) months, hazard ratio (trial-ineligible versus potentially trial-eligible) of 1.43 (95% CI: 1.19–1.72), p less than 0.001; median overall survival: 15.9 (95% CI: 11.4–20.3) versus 25.3 (95% CI: 19.8–30.4) months, hazard ratio of 1.36 (95% CI: 1.10–1.67), p equals 0.004. Conclusions: Our data reveal that a considerable proportion of patients with mNSCLC are not eligible to participate in a clinical trial and were found to have worse outcomes than potentially trial-eligible patients, whose outcomes were comparable with those obtained from pivotal clinical trials. This is of substantial clinical relevance for physicians discussing outcomes to be expected with their patients and stresses the need for real-world effectiveness analyses.

Abstract Background Over the years, the knowledge translation (KT) field has moved from promoting linearized models to embracing the importance of interaction and learning. Likewise, there is now increased attention on the transfer of KT approaches to new environments. Some scholars, however, have warned that ideas about transferability still hinge on linear thinking and doing. In the current study, we therefore sought to use a more reflexive approach to KT and to study how actors align KT approaches with their local environments. Methods Our (auto) ethnographic study took place in a wider KT project. This project intended to combine three components: (1) co-organizing demand-driven, locally led and embedded KT cycles in Cameroon, Jordan, and Nigeria, (2) building upon established KT methods and (3) equipping and empowering local teams. We conducted 63 semi-structured interviews with key KT actors, observed 472 h of KT practices, and collected a paper trail of documents. At the same time, we also compiled project exchanges, such as project documents, plans, protocols, field notes, meeting notes and an archive of (email) correspondence between project members. We analysed all data abductively. Results We show that there were numerous moments where the design of our project indeed enabled us to align with local practices and needs. Yet this often did not suffice, and the project design sometimes conflicted with other logics and values. By analysing these tensions, we want to show that doing KT work which acts upon different values and knowledges and is sensitive towards the different effects that it produces demands both structuring projects in a specific way and requires significant alignment work of KT actors in practice. Conclusions We show that practising KT more reflexively relies on two important conditions. First, KT projects have to be structured with sufficient discretionary space. Second, even though the structure of a project is important, there will be continuous need for alignment work. It is important to facilitate such alignment work and to further support it. In the discussion of this paper, we therefore articulate three design principles and three sensitivities. These elements can be used to make future KT projects more reflexive and sensitive to (social) complexity.

Abstract Introduction Neuroendocrine neoplasms (NEN) are rare and heterogeneous epithelial tumors, occurring throughout the body. For gastroenteropancreatic (GEP)‐NEN, rising incidence rates were reported for the last decades, with underlying causes remaining largely unexplained. We evaluated NEN trends stratifying by their histologic subtypes. Methods Incident cases of GEP‐NEN diagnosed between 2005 and 2019 were retrieved from the prospective, population‐based Bavarian Cancer Registry. GEP‐NEN were divided in their histologic subtypes, that is, neuroendocrine tumors (NET) G1, NET G2/G3, other NET versus small‐cell neuroendocrine carcinoma (NEC), large‐cell NEC, and other NEC. We calculated annual age‐standardized incidence rates (ASIRs) per 100,000 persons for the total of GEP‐NEN, NEN histologic subtypes, and tumor sites. We used an annual percentage change (APC) approach including a joinpoint analysis to investigate NEN incidence trends. Results ASIR of GEP‐NEN rose from 2.2 in 2005 to 4.8 in 2019, characterized by a significant increase until 2012 (APC 2005–2012: 10.1%), followed by modest rise (APC 2012–2019: 1.5%). In the last decade, this increase was mainly driven by the rise of NET G1 and G2/G3, while incidence for NEC declined. Over the study period, ASIR increased significantly for all GEP‐sites except the colon. APCs were largest for the stomach, the appendix, the pancreas, and the rectum. Conclusions This study found a significant increase in the incidence of GEP‐NET. Though this development may partially be attributable to the increased use of advanced detection techniques and changes in NEN classification, further research should also focus on the identification of NEN risk factors.

Abstract The structures, strain fields, and defect distributions in solid materials underlie the mechanical and physical properties across numerous applications. Many modern microstructural microscopy tools characterize crystal grains, domains and defects required to map lattice distortions or deformation, but are limited to studies of the (near) surface. Generally speaking, such tools cannot probe the structural dynamics in a way that is representative of bulk behavior. Synchrotron X-ray diffraction based imaging has long mapped the deeply embedded structural elements, and with enhanced resolution, dark field X-ray microscopy (DFXM) can now map those features with the requisite nm-resolution. However, these techniques still suffer from the required integration times due to limitations from the source and optics. This work extends DFXM to X-ray free electron lasers, showing how the $$10^{12}$$ 10 12 photons per pulse available at these sources offer structural characterization down to 100 fs resolution (orders of magnitude faster than current synchrotron images). We introduce the XFEL DFXM setup with simultaneous bright field microscopy to probe density changes within the same volume. This work presents a comprehensive guide to the multi-modal ultrafast high-resolution X-ray microscope that we constructed and tested at two XFELs, and shows initial data demonstrating two timing strategies to study associated reversible or irreversible lattice dynamics.

Background: Evidence from network meta-analyses (NMAs) and real-world propensity score (PS) analyses suggest monoclonal antibodies (mAbs) offer a therapeutic advantage over currently available oral therapies and, therefore, warrant consideration as a distinct group of high-efficacy disease-modifying therapies (DMTs) for patients with relapsing multiple sclerosis (RMS). This is counter to the current perception of these therapies by some stakeholders, including payers. Objectives: A multifaceted indirect treatment comparison (ITC) approach was undertaken to clarify the relative efficacy of mAbs and oral therapies. Design: Two ITC methods that use individual patient data (IPD) to adjust for between-trial differences, PS analyses and simulated treatment comparisons (STCs), were used to compare the mAb ofatumumab versus the oral therapies cladribine, fingolimod, and ozanimod. Data sources and methods: As IPD were available for trials of ofatumumab and fingolimod, PS analyses were conducted. Given summary-level data were available for cladribine, fingolimod, and ozanimod trials, STCs were conducted between ofatumumab and each of these oral therapies. Three efficacy outcomes were compared: annualized relapse rate (ARR), 3-month confirmed disability progression (3mCDP), and 6-month CDP (6mCDP). Results: The PS analyses demonstrated ofatumumab was statistically superior to fingolimod for ARR and time to 3mCDP but not time to 6mCDP. In STCs, ofatumumab was statistically superior in reducing ARR and decreasing the proportion of patients with 3mCDP compared with cladribine, fingolimod, and ozanimod and in decreasing the proportion with 6mCP compared with fingolimod and ozanimod. These findings were largely consistent with recently published NMAs that identified mAb therapies as the most efficacious DMTs for RMS. Conclusion: Complementary ITC methods showed ofatumumab was superior to cladribine, fingolimod, and ozanimod in lowering relapse rates and delaying disability progression among patients with RMS. Our study supports the therapeutic superiority of mAbs over currently available oral DMTs for RMS and the delineation of mAbs as high-efficacy therapies.

Introduction: Magnetic resonance elastography (MRE) is a non-invasive method to quantify biomechanical properties of human tissues. It has potential in diagnosis and monitoring of kidney disease, if established in clinical practice. The interplay of flow and volume changes in renal vessels, tubule, urinary collection system and interstitium is complex, but physiological ranges of in vivo viscoelastic properties during fasting and hydration have never been investigated in all gross anatomical segments simultaneously.Method: Ten healthy volunteers underwent two imaging sessions, one following a 12-hour fasting period and the second after a drinking challenge of >10 mL per kg body weight (60–75 min before the second examination). High-resolution renal MRE was performed using a novel driver with rotating eccentric mass placed at the posterior-lateral wall to couple waves (50 Hz) to the kidney. The biomechanical parameters, shear wave speed (cs in m/s), storage modulus (Gd in kPa), loss modulus (Gl in kPa), phase angle (Υ=2πatanGlGd) and attenuation (α in 1/mm) were derived. Accurate separation of gross anatomical segments was applied in post-processing (whole kidney, cortex, medulla, sinus, vessel).Results: High-quality shear waves coupled into all gross anatomical segments of the kidney (mean shear wave displacement: 163 ± 47 μm, mean contamination of second upper harmonics

Can one acquire one or more foreign languages equally well at any age? From the perspective of cognitive neuroscience, this article takes stock of the current situation. In this context, the limitations and possibilities of the imaging methods used today to examine brain structures and functions are discussed. In summary, from the point of view of brain research it can be said that the ability to learn foreign languages decreases over the course of one’s life, which can be explained both by processes of maturation (specialisation) and degradation (dedifferentiation). However, future research in this area will have to give greater weight to individual aspects and focus on the use of longitudinal models and innovative statistical models.

Microorganisms can contaminate eggs at many stages of production, handling, preparation, and consumption. The aim of our study was the microbiological quality of the internal contents of eggs from different layer housing systems. Total bacteria, coliforms, and Salmonella spp. were isolated and identified by mass spectrometry. Total bacterial counts were isolated on Plate count agar for 48 hours at 30 °C, coliforms on Violet red bile lactose agar for 24 hours at 37 °C and Salmonella spp. on Xylose lysine deoxycholate agar for 24 hours at 37 °C. The lowest total bacterial counts were found in the cage-rearing system and the highest in the aviary-rearing system for hens housing. The number of microorganisms was evaluated on days 0. and 21. Twenty species, eighteen genera, and sixteen families were isolated from enriched cages in 0 days, while three families, three genera, and five species were isolated in 21 days, according to egg content samples. Thirteen families, sixteen genera, and twenty species were isolated from egg contents samples in the deep litter on day zero and day twenty-one, respectively, by third families, fourth genera, and seventh species. Nine families, twenty genera, and fifteen species were identified in aviaries using egg content samples on day 0, and three families, three genera, and five species on day 21. Ralstonia pickettii was the most isolated species among all samples.

Background: Applications emitting radiofrequency electromagnetic fields (RF-EMF; 100 kHz to 300 GHz) are widely used for communication (e.g. mobile phones), in medicine (diathermy) and in industry (RF heaters). Objectives: The objective is to systematically review the effects of longer-term or repeated local and whole human body radiofrequency electromagnetic field (RF-EMF) exposure on the occurrence of symptoms. Primary hypotheses were tinnitus, migraine and headaches in relation to RF-EMF exposure of the brain, sleep disturbances and composite symptom scores in relation to whole-body RF-EMF exposure. Methods: Eligibility criteria: We included case-control and prospective cohort studies in the general population or workers estimating local or whole-body RF-EMF exposure for at least one week.Information sources: We conducted a systematic literature search in various databases including Web of Science and Medline.Risk of bias: We used the Risk of Bias (RoB) tool developed by OHAT adapted to the topic of this review.Synthesis of results: We synthesized studies using random effects meta-analysis. Results: Included studies: We included 13 papers from eight distinct cohort and one case-control studies with a total of 486,558 participants conducted exclusively in Europe. Tinnitus is addressed in three papers, migraine in one, headaches in six, sleep disturbances in five, and composite symptom scores in five papers. Only one study addressed occupational exposure.Synthesis of results: For all five priority hypotheses, available research suggests that RF-EMF exposure below guideline values does not cause symptoms, but the evidence is very uncertain. The very low certainty evidence is due the low number of studies, possible risk of bias in some studies, inconsistencies, indirectness, and imprecision. In terms of non-priority hypotheses numerous exposure-outcome combinations were addressed in the 13 eligible papers without indication for an association related to a specific symptom or exposure source. Discussion: Limitations of evidence: This review topic includes various challenges related to confounding control and exposure assessment. Many of these aspects are inherently present and not easy to be solved in future research. Since near-field exposure from wireless communication devices is related to lifestyle, a particular challenge is to differentiate between potential biophysical effects and other potential effects from extensive use of wireless communication devices that may compete with healthy behaviour such as sleeping or physical activity. Future research needs novel and innovative methods to differentiate between these two hypothetical mechanisms.Interpretation: This is currently the best available evidence to underpin safety of RF-EMF. There is no indication that RF-EMF below guideline values causes symptoms. However, inherent limitations of the research results in substantial uncertainty. Other: Funding: This review was partially funded by the WHO radioprotection programme.Registration: The protocol for this review has been registered in Prospero (reg no CRD42021239432) and published in Environment International (Röösli et al., 2021)

Will protein structure search tools like AlphaFold replace protein sequence search with BLAST? We discuss the promises, using structure search for remote homology detection, and why protein BLAST, as the leading sequence search tool, should strive to incorporate structural information

Abstract The COVID-19 pandemic and SARS-CoV-2 variants have dramatically illustrated the need for a better understanding of antigen (epitope)-antibody (paratope) interactions. To gain insight into the immunogenic characteristics of epitopic sites (ES), we systematically investigated the structures of 340 Abs and 83 nanobodies (Nbs) complexed with the Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein. We identified 23 distinct ES on the RBD surface and determined the frequencies of amino acid usage in the corresponding CDR paratopes. We describe a clustering method for analysis of ES similarities that reveals binding motifs of the paratopes and that provides insights for vaccine design and therapies for SARS-CoV-2, as well as a broader understanding of the structural basis of Ab-protein antigen (Ag) interactions.

Abstract Problems in understanding speech in noisy environments are characteristic for age-related hearing loss. Since hearing aids do not mitigate these communication problems in every case, potential alternatives in a clinical rehabilitation plan need to be explored. This study investigates whether a computer-based speechreading training improves audiovisual speech perception in noise in a sample of middle-aged and older adults (N = 62, 47–83 years) with 32 participants completing a speechreading training and 30 participants of an active control group completing a foreign language training. Before and after training participants performed a speech-in-noise task mimicking real-life communication settings with participants being required to answer a speaker’s questions. Using generalized linear mixed-effects models we found a significant improvement in audiovisual speech perception in noise in the speechreading training group. This is of great relevance as these results highlight the potential of a low-cost and easy-to-implement intervention for a profound and widespread problem as speech-in-noise comprehension impairment.

Abstract We reconstructed hydroclimate variability in the Yucatán Peninsula (YP) based on stalagmite oxygen and carbon isotope records from a well-studied cave system located in the northeastern YP, a region strongly influenced by Caribbean climate dynamics. The new stalagmite isotopic records span the time interval between 43 and 26.6 ka BP, extending a previously published record from the same cave system covering the interval between 26.5 and 23.2 ka BP. Stalagmite stable isotope records show dominant decadal and multidecadal variability, and weaker variability on millennial timescales. These records suggest significant precipitation declines in the broader Caribbean region during Heinrich events 4 and 3 of ice-rafted discharge into the North Atlantic, in agreement with the antiphase pattern of precipitation variability across the equator suggested by previous studies. On millennial timescales, the stalagmite isotope records do not show the distinctive saw-tooth pattern of climate variability observed in Greenland during Dansgaard–Oeschger (DO) events, but a pattern similar to North Atlantic sea surface temperature (SST) variability. We propose that shifts in the mean position of the Intertropical Convergence Zone (ITCZ), per se, are not the dominant driver of last glacial hydroclimate variability in the YP on millennial timescales but instead that North Atlantic SSTs played a dominant role. Our results support a negative climate feedback mechanism whereby large low latitude precipitation deficits resulting from AMOC slowdown would lead to elevated salinity in the Caribbean and ultimately help reactivate AMOC and Caribbean precipitation. However, because of the unique drivers of future climate in the region, predicted twenty-first century YP precipitation reductions are unlikely to be modulated by this negative feedback mechanism.

Background and aims: Familial hypercholesterolemia (FH) is among the most common genetic disorders in primary care. However, only 15% or less of patients are diagnosed, and few achieve the goals for low-density lipoprotein cholesterol (LDL-C). In this analysis of the German Cascade Screening and Registry for High Cholesterol (CaRe High), we examined the status of lipid management, treatment strategies, and LDL-C goal attainment according to the ESC/EAS dyslipidemia guidelines. Methods: We evaluated consolidated datasets from 1501 FH patients diagnosed clinically and seen either by lipid specialists or general practitioners and internists. We conducted a questionnaire survey of both the recruiting physicians and patients. Results: Among the 1501 patients, 86% regularly received lipid-lowering drugs. LDL-C goals were achieved by 26% and 10% of patients with atherosclerotic cardiovascular disease (ASCVD) according to the 2016 and 2019 ESC/EAS dyslipidemia guidelines, respectively. High intensity lipid-lowering was administered more often in men than in women, in patients with ASCVD, at higher LDL-C and in patients with a genetic diagnosis of FH. Conclusions: FH is under-treated in Germany compared to guideline recommendations. Male gender, genetic proof of FH, treatment by a specialist, and presence of ASCVD appear to be associated with increased treatment intensity. Achieving the LDL-C goals of the 2019 ESC/EAS dyslipidemia guidelines remains challenging if pre-treatment LDL-C is very high.

La fenomenología del espacio vivido, formulada por Gastón Bachelard en 1957, busca explorar las representaciones de espacios felices a través de una perspectiva topofílica. Este artículo se adentra en una reflexión profunda sobre la topofobia, derivada del análisis de relatos de mujeres víctimas de la dictadura militar en Bolivia (1979-1981). El conjunto de testimonios, extraído de la obra Libres (2013), se enfoca en la caracterización del ominoso recinto de tortura conocido como el “Cuartito azul”. El propósito central de esta investigación es ofrecer una caracterización analítica de las imágenes poéticas de tristeza presentes en los testimonios de tortura, ampliando así los fundamentos del topoanálisis bachelardiano. Inicialmente, se esboza de manera concisa el concepto de topofilia en el contexto del proyecto de topoanálisis de Bachelard. Posteriormente, se presenta un análisis topofóbico detallado del conjunto de testimonios, expandiendo el diálogo a través de la interacción con los conceptos de la Nueva Fenomenología propuesta por Hermann Schmitz. La conclusión central de este trabajo radica en la afirmación de que la topofobia representa el estudio y exploración de las imágenes poéticas que encapsulan la experiencia de humillación en el ser humano. A través de esta indagación, se persigue una comprensión enriquecida del topoanálisis bachelardiano, mediante la incorporación de contextos históricos y vivencias personales en la investigación antropológico-filosófica, resaltando así la significativa influencia de los espacios en la experiencia emocional y existencial de las personas.

Abstract The importance of B cells in multiple sclerosis (MS) has been demonstrated through the advent of B-cell-depleting anti-CD20 antibody therapies. Ofatumumab is the first fully human anti-CD20 monoclonal antibody (mAb) developed and tested for subcutaneous (SC) self-administration at monthly doses of 20 mg, and has been approved in the US, UK, EU, and other regions and countries worldwide for the treatment of relapsing MS. The development goal of ofatumumab was to obtain a highly efficacious anti-CD20 therapy, with a safety and tolerability profile that allows for self-administration by MS patients at home and a positive benefit–risk balance for use in the broad relapsing MS population. This development goal was enabled by the unique binding site, higher affinity to B cells, and higher potency of ofatumumab compared to previous anti-CD20 mAbs; these properties of ofatumumab facilitate rapid B-cell depletion and maintenance with a low dose at a low injection volume (20 mg/0.4 ml). The high potency in turn enables the selective targeting of B cells that reside in the lymphatic system via subcutaneous (SC) administration. Through a comprehensive dose-finding program in two phase 2 studies (one intravenous and one SC) and model simulations, it was found that safety and tolerability can be further improved, and the risk of systemic injection-related reactions (IRRs) minimized, by avoiding doses ≥ 30 mg, and by reaching initial and rapid B-cell depletion via stepwise weekly administration of ofatumumab at Weeks 0, 1, and 2 (instead of a single high dose). Once near-complete B-cell depletion is reached, it can be maintained by monthly doses of 20 mg/0.4 ml. Indeed, in phase 3 trials (ASCLEPIOS I/II), rapid and sustained near-complete B-cell depletion (largely independent of body weight, race and other factors) was observed with this dosing regimen, which resulted in superior efficacy of ofatumumab versus teriflunomide on relapse rates, disability worsening, neuronal injury (serum neurofilament light chain), and imaging outcomes. Likely due to its fully human nature, ofatumumab has a low immunogenic risk profile—only 2 of 914 patients receiving ofatumumab in ASCLEPIOS I/II developed anti-drug antibodies—and this may also underlie the infrequent IRRs (20% with ofatumumab vs. 15% with the placebo injection in the teriflunomide arm) that were mostly (99.8%) mild to moderate in severity. The overall rates of infections and serious infections in patients treated with ofatumumab were similar to those in patients treated with teriflunomide (51.6% vs. 52.7% and 2.5% vs. 1.8%, respectively). The benefit–risk profile of ofatumumab was favorable compared to teriflunomide in the broad RMS population, and also in the predefined subgroups of both recently diagnosed and/or treatment-naïve patients, as well as previously disease-modifying therapy-treated patients. Interim data from the ongoing extension study (ALITHIOS) have shown that long-term treatment with ofatumumab up to 4 years is well-tolerated in RMS patients, with no new safety risks identified. In parallel to the phase 3 trials in which SC administration was carried out with a pre-filled syringe, an autoinjector pen for more convenient self-administration of the ofatumumab 20 mg dose was developed and is available for use in clinical practice. Graphical Abstract

Plant-based indicators of water status, such as midday stem water potential (Ψstem) and leaf stomatal conductance (gs), are used to optimise irrigation scheduling in horticultural crops because they integrate the effect of soil and climatic conditions and the internal physiological constraints. The use of these indicators relies on experimentally acquired thresholds that relate the value of the indicator to negative effects on yield. In five irrigation treatments, we monitored yield, fruit size and the courses of Ψstem and gs throughout four consecutive growing seasons. We found that Ψstem was more sensitive to irrigation treatment than gs. Both indicators increased with available soil water content (ASWC) and decreased with evaporative demands of the atmosphere (ETC). On a seasonal basis, crop load had a stronger impact on gs than Ψstem. In summary, our study explored the effect of environmental conditions and crop load on plant-based indicators of tree water status and can be useful for establishing thresholds for irrigation scheduling in apple tree orchards.

The signs and symptoms of chronic urticaria (CU) are caused by the activation and degranulation of skin mast cells (MCs). Recent studies have added to our understanding of how and why skin MCs are involved and different in CU. Also, novel and relevant mechanisms of MC activation in CU have been identified and characterized. Finally, the use of MC-targeted and MC mediator-specific treatments has helped to better define the role of the skin environment, the contribution of specific MC mediators, and the relevance of MC crosstalk with other cells in the pathogenesis of CU. Here, we review these recent findings and their impact on our understanding of CU, with a focus on chronic spontaneous urticaria (CSU). Also, we highlight open questions, issues of controversy, and unmet needs, and we suggest what studies should be performed moving forward.

Combining proton and phosphorus magnetic resonance spectroscopy offers a unique opportunity to study the oxidative and glycolytic components of metabolism in working muscle. This paper presents a 7 T proton calf coil design that combines dipole and loop elements to achieve the high performance necessary for detecting metabolites with low abundance and restricted visibility, specifically lactate, while including the option of adding a phosphorus array. We investigated the transmit, receive, and parallel imaging performance of three transceiver dipoles with six pair-wise overlap-decoupled standard or twisted pair receive-only coils. With a higher SNR and more efficient transmission decoupling, standard loops outperformed twisted pair coils. The dipoles with standard loops provided a four-fold-higher image SNR than a multinuclear reference coil comprising two proton channels and 32% more than a commercially available 28-channel proton knee coil. The setup enabled up to three-fold acceleration in the right–left direction, with acceptable g-factors and no visible aliasing artefacts. Spectroscopic phantom measurements revealed a higher spectral SNR for lactate with the developed setup than with either reference coil and fewer restrictions in voxel placement due to improved transmit homogeneity. This paper presents a new use case for dipoles and highlights their advantages for the integration in multinuclear calf coils.

Pleural mesothelioma (PM) is a very aggressive malignancy with a poor prognosis. Most patients receive systemic treatment only; however, some patients may benefit from multimodality treatment. A precise staging of patients undergoing multimodal treatment is mandatory. We investigated the pattern of metastasis in a cohort of patients screened for multimodal treatment to define the extent of staging examinations. Additionally, we investigated the occurrence of metastasis during follow-up. We investigated a single-center experience of 545 patients newly diagnosed and/or treated with PM between the years 2010 and 2022. Patients who were treated naïvely and had a whole set of imaging of the brain were included and further analyzed. A total of 54% of all patients with cerebral imaging had an available 18FDG-PET CT scan. We also recorded metastasis during treatment follow-up. There were 110 patients who had a whole set of imaging (CT = 89% and MRI = 11%) of the brain, and 54% of all patients with cerebral imaging had an available 18FDG-PET CT scan. We identified four patients with cerebral metastasis at the time of first diagnosis, which means that 5.4% of the cohort had cerebral metastasis and 13.3% of all patients in the subgroup with complete data of 18FDG-PET CT had distant non-cerebral metastasis. During the longitudinal follow-up, we found 11 patients with newly diagnosed metastases after a median time of 1.6 years (range: 2 months to 3.3 years) after first diagnosis without metastases. Distant metastases are more frequent in mesothelioma patients than previously thought. This implies that extensive staging is needed for patients selected for multimodal treatment, including brain imaging and 18FDG-PET CT.

Introducción: La enfermedad degenerativa de la columna lumbar es frecuente, pero aún existen dudas en relación con los criterios de inestabilidad. Objetivos: Analizar la relación del signo del fluido facetario lumbar como criterio de inestabilidad vertebral segmentaria. Materiales y Métodos: Pacientes con enfermedad lumbar crónica, que presentan hidrartrosis facetaria en la resonancia magnética y las radiografías de columna lumbar dinámicas. Se analizan la prevalencia del sexo, la edad, la sintomatología principal y el dolor a la extensión unilateral o bilateral. Resultados: Se evaluó a 139 pacientes (62% mujeres), con un promedio de edad de 50.8 años; el principal motivo de consulta fue lumbalgia (76%). El 65% refería dolor en extensión; el 35%, dolor unilateral y el 30%, dolor bilateral. El 14% tenía espondilolistesis de bajo grado en L4-L5 y el 7%, en L5-S1. La hidrartrosis era unilateral en el 20% y bilateral en el 80%; el nivel de hidrartrosis más frecuente era en L4-L5 (58%). El 6% tenía solo inestabilidad traslacional y el 2%, mixta. Un 8% presentaba Modic I y un 5%, Modic II. Conclusiones: La presencia de fluido facetario no es un criterio de inestabilidad vertebral segmentaria, al margen del nivel y el segmento localizado, o la presentación facetaria lumbar unilateral o bilateral.

Introducción: Los bloqueos facetarios intrarticulares y radiculares selectivos son útiles como método diagnóstico y terapéutico para el manejo del dolor lumbar crónico. El objetivo de este estudio fue describir y analizar los resultados de dichos bloqueos. Materiales y Métodos: Se realizó un estudio de cohorte retrospectivo con datos de pacientes sometidos a bloqueos facetarios intrarticulares y radiculares selectivos guiados por tomografía computarizada, entre enero de 2014 y febrero de 2015. Se analizaron los datos demográficos, el puntaje en la escala analógica visual antes del bloqueo y después, y se analizó la asociación de estos factores con los resultados. Resultados: El estudio incluyó a 68 pacientes con bloqueo facetario intrarticular y 89 con bloqueo radicular selectivo. En ambos grupos, el dolor mejoró significativamente (p

Apples are an important source of polyphenolic substances that contribute to the antioxidant activity of the fruit. Presence of apples in the diet significantly contributes to the intake of polyphenols. Apple consumption is associated with prevention of degenerative diseases. Polyphenolic profiles of apples from different regions of the Czech Republic and Poland were analyzed using high-performance liquid chromatography with diode array detection. Four phenolic substances quercitric, epicatechin, phloridzin, and chlorogenic acid were determined in selected apples samples. No statistically significant differences between the regions of the given country were determined for the varieties ‘Golden Delicious’ and ‘Idared’. Chlorogenic acid was the major polyphenol in apples from Poland and its content tended to be higher being 45.4 ± 20.2 µg/g for the ‘Golden Delicious’ and 74.1 ± 2.6 µg/g for the ‘Idared’ varieties, while in the Czech Republic it was 34.2 ± 14.0, respectively 44.3 ± 21.3 µg/g. In contrast, Czech apples contained more epicatechin and quercitrin in these varieties.

Introducción: Las lesiones raquídeas son frecuentes en hombres adultos jóvenes. Reconocer la cinemática ayuda a disminuir la tasa de diagnósticos tardíos, principalmente si hay trastornos de la conciencia. Las fracturas vertebrales pueden ser únicas o múltiples, y asociarse con lesiones extravertebrales. Los objetivos de este estudio fueron analizar la distribución de la lesión según el mecanismo de producción, caracterizar el cuadro neurológico, evaluar el patrón de lesión y la asociación con lesiones extravertebrales, y analizar el tratamiento. Materiales y Métodos: Estudio multicéntrico, prospectivo de pacientes con lesiones vertebrales postrauma, que ingresaron entre el 1 de julio de 2018 y el 30 de junio de 2020. Se analizaron los siguientes parámetros: edad, sexo, cinemática, cuadro neurológico, sector afectado, patrón de lesión, lesiones extravertebrales asociadas. Resultados: Se evaluó a 281 pacientes (60% hombres) con 400 lesiones vertebrales y 118 extravertebrales que, en 62 casos, conformaban un cuadro de politraumatismo; 147 con trauma por caída de altura y 98, por accidente de tránsito. El cuadro neurológico más observado fue ASIA E (8 casos), no determinado al ingreso. El sector T2-L5 fue el más afectado, en su mayoría, por lesiones por compresión. Las lesiones extravertebrales más frecuentes fueron el trauma de cráneo y de tórax; hubo un caso de SCIWORA y un óbito temprano. Conclusiones: Los sectores raquídeos más afectados fueron: el toracolumbar, el torácico y el lumbar; las lesiones suelen deberse a caídas de altura y suelen ser únicas, sin cuadro neurológico. El tratamiento se decide según la estabilidad y el cuadro neurológico.

Introducción: La sarcopenia está revistiendo importancia en el estudio de diferentes enfermedades para predecir la morbimortalidad en el perioperatorio. Los objetivos de este estudio fueron evaluar la eficacia de la tomografía y la resonancia en la medición de la musculatura del psoas y los paraespinales, y comparar estos índices con la edad, el sexo y la enfermedad. Materiales y Métodos: Se utilizaron las tomografías computarizadas y las resonancias magnéticas de pacientes ambulatorios. La medición de los músculos se realizó en los pedículos de L3 y L4. Resultados: El estudio incluyó 18 tomografías y 34 resonancias. El rango de edad de los pacientes era de 15 a 80 años, divididos en grupos etarios. En los promedios globales, en ambos estudios, el sexo masculino estaba por encima del promedio global. Con respecto a los rangos etarios, se observó que el primer grupo (15-29 años) tenía un mayor volumen muscular y de unidades Hounsfield en el psoas comparado con el grupo >60 años. Los pacientes que consultaron por espondilolistesis tenían menos masa muscular que aquellos con discopatías. Conclusiones: No existe diferencia entre la resonancia magnética y la tomografía computarizada en cuanto a la medición de los músculos paraespinales y psoas. Queda en evidencia que la disminución del volumen muscular es común en pacientes de mayor edad y con enfermedades que afectan el balance espinal.

Abstract Lassa fever (LF) remains endemic in Nigeria with the country reporting the highest incidence and mortality globally. Recent national data suggests increasing incidence and expanding geographic spread. Predictors of LF case positivity in Nigeria have been sparsely studied. We thus sought to determine the sociodemographic and clinical determinants of LF positivity amongst suspected cases presenting to health facilities from 2018 to 2021. A secondary analysis of the national LF surveillance data between January 2018 and December 2021. Socio-demographic and clinical data of 20,027 suspected LF cases were analysed using frequencies and Chi-square statistics with significant p-value set at p

Life threatening burns of non-accidental origin in neonates are extremely rare. Their management represents a great challenge, particularly since necrosectomy of deep burns and grafting at this young age are technically very demanding. Thus, a strategic surgical master plan is mandatory to achieve rapid and definitive autologous coverage and avoidance of undue risks and iatrogenic burden for the fragile neonatal patient. We present the case of a four day-old neonate who sustained non-accidental deep burns involving 40 % of its total body surface area (TBSA) and the successful application of a laboratory grown, autologous dermo-epidermal skin analogue, termed Zurich Skin (also named denovoSkin), within a clinical trial sub-study. Due to COVID-19 pandemic restrictions, a telemedicine-based approach was installed and a total of 260 cm2 Zurich Skin were transplanted, video assisted, on a wound bed previously prepared with a dermal substitute, thereby covering 20 % TBSA. Take of Zurich Skin was excellent on the chest, good to moderate on the abdomen, and poor on other small areas, where we observed a prolonged healing. After maturation, Zurich Skin showed a close to natural skin coverage without need for further reconstructive surgery. This unique case delivers the proof of concept that Zurich Skin can be successfully applied in early life and even under most adverse medical and paramedical circumstances, provided a carefully crafted masterplan properly addressing the key issues can be executed by joint forces of committed partner institutions.