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Rationale and objectives: To analyse the programme activity and clinical innovation and/or technology developed over a period of 17 years with regard to the introduction and the use of intraoperative radiotherapy (IORT) as a therapeutic component in a medical-surgical multidisciplinary cancer hospital. Material and methods: To standardise and record this procedure, the Radiation Oncology service has an institutional programme and protocols that must be completed by the different specialists involved. For 17 years, IORT procedures were recorded on a specific database that includes 23 variables with information recorded on institutional protocols. As part of the development and innovation activity, two technological tools were implemented (RADIANCE and MEDTING) in line with the standardisation of this modality in clinical practice. Results: During the 17 years studied, 1,004 patients were treated through 1,036 IORT procedures. The state of the disease at the time of IORT was 77% primary and 23% recurrent. The origin and distribution of cancers were 62% gastrointestinal, 18% sarcomas, 5% pancreatic, 2% paediatric, 3% breast, 7% less common locations, and 2% others. The research and development projects have generated a patent on virtual planning (RADIANCE) and proof of concept to explore as a professional social network (MEDTING). During 2012, there were 69 IORT procedures. There was defined treatment volume (target or target region) in all of them, and 43 were conducted by the virtual planning RADIANCE system. Eighteen have been registered on the platform MEDTING as clinical cases. Conclusion: The IORT programme, developed in a university hospital with an academic tradition, and interdisciplinary surgical oncology, is a feasible care initiative, able to generate the necessary intense clinical activity for tending to the cancer patient. Moreover, it is a competitive source for research, development, and scientific innovation. [ABSTRACT FROM AUTHOR]

Sanfilippo syndrome, or mucopolysaccharidosis type III (MPS III), is a rare lysosomal disease caused by congenital enzymatic deficiencies in heparan sulfate (HS) degradation, leading to organ dysfunction. The most severe hallmark of MPS III comprises neurological alterations, although gastrointestinal symptoms (GISs) have also been shown to be relevant in many patients. Here, we explored the contribution of the gut microbiota to MPS III GISs. We analyzed the composition and functionality of the gut microbiota in two MPS III siblings with the same mutation (c.544C > T, c.1080delC, in the SGSH gene) and the same diet, but with differences in their GISs, including recurrent diarrhea in one of them. Using 16S sequencing, we observed that the MPS III patients exhibited decreased alpha diversity and a lower abundance of Lachnospiraceae and Bifidobacteriaceae accompanied by a higher abundance of the Ruminococcaceae and Rikenellaceae families than the healthy control subjects. Comparing siblings, we found an increased abundance of Bacteroidaceae and a lower abundance of Ruminococcaceae and Akkermansiaceae in the GIS-free patient. This patient also had a higher relative abundance of Sus genes ( SusA , SusB , SusE , and SusG ) involved in glycosaminoglycan metabolism. We found higher HS levels in the stool of the two MPS III patients than in healthy volunteers, particularly in the patient with GISs. Functionally, whole fecal metabolites from the patient with GISs induced oxidative stress in vitro in healthy monocytes. Finally, the Bacteroides thetaiotaomicron strain isolated from MPS III stool samples exhibited HS degradation ability. Overall, our results reveal different microbiota compositions and functionalities in MPS III siblings, who exhibited differential gastrointestinal symptomatology. Our study may serve as a gateway to explore the impact of the gut microbiota and its potential to enhance the quality of life in Sanfilippo syndrome patients.

Future multi-year crewed planetary missions will motivate advances in aerospace nutrition and telehealth. On Earth, the Human Cell Atlas project aims to spatially map all cell types in the human body. Here, we propose that a parallel Human Cell Space Atlas could serve as an openly available, global resource for space life science research. As humanity becomes increasingly spacefaring, high-resolution omics on orbit could permit an advent of precision spaceflight healthcare. Alongside the scientific potential, we consider the complex ethical, cultural, and legal challenges intrinsic to the human space omics discipline, and how philosophical frameworks may benefit from international perspectives., (© 2024. The Author(s).)

Periodically, the European Space Agency (ESA) updates scientific roadmaps in consultation with the scientific community. The ESA SciSpacE Science Community White Paper (SSCWP) 9, "Biology in Space and Analogue Environments", focusses in 5 main topic areas, aiming to address key community-identified knowledge gaps in Space Biology. Here we present one of the identified topic areas, which is also an unanswered question of life science research in Space: "How to Obtain an Integrated Picture of the Molecular Networks Involved in Adaptation to Microgravity in Different Biological Systems?" The manuscript reports the main gaps of knowledge which have been identified by the community in the above topic area as well as the approach the community indicates to address the gaps not yet bridged. Moreover, the relevance that these research activities might have for the space exploration programs and also for application in industrial and technological fields on Earth is briefly discussed., (© 2024. The Author(s).)

Immune checkpoint inhibitors have been proposed as the standard treatment for different stages of non-small-cell lung cancer in multiple indications. Not all patients benefit from these treatments, however, and certain patients develop immune-related adverse events. Although the search for predictors of response to these drugs is a major field of research, these issues have yet to be resolved. It has been postulated that microbiota could play a relevant role in conditioning the response to cancer treatments; however, the human factor of intestinal permeability also needs to be considered as it is closely related to the regulation of host-microbiota interaction. In this article, we analyzed the possible relationship between the response to immune checkpoint inhibitors and the onset of immune-related adverse events, gut microbiota status, and intestinal membrane permeability. In a pioneering step, we also measured short-chain fatty acid content in feces. Although the correlation analyses failed to identify predictive biomarkers, even when all variables were integrated, our patients' microbial gut ecosystems were rich and diverse, and the intestinal barrier's integrity was preserved. These results add new knowledge on the composition of microbiota and its correlation with barrier permeability and short-chain fatty acids and suggest that more studies are required before these potential biomarkers can be incorporated into the clinical management of patients via immune checkpoint inhibitor treatment.

Progress in mechanobiology allowed us to better understand the important role of mechanical forces in the regulation of biological processes. Space research in the field of life sciences clearly showed that gravity plays a crucial role in biological processes. The space environment offers the unique opportunity to carry out experiments without gravity, helping us not only to understand the effects of gravitational alterations on biological systems but also the mechanisms underlying mechanoperception and cell/tissue response to mechanical and gravitational stresses. Despite the progress made so far, for future space exploration programs it is necessary to increase our knowledge on the mechanotransduction processes as well as on the molecular mechanisms underlying microgravity-induced cell and tissue alterations. This white paper reports the suggestions and recommendations of the SciSpacE Science Community for the elaboration of the section of the European Space Agency roadmap "Biology in Space and Analogue Environments" focusing on "How are cells and tissues influenced by gravity and what are the gravity perception mechanisms?" The knowledge gaps that prevent the Science Community from fully answering this question and the activities proposed to fill them are discussed., (© 2024. The Author(s).)

The present white paper concerns the indications and recommendations of the SciSpacE Science Community to make progress in filling the gaps of knowledge that prevent us from answering the question: "How Do Gravity Alterations Affect Animal and Human Systems at a Cellular/Tissue Level?" This is one of the five major scientific issues of the ESA roadmap "Biology in Space and Analogue Environments". Despite the many studies conducted so far on spaceflight adaptation mechanisms and related pathophysiological alterations observed in astronauts, we are not yet able to elaborate a synthetic integrated model of the many changes occurring at different system and functional levels. Consequently, it is difficult to develop credible models for predicting long-term consequences of human adaptation to the space environment, as well as to implement medical support plans for long-term missions and a strategy for preventing the possible health risks due to prolonged exposure to spaceflight beyond the low Earth orbit (LEO). The research activities suggested by the scientific community have the aim to overcome these problems by striving to connect biological and physiological aspects in a more holistic view of space adaptation effects., (© 2023. Springer Nature Limited.)

Objective: The aim of this work was to estimate the conditioned probability for the diagnosis of SARS-CoV-2 infection with reverse transcription polymerase chain reaction (RT-PCR), viral antigen rapid diagnostic tests (Ag-RDT), and antibody detection tests depending on the prevalence in the specific healthcare settings in Spain in 2020, and on the pre-test probability (PTP) according to the clinical situation, age and unknown or close contacts of the patient., Methods: Performance parameters of tests were obtained from literature. Prevalence data and PTP were obtained from Spanish sources and a survey, respectively. The post-test probability is the positive predictive value (PPV) when test is positive. For negative result, we also calculated the probability of having the infection (false negatives)., Results: For both RT-PCR and viral Ag-RDT, the lowest PPV values were for the population screenings. This strategy proved to be useful in ruling out infection but generates a high number of false positives. At individual level, both tools provided high PPV (≥ 97%) when the PTP values are over 35%. In seroprevalence studies, though the specificity of IgG alone tests is high, under low seroprevalence, false positives cannot be avoided. Total antibodies tests are useful for diagnosis of COVID-19 in those doubtful cases with RT-PCR or Ag-RDT tests being repeatedly negative., Conclusions: The interpretating of results depends not only on the accuracy of the test, but also on the prevalence of the infection in different settings, and the PTP associated to the patient before performing the test., (©The Author 2023. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Advancements in plant space biology are required for the realization of human space exploration missions, where the re-supply of resources from Earth is not feasible. Until a few decades ago, space life science was focused on the impact of the space environment on the human body. More recently, the interest in plant space biology has increased because plants are key organisms in Bioregenerative Life Support Systems (BLSS) for the regeneration of resources and fresh food production. Moreover, plants play an important role in psychological support for astronauts. The definition of cultivation requirements for the design, realization, and successful operation of BLSS must consider the effects of space factors on plants. Altered gravitational fields and radiation exposure are the main space factors inducing changes in gene expression, cell proliferation and differentiation, signalling and physiological processes with possible consequences on tissue organization and organogenesis, thus on the whole plant functioning. Interestingly, the changes at the cellular and molecular levels do not always result in organismic or developmental changes. This apparent paradox is a current research challenge. In this paper, the main findings of gravity- and radiation-related research on higher plants are summarized, highlighting the knowledge gaps that are still necessary to fill. Existing experimental facilities to simulate the effect of space factors, as well as requirements for future facilities for possible experiments to achieve fundamental biology goals are considered. Finally, the need for making synergies among disciplines and for establishing global standard operating procedures for analyses and data collection in space experiments is highlighted., (© 2023. Springer Nature Limited.)

Introduction: Laser surgery of the larynx is currently the standard of clinical practice in a multitude of procedures. Lasers with photoangiolytic properties have a wide application in endolaryngeal lesions. One of their most prominent features is the ability to coagulate blood vessels, reducing unwanted tissue damage. Our objective is to expose the uses of the blue laser (445 nm) in the larynx., Material and Methods: A retrospective study was carried out including 47 patients treated with blue photoangiolytic laser from October 2021 to January 2023 at a university hospital. Demographic data, type of lesion presented, date of intervention and scope of the procedure, as well as the parameters of the laser used, were recorded. The number of sessions received per patient, the result and complications were also collected., Results: A total of 47 patients with laryngeal lesions were treated, including vascular angiomas, laryngeal sulcus vocali, vocal cord polyps, Reinke's edemas, laryngeal papillomatoses, subglottic stenosis, laryngeal synechiae, subglottic granulomas, glottic scars, vocal fold leukoplakias, laryngeal dysplasias and tracheostomal granulomas. The mean age was 52.5 years, and 64.3% of the patients were women. The range of power used in the resective surgeries was 2-10 Watts with a 20-millisecond window. The average number of sessions received was 2.1 (range 1-4). A satisfactory situation was obtained in 45 of the 47 patients treated (95.75%), and an evident decrease in lesions was seen in the remaining two. There was no evidence of any complications directly derived from the use of the blue laser. Twenty-seven cases (54%) were treated exclusively in-office., Conclusions: The blue laser is safe and effective in the treatment of a wide range of laryngeal pathologies. Its advantages include its portability, its photoangiolytic qualities as well as its ability to vaporize tissue in contact mode, which can treat subepithelial vessels or resect lesions.

Following on from the NASA twins' study, there has been a tremendous interest in the use of omics techniques in spaceflight. Individual space agencies, NASA's GeneLab, JAXA's ibSLS, and the ESA-funded Space Omics Topical Team and the International Standards for Space Omics Processing (ISSOP) groups have established several initiatives to support this growth. Here, we present recommendations from the Space Omics Topical Team to promote standard application of space omics in Europe. We focus on four main themes: i) continued participation in and coordination with international omics endeavors, ii) strengthening of the European space omics infrastructure including workforce and facilities, iii) capitalizing on the emerging opportunities in the commercial space sector, and iv) capitalizing on the emerging opportunities in human subjects research., Competing Interests: F.M. is CEO/Co-Founder at Genegoggle, D.B. is a cofounder of Poppy Health, Inc. and CSO of Yuri Gravity GmbH and declares affiliations at the NGS Competence Center Tübingen (NCCT), University of Tübingen, Tübingen and Yuri Gravity, Meckenbeuren, Germany. M.F.R. declares additional affiliation at Diamantina Institute, The University of Queensland, St Lucia, Queensland 4072, Australia. S.G. is a scientific consultant of 10x Genomics., (© 2023 The Authors.)

Background: Neutrophils, key players of the immune system, also promote tumor development through the formation of neutrophil extracellular traps (NETs) in a process called NETosis. NETs are extracellular networks of DNA, histones and cytoplasmic and granular proteins (calprotectin, myeloperoxidase, elastase, etc.) released by neutrophils upon activation. NETs regulate tumor growth while promoting angiogenesis and invasiveness, and tumor cells also stimulate NETosis. Although NETosis seems to be increased in cancer patients, an increase of NETs in plasma may also be mediated by an impaired degradation by plasma DNaseI, as evidenced in several immunological disorders like lupus nephritis. However, this has never been evidenced in bladder cancer (BC) patients. Herein, we aimed to evaluate the occurrence of increased NETosis in plasma and tumor tissue of BC patients, to ascertain whether it is mediated by a reduced DNaseI activity and degradation, and to in vitro explore novel therapeutic interventions., Methods: We recruited 71 BC patients from whom we obtained a plasma sample before surgery and a formalin-fixed paraffin embedded tumor tissue sample, and 64 age- and sex-matched healthy controls from whom we obtained a plasma sample. We measured NETs markers (cell-free fDNA, calprotectin, nucleosomes and neutrophil elastase) and the DNaseI activity in plasma with specific assays. We also measured NETs markers in BC tissue by immunofluorescence. Finally, we evaluated the ability of BC and control plasma to degrade in vitro -generated NETs, and evaluated the performance of the approved recombinant human DNaseI (rhDNaseI, Dornase alfa, Pulmozyme ® , Roche) to restore the NET-degradation ability of plasma. In vitro experiments were performed in triplicate. Statistical analysis was conducted with Graphpad (v.8.0.1)., Results: NETosis occurs in BC tissue, more profusely in the muscle-invasive subtype ( P <0.01), that with the worst prognosis. Compared to controls, BC patients had increased NETosis and a reduced DNaseI activity in plasma ( P <0.0001), which leads to an impairment to degrade NETs ( P <0.0001). Remarkably, this can be therapeutically restored with rhDNaseI to the level of healthy controls., Conclusion: To the best of our knowledge, this is the first report demonstrating that BC patients have an increased NETosis systemically and in the tumor microenvironment, in part caused by an impaired DNaseI-mediated NET degradation. Remarkably, this defect can be therapeutically restored in vitro with the approved Dornase alfa, thus Pulmozyme ® could become a potential therapeutic tool to locally reduce BC progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Herranz, Oto, Hueso, Plana, Cana, Castaño, Cordón, Ramos-Soler, Bonanad, Vera-Donoso, Martínez-Sarmiento and Medina.)

Many of the patients with COVID-19 have suffered respiratory distress requiring prolonged endotracheal intubation (ETI) resulting in laryngotracheal complication with an impact on breathing, phonation, and swallowing. Our aim is to describe laryngeal injuries diagnosed after ETI in patients with COVID-19 in a multicentre study., Methods: A prospective descriptive observational study was conducted from January 2021 to December 2021, including COVID-19 patients with laryngeal complications due to ETI diagnosed in several Spanish hospitals. We analyzed the epidemiological data, previous comorbidities, mean time to ICU admission and ETI, need for tracheostomy, mean time on invasive mechanical ventilation until tracheostomy or weaning, mean time in ICU, type of residual lesions, and their treatment., Results: We obtained the collaboration of nine hospitals during the months of January 2021 to December 2021. A total of 49 patients were referred. Tracheostomy was performed in 44.9%, being late in most cases (more than 7-10 days). The mean number of days of ETI until extubation was 17.63 days, and the main post-intubation symptoms were dysphonia, dyspnea, and dysphagia, in 87.8%, 34.7%, and 42.9%, respectively. The most frequent injury was altered laryngeal mobility, present in 79.6%. Statistically, there is a greater amount of stenosis after late ETI and after delayed tracheostomy, not observing the data with the immobility alterations., Conclusion: The mean number of days of ETI was long, according to the latest guidelines, with the need for several cycles of pronation. This long ETI may have had an impact on the increase of subsequent laryngeal sequelae, such as altered laryngeal mobility or stenosis.

Purpose: The aim of this study was to identify, assess, and reach a consensus on the professional competencies that optometrists must acquire during their undergraduate training at the University of Valladolid. The results obtained may be useful in the revision of the current curriculum., Methods: A three round Delphi study was carried out with the participation of 116 participants grouped in 7 panels. In the first round, competencies were identified through an open-ended question and their frequency calculated. In the successive 2nd and 3rd rounds, the consensus and stability of each competency was established., Results: A total of 56 professional competencies were identified, with 43 of them (77%) achieving a consensus among participants, of which the highest scores were obtained by the competencies that correspond to health functions of primary visual care. Out of the 13 competencies without consensus, for 11 of them this was due to the significant differences in assessment among the consulted participants; for 8 competencies (14%) response stability was found, while neither consensus nor stability were reached in 5 (9%) of the identified competencies., Conclusions: The results obtained with this Delphi study provide a set of relevant competencies for updating the curriculum of the university Degree in Optics and Optometry at the University of Valladolid, improving its suitability to current and future professional reality., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2022 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.)