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Abstract The orphan G protein-coupled receptor 37 (GPR37), widely associated with Parkinson’s disease (PD), undergoes proteolytic processing under physiological conditions. The N-terminus domain is proteolyzed by a disintegrin and metalloproteinase 10 (ADAM-10), which generates various membrane receptor forms and ectodomain shedding (ecto-GPR37) in the extracellular environment. We investigated the processing and density of GPR37 in several neurodegenerative conditions, including Lewy body disease (LBD), multiple system atrophy (MSA), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and Alzheimer’s disease (AD). The presence of ecto-GPR37 peptides in the cerebrospinal fluid (CSF) of PD, MSA, CBD and PSP patients was assessed through an in-house nanoluciferase-based immunoassay. This study identified increased receptor processing in early-stage LBD within the PFC and striatum, key brain areas in neurodegeneration. In MSA only the 52 kDa form of GPR37 appeared in the striatum. This form was also significantly elevated in the striatum of AD necropsies. On the contrary, GPR37 processing remained unchanged in the brains of CBD and PSP patients. Furthermore, while CSF ecto-GPR37 increased in PD patients, its levels remained unchanged in MSA, CBD, and PSP subjects. Importantly, patients with PD with rapid progression of the disease did not have elevated ecto-GPR37 in the CSF, while those with slow progression showed a significant increase, suggesting a possible prognostic use of ecto-GPR37 in PD. This research underscores the distinctive processing and density patterns of GPR37 in neurodegenerative diseases, providing crucial insights into its potential role as an indicator of PD progression rates.

Introduction: Nonalcoholic fatty liver disease (NAFLD), now termed metabolic dysfunction-associated steatotic liver disease (MASLD), is an escalating health concern linked to obesity and type 2 diabetes. Despite liver biopsy being the gold standard, its invasiveness underscores the need for noninvasive diagnostic methods. Methods: A cross-sectional study was performed to assess MASLD using the noninvasive OWLiver® serum lipidomics test in a cohort of 117 patients with severe obesity undergoing bariatric surgery, comparing outcomes with liver biopsy. Exclusions (n = 24) included insufficient data, liver disease etiology other than MASLD, corticosteroid treatment, excessive alcohol consumption, low glomerular filtration rate, and declination to participate. Comprehensive laboratory tests, demographic assessments, and liver biopsies were performed. Serum metabolites were analyzed using OWLiver®, a serum lipidomic test that discriminates between healthy liver, steatosis, metabolic dysfunction-associated steatohepatitis (MASH), and MASH with fibrosis ≥2 by means of three algorithms run sequentially. Results: Liver biopsy revealed a MASLD prevalence of 95.7%, with MASH present in 28.2% of cases. OWLiver® demonstrated a tendency to diagnose more severe cases. Body mass index (BMI), rather than the presence of type 2 diabetes, emerged as the sole independent factor linked to the probability of concordance. Therefore, the all-population concordance of 63.2% between OWLiver® and liver biopsy notably raised to 77.1% in patients with a BMI

The focus of the research carried out by Zones Portuaires and Corpi Idirici for the digital map of Genoa is water. The map is broken down into the theme of the "immersed" with a dual meaning of "invisible underground or underwater'' due to it being submerged or forced, and of "invisible - unknown or hidden" as a result of it being abandoned or unused. The map tells the stories of a select number of noteworthy places along fresh and saltwater routes, land and maritime passages, stories made invisible by anthropogenic hyper-infrastructures and immersed in physical conditions that lack knowledge and accessibility. The phenomenon has been studied from a point of view that moves from the sea to the hinterland and vice versa using a transdisciplinary approach method of investigation and restitution that makes use of the hybridization between artistic practice and scientific research.

Abstract Accurate short-term predictions of COVID-19 cases with empirical models allow Health Officials to prepare for hospital contingencies in a two–three week window given the delay between case reporting and the admission of patients in a hospital. We investigate the ability of Gompertz-type empiric models to provide accurate prediction up to two and three weeks to give a large window of preparation in case of a surge in virus transmission. We investigate the stability of the prediction and its accuracy using bi-weekly predictions during the last trimester of 2020 and 2021. Using data from 2020, we show that understanding and correcting for the daily reporting structure of cases in the different countries is key to accomplish accurate predictions. Furthermore, we found that filtering out predictions that are highly unstable to changes in the parameters of the model, which are roughly 20%, reduces strongly the number of predictions that are way-off. The method is then tested for robustness with data from 2021. We found that, for this data, only 1–2% of the one-week predictions were off by more than 50%. This increased to 3% for two-week predictions, and only for three-week predictions it reached 10%.

Abstract Analyses of registries and medical imaging suggest that laparoscopic surgery may be penalized with a high incidence of trocar-site hernias (TSH). In addition to trocar diameter, the location of the surgical wound (SW) may affect TSH incidence. The intra-abdominal pressure (IAP) exerted on the abdominal wall (AW) might also influence the appearance of TSH. In the present study, we used finite element (FE) simulations to predict the influence of trocar location and SW characteristics (stiffness) on the mechanical behavior of the AW subject to an IAP. Two models of laparoscopy patterns on the AW, with trocars in the 5–12 mm range, were generated. FE simulations for IAP values within the 4 kPa–20 kPa range were carried out using the Code Aster open-source software. Different stiffness levels of the SW tissue were considered. We found that midline-located surgical wounds barely deformed, even though they moved outwards along with the regular LA tissue. Laterally located SWs hardly changed their location but they experienced significant variations in their volume and shape. The amount of deformation of lateral SWs was found to strongly depend on their stiffness. Trocar incisions placed in a LA with non-diastatic dimensions do not compromise its mechanical integrity. The more lateral the trocars are placed, the greater is their deformation, regardless of their size. Thus, to prevent TSH it might be advisable to close lateral trocars with a suture, or even use a prosthetic reinforcement depending on the patient's risk factors (e.g., obesity).

Abstract Background Lactic Acid Bacteria such as Lactococcus lactis, Latilactobacillus sakei (basonym: Lactobacillus sakei) and Lactiplantibacillus plantarum (basonym: Lactobacillus plantarum) have gained importance as recombinant cell factories. Although it was believed that proteins produced in these lipopolysaccharides (LPS)-free microorganisms do not aggregate, it has been shown that L. lactis produce inclusion bodies (IBs) during the recombinant production process. These protein aggregates contain biologically active protein, which is slowly released, being a biomaterial with a broad range of applications including the obtainment of soluble protein. However, the aggregation phenomenon has not been characterized so far in L. plantarum. Thus, the current study aims to determine the formation of protein aggregates in L. plantarum and evaluate their possible applications. Results To evaluate the formation of IBs in L. plantarum, the catalytic domain of bovine metalloproteinase 9 (MMP-9cat) protein has been used as model protein, being a prone-to-aggregate (PTA) protein. The electron microscopy micrographs showed the presence of electron-dense structures in L. plantarum cytoplasm, which were further purified and analyzed. The ultrastructure of the isolated protein aggregates, which were smooth, round and with an average size of 250–300 nm, proved that L. plantarum also forms IBs under recombinant production processes of PTA proteins. Besides, the protein embedded in these aggregates was fully active and had the potential to be used as a source of soluble protein or as active nanoparticles. The activity determination of the soluble protein solubilized from these IBs using non-denaturing protocols proved that fully active protein could be obtained from these protein aggregates. Conclusions These results proved that L. plantarum forms aggregates under recombinant production conditions. These aggregates showed the same properties as IBs formed in other expression systems such as Escherichia coli or L. lactis. Thus, this places this LPS-free microorganism as an interesting alternative to produce proteins of interest for the biopharmaceutical industry, which are obtained from the IBs in an important number of cases.

IntroductionMusic has the capacity to evoke emotions and memories. This capacity is influenced by whether or not the music is from the reminiscence bump (RB) period. However, research on the neural correlates of the processes of evoking autobiographical memories through songs is scant. The aim of this study was to analyze the differences at the level of frequency band activation in two situations: (1) whether or not the song is able to generate a memory; and (2) whether or not the song is from the RB period.MethodsA total of 35 older adults (22 women, age range: 61–73 years) listened to 10 thirty-second musical clips that coincided with the period of their RB and 10 from the immediately subsequent 5 years (non-RB). To record the EEG signal, a brain-computer interface (BCI) with 14 channels was used. The signal was recorded during the 30-seconds of listening to each music clip.ResultsThe results showed differences in the activation levels of the frequency bands in the frontal and temporal regions. It was also found that the non-retrieval of a memory in response to a song clip showed a greater activation of low frequency waves in the frontal region, compared to the trials that did generate a memory.DiscussionThese results suggest the importance of analyzing not only brain activation, but also neuronal functional connectivity at older ages, in order to better understand cognitive and emotional functions in aging.

Compounded insulin eye drops were prepared at 1 IU/mL from commercially available subcutaneous insulin by dilution in saline solution or artificial tears. Physicochemical characterization and in vitro tolerance testing in human and conjunctival cells were followed by a 28-day short-term stability study under various conditions. The formulations were isotonic (280–300 mOsm/L), had a pH close to neutral (7–8), medium surface-tension values (−1), and low (≈1 mPa·s) and medium (≈5 mPa·s) viscosities (compounded normal saline solution and artificial tear-based preparation, respectively). These values remained stable for 28 days under refrigeration. Microbiological stability was also excellent. Insulin potency remained in the 90–110% range in the compounded formulations containing normal saline solution when stored at 2–8 °C for 28 days, while it decreased in those based on artificial tears. Although both formulations were well tolerated in vitro, the compounded insulin diluted in a normal saline solution exhibited better cell tolerance. Preliminary data in humans showed that insulin in saline solution was an effective and safe treatment for persistent corneal epithelial defects. Compounded insulin eye drops diluted in normal saline solution could, therefore, constitute an emergent therapy for the treatment of persistent corneal epithelial defects.

Este artículo presenta resultados de una investigación orientada a comprender los sentidos y las prácticas políticas de niños y niñas en situación de vulnerabilidad en Eje Cafetero, Antioquia y Bogotá (Colombia) en torno a paz, reconciliación y democracia. El estudio se basó en la hermenéutica ontológica política, la cual brindó elementos para realizar una lectura y comprender transformaciones desde las narrativas, la reconciliación y la construcción de paz. Los resultados revelan que la construcción de niños y niñas como sujetos políticos de reconciliación es dada desde una lectura creativa de la realidad distinta a la que tienen las personas adultas, dado que los niños y las niñas viven la reconciliación de manera cotidiana a través del juego y la lúdica.

IntroductionThis study aims to assess the extent of rejection and instances of stigmatization linked to obesity within the Spanish population, encompassing a diverse spectrum of weights ranging from normal weight to morbid obesity. Additionally, the study seeks to identify the primary factors influencing these experiences and further examines the impact of bariatric surgery on such dynamics.Materials and methodsMulticenter observational study with involving a total of 1,018 participants who were recruited from various Obesity Units. Negatives attitudes towards people with obesity were assessed through three questionnaires: (i) Antifat Attitudes Scale (AFA), (ii) Stigmatizing Situations Inventory (SSI) and (iii) Weight Bias Internalization Scale (WBIS). Subjects were categorized into four groups based on their BMI and history of prior bariatric surgery.ResultsThe cumulative score across all questionnaires (AFA, SSI and WBIS) exhibited a progressive increase, from participants with normal weight to those with obesity (p

Background: Growing evidence on the use of mesh as a prophylactic measure to prevent parastomal hernia and advances in guideline development methods prompted an update of a previous guideline on parastomal hernia prevention.Objective: To develop evidence-based, trustworthy recommendations, informed by an interdisciplinary panel of stakeholders.Methods: We updated a previous systematic review on the use of a prophylactic mesh for end colostomy, and we synthesized evidence using pairwise meta-analysis. A European panel of surgeons, stoma care nurses, and patients developed an evidence-to-decision framework in line with GRADE and Guidelines International Network standards, moderated by a certified guideline methodologist. The framework considered benefits and harms, the certainty of the evidence, patients’ preferences and values, cost and resources considerations, acceptability, equity and feasibility.Results: The certainty of the evidence was moderate for parastomal hernia and low for major morbidity, surgery for parastomal hernia, and quality of life. There was unanimous consensus among panel members for a conditional recommendation for the use of a prophylactic mesh in patients with an end colostomy and fair life expectancy, and a strong recommendation for the use of a prophylactic mesh in patients at high risk to develop a parastomal hernia.Conclusion: This rapid guideline provides evidence-informed, interdisciplinary recommendations on the use of prophylactic mesh in patients with an end colostomy. Further, it identifies research gaps, and discusses implications for stakeholders, including overcoming barriers to implementation and specific considerations regarding validity.

Objetivo: Describir la reflexión autocrítica que médicos especialistas en medicina interna hacen de la calidad del registro de la información en la historia clínica electrónica, en el Hospital Pablo Tobón Uribe. Métodos: Estudio cualitativo que aplicó técnicas de la teoría fundamentada, con entrevistas semiestructuradas en profundidad a quince médicos internistas de un hospital de alta complejidad en Medellín, Colombia. El análisis partió de una conceptualización con codificación abierta y, luego, se hizo la agrupación de códigos en categorías descriptivas. Se identificaron propiedades y dimensiones que fueron relacionadas mediante la codificación axial con la matriz del paradigma de la teoría fundamentada, que permitió la emergencia de una categoría más abstracta. Resultados: Los entrevistados manifestaron que la historia clínica guarda información fundamental e invaluable, que contribuye al mejoramiento de la sa¬lud de los pacientes. Relacionaron la calidad del diligenciamiento de la historia clínica con un contexto regulatorio nacional, el cual tiene exigencias administrativas y financieras que ejercen presión de requerimientos externos a la clínica sobre su diligenciamiento. Se reconoce la influencia de la cultura digital y del inmediatismo, debilidades en la formación del diligenciamiento de la historia clínica tanto en pregrado y posgrado. Lo anterior distancia al médico del paciente, genera desmotivación en el ejercicio de su profesión y facilita cometer errores. Conclusiones: Existe una contradicción entre el “deber ser” del diligenciamiento con calidad de la historia clínica y lo que sucede en la práctica, pues su intencionalidad original de ser una herramienta al servicio de la asistencia clínica se desvirtúa, al privilegiar el haberse convertido en un instrumento que responde a otros factores externos del sistema de salud del país.