[Tixagevimab-cilgavimab as pre-exposure prophylactic treatment against SARS-CoV-2 in kidney transplantation patients]. / Tixagevimab-cilgavimab como tratamiento profiláctico preexposición frente a SARS-CoV-2 en pacientes trasplantados renales.

INTRODUCTION: It has been reported that after vaccination with RNAm or viral vectors from SARS-CoV-2 a significant number of solid organ transplant recipients do not develop an effective immune response. In this scenario, the use of tixagevimab-cilgavimab was approved by the European Medicines Agency for COVID-19 prophylaxis in immunocompromised patients in March 2022. We present our experience with a group of kidney transplant recipients who received prophylactic treatment with tixagevimab-cilgavimab. MATERIAL AND METHODS: Prospective study from a cohort of kidney transplant recipients who had been previously vaccinated with 4 doses and did not achieve a satisfactory immune response to vaccination, presenting antibody titers lower than 260 BAU/mL when measured by ELISA. A total of 55 patients who received a single dose of 150mg of tixagevimab and 150mg of cilgavimab between May and September of 2022 were included in this study. RESULTS: No immediate or severe adverse reactions, including worsening of kidney function, were observed after administering the drug or during follow up. All patients who had received the drug 3 months prior presented positive antibody titers (>260 BAU/mL). Seven patients were diagnosed with COVID, and one of those patients had to be admitted to the hospital and died 5 days later from infectious complications and a suspected diagnosis of bacterial coinfection. CONCLUSIONS: In our experience, all kidney transplant recipients reached antibody titers higher than 260 BAU/mL 3 months after receiving prophylactic treatment with tixagevimab-cilgavimab with no severe or irreversible adverse reactions.

[Tixagevimab-cilgavimab as pre-exposure prophylactic treatment against SARS-CoV-2 in kidney transplantation patients]. / Tixagevimab-cilgavimab como tratamiento profiláctico preexposición frente a SARS-CoV-2 en pacientes trasplantados renales.

Introduction: It has been reported that after vaccination with RNAm or viral vectors from SARS-CoV-2 a significant number of solid organ transplant recipients do not develop an effective immune response. In this scenario, the use of tixagevimab-cilgavimab was approved by the European Medicines Agency for COVID-19 prophylaxis in immunocompromised patients in March 2022. We present our experience with a group of kidney transplant recipients who received prophylactic treatment with tixagevimab-cilgavimab. Material and methods: Prospective study from a cohort of kidney transplant recipients who had been previously vaccinated with 4 doses and did not achieve a satisfactory immune response to vaccination, presenting antibody titers lower than 260 BAU/mL when measured by ELISA. A total of 55 patients who received a single dose of 150 mg of tixagevimab and 150 mg of cilgavimab between May and September of 2022 were included in this study. Results: No immediate or severe adverse reactions, including worsening of kidney function, were observed after administering the drug or during follow up. All patients who had received the drug 3 months prior presented positive antibody titers (> 260 BAU/mL). Seven patients were diagnosed with COVID, and one of those patients had to be admitted to the hospital and died 5 days later from infectious complications and a suspected diagnosis of bacterial coinfection. Conclusions: In our experience, all kidney transplant recipients reached antibody titers higher than 260 BAU/mL 3 months after receiving prophylactic treatment with tixagevimab-cilgavimab with no severe or irreversible adverse reactions.

Síndrome doloroso del trocánter mayor (SDTM): enfoque multifactorial actualizado / Greater trochanter pain syndrome (GTPS): updated multifactorial approach

Introducción: El Síndrome Doloroso del Trocante Mayor (SDTM) es una patología clínica mal definida. Los avances en pruebasde imagen junto al interés de la medicina deportiva podrían conducir a una mejor comprensión de los factores predisponentesy en la elección del tratamiento más efectivo.Objetivo: Dada su variabilidad etiológica, este estudio plantea una revisión actualizada de los principales factores etiológicosvinculados al desarrollo de esta patología multifactorial que cursa con dolor en la cara lateral de muslo y cadera.Material y método: Se realiza búsqueda electrónica sin restricciones por idioma y fecha hasta finales de septiembre de 2022para estudios relacionados con factores etiológicos en el SDTM. Se realiza búsqueda en Cochrane Library y bases de datosEMBASE, MEDLINE y PUBMED. Se analizan 9 articulo originales, 1 estudio multicéntrico y 1 estudio observacional, 6 revisionesbibliográficas (que analizan un total de 648 artículos), 3 ECA y 4 estudios de caso-control.Resultados: De los factores etiológicos encontrados, el 47,8% de artículos señalan que el más importante es el factor mor-fológico, seguido por los factores biomecánicos en el 30,4% y musculares en el 21,8%.Conclusión: Se evidencia la necesidad de reconocer los posibles factores etiológicos que permitan diseñar un tratamientoeficaz individualizado según factor etiológico prevalente en cada paciente.(AU)

Introduction: Greater Trochanter Pain Syndrome (GTPS) is an ill-defined clinical pathology. Advances in imaging tests coupledwith the interest in sports medicine could lead to a better understanding of predisposing factors and in choosing the mosteffective treatment.Objective: Given its etiological variability, this study proposes an updated review of the main etiological factors linked to thedevelopment of this multifactorial pathology that occurs with pain in the lateral aspect of the thigh and hip.Material and method: We conduct an unrestricted electronic search by language and date to the end of September 2022for studies related to etiological factors in the SDTM. We searched Cochrane Library and databases EMBASE, MEDLINE andPUBMED. We analyze 9 original articles, 1 multicenter study and 1 observational study, 6 reviews (analyzing a total of 648articles), 3 RCTs and 4 case-control studies.Results: Of the etiological factors found, 47.8% of articles indicate that the most important is the morphological factor,followed by biomechanical factors in 30.4% and muscular factors in 21.8%.Conclusion: The need to recognize the possible etiological factors that allow designing an effective individualized treatmentaccording to the etiological factor prevalent in each patient is evident.(AU)

Changing trends in transgender demographics and morbidity: baseline data from a Spanish cohort.

The number of transgender people who request hormone treatment is increasing worldwide. We obtained base clinical and demographic information from transgender people treated at a specialised clinic in Spain (n =484) and studied changes over time. Transgender women treated in 2009-14 were older than those treated in 2015-20 (29years vs 17years), had a lower academic level and had higher anxiolytics consumption. Transgender men treated in 2009-14 were older than those treated later (27years vs 17years) and had a lower academic level. These trends reflect favourable changes in how the transgender population is treated by society and health services.

Dirofilaria immitis in Dog Imported from Venezuela to Chile.

We report a case of Dirofilaria immitis nematode infection in a dog imported from Venezuela that had been living for 2 years in Santiago, Chile, where this parasite had not been reported before. Our findings warrant surveillance for all dogs imported to Chile, given that suitable conditions exist for establishing this parasite.

Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damage.

Background: Neuropathic pain is one of the most difficult to treat chronic pain syndromes. It has significant effects on patients' quality of life and substantially adds to the burden of direct and indirect medical costs. There is a critical need to improve therapies for peripheral nerve regeneration. The aim of this study is to address this issue by performing a detailed analysis of the therapeutic benefits of two treatment options: adipose tissue derived-mesenchymal stem cells (ASCs) and ASC-conditioned medium (CM). Methods: To this end, we used an in vivo rat sciatic nerve damage model to investigate the molecular mechanisms involved in the myelinating capacity of ASCs and CM. Furthermore, effect of TNF and CM on Schwann cells (SCs) was evaluated. For our in vivo model, biomaterial surgical implants containing TNF were used to induce peripheral neuropathy in rats. Damaged nerves were also treated with either ASCs or CM and molecular methods were used to collect evidence of nerve regeneration. Post-operatively, rats were subjected to walking track analysis and their sciatic functional index was evaluated. Morphological data was gathered through transmission electron microscopy (TEM) of sciatic nerves harvested from the experimental rats. We also evaluated the effect of TNF on Schwann cells (SCs) in vitro. Genes and their correspondent proteins associated with nerve regeneration were analyzed by qPCR, western blot, and confocal microscopy. Results: Our data suggests that both ASCs and CM are potentially beneficial treatments for promoting myelination and axonal regeneration. After TNF-induced nerve damage we observed an upregulation of c-Jun along with a downregulation of Krox-20 myelin-associated transcription factor. However, when CM was added to TNF-treated nerves the opposite effect occurred and also resulted in increased expression of myelin-related genes and their corresponding proteins. Conclusion: Findings from our in vivo model showed that both ASCs and CM aided the regeneration of axonal myelin sheaths and the remodeling of peripheral nerve morphology.

Effect of the Consumption of Alcohol-Free Beers with Different Carbohydrate Composition on Postprandial Metabolic Response.

BACKGROUND: We investigated the postprandial effects of an alcohol-free beer with modified carbohydrate (CH) composition compared to regular alcohol-free beer. METHODS: Two randomized crossover studies were conducted. In the first study, 10 healthy volunteers received 25 g of CH in four different periods, coming from regular alcohol-free beer (RB), alcohol-free beer enriched with isomaltulose and a resistant maltodextrin (IMB), alcohol-free beer enriched with resistant maltodextrin (MB), and a glucose-based beverage. In the second study, 20 healthy volunteers were provided with 50 g of CH from white bread (WB) plus water, or with 14.3 g of CH coming from RB, IMB, MB, and extra WB. Blood was sampled after ingestion every 15 min for 2 h. Glucose, insulin, incretin hormones, TG, and NEFAs were determined in all samples. RESULTS: The increase in glucose, insulin, and incretin hormones after the consumption of IMB and MB was significantly lower than after RB. The consumption of WB with IMB and MB showed significantly less increase in glucose levels than WB with water or WB with RB. CONCLUSIONS: The consumption of an alcohol-free beer with modified CH composition led to a better postprandial response compared to a conventional alcohol-free beer.

High-dose ivermectin for early treatment of COVID-19 (COVER study): a randomised, double-blind, multicentre, phase II, dose-finding, proof-of-concept clinical trial.

High concentrations of ivermectin demonstrated antiviral activity against SARS-CoV-2 in vitro. The aim of this study was to assess the safety and efficacy of high-dose ivermectin in reducing viral load in individuals with early SARS-CoV-2 infection. This was a randomised, double-blind, multicentre, phase II, dose-finding, proof-of-concept clinical trial. Participants were adults recently diagnosed with asymptomatic/oligosymptomatic SARS-CoV-2 infection. Exclusion criteria were: pregnant or lactating women; CNS disease; dialysis; severe medical condition with prognosis <6 months; warfarin treatment; and antiviral/chloroquine phosphate/hydroxychloroquine treatment. Participants were assigned (ratio 1:1:1) according to a randomised permuted block procedure to one of the following arms: placebo (arm A); single-dose ivermectin 600 µg/kg plus placebo for 5 days (arm B); and single-dose ivermectin 1200 µg/kg for 5 days (arm C). Primary outcomes were serious adverse drug reactions (SADRs) and change in viral load at Day 7. From 31 July 2020 to 26 May 2021, 32 participants were randomised to arm A, 29 to arm B and 32 to arm C. Recruitment was stopped on 10 June because of a dramatic drop in cases. The safety analysis included 89 participants and the change in viral load was calculated in 87 participants. No SADRs were registered. Mean (S.D.) log10 viral load reduction was 2.9 (1.6) in arm C, 2.5 (2.2) in arm B and 2.0 (2.1) in arm A, with no significant differences (P = 0.099 and 0.122 for C vs. A and B vs. A, respectively). High-dose ivermectin was safe but did not show efficacy to reduce viral load.

Developing an International Occupational Therapy Service: Perspectives and Implications.

Mali is one of the poorest countries in sub-Saharan Africa. Limited infrastructure renders access to health care difficult. There is a need to establish functional ways to improve Malian people's health and treat disability. From this point of view, our project aims to implement a remote occupational therapy service for the beneficiaries of the Kalana clinic in Mali through international cooperation. Using a spiral iterative model, a proposal for a remote occupational therapy service was developed and refined for a multidisciplinary context. The International Classification of Functioning, Disability, and Health (ICF) was used as a means to work from a multidisciplinary approach to treat all needs. The results are exemplified with a case report and qualitative impressions of the services.

A collaborative escape room as gamification strategy to increase learning motivation and develop curricular skills of occupational therapy students.

BACKGROUND: This study presents an experiment regarding the introduction of gamification strategies in occupational therapy courses. Based on previous studies, the objective is to adapt the idea of recreational escape rooms to educational environments of health sciences like occupational therapy to increase student motivation and promote game-based learning and key skills, such as teamwork. METHODS: Computer software was created for a collaborative escape room which allows on-line simultaneous play of up to 24-30 students. It was tested three times in an occupational therapy degree program with 75 students and it was based on two different subjects, although it can be adapted to others. The escape room was evaluated using feedback surveys and comparing students' performances before and after the game. Descriptive exploratory statistical analysis was performed using SPSS version 24. RESULTS: An appropriate use of educational escape rooms can have significant positive impacts on students' engagement and learning. Students were found to prefer using gamification tools in their learning. Their degrees of satisfaction exceeded their expectations. CONCLUSIONS: Educational escape rooms may have a positive impact on students' motivation and a statistically significant improvement of test scores after playing was found. Comments from the feedback surveys were used to improve successive versions of the software and design of the game. TRIAL REGISTRATION: T.F.G. n° 2020.038 (Research Ethics Committee of the Principality of Asturias).

Defining a Methylation Signature Associated With Operational Tolerance in Kidney Transplant Recipients.

Operational tolerance after kidney transplantation is defined as stable graft acceptance without the need for immunosuppression therapy. However, it is not clear which cellular and molecular pathways are driving tolerance in these patients. We performed genome-wide analysis of DNA methylation in peripheral blood mononuclear cells from kidney transplant recipients with chronic rejection and operational tolerance from the Genetic Analysis of Molecular Biomarkers of Immunological Tolerance (GAMBIT) study. Our results showed that both clinical stages diverge in 2737 genes, indicating that each one has a specific methylation signature associated with transplant outcome. We also observed that tolerance is associated with demethylation in genes involved in immune function, including B and T cell activation and Th17 differentiation, while in chronic rejection it is associated with intracellular signaling and ubiquitination pathways. Using co-expression network analysis, we selected 12 genomic regions that are specifically hypomethylated or hypermethylated in tolerant patients. Analysis of these genes in transplanted patients with low dose of steroids showed that these have a similar methylation signature to that of tolerant recipients. Overall, these results demonstrate that methylation analysis can mirror the immune status associated with transplant outcome and provides a starting point for understanding the epigenetic mechanisms associated with tolerance.

Deep Phenotyping and Genetic Characterization of a Cohort of 70 Individuals With 5p Minus Syndrome.

Chromosome-5p minus syndrome (5p-Sd, OMIM #123450) formerly known as Cri du Chat syndrome results from the loss of genetic material at the distal region of the short arm of chromosome 5. It is a neurodevelopmental disorder of genetic cause. So far, about 400 patients have been reported worldwide. Individuals affected by this syndrome have large phenotypic heterogeneity. However, a specific phenotype has emerged including global developmental delay, microcephaly, delayed speech, some dysmorphic features, and a characteristic and monochromatic high-pitch voice, resembling a cat's cry. We here describe a cohort of 70 patients with clinical features of 5p- Sd characterized by means of deep phenotyping, SNP arrays, and other genetic approaches. Individuals have a great clinical and molecular heterogeneity, which can be partially explained by the existence of additional significant genomic rearrangements in around 39% of cases. Thus, our data showed significant statistical differences between subpopulations (simple 5p deletions versus 5p deletions plus additional rearrangements) of the cohort. We also determined significant "functional" differences between male and female individuals.

Isolation and morphological characterization of equine mesenchymal stem cells from harvested adipose tissue and bone marrow and stably transfected with green fluorescent protein.

OBJECTIVE: To characterize the ultrastructure of mesenchymal stem cells (MSCs) that were harvested from the adipose tissue (AT-MSCs) and bone marrow (BM-MSCs) of horses and transfected with green fluorescent protein. SAMPLE: MSCs from adipose tissue and bone marrow of 6 adult female Hispano-Bretón horses. PROCEDURES: Harvested equine MSCs were cultivated and transfected with green fluorescent protein, and the immunophenotypes of the MSCs were characterized by use of anti-CD90 and anti-CD105 monoclonal antibodies. When stable transfection of MSCs was achieved, the morphological and ultrastructural characteristics of transfected and nontransfected AT-MSCs and BM-MSCs were compared with electron microscopy. RESULTS: The protocols for transfection and subsequent isolation of transfected cells with use of G418 were suitable for obtaining transfected MSCs. Transfection efficiency was 5% in AT-MSCs and 4% in BM-MSCs. Characterization of transfected and nontransfected MSCs revealed that they share immunocytochemical and morphological profiles. Expression of CD90 was significantly higher for transfected versus nontransfected AT-MSCs (97% vs 92%). Expression of CD105 was significantly lower for transfected versus nontransfected BM-MSCs (85% vs 94%). Transfected BM-MSCs had differences in organelles, compared with the other cell types, specifically including most commonly the rough endoplasmic reticulum with dilated cisternae and mitochondria. CONCLUSION AND CLINICAL RELEVANCE: These findings contribute to the knowledge base of the characteristics of equine AT-MSCs and BM-MSCs and of transfected versus nontransfected equine MSCs. The data provided a valuable starting point for researchers wishing to further study the morphological characteristics of equine MSCs.

A Current Review of the Etiology, Clinical Features, and Diagnosis of Urinary Tract Infection in Renal Transplant Patients.

Urinary tract infection (UTI) represents the most common infection after kidney transplantation and remains a major cause of morbidity and mortality in kidney transplant (KT) recipients, with a potential impact on graft survival. UTIs after KT are usually caused by Gram-negative microorganisms. Other pathogens which are uncommon in the general population should be considered in KT patients, especially BK virus since an early diagnosis is necessary to improve the prognosis. UTIs following kidney transplantation are classified into acute simple cystitis, acute pyelonephritis/complicated UTI, and recurrent UTI, due to their different clinical presentation, prognosis, and management. Asymptomatic bacteriuria (ASB) represents a frequent finding after kidney transplantation, but ASB is considered to be a separate entity apart from UTI since it is not necessarily a disease state. In fact, current guidelines do not recommend routine screening and treatment of ASB in KT patients, since a beneficial effect has not been shown. Harmful effects such as the development of multidrug-resistant (MDR) bacteria and a higher incidence of Clostridium difficile diarrhea have been associated with the antibiotic treatment of ASB.

Effect of mesenchymal stem cells combined with chondroitin sulfate in an in vitro model of osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease affecting the whole joint structure. The specific molecules responsible for the inflammatory processes involved in the development of OA have been the focus of many studies. Adipose tissue-derived mesenchymal stem cells (ASCs) constitute a promising cell-based therapy which could be used as an alternative to or in combination with drug therapies. Chondroitin sulfate (CS) plays a protective role in the joint by decreasing concentrations of pro-inflammatory cytokines and therefore has an important part in moderating chondrocyte metabolism. The aim of this study is to use an in vitro model of OA to evaluate the combined effectiveness of CS and ASCs as a treatment. We give a detailed discussion of the roles of cytokines and other key molecules involved in OA. In addition, we report the effects of treating inflamed chondrocytes with ASCs and CS on the expression of specific cartilage genes. Findings show that both treatments reduced expression of all genes associated with the pro-inflammatory cytokines we analyzed. However, we saw no increase in the expression of the specific genes encoding for cartilage matrix proteins, such as collagen type II and aggrecan. This study shows the effectiveness of combining ASCs and CS in the treatment of OA.

Isolation and characterization of exosomes from adipose tissue-derived mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are the subject of intense research as they are a potential therapeutic tool for several clinical applications. The new MSCs action models are focused on the use of MSC-derived secretome which contains several growth factors, cytokines, microRNAs, and extracellular vesicles such as exosomes. Exosomes have recently emerged as a component with great potential involved as mediators in cellular communication. The isolation and identification of exosomes has made it possible for them to be used in cell-free therapies. The purposes of this study are: (i) to detect exosomes released into adipose-derived MSC conditioned cell culture medium, (ii) to identify exosome morphology, and (iii) to carry out a complete characterization of said exosomes. Moreover, it is aimed at determining which method for exosome isolation would be best to use. Precipitation has been identified as a highly useful method of exosome isolation since it provides higher efficiency and purity values than other methods. A broad characterization of the exosomes present in the MSC-conditioned medium was also carried out. This work fills a gap in the existing literature on bioactive molecules which have attracted a great deal of interest due to their potential use in cellular therapies.

Assessment of bioclimatic change in Kazakhstan, end 20th-middle 21st centuries, according to the PRECIS prediction.

We evaluate bioclimatic changes in Kazakhstan from the end of the 20th century until the middle of the 21st century to offer natural resource managers a tool that facilitates their decision-making on measures to adapt agriculture and environmental care to foreseeable climate change. We use climatic data from the "Providing REgional Climates for Impact Studies" (PRECIS) prediction and study them following the Worldwide Bioclimatic Classification System (WBCS) of Rivas-Martínez. For three 25-year intervals (1980-2004, 2010-2034 and 2035-2059), we identify the continentality, macrobioclimates, bioclimates, bioclimatic variants, thermotypes, ombrotypes and isobioclimates of the study area. The results of the work allow us to: locate the territories where bioclimatic conditions will change, quantify the magnitude of the predicted climate changes, and determine the trends of predictable climate change. We present the results in maps, tables and graphs. For the 80-year interval, we identify 3 macroclimates, 3 bioclimatic variants, 10 bioclimates, 11 thermotypes, 10 ombrotypes and 43 isobioclimates. Some of those found bioclimates, thermotypes, ombrotypes and isobioclimates are only located in the E, SE and S mountains, where they occupy very small areas, that decrease in a generalized way as the 20th century progresses. Comparing the three successive periods, the following trends are observed: 36.2% of the territory increases in thermicity; 7.3% of the territory increases in continentality; 9.7% of the territory increases in annual aridity; 9.5% of the territory increases in summer aridity or mediterraneity; and generalized losses occur in the areas of all mountain isobioclimates. The climate change foreseen by the PRECIS model for the middle of the 21st century leads to bioclimatic homogenization, with 20.8% losses in bioclimatic diversity. We indicate on maps the locations of all the predicted bioclimatic changes; these maps may provide decision makers with a scientific basis to take necessary adaptation measures.

Hemorragia alveolar difusa unilateral en paciente con granulomatosis con poliangitis / Unilateral diffuse alveolar hemorrhage in a patient with granulomatous polyangiitis

No disponible