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Abstract The digitization of natural history specimens and the popularization of citizen science are creating an unprecedented availability of large amounts of biodiversity data. These biodiversity inventories can be severely affected by species misidentification, a source of taxonomic uncertainty that is rarely acknowledged in biodiversity data management. For these reasons, taxonomists debate the use of online repositories to address biological questions at the species level. Hedera L. (ivies) provides an excellent case study as it is well represented in both herbaria and online repositories with thousands of records likely to be affected by high taxonomic uncertainty. We analyze the sources and extent of taxonomic errors in the identification of the European ivy species by reviewing herbarium specimens and find a high misidentification rate (18% on average), which varies between species (maximized in H. hibernica: 55%; H. azorica: 48%; H. iberica: 36%) and regions (maximized in the UK: 38% and Spain: 27%). We find a systematic misidentification of all European ivies with H. helix behind the high misidentification rates in herbaria and warn of even higher rates in online records. We compile a spatial database to overcome the large discrepancies we observed in species distributions between online and morphologically reviewed records.

Oral cancer holds the sixth position in malignancies worldwide; 90% correspond to oral squamous cell carcinoma (OSCC). Diverse reports suggest that NTRK genes and their receptors are key oncogenesis regulators to tumor progression in human cancers. Objective: To analyze the NTRK and Trk expression and their association with clinicopathological features of OSCC in Mexican patients’ samples. Material and Methods: We analyzed 95 OSCC cases of pan-trk immunoexpression through a software-assisted method. Gene expression was analyzed by RT-qPCR employing the ΔΔCT method. Kruskal–Wallis and Spearman’s correlation tests were performed. Results: Our mean age was 62.4 (±16.9) years. A total of 37 cases were tumors in the lateral border of the tongue. Age was significantly associated with the anatomical site. 42% (40 of 95) cases were pan-trk positive. A total of 21 cases showed intense immunoexpression predominantly in poorly differentiated OSCC, with a significant correlation between immunoexpression and age and gender. Gene expression showed that poorly differentiated cases exhibited higher NTRK2 expression, while well-differentiated cases demonstrated NTRK3 significantly higher expression. Conclusions: Our results suggest that NTRK family expression is present in OSCC, with differential expression related to differentiation degree. Additional information about their activation or mutational status could reinforce their potential as a possible primary or adjuvant treatment target.

Gingiva hyperpigmentation resulting from physiological melanosis causes aesthetic discomfort and is usually perceived as a disease by patients because healthy attached gingiva is typically characterized by coral pink coloring with stippling and scalloped contours. When physiological melanosis compromises the aesthetics of smiling, it may induce insecurity in patients, who usually seek out alternatives for reducing or eliminating hyperpigmentation. We present a case report of a surgical procedure combining gingivectomy with gingivoplasty for the management of physiological melanosis. The surgical procedure was performed on a 40-year-old female patient with bilateral pigmentation in both arches. The results of the histological analysis confirm the diagnoses of melanotic macula, with papillary hyperplasia and cytopathic changes being suggestive of HPV infection, which was verified using an immunohistochemistry analysis based on the detection of a major capsid protein of HPV. Acceptable functional and aesthetic results were obtained for the patient without major discomfort during the postoperative period. In cases when HPV infection is present, long-term follow-up becomes necessary.

Conclusion: The solid ameloblastoma may have a cystic component, in which there is the possibility of diagnostic errors when studying an incisional biopsy; for this reason, the definitive diagnosis should be established until complete enucleation of the lesion is performed. This characteristic in a solid ameloblastoma makes possible a positive response to decompression, making it easier to perform the enucleation subsequently, avoiding other aggressive treatments that can dramatically affect the patient’s quality of life and also avoiding costly reconstruction bills.

Chickpeas (Cicer arietinum L.) are a valuable legume crop due to their nutritional value. To maintain chickpea productivity and avoid the adverse effects of climate change on soil and plant processes, it is crucial to address demand. Achieving this necessitates implementing sustainable agricultural practices incorporating the use of biostimulants, adaptable crops for arid conditions, as well as pest and disease-resistant crops that are sustainable over time. Three varieties of chickpeas were analysed to determine the effect of two different biostimulant application methods on both germination and vegetative growth. Possible effects due to location were also examined by conducting tests at two different sites. Significant variations in biostimulant response were evident only during the germination period, but not during the vegetative development stage, where the observed statistical differences were influenced more by the location or variety of chickpeas employed. Furthermore, this study examined the effect of biostimulants on nutrient cycling within the soil–plant microbiota system. Nitrogen-fixing bacteria (NFB) are present in the soil of chickpea crops at an order of magnitude of 107 CFU/g DS. Additionally, an average concentration of 106 CFU/g DS of phosphorus-mobilising bacteria was observed. Applying biostimulants (BioE) to seeds resulted in a successful germination percentage (GP) for both Amelia (AM) and IMIDRA 10 (IM) varieties.

Abstract Background Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. Results A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017–1.109 and OR = 2.438, 95%CI 1.023–5.813, respectively). Conclusions Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.

Antecedentes/Objetivo: Describir el empleo de la herramienta de telemonitorización con Claria-Sharesource (CSS) durante el periodo de confinamiento por COVID-19, y su relación con variables clínicas, en pacientes en diálisis peritoneal automatizada. Material y métodos: Estudio observacional retrospectivo realizado en dos hospitales españoles. Resultados: Se incluyeron 74 sujetos, con media de edad de 61.9 ± 12.8 años, el 33% mujeres, con diuresis promedio 1,000.1 ± 630.9 ml. La reducción del número de visitas presenciales se acompañó de un incremente significativo de las visitas virtuales. Además, hubo una alta adherencia a la técnica: el 80% de los pacientes realizó el 90% o más de las sesiones. La media mensual de alarmas leves por paciente fue de 11 ± 1.3, y de alarmas graves de 5 ± 0.3, similares a los valores previos al confinamiento. Conclusiones: Los pacientes tratados con CSS durante el periodo de confinamiento presentaron un descenso de las visitas presenciales del 80%. La combinación de telemonitorización con otras herramientas que facilitaban las visitas virtuales permitieron un control adecuado del paciente en su domicilio desde el hospital.

Abstract Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) is a rare entity associated with an increased risk of hemorrhage. Corticosteroids have been used in its treatment with favorable results. We present the case of a 54‐year‐old female patient with a personal history of Lupus diagnosed with LAHPS following an episode of cerebellar hemorrhage.

Summary: Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, −3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; −9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols.

SARS-Cov2 s, caused a high mortality in patients with some degree of immunosuppression, like those that receive a hematopoietic progenitor transplant. Since December 2020, several vaccines have been developed having been key in decreasing complications and mortality in this group of patients. Different articles have described the presence of thrombopenia related to the administration of vaccines, however, there are few data on the occurrence of neutropenia as a side effect after administration. We present several cases of neutropenia (defined as absolute neutrophil count (ANC) less than 2,000/mm3), after vaccination in hematopoietic progenitor transplant (HPT) recipients performed in our center during 2021.

The path followed by species in the colonization of remote oceanic islands ultimately depends on their phylogenetic constraints and ecological responses. In this study, we aim to evaluate the relative role of geographical and ecological forces in the origin and evolution of the Madeiran ivy (Hedera maderensis), a single-species endemic belonging to the western polyploid clade of Hedera. To determine the phylogenetic placement of H. maderensis within the western polyploid clade, we analyzed 40 populations (92 individuals) using genotyping-by-sequencing and including Hedera helix as outgroup. Climatic niche differences among the study species were evaluated using a database with 867 records representing the entire species ranges. To test species responses to climate, 13 vegetative and reproductive functional traits were examined for 70 populations (335 individuals). Phylogenomic results revealed a nested pattern with H. maderensis embedded within the south-western Iberian H. iberica. Gradual niche differentiation from the coldest and most continental populations of H. iberica to the warm and stable coastal population sister to H. maderensis parallels the geographical pattern observed in the phylogeny. Similarity in functional traits is observed for H. maderensis and H. iberica. The two species show leaves with higher specific leaf area (SLA), lower leaf dry matter content (LDMC) and thickness and fruits with lower pulp fraction than the other western polyploid species H. hibernica. Acquisition of a Macaronesian climatic niche and the associated functional syndrome in mainland European ivies (leaves with high SLA, and low LDMC and thickness, and fruits with less pulp content) was a key step in the colonization of Madeira by the H. iberica/H. maderensis lineage, which points to climatic pre-adaptation as key in the success of island colonization (dispersal and establishment). Once in Madeira, budding speciation was driven by geographical isolation, while ecological processes are regarded as secondary forces with a putative impact in the lack of further in situ diversification.

Relapse following BCMA targeted CAR T-cell therapy is frequently observed in patients with multiple myeloma (MM). Here, by single cell transcriptome profiling on serially collected bone marrow samples, the authors report biallelic loss of BCMA as the mechanism of resistance underlying both relapse and lack of response to a second CAR T infusion in a patient with MM.

El neuroma traumático no es una verdadera neoplasia sino una proliferación reactiva del tejido neural después de la transección u otro daño de un haz de nervios. Pueden desarrollarse en cualquier lugar, pero son más comunes en el área del foramen mentoniano, la lengua y el labio inferior. La formación de neuromas traumáticos es una causa importante de dolor neuropático, que sigue siendo un problema difícil al que se enfrentan los cirujanos. El mecanismo exacto del dolor asociado al neuroma aún no se comprende completamente y la prevención de su formación es primordial para evitarlo. Hasta la fecha el tratamiento más efectivo ha sido la extirpación quirúrgica. Se reporta el caso de un paciente de sexo femenino de 23 años de edad que presenta un aumento de volumen en el fondo de surco vestibular a nivel de los dientes 44 y 45, así como dolor espontáneo de tipo ardoroso con una evolución de aproximadamente cinco meses. Se decide realizar la resección quirúrgica de la lesión y el resultado histopatológico fue de un neuroma traumático. A los 7 días de seguimiento, se observa un ligero edema en la región bucal y mentoniana; así como anestesia a nivel de la piel del mentón y labio inferior. A 10 meses de seguimiento persistió la anestesia y no se observaron datos de recidiva.

Ameloblastoma is a rare benign epithelial odontogenic neoplasm, but with great clinical implications, as despite its benignity and slow growth, most cases are locally aggressive with a significant recurrence rate. Histological, cellular, or molecular analyses of its pathogenesis have confirmed the complexity of this neoplasm. We present the case of a 20-year-old patient with a suggestive clinical and radiographic diagnosis of ameloblastoma. An incisional biopsy was obtained confirming the diagnosis of conventional ameloblastoma. Left hemimandibulectomy and plate reconstruction were performed. Histopathological analysis of the surgical specimen confirmed the conventional ameloblastoma with a plexiform pattern and significant areas of cystic degeneration and amyloid-like-like deposits. Additionally, a microarray was carried out with bioinformatic analysis for the enrichment, protein interaction, and determination of eight hub genes (CRP, BCHE, APP, AKT1, AGT, ACTC1, ADAM10, and APOA2) related to their pathogenesis.

Tapia's syndrome is characterized by peripheral damage of the hypoglossal and vagal nerves in the recurrent laryngeal branch at the cervical level. It is associated with trauma due to endotracheal intubation, direct damage to nerves X and XII, carotid dissection involving the ascending pharyngeal artery, fungal infections, and tumors. Diagnosis is based on clinical findings, primarily alterations in swallowing, speech, and tongue mobility. Reports of this syndrome are scarce in the Oral and Maxillofacial Surgery literature and the treatment remains controversial. The present report describes a 25-year-old male patient who presented Tapia's syndrome with a fracture of the mandibular ramus and the first cervical vertebra due to a firearm projectile.

Syphilis is one of the most exciting diseases explored in paleopathology and, therefore, tracing back its origin and development has provided a prolific debate. The combination of paleopathological data with historical sources, iconography, and archaeological contexts were the primary sources used to reconstruct its historical path. However, there are some limitations to paleopathological diagnosis due to the nature of bone reaction to stimuli. In addition, historical sources are subjected to a bias of social and cultural nature and the knowledge of those who wrote them. Hence, ancient DNA analysis offers the possibility of acquiring proof of cause by identifying pathogens in an organism. We undertook a metagenomic study of a skeleton exhumed from the Royal Hospital of All Saints (Portugal), renowned for treating syphilis from the 16th century onwards. The skeleton had previously been diagnosed with syphilis according to paleopathological analysis. However, the metagenomics analysis showed no presence of the pathogen associated with syphilis (i.e., Treponema pallidum) but revealed pathogenic microorganisms related to respiratory diseases (pneumonia), nonspecific bone infections (osteomyelitis), and oral bacterial pathologies as well as Hansen’s disease (also known as leprosy). The results are exciting and demand a reappraisal of the observed bone changes, recontextualizing their characterization as syphilis related. They prove that past reconstruction of health and disease diagnoses based on assessing human osteological remains of known context (such as a syphilitic hospital) may bias interpretations and, therefore, caution is recommended, not forgetting that the absence of evidence is not evidence of absence (in this case of syphilis) in life.

The causal agent of bacterial wilt, Ralstonia solanacearum, is a soilborne pathogen that invades plants through their roots, traversing many tissue layers until it reaches the xylem, where it multiplies and causes plant collapse. The effects of R. solanacearum infection are devastating, and no effective approach to fight the disease is so far available. The early steps of infection, essential for colonization, as well as the early plant defense responses remain mostly unknown. Here, we have set up a simple, in vitro Arabidopsis thaliana–R. solanacearum pathosystem that has allowed us to identify three clear root phenotypes specifically associated to the early stages of infection: root-growth inhibition, root-hair formation, and root-tip cell death. Using this method, we have been able to differentiate, on Arabidopsis plants, the phenotypes caused by mutants in the key bacterial virulence regulators hrpB and hrpG, which remained indistinguishable using the classical soil-drench inoculation pathogenicity assays. In addition, we have revealed the previously unknown involvement of auxins in the root rearrangements caused by R. solanacearum infection. Our system provides an easy-to-use, high-throughput tool to study R. solanacearum aggressiveness. Furthermore, the observed phenotypes may allow the identification of bacterial virulence determinants and could even be used to screen for novel forms of early plant resistance to bacterial wilt.

Deception Island is a geothermal location in Antarctica that presents active fumaroles, which confers unique characteristics to this habitat. Several studies about microbial communities in Antarctica have been carried out, nevertheless, Antarctic microbiota is still partially unknown. Here we present a multidisciplinary study about sediments obtained by deposition during 4 years in which several approaches have been considered for their characterization. First, a physicochemical characterization, using ionic chromatography and mass spectrometry for the determination of most abundant ions (chloride and sulphate) and elements (mainly silicon), was conducted. In addition, the total microbial community was studied using a metataxonomical approach, revealing a bacterial community dominated by Proteobacteria and Thaumarchaeota as the main archaeal genera and a fungal community mainly composed by Aspergillaceae. Culture-dependent studies showed low microbial diversity, only achieving the isolation of Bacillus-related species, some of them thermophilic, and the isolation of common fungi of Aspergillus or Penicillium spp. Furthermore, diatoms were detected in the sediment and characterized attending to their morphological characteristics using scanning electron microscopy. The study reveals a high influence of the physicochemical conditions in the microbial populations and their distribution, offering valuable data on the interaction between the island and water microbiota.

Resumen: En los sistemas distribuidos modernos, como la Internet o Web de las Cosas, la seguridad juega un papel preponderante. Debe prestarse especial atencioân a la consideracioân de estos aspectos en las primeras etapas de desarrollo. En este contexto, el desarrollo guiado por modelos de requisitos no funcionales (NF) presenta especial intere's, ya que aborda dichas caracterâısticas NF en la etapa de disenÌo, cuando todavâıa se pueden realizar anaâlisis, y auân hay margen para modificaciones antes de que e'stas sean muy costosas. El uso de estas metodologâıas guiadas por modelos ofrece beneficios tales como el aumento de la productividad, una mayor reutilizacioân de los elementos de disenÌo, o una mejor mantenibilidad del sistema. Este artâıculo presenta una estrategia de desarrollo que permite integrar aspectos NF de seguridad (confidencialidad, integridad, y control de acceso) en los sistemas de software empotrado. Abstract: In modern distributed systems, such as in the Internet or Web of Things, security plays a fundamental role. Special atention must be placed, then, in considering these aspects in the first stages of development. In this context, the model-driven development of non functional (NF) requirements is of great interest, as it addresses those NF characteristics in the design stage, when analyses can be performed, and there is room for changes while they are still not too costly. The use of modeldriven methodologies brings with them some intrinsic benefits, such as the increase in productivity, a greater reuse of design elements, or an improved maintainability of the system. This paper presents a development strategy that allows integrating non-functional security aspects (such as as confidentiality, integrity, or access control) in embedded systems design. Palabras clave: Desarrollo Guiado por Modelos, Perfil de Dispositivos para Servicios Web, Polâıticas de Servicios Web, Seguridad en Servicios Web, Keywords: MDD DPWS, WS-Policy, WS-SecurityPolicy

In winemaking processes, there is a current tendency to develop spontaneous fermentations taking advantage of the metabolic diversity of derived from the great microbial diversity present in grape musts. This enological practice enhances wine complexity, but undesirable consequences or deviations could appear on wine quality. Soil is a reservoir of important microorganisms for different beneficial processes, especially for plant nutrition, but it is also the origin of many of the phytopathogenic microorganisms that affect vines. In this study, a meta-taxonomic analysis of the microbial communities inhabiting vineyard soils was realized. A significant impact of the soil type and climate aspects (seasonal patterns) was observed in terms of alpha and beta bacterial diversity, but fungal populations appeared as more stable communities in vineyard soils, especially in terms of alpha diversity. Focusing on the presence and abundance of wine-related microorganisms present in the studied soils, some seasonal and soil-dependent patterns were observed. The Lactobacillaceae family, containing species responsible for the malolactic fermentation, was only present in non-calcareous soils samples and during the summer season. The study of wine-related fungi indicated that the Debaryomycetaceae family dominates the winter yeast population, whereas the Saccharomycetaceae family, containing the most important fermentative yeast species for winemaking, was detected as dominant in summer.

Resumen: Las facilidades e independencia de plataforma de Java han generado un gran interés en la comunidad de tiempo real. Dicho interés se ha reflejado en la especificación RTSJ (Real-Time Specification for Java), que extiende y adapta el lenguaje Java para permitir el desarrollo de sistemas de tiempo real. Adicionalmente, se han desarrollado perfiles de RTSJ para garantizar la predecibilidad en sistemas de tiempo real críticos. Sin embargo, RTSJ y sus perfiles no proporcionan facilidades para sistemas distribuidos. El objetivo de este trabajo es afrontar dicha limitación definiendo un nuevo modelo de RMI (Remote Method Invocation) basado en los principales perfiles de RTSJ para sistemas de tiempo real crítico. Este trabajo presenta el diseño y la implementación de RMI-HRT (RMI-Hard Real-Time) que está enfocado a sistemas de tiempo real crítico con requisitos de alta integridad. Abstract: Distributed real-time embedded systems are becoming increasingly important to society. More demands will be made on them and greater reliance will be placed on the delivery of their services. A relevant subset of them is high-integrity or hard real-time systems, where failure can cause loss of life, environmental harm, or significant financial loss.Additionally, the evolution of communication networks and paradigms as well as the necessity of demanding processing power and fault tolerance, motivated the interconnection between electronic devices; many of the communications have the possibility of transferring data at a high speed. The concept of distributed systems emerged as systems where different parts are executed on several nodes that interact with each other via a communication network.Java's popularity, facilities and platform independence have made it an interesting language for the real-time and embedded community. This was the motivation for the development of RTSJ (Real-Time Specification for Java), which is a language extension intended to allow the development of real-time systems. The use of Java in the development of high-integrity systems requires strict development and testing techniques.However, neither RTSJ nor its profiles provide facilities to develop distributed real-time applications. This is an important issue, as most of the current and future systems will be distributed. The Distributed RTSJ (DRTSJ) Expert Group was created under the Java community process (JSR-50) in order to define appropriate abstractions to overcome this problem. Currently there is no formal specification.The aim of this work is to describe the design and develop a communication middleware that is suitable for the development of distributed hard real-time systems in Java, based on the integration between the RMI (Remote Method Invocation) model and the HRTJ profile. It has been designed and implemented keeping in mind the main requirements such as the predictability and reliability in the timing behavior and the resource usage.The design starts with the definition of a computational model which identifies among other things: the communication model, most appropriate underlying network protocols, the analysis model, and a subset of Java for hard real-time systems. In the design, the remote references are the basic means for building distributed applications which are associated with all nonfunctional parameters and resources needed to implement synchronous or asynchronous remote invocations with real-time attributes.The proposed middleware separates the resource allocation from the execution itself by defining two phases and a specific threading mechanism that guarantees a suitable timing behavior. It also includes mechanisms to monitor the functional and the timing behavior. It provides independence from network protocol defining a network interface and modules. The JRMP protocol was modified to include two phases, non-functional parameters, and message size optimizations. Although serialization is one of the fundamental operations to ensure proper data transmission, current implementations are not suitable for hard real-time systems and there are no alternatives. This work proposes a predictable serialization that introduces a new compiler to generate optimized code according to the computational model. The proposed solution has the advantage of allowing us to schedule the communications and to adjust the memory usage at compilation time.In order to validate the design and the implementation a demanding validation process was carried out with emphasis in the functional behavior, the memory usage, the processor usage (the end-to-end response time and the response time in each functional block) and the network usage (real consumption according to the calculated consumption). Palabras clave: Sistemas críticos, Sistemas de tiempo real, Sistemas distribuidos, Java, Keywords: Safety Systems, Real-Time Systems, Distributed Systems, Java

Cardiac amyloidosis is a cardiomyopathy resulting from the extracellular deposition of proteins such as transthyretin (TTR). We present the case of a 72-year-old male with hereditary cardiac amyloidosis. After confirming the diagnosis, tafamidis, a TTR stabilizer, was administered. Remarkably, tafamidis, when coupled with peritoneal dialysis for chronic kidney disease, maintained stability in both cardiac and renal functions. Previous studies have demonstrated the efficacy of tafamidis in reducing all-cause mortality and cardiovascular hospitalizations, although its use in severe renal failure lacks specific evaluation. This case suggests a potential application of tafamidis in moderate–severe kidney disease, emphasizing the need for further research in this population. [ABSTRACT FROM AUTHOR]