Unifying biophysical consciousness theories with MaxCon: maximizing configurations of brain connectivity.

There is such a vast proliferation of scientific theories of consciousness that it is worrying some scholars. There are even competitions to test different theories, and the results are inconclusive. Consciousness research, far from converging toward a unifying framework, is becoming more discordant than ever, especially with respect to theoretical elements that do not have a clear neurobiological basis. Rather than dueling theories, an integration across theories is needed to facilitate a comprehensive view on consciousness and on how normal nervous system dynamics can develop into pathological states. In dealing with what is considered an extremely complex matter, we try to adopt a perspective from which the subject appears in relative simplicity. Grounded in experimental and theoretical observations, we advance an encompassing biophysical theory, MaxCon, which incorporates aspects of several of the main existing neuroscientific consciousness theories, finding convergence points in an attempt to simplify and to understand how cellular collective activity is organized to fulfill the dynamic requirements of the diverse theories our proposal comprises. Moreover, a computable index indicating consciousness level is presented. Derived from the level of description of the interactions among cell networks, our proposal highlights the association of consciousness with maximization of the number of configurations of neural network connections -constrained by neuroanatomy, biophysics and the environment- that is common to all consciousness theories.

Mind the gap: Epigenetic regulation of chromatin accessibility in plants.

Chromatin plays a crucial role in genome compaction and is fundamental for regulating multiple nuclear processes. Nucleosomes, the basic building blocks of chromatin, are central in regulating these processes, determining chromatin accessibility by limiting access to DNA for various proteins and acting as important signaling hubs. The association of histones with DNA in nucleosomes and the folding of chromatin into higher-order structures are strongly influenced by a variety of epigenetic marks, including DNA methylation, histone variants, and histone post-translational modifications. Additionally, a wide array of chaperones and ATP-dependent remodelers regulate various aspects of nucleosome biology, including assembly, deposition, and positioning. This review provides an overview of recent advances in our mechanistic understanding of how nucleosomes and chromatin organization are regulated by epigenetic marks and remodelers in plants. Furthermore, we present current technologies for profiling chromatin accessibility and organization.

Validación del test FLI (Fatty Liver Index) para el diagnóstico de esteatosis hepática en pacientes con obesidad y/o diabetes mellitus para su utilización en Atención Primaria. Estudio FLIAP / Validation of the FLI (Fatty Liver Index) test to diagnose hepatic steatosis in patients with obesity and/or diabetes mellitus for use in primary care. FLIAP study

Objetivo: validación de la prueba diagnóstica Fatty Liver Index (FLI) mediante un diseño transversal. Métodos: se incluyeron pacientes con diagnóstico previo de obesidad y/o diabetes en los que estaría indicado hacer una ecografía para descartar esteatosis. Se les realizó el FLI y la prueba Gold Estándar (ecografía). Tamaño muestral: se incluyeron 135 individuos. Se calculó curva ROC, el área bajo la curva y el punto de corte del FLI para la clasificación como esteatosis. Se estimó sensibilidad, especificidad, los valores predictivos positivos y negativos del FLI. Se utilizó el programa SPSS para el análisis. A todos los pacientes se les entregó una hoja informativa del estudio y se pidió consentimiento informado. Resultados: prevalencia de esteatosis del 60,7%, predominando esteatosis leve y moderada. Hubo relación significativa entre esteatosis y triglicéridos, no así para índice de masa corporal (IMC), gamma-glutamil transferasa (GGT) y perímetro abdominal. La curva ROC del FLI se mostró muy cercana a la línea media, y el área bajo la curva fue 0,666 (0,571-0,759; intervalo de confianza [IC] del 95%), que indica una capacidad predictiva del FLI baja. Considerando un punto de corte de 76 para el FLI, la sensibilidad fue del 75,6%, la especificidad del 50,94%, el valor predictivo positivo (VPP) del 70,45% y el valor predictivo negativo (VPN) del 57,45%. Los coeficientes de probabilidad positivo y negativo fueron 1,53 y 0,49, respectivamente, que indican que el FLI no puede considerarse una buena prueba para el diagnóstico de esteatosis. Conclusiones: el test FLI no predice de forma adecuada qué pacientes con diabetes y/o obesidad tendrían esteatosis asociada. Por ello, no se puede recomendar de forma generalizada el uso del FLI para el diagnóstico de esteatosis ni tampoco para sustituir la ecografía. (AU)

Aim: Validation of the FLI (Fatty Liver Index) diagnostic test by means of a cross-sectional design. Methods: Patients with a prior diagnosis of obesity and/or diabetes in whom an ultrasound would be indicated to rule out steatosis were included. The FLI and the Gold Standard test (ultrasound) were performed. Sample size: 135 individuals were included. ROC curve, area under the curve and the FLI threshold for classification as steatosis were all calculated. Sensitivity, specificity and the positive and negative predictive values for FLI were estimated. The SPSS programme was used for the analysis. All patients were given a study information sheet and informed consent was requested. Results: Prevalence of steatosis of 60.7%, with mild and moderate steatosis predominating. There was a statistically significant relationship between steatosis and triglycerides, but not for BMI (body mass index), GGT (gamma-glutamyl transferase) and abdominal perimeter. The FLI ROC curve was very close to the midline, and the area under the curve was 0.666. This reveals a low predictive capacity for FLI. Considering a threshold of 76 for the FLI, the sensitivity, specificity, positive and negative predictive values (PPV and NPV) were 75.6%, 50.94%, 70.45% and 57.45%, respectively. The Positive and Negative Likelihood Ratios were 1.53 and 0.49, respectively. This reveals that FLI cannot be deemed a good test to diagnose steatosis. Conclusions: The Fatty Liver Index test does not adequately predict patients with diabetes and/or obesity who would have associated steatosis. Therefore, the use of FLI to diagnose steatosis or to replace ultrasound cannot be recommended in general. (AU)

Modified gastrocnemius splitting anatomic approach to the tibial plateau. Medium-term evaluation.

BACKGROUND: Posterior tibial plateau fractures, including avulsion fractures of the posterior cruciate ligament (PCL) insertion, represent a challenge for the orthopedic trauma surgeon. These injuries have gained a new perspective both diagnostically and therapeutically after the regular use of multiplanar computed tomography. In the herein study, we describe the outcome of patients sustaining a tibial plateau fracture with posterior articular involvement treated by open reduction and internal fixation (ORIF) using our modified gastrocnemius splitting anatomic approach. METHODS: This observational retrospective descriptive study was conducted at Complejo Medico de la Policia Federal Argentina Churruca-Visca. All patients were treated by ORIF by our team through our modified gastrocnemius splitting anatomic approach, and followed-up for a minimum of 12 months. RESULTS: A total of 18 patients sustaining plateau fracture were treated by this approach. Satisfactory tomographic reduction with articular gap and/or step-off <2 mm was achieved in 16. The mean time to the return to activities of daily living was 192.2 days. CONCLUSION: The modified gastrocnemius splitting anatomic approach represents a good alternative for the management of tibial plateau fractures involving the posterior quadrants.

Computational Analysis of the Influence of Menopause and Ageing on Bone Mineral Density, Exploring the Impact of Bone Turnover and Focal Bone Balance-A Study on Overload and Underload Scenarios.

This study aims to investigate the impact of hormonal imbalances during menopause, compounded by the natural ageing process, on bone health. Specifically, it examines the effects of increased bone turnover and focal bone balance on bone mass. A three-dimensional computational bone remodeling model was employed to simulate the response of the femur to habitual loads over a 19-year period, spanning premenopause, menopause, and postmenopause. The model was calibrated using experimental bone mineral density data from the literature to ensure accurate simulations. The study reveals that individual alterations in bone turnover or focal bone balance do not fully account for the observed experimental outcomes. Instead, simultaneous changes in both factors provide a more comprehensive explanation, leading to increased porosity while maintaining the material-to-apparent density ratio. Additionally, different load scenarios were tested, demonstrating that reaching the clinical osteoporosis threshold is independent of the timing of load changes. However, underload scenarios resulted in the threshold being reached approximately 6 years earlier than overload scenarios. These findings hold significant implications for strategies aimed at delaying the onset of osteoporosis and minimizing fracture risks through targeted mechanical stimulation during the early stages of menopause.

Selective inhibition of the amyloid matrix of Escherichia coli biofilms by a bifunctional microbial metabolite.

The propensity of bacteria to grow collectively in communities known as biofilms and their ability to overcome clinical treatments in this condition has become a major medical problem, emphasizing the need for anti-biofilm strategies. Antagonistic microbial interactions have extensively served as searching platforms for antibiotics, but their potential as sources for anti-biofilm compounds has barely been exploited. By screening for microorganisms that in agar-set pairwise interactions could antagonize Escherichia coli's ability to form macrocolony biofilms, we found that the soil bacterium Bacillus subtilis strongly inhibits the synthesis of amyloid fibers -known as curli-, which are the primary extracellular matrix (ECM) components of E. coli biofilms. We identified bacillaene, a B. subtilis hybrid non-ribosomal peptide/polyketide metabolite, previously described as a bacteriostatic antibiotic, as the effector molecule. We found that bacillaene combines both antibiotic and anti-curli functions in a concentration-dependent order that potentiates the ecological competitiveness of B. subtilis, highlighting bacillaene as a metabolite naturally optimized for microbial inhibition. Our studies revealed that bacillaene inhibits curli by directly impeding the assembly of the CsgB and CsgA curli subunits into amyloid fibers. Moreover, we found that curli inhibition occurs despite E. coli attempts to reinforce its protective ECM by inducing curli genes via a RpoS-mediated competition sensing response trigged by the threatening presence of B. subtilis. Overall, our findings illustrate the relevance of exploring microbial interactions not only for finding compounds with unknown and unique activities, but for uncovering additional functions of compounds previously categorized as antibiotics.

Impact of core protein naturally selected mutants associated with HBeAg-negative status in HBV biosynthesis.

Hepatitis B e antigen (HBeAg) loss represents a late stage of chronic hepatitis B virus (HBV) infection associated with a drastic decrease in HBV-DNA, a lower risk of disease progression, and the occurrence of several mutations in the preCore/core region. However, the underlying mechanisms supporting the downregulation of viral replication have yet to be elucidated. In the present study, the analysis of the frequency of subgenotype D1 core protein (HBc) mutations associated with HBeAg status revealed a higher mutation rate in HBeAg-negative sequences compared to HBeAg-positive ones. Particularly, 22 amino acids exhibited a higher frequency of mutation in HBeAg-negative sequences, while the remaining residues showed a high degree of conservation. Subsequently, the assessment of HBc mutants derived from HBeAg-negative patients in viral structure and replicative capacity revealed that HBc mutations have the ability to modulate the subcellular localization of the protein (either when the protein was expressed alone or in the context of viral replication), capsid assembly, and, depending on specific mutation patterns, alter covalently closed circular DNA (cccDNA) recycling and up- or downregulate viral replication. In conclusion, HBc mutations associated with HBeAg-negative status impact on various stages of the HBV life cycle modulating viral replication during the HBeAg-negative stage of infection.

Revisión exploratoria sobre la evidencia de cultivos andinos con efecto hipoglucemiante y de sus componentes bioactivos / Exploratory review on the evidence of Andean crops with hypoglycemic effect and their bioactive components

RESUMEN La diabetes es una enfermedad crónica que afecta a varias personas en todo el mundo. Algunos cultivos domesticados y compartidos en el continente sudamericano se han reportado como una fuente prometedora de componentes bioactivos con posibles efectos hipoglucemiantes. En esta revisión se tuvo como objetivo explorar y sintetizar la evidencia existente en la literatura científica sobre el efecto hipoglucemiante de los cultivos andinos y sus componentes bioactivos. Se incluyó distintos tipos de estudios primarios de tres bases de datos (Scopus, Pubmed y Web of Science) durante junio de 2023, sin restricciones, por medio del lenguaje controlado y no controlado, según la estrategia PICO. Se encontró 30 estudios realizados entre 2005 y 2022 que demostraron tener efecto hipoglucemiante, mediante la inhibición enzimática en estudios in vitro y reducción significativa de la glucosa en estudios preclínicos y ensayos clínicos. Dicho efecto fue atribuido a diferentes componentes bioactivos que se identificaron con mecanismos independientes sobre la reducción de la glucosa e inhibición enzimática. Los cultivos más utilizados fueron Smallanthus sonchifolius (9/30), Lupinus mutabilis (5/30) y Solanum tuberosum (4/30). De los cuales se asignó el efecto hipoglucémico a los componentes bioactivos, como polifenoles, flavonoides, subclases de ácidos fenólicos, fructanos, alcaloides, hidrolizados, antocianinas y fibra dietética. A pesar de los resultados alentadores en distintos tipos de estudio, para que estos sean considerados como tratamientos seguros y efectivos, se requiere investigaciones adicionales que profundicen en los mecanismos de acción, comparen su eficacia con los tratamientos convencionales y evalúen su seguridad a largo plazo.

ABSTRACT Diabetes is a chronic disease that affects several people around the world. Some domesticated crops in South America have been reported to be a promising source of bioactive compounds with possible hypoglycemic effects. In this review we aimed to explore and synthesize the existing evidence in the scientific literature on the hypoglycemic effect of Andean crops and their bioactive components. We included different types of primary studies from three databases (Scopus, Pubmed and Web of Science) during June 2023, without restrictions, by means of controlled and uncontrolled language, according to the PICO strategy. We found 30 studies conducted between 2005 and 2022 that reported a hypoglycemic effect, through enzymatic inhibition in in vitro studies and significant glucose reduction in preclinical studies and clinical trials. This effect was attributed to different bioactive components that were identified with independent mechanisms related to glucose reduction and enzymatic inhibition. The most commonly used cultures were Smallanthus sonchifolius (9/30), Lupinus mutabilis (5/30) and Solanum tuberosum (4/30). The hypoglycemic effect was assigned to bioactive components such as polyphenols, flavonoids, phenolic acid subclasses, fructans, alkaloids, hydrolysates, anthocyanins and dietary fiber. Despite encouraging results from different types of studies, further research on their mechanisms of action, their efficacy compared to conventional treatments and their long-term safety is required for these to be considered safe and effective treatments.

A Case of Urbanorum spp. in a Woman from an Urban-Marginal Sector of Ecuador.

BACKGROUND Worldwide, there are few cases of Urbanorum spp. in humans; however, it is associated with gastrointestinal pathologies, where humans probably acquire the disease by fecal-oral transmission, by ingesting food or water with infective cysts. The main symptoms of the patients who have this presumed parasite are fever, vomiting, colic, dyspepsia, and watery diarrhea. Since the first case of Urbanorum spp. was reported in 1994 in Colombia, cases have subsequently been reported in Peru, Ecuador, Colombia, Brazil, and Mexico. In Ecuador, a prevalence of 1.16% has been reported, and the objective of this study was to record another case of Urbanorum spp. infection in Ecuador. CASE REPORT A female patient (mixed race; 40 years old; and thin, weighing 57 to 62 kg) requested help from the FCI Project approved and financed by the University of Guayaquil (Ecuador). She underwent routine tests, such as direct parasitology and sedimentation with centrifugation using saline solution. Samples were observed under an optical microscope with 10x and 40x objectives and stained with and without Lugol's solution. We detected a rounded structure with several filaments similar to light yellow pseudopods. CONCLUSIONS Herein, a case of Urbanorum spp. infection in Ecuador, where current environmental and sanitary conditions have contributed to new cases, is reported, indicating that the community was exposed to this probable parasite with importance in public health. Further studies are recommended to confirm its etiology, life cycle, and epidemiology, in order to create a national registry, in case it is defined as a protozoan.

Sleep and cognition in aging dogs. A polysomnographic study.

Introduction: Sleep is fundamental for cognitive homeostasis, especially in senior populations since clearance of amyloid beta (key in the pathophysiology of Alzheimer's disease) occurs during sleep. Some electroencephalographic characteristics of sleep and wakefulness have been considered a hallmark of dementia. Owners of dogs with canine cognitive dysfunction syndrome (a canine analog to Alzheimer's disease) report that their dogs suffer from difficulty sleeping. The aim of this study was to quantify age-related changes in the sleep-wakefulness cycle macrostructure and electroencephalographic features in senior dogs and to correlate them with their cognitive performance. Methods: We performed polysomnographic recordings in 28 senior dogs during a 2 h afternoon nap. Percentage of time spent in wakefulness, drowsiness, NREM, and REM sleep, as well as latency to the three sleep states were calculated. Spectral power, coherence, and Lempel Ziv Complexity of the brain oscillations were estimated. Finally, cognitive performance was evaluated by means of the Canine Dementia Scale Questionnaire and a battery of cognitive tests. Correlations between age, cognitive performance and sleep-wakefulness cycle macrostructure and electroencephalographic features were calculated. Results: Dogs with higher dementia scores and with worse performance in a problem-solving task spent less time in NREM and REM sleep. Additionally, quantitative electroencephalographic analyses showed differences in dogs associated with age or cognitive performance, some of them reflecting shallower sleep in more affected dogs. Discussion: Polysomnographic recordings in dogs can detect sleep-wakefulness cycle changes associated with dementia. Further studies should evaluate polysomnography's potential clinical use to monitor the progression of canine cognitive dysfunction syndrome.

Hymenolepiasis Caused by Hymenolepis nana in Humans and Natural Infection in Rodents in a Marginal Urban Sector of Guayaquil, Ecuador.

BACKGROUND Hymenolepiasis is a globally prevalent zoonosis of the monoxenic cycle. Humans acquire the disease through fecal-oral transmission by ingesting food or water with infective eggs from infected rodents. This report presents 3 cases of hymenolepiasis in children, due to zoonotic transmission from rodents and presumably associated with the consumption of powdered milk contaminated with infective eggs of Hymenolepis nana, and shows that awareness and early diagnosis contributed to timely treatment of the disease. CASE REPORT Three children, aged 9, 12, and 13 years, living in a marginal urban area of Guayaquil, Guayas province, Ecuador, presented symptoms of diarrhea, low body weight, abdominal discomfort, anorexia, paleness, and anal itching. Subsequently, their fecal samples were analyzed by direct coproparasitic methods, flotation and sedimentation with centrifugation using saline solution; the presence of H. nana eggs was determined. Blood biometry was performed. Further, 10 rodents were captured and necropsied to obtain intestinal contents. The powdered milk consumed by the children was analyzed, the same powder that contained rodent feces. Subsequently, these were studied with the above-mentioned coproparasitic methods. H. nana eggs were identified in the 6 trapped rodents, the powdered milk, and the feces of rodents found in the milk powder. CONCLUSIONS Hymenolepiasis can affect populations of endemic areas. In this case, the disease was identified in 3 children, who were diagnosed with eosinophilia and anemia. Additionally, the presence of H. nana eggs in captured rodents and in powdered milk was determined, indicating that the community was exposed to this zoonotic disease.

The Interaction of Slaughtering, Drying, and Defatting Methods Differently Affects Oxidative Quality of the Fat from Black Soldier Fly (Hermetia illucens) Larvae.

The interrelation effect of slaughtering, drying, and defatting methods of BSFL on the oxidative quality of the derived fat was studied. Blanching and freezing were compared as slaughtering methods, followed by oven or freeze-drying for drying and mechanical pressing or SFE for defatting. The oxidative state and stability of the extracted fat and defatted meals were monitored immediately after their production, using peroxide value (PV) and Rancimat test, and over 24 weeks of storage. Slaughtering and drying methods had an independent effect on PV, with freezing and freeze-drying being the best methods. Mechanical pressing and SFE were comparable and superior to conventional hexane defatting. Interactions were observed between slaughtering and defatting, drying and defatting, and between all three factors. Generally, freeze-drying combined with any of the slaughtering and defatting methods resulted in the lowest PVs, with mechanical pressing being preferred. Freeze-drying plus mechanical pressing also produced the most stable fats during storage according to the evolution of PV, while the combination of blanching and SFE produced the least stable. A significant correlation was found between the PV at 24 weeks and the antioxidant activity of the fats. Contrary to storage assays, in accelerated Rancimat assays, freeze-dried samples were the least stable, which was partially attributed to the significant correlation with the acid values of the samples. Defatted meals followed a similar pattern to the extracted fat, except for worse oxidation for SFE defatting. Therefore, the different processing methods of slaughtering, drying, and defatting of BSFL differently affect lipid oxidation, with interactions between such successive steps.

Enfermedad de Fabry: revisión para el cardiólogo clínico / Fabry disease: review for the clinical cardiologist / Doença de Fabry: revisão para o cardiologista clínico

La enfermedad de Fabry es una afección genética producida por un déficit total o parcial de la enzima alfagalactosidasa A implicada en el catabolismo de glicoesfingolípidos. Dicha alteración genera el depósito lisosomal del residuo globotriasilceramida (Gb-3) a nivel multitisular, a predominio de los sistemas renal, cardíaco, nervioso y cutáneo. Debido a su baja prevalencia y su variada presentación clínica representa un verdadero reto diagnóstico. La combinación de antecedentes familiares de cardiopatía y afección renal, diferentes grados de hipertrofia del ventrículo izquierdo, sumado a afecciones cutáneas, neurológicas y enfermedad renal progresiva, deben hacer plantear la posibilidad de una enfermedad de Fabry. El cardiólogo que estudia un paciente con hipertrofia ventricular es quien debe sospecharla, y debe hacer un diagnóstico diferencial con miocardiopatías hipertróficas, cardiopatía hipertensiva u otras miocardiopatías por depósitos. Los aportes diagnósticos de la resonancia magnética cardíaca han sido de suma importancia en los últimos años. Los estudios enzimáticos y genéticos, antes de muy difícil adquisición en nuestro medio, son factibles en la actualidad. Un diagnóstico temprano es clave para iniciar el tratamiento enzimático sustitutivo, evitar un daño más extenso e irreversible, e identificar los familiares afectados en fases iniciales.

Fabry disease is a genetic condition caused by a total or partial deficiency of the enzyme alphagalactosidase A involved in the catabolism of glycosphingolipids. This alteration generates the lysosomal deposit of the globotriasylceramide residue (Gb-3) at the multi-tissue level, predominantly in the kidneys, heart, nervous system and skin. Due to its low prevalence and its varied clinical presentation, it represents a true diagnostic challenge. The combination of family history of heart disease and kidney disease, different degrees of hypertrophy of the left ventricle, added to skin and neurological conditions and progressive kidney disease, should raise the possibility of Fabry disease. The cardiologist who studies a patient with ventricular hypertrophy is the one who should suspect it and make a differential diagnosis of hypertrophic cardiomyopathies, hypertensive heart disease or other cardiomyopathies due to deposits. Diagnostic complementation with a cardiac resonance study has been extremely important in recent years. Enzymatic and genetic studies, previously very difficult to acquire in our environment, are currently feasible. An early diagnosis is key to starting enzyme replacement therapy, avoiding more extensive and irreversible damage, and allowing affected family members to be identified in the early stages.

A doença de Fabry é uma condição genética causada por uma deficiência total ou parcial da enzima alfagalactosidase A envolvida no catabolismo de glicoesfingolipídeos. Essa alteração gera o depósito lisossomal do resíduo globotriasilceramida (Gb-3) em nível multitecidual, predominantemente nos rins, coração, sistema nervoso e pele. Devido à sua baixa prevalência e à sua apresentação clínica variada, representa um verdadeiro desafio diagnóstico. A combinação de história familiar de cardiopatia e doença renal, diferentes graus de hipertrofia do ventrículo esquerdo, somada a condições dermatológicas e neurológicas e doença renal progressiva, deve levantar a possibilidade de doença de Fabry. O cardiologista que estuda um paciente com hipertrofia ventricular é quem deve suspeitar e fazer um diagnóstico diferencial de cardiomiopatias hipertróficas, cardiopatias hipertensivas ou outras cardiomiopatias por depósitos. A complementação diagnóstica com estudo de ressonância cardíaca tem sido de extrema importância nos últimos anos. Estudos enzimáticos e genéticos, anteriormente muito difíceis de adquirir em nosso meio, são atualmente viáveis. O diagnóstico precoce é fundamental para iniciar a terapia de reposição enzimática, para evitar danos mais extensos e irreversíveis, e permite que os familiares afetados sejam identificados nos estágios iniciais.

Reporte de caso: enfermedad de Fabry en un adulto con enfermedad renal crónica y síntomas sistémicos característicos / A case report: Fabry disease in an adult with chronic kidney disease and characteristic systemic symptoms / Relato de um caso: doença de Fabry em um adulto com doença renal crônica e sintomas sistémicos característicos

Se presenta el caso de un paciente de sexo masculino, de 62 años, con antecedentes familiares de cardiopatía y enfermedad renal, y antecedentes personales de enfermedad renal crónica severa, por la que recibió trasplante renal. Es enviado a consulta cardiológica por dolores torácicos atípicos y episodios de hipotensión sintomática, se constata en el ecocardiograma: hipertrofia ventricular izquierda concéntrica y deformación miocárdica longitudinal del ventrículo izquierdo patológica. La resonancia magnética cardíaca encuentra un patrón de realce tardío sugestivo de enfermedad de Fabry, diagnóstico que se confirma con dosificación enzimática y estudio genético. Recibe tratamiento específico con una buena respuesta inicial. Esta es una enfermedad sistémica metabólica congénita en la que el diagnóstico y el tratamiento específico se realiza en la edad adulta.

It is presented a 62-year-old male patient with a family history of heart and kidney disease, and a personal history of chronic kidney disease, for which he received a kidney transplant. He was sent to the cardiology department due to atypical chest pain and episodes of symptomatic hypotension. The echocardiogram revealed: concentric left ventricular hypertrophy and pathological longitudinal myocardial deformation of the left ventricle. Cardiac magnetic resonance finds a pattern of late enhancement suggestive of Fabry disease, a diagnosis that is confirmed with enzyme dosage and genetic study. He receives specific treatment with a good initial response. This is a congenital metabolic systemic disease in which the diagnosis and specific treatment is carried out in adulthood.

Se apresenta o caso de um paciente do sexo masculino, 62 anos, com histórico familiar de cardiopatia e doença renal e histórico pessoal de doença renal crônica grave, para o qual recebeu transplante de rim. Foi encaminhado ao serviço de cardiologia por dor torácica atípica e episódios de hipotensão sintomática. O ecocardiograma revelou: hipertrofia ventricular esquerda concêntrica e deformação miocárdica longitudinal patológica do ventrículo esquerdo. A ressonância magnética cardíaca encontra um padrão de realce tardio sugestivo de doença de Fabry, diagnóstico confirmado com dosagem enzimática e estudo genético. Recebe tratamento específico com boa resposta inicial. Tratase de uma doença sistêmica metabólica congênita em que o diagnóstico e o tratamento específico são realizados na idade adulta.

Which biological pathways are responsible for the late appearance of brain metastases in renal cell carcinoma? Analysis of eight cases.

Background: Renal cell carcinoma (RCC) represents 1% of all cancers and its brain metastases amount to 8.1% of all metastatic tumors. Late brain metastases are defined as tumors that appear 10 years after diagnosis of the primary lesion. The objective of this work is to discuss which biological pathways are responsible for the late appearance of these metastases analyzing eight cases. Case Description: We report here eight cases of late brain metastases of RCC treated between 2018 and 2021. Patients consulted for different clinical complaints. Brain magnetic resonance imaging and computed tomography scan were performed on all patients. They were treated by complete surgical resection plus radiosurgery or by radiosurgery alone. The histology of most metastases showed clear cell RCC. Conclusion: In the presence of a patient with an intracranial tumor and a history of RCC with more than 10 years of evolution, the presence of late metastasis should always be considered. There are many theories described in the literature that try to explain the late appearance of brain metastases from RCC (low mitotic index, impaired immune system, cross talk, self-seeding, and among others).

The TRIPLE PHD FINGERS proteins are required for SWI/SNF complex-mediated +1 nucleosome positioning and transcription start site determination in Arabidopsis.

Eukaryotes have evolved multiple ATP-dependent chromatin remodelers to shape the nucleosome landscape. We recently uncovered an evolutionarily conserved SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeler complex in plants reminiscent of the mammalian BAF subclass, which specifically incorporates the MINUSCULE (MINU) catalytic subunits and the TRIPLE PHD FINGERS (TPF) signature subunits. Here we report experimental evidence that establishes the functional relevance of TPF proteins for the complex activity. Our results show that depletion of TPF triggers similar pleiotropic phenotypes and molecular defects to those found in minu mutants. Moreover, we report the genomic location of MINU2 and TPF proteins as representative members of this SWI/SNF complex and their impact on nucleosome positioning and transcription. These analyses unravel the binding of the complex to thousands of genes where it modulates the position of the +1 nucleosome. These targets tend to produce 5'-shifted transcripts in the tpf and minu mutants pointing to the participation of the complex in alternative transcription start site usage. Interestingly, there is a remarkable correlation between +1 nucleosome shift and 5' transcript length change suggesting their functional connection. In summary, this study unravels the function of a plant SWI/SNF complex involved in +1 nucleosome positioning and transcription start site determination.

Insights into induction of the immune response by the hepatitis B vaccine.

After more than four decades of hepatitis B virus (HBV) vaccine implementation, its safety and efficacy in preventing HBV infection have been proven and several milestones have been achieved. Most countries have included HBV immunization schedules in their health policies and progress has been made regarding universalization of the first HBV vaccine dose at birth. All of these actions have significantly contributed to reducing both the incidence of HBV infection and its related complications. However, there are still many drawbacks to overcome. The main concerns are the deficient coverage rate of the dose at birth and the large adult population that has not been reached timely by universal immunization. Additionally, the current most widely used second-generation vaccines do not induce protective immunity in 5% to 10% of the population, particularly in people over 40-years-old, obese (body mass index > 25 kg/m2), heavy smokers, and patients undergoing dialysis or infection with human immunodeficiency virus. Recently developed and approved novel vaccine formulations using more potent adjuvants or multiple antigens have shown better performance, particularly in difficult settings. These advances re-launch the expectations of achieving the World Health Organization's objective of completing hepatitis control by 2030.

Molecular and biological characterization of hepatitis B virus subgenotype F1b clusters: Unraveling its role in hepatocarcinogenesis.

Hepatitis B virus (HBV) subgenotype F1b infection has been associated with the early occurrence of hepatocellular carcinoma in chronically infected patients from Alaska and Peru. In Argentina, however, despite the high prevalence of subgenotype F1b infection, this relationship has not been described. To unravel the observed differences in the progression of the infection, an in-depth molecular and biological characterization of the subgenotype F1b was performed. Phylogenetic analysis of subgenotype F1b full-length genomes revealed the existence of two highly supported clusters. One of the clusters, designated as gtF1b Basal included sequences mostly from Alaska, Peru and Chile, while the other, called gtF1b Cosmopolitan, contained samples mainly from Argentina and Chile. The clusters were characterized by a differential signature pattern of eight nucleotides distributed throughout the genome. In vitro characterization of representative clones from each cluster revealed major differences in viral RNA levels, virion secretion, antigen expression levels, as well as in the localization of the antigens. Interestingly, a differential regulation in the expression of genes associated with tumorigenesis was also identified. In conclusion, this study provides new insights into the molecular and biological characteristics of the subgenotype F1b clusters and contributes to unravel the different clinical outcomes of subgenotype F1b chronic infections.

Comprehensive identification of SWI/SNF complex subunits underpins deep eukaryotic ancestry and reveals new plant components.

Over millions of years, eukaryotes evolved from unicellular to multicellular organisms with increasingly complex genomes and sophisticated gene expression networks. Consequently, chromatin regulators evolved to support this increased complexity. The ATP-dependent chromatin remodelers of the SWI/SNF family are multiprotein complexes that modulate nucleosome positioning and appear under different configurations, which perform distinct functions. While the composition, architecture, and activity of these subclasses are well understood in a limited number of fungal and animal model organisms, the lack of comprehensive information in other eukaryotic organisms precludes the identification of a reliable evolutionary model of SWI/SNF complexes. Here, we performed a systematic analysis using 36 species from animal, fungal, and plant lineages to assess the conservation of known SWI/SNF subunits across eukaryotes. We identified evolutionary relationships that allowed us to propose the composition of a hypothetical ancestral SWI/SNF complex in the last eukaryotic common ancestor. This last common ancestor appears to have undergone several rounds of lineage-specific subunit gains and losses, shaping the current conformation of the known subclasses in animals and fungi. In addition, our results unravel a plant SWI/SNF complex, reminiscent of the animal BAF subclass, which incorporates a set of plant-specific subunits of still unknown function.