Abstract Introduction. Heavy metal pollution is a growing problem due to human activities. Plants can remove, destroy, or transform contaminants from soil, water, and air. By using plant growth regulators and chelating agents, heavy metal toxicity can be reduced. Objective. To evaluate the effect of applying a mixture of oligogalacturonides on peroxidase activity and the contents of malondialdehyde, total protein, and chlorophylls in tomato plants (Solanum lycopersicum L.) var. Amalia subjected to high levels of heavy metals. Materials and methods. Soil contaminated with Cu, Cd, and Fe was collected from the Adalberto Vidal White Ceramic Company in Mayabeque, Cuba, in 2020. The experiment was conducted in 7 kg capacity bags using tomato plants, under semi-controlled conditions at the Instituto Nacional de Ciencias Agrícolas (INCA), with a completely randomized experimental design with each treatment having ten replicates. The treatments with the oligogalacturonides (Ogal) were soil application (30 mg kg-1); foliar spray (20 mg L-1), the combination of these application forms, and a control. Peroxidase activity and the contents of malondialdehyde, total protein, and chlorophylls were determined at 35 and 56 days after the plant’s emergence. Results. The effect of Cu, Cd, and Fe on the seedlings was attenuated by all the use of the Ogal mixture variants use, indicating that they have developed adaptation mechanisms to high metal concentrations which allows to withstand abiotic stress. Conclusions. The Ogal mixture attenuated the effect of heavy metals on peroxidase activity, malondialdehyde content, total proteins, and chlorophylls in Amalia tomato plants.

Resumen Introducción. La contaminación por metales pesados es un problema que ha ido en aumento, debido a las actividades antrópicas. Las plantas pueden eliminar, destruir o transformar contaminantes del suelo, agua y aire. Con el empleo de reguladores del crecimiento vegetal y agentes quelantes se puede reducir la toxicidad por metales pesados. Objetivo. Evaluar el efecto de la aplicación de una mezcla de oligogalacturónidos sobre la actividad peroxidasa y los contenidos de malondialdehido, proteinas totales y clorofilas, en plantas de tomate (Solanum lycopersicum L.) var. Amalia sometidas a altos niveles de metales pesados. Materiales y métodos. Se colectó suelo contaminado con Cu, Cd y el Fe, en la Empresa cerámica blanca Adalberto Vidal de Mayabeque, Cuba en el año 2020. El experimento se desarrolló en bolsas de 7 kg de capacidad y se utilizaron plantas de tomate, en condiciones semi controladas en áreas del Instituto Nacional de Ciencias Agrícolas (INCA), con un diseño experimental completamente aleatorizado con siete tratamientos y diez réplicas. Los tratamientos del producto a base de oligogalacturónidos (Ogal) fueron: aplicación al suelo (30 mg kg-1); aspersión foliar (20 mg L-1), la combinación de estas formas de aplicación y un testigo. A los 35 y 56 días de emergidas las plantas, se determinó la actividad peroxidasa y los contenidos de malondialdehido, proteinas totales y clorofilas. Resultados. El efecto que provocan el Cu, Cd y el Fe en las plántulas, fue atenuado por todas las variantes de uso de la mezcla Ogal, por lo que las mismas han desarrollado mecanismos de adaptación ante las altas concentraciones metálicas que le permiten subsistir al estrés abiótico. Conclusiones. La mezcla de Ogal atenuó el efecto que provocan los metales pesados en la actividad peroxidasa, el contenido malondialdehido, proteínas totales y clorofilas en plantas de tomate var. Amalia.

Abstract In this research, we study the real-time development of the assibilation of prepausal /ɾ/ in the Spanish spoken in the state of Guanajuato. For this purpose, we analyze data on the Spanish spoken in the cities of Guanajuato (capital), Pénjamo (southwest), and San Luis de la Paz (northeast) from both a corpus of sociolinguistic interviews collected in 2019 and from interviews conducted in the same towns in 1972-1973 for the Atlas lingüístico de México (Lope Blanch 1990-2000). Our working hypothesis is that assibilation has spread in the state of Guanajuato by relocation. The data provided by both real-time and apparent time have allowed us to corroborate this hypothesis, with San Luis de la Paz being the locality where assibilation is just reaching its greatest vitality. As for other sociolinguistic dimensions of this process, we have once again confirmed that it is women who adopt the assibilant variants of /ɾ/ at the highest rate. Finally, on a purely linguistic level, our findings point to the fact that it is the front vowels /i e/ as a previous phonetic context and the lexical items of verbal category that are the linguistic variables favoring assibilation.

Resumen En esta investigación, se estudia el desarrollo en tiempo real de la asibilación de la /ɾ/ prepausal en el español del estado de Guanajuato. Para ello, se analizaron los datos del español hablado en las ciudades de Guanajuato (capital), Pénjamo (suroeste) y San Luis de la Paz (noreste) provenientes tanto de un corpus de entrevistas sociolingüísticas recogidas en 2019 como de las entrevistas realizadas en las mismas poblaciones en 1972-1973 para el Atlas lingüístico de México (Lope Blanch 1990-2000). Nuestra hipótesis de trabajo es que la asibilación se ha difundido en el estado de Guanajuato por relocalización. Los datos aportados tanto por el tiempo real como por el tiempo aparente nos han permitido corroborar esta hipótesis, siendo San Luis de la Paz la localidad donde la asibilación apenas está alcanzando su mayor vitalidad. En cuanto a otras dimensiones sociolingüísticas de este proceso, hemos confirmado una vez más que son las mujeres quienes patrocinan las variantes asibiladas de /ɾ/. Finalmente, en el plano netamente lingüístico, nuestros hallazgos apuntan a que son las vocales anteriores /i e/ como contexto fónico previo y las piezas léxicas de categoría verbal las variables lingüísticas que favorecen la asibilación.

Abstract Introduction: Hermetia illucens is a fly found worldwide in tropical and temperate regions that feeds on decaying organic matter in its larval stage, which makes them useful to accelerate composing processes. Bacterial component on the larval guts that helps to degrade organic matter is well studied, however fungal communities information is more scarse, specially in tropical regions. Objective: To determine fungal communities in the gut of H. illucens larvae naturally occurring during urban composting processes in a tropical region. Methods: ITS sequencing was employed to characterize fungal communities present in H. illucens larval gut. Results: The analysis of amplicon sequence variants (ASVs) unveiled a notable dominance of Saccharomycetales, being yeasts of the genus Pichia the most abundant. Other relatively abundant yeasts were Candida and Galactomyces and the genus Archaeospora from Archaeosporales. The last two groups not being reported in H. illucens before. Conclusions: Yeasts of the genus Pichia are the most abundant group, this result is in concordance with previous studies which suggest a stable insect-yeast relation. The description of previously unreported fungal groups highlights the importance of continuing to explore the mycobiome dynamics of this larva. This study offers insight into the mycobiome of naturally occurring H. illucens larvae in a tropical region.

Resumen Introducción: Hermetia illucens se distribuye mundialmente en regiones tropicales y templadas. En su estado larval se alimenta de materia orgánica en descomposición, lo que las hace útiles para acelerar los procesos de compostaje. Se han realizado diversos estudios sobre el componente bacteriano de los intestinos de las larvas que ayuda a degradar la materia orgánica, sin embargo, información sobre las comunidades de microhongos es más escasa, especialmente en regiones tropicales. Objetivo: Determinar el micobioma presente en los intestinos de las larvas de H. illucens que se desarrollaron naturalmente en compostajes urbanos en una región tropical. Métodos: Se realizó secuenciación ITS para caracterizar las comunidades de microhongos presentes en el intestino de las larvas. Resultados: El análisis de variantes de secuencia de amplicones (ASV) reveló una notable dominancia de Saccharomycetales, siendo las levaduras del género Pichia las más abundantes. Otras levaduras relativamente abundantes fueron Candida y Galactomyces y el género Archaeospora de Archaeosporales. Los dos últimos grupos no han sido reportados previamente en H. illucens. Conclusión: Determinamos que las levaduras del género Pichia son el grupo más abundante. Este resultado concuerda con estudios previos, lo que sugiere una relación estable entre estos dos organismos. La descripción de grupos de hongos no reportados previamente resalta la importancia de continuar explorando la dinámica del micobioma de esta larva. Este estudio proporciona información sobre el micobioma de las larvas de H. illucens que se presentan naturalmente en una región tropical.

Abstract Prurigo is a reactive, hyperplastic skin condition characterized by pruritic papules, plaques, and/or nodules. The temporal classification includes acute/subacute and chronic disease (≥ 6 weeks), with different clinical variants, synonymies, and underlying etiological factors. The immunology of chronic prurigo shows similarities with atopic dermatitis due to the involvement of IL-4 and IL-13, IL-22, and IL-31. Treatment includes antihistamines, topical steroids, dupilumab, and JAK inhibitors. Several conditions manifest clinically as prurigo-like lesions, and the correct clinical diagnosis must precede correct treatment. Furthermore, chronic prurigos represent a recalcitrant and distressing dermatosis, and at least 50% of these patients have atopic diathesis, the treatment of which may induce adverse effects, especially in the elderly. The quality of life is significantly compromised, and topical treatments are often unable to control symptoms and skin lesions. Systemic immunosuppressants, immunobiologicals, and JAK inhibitors, despite the cost and potential adverse effects, may be necessary to achieve clinical improvement and quality of life. This manuscript reviews the main types of prurigo, associated diseases, their immunological bases, diagnosis, and treatment. reactive papules plaques andor or nodules acutesubacute acute subacute ≥ ( weeks, weeks , weeks) variants synonymies factors IL4 IL 4 IL- IL13, IL13 13, 13 IL-13 IL22, IL22 22, 22 IL-22 IL31. IL31 31. 31 IL-31 antihistamines steroids dupilumab inhibitors prurigolike like lesions Furthermore dermatosis 50 diathesis effects elderly compromised immunosuppressants immunobiologicals diseases bases IL1 1 IL-1 IL2 2 IL-2 IL3 3 IL-3 5

Abstract Background Tuberous sclerosis complex (TSC) is a multisystem neurocutaneous syndrome with variable phenotypes. Recent updates of TSC diagnostic criteria reaffirmed the defined genetic diagnostic criterion as the finding of a pathogenic DNA alteration in either TSC1 or TSC2 genes. It also slightly modified definite clinical diagnostic criteria. TSC-associated skin lesions in infancy are important clinical signs to select individuals with possible TSC for a closer clinical follow-up and genetic testing. Objective To raise awareness of the updated TSC diagnosis criteria; to assess the frequency of skin lesions in TSC patients as well as the first dermatological presentation; and to associate the findings with either TSC1 or TSC2 mutations. Methods Observational cross-sectional study. Clinical and genetic data were retrospectively collected from 37 TSC patients from a Brazilian University Hospital. Patients with skin signs were examined and prospectively assessed for 12 months. Results The earliest cutaneous lesions were hypomelanotic macules, which together with angiofibromas were the most frequent dermatological lesions. The total pathogenic DNA alteration ratio between TSC2 and TSC1 genes was 8:1. The frequency of a TSC2 pathogenic variant was 10-fold greater in the presence of ungual fibromas. Study limitations Small sample and a limited number of patients with TSC1 pathogenic variants. Conclusion Clinicians should be knowledgeable about TSC updated diagnostic criteria. Patients need to be followed up by a multidisciplinary team and treated accordingly. Early detection of cutaneous lesions is important for TSC diagnosis. A significant association between TSC2 gene pathogenic alterations and ungual fibromas is described. (TSC phenotypes TSCassociated associated followup follow testing presentation mutations crosssectional cross sectional study 3 Hospital 1 months macules 81. 81 8 1. 8:1 10fold fold 10 variants accordingly described 8:

Abstract Hydrops fetalis corresponds to the accumulation of fluid in soft tissues and/or body cavities. Hydrops fetalis is classified as immune (IFH) and non-immune (NIFH). NIFH can be secondary to multiple etiologies: aneuploidy, congenital heart disease, and various monogenic disorders. The prenatal exome increases the diagnostic yield by 3-19% in cases of NIFH with normal karyotype and microarray, if isolated or associated with other anomalies, respectively. Aberrant development of the lymphatic system has been associated with more than 20 genetic variants, one of them in the PIEZO1 gene that produces two diseases: hereditary dehydrated stomatocytosis and lymphatic malformation 6, both conditions related to NIFH with similar phenotypes. We report a case of NIFH with normal conventional cytogenetic study in which a prenatal exome study was performed identifying a pathogenic variant in PIEZO1 gene allowing to establish that both conditions have a favorable perinatal prognosis. The prenatal exome study of NIFH with normal karyotype is widely justified, despite its high cost and low accessibility in our setting, to stablish the perinatal prognosis and adequately advise parents in terms of recurrence.

Resumen La hidropesía fetal corresponde a la acumulación de líquido en tejidos blandos y/o cavidades corporales. La hidropesía fetal se clasifica en inmune (HFI) y no inmune (HFNI). La HFNI puede ser secundaria a múltiples causas: aneuploidías, cardiopatías congénitas y diversos trastornos monogénicos que afectan a diversos sistemas. El exoma prenatal aumenta el rendimiento diagnóstico un 3-19% en casos de HFNI con cariotipo y microarreglo normal, si es aislado o está asociado a otras anomalías, respectivamente. El desarrollo anómalo del sistema linfático se ha asociado con más de 20 variantes, una de ellas en el gen PIEZO1 que produce dos enfermedades: estomatocitosis hereditaria deshidratada y la malformación linfática 6, ambas condiciones relacionadas con HFNI con fenotipos similares. Se reporta un caso de HFNI con estudio citogenético convencional normal en que se realiza estudio del exoma prenatal identificando una variante patogénica en gen PIEZO1, permitiendo establecer que ambas condiciones poseen un pronóstico perinatal favorable. El estudio con exoma prenatal de la HFNI con cariotipo normal se justifica ampliamente, a pesar de su alto costo y escasa disponibilidad aún en nuestro medio, para precisar el pronóstico perinatal y asesorar de forma adecuada a los padres en términos de recurrencia.

Abstract Sideroblastic anemias (SAs) are a heterogeneous group of rare pathologies in which heme biosynthesis and iron utilization during hemoglobin synthesis is affected. They are characterized by the presence in the bone marrow of erythroid precursors with pathological iron deposits in the mitochondria. They can be congenital or acquired. The most common hereditary form is X-linked (XLSA), caused by genetic variants in the ALAS2 gene, which encodes for the first enzyme in heme biosynthesis, the delta-aminolevulinic acid synthetase 2 (ALAS2). It predominantly affects hemizygous males, who present with microcytic hypochromic anemia. In some patients, treatment with pyridoxal phosphate is effective. We present three related cases of XLSA due to alteration in the ALAS2 gene.

Resumen Las anemias sideroblásticas (AS) son un grupo heterogéneo de patologías raras en las que se ve afectada la biosíntesis del hemo y la utilización del hierro durante la síntesis de la hemoglobina. Se caracterizan por la presencia en médula ósea de precursores eritroides con depósitos patológicos de hierro en las mitocondrias. Pueden ser congénitas o adquiridas. La forma hereditaria más común es la ligada al cromosoma X (ASLX), debido a variantes genéticas en el gen ALAS2 que codifica para la primera enzima en la biosíntesis del hemo, la delta aminolevulinato sintetasa 2 (ALAS2). Afecta predominantemente a varones hemicigotas, que se presentan con anemia microcítica hipocrómica. En algunos pacientes es efectivo el tratamiento con fosfato de piridoxal. Presentamos tres casos relacionados de ASLX por alteración del gen ALAS2.

Abstract Renal involvement is one of the most severe morbidities of Fabry disease (FD), a multisystemic lysosomal storage disease with an X-linked inheritance pattern. It results from pathogenic variants in the GLA gene (Xq22.2), which encodes the production of alpha-galactosidase A (α-Gal), responsible for glycosphingolipid metabolism. Insufficient activity of this lysosomal enzyme generates deposits of unprocessed intermediate substrates, especially globotriaosylceramide (Gb3) and derivatives, triggering cellular injury and subsequently, multiple organ dysfunction, including chronic nephropathy. Kidney injury in FD is classically attributed to Gb3 deposits in renal cells, with podocytes being the main target of the pathological process, in which structural and functional alterations are established early and severely. This configures a typical hereditary metabolic podocytopathy, whose clinical manifestations are proteinuria and progressive renal failure. Although late clinical outcomes and morphological changes are well established in this nephropathy, the molecular mechanisms that trigger and accelerate podocyte injury have not yet been fully elucidated. Podocytes are highly specialized and differentiated cells that cover the outer surface of glomerular capillaries, playing a crucial role in preserving the structure and function of the glomerular filtration barrier. They are frequent targets of injury in many nephropathies. Furthermore, dysfunction and depletion of glomerular podocytes are essential events implicated in the pathogenesis of chronic kidney disease progression. We will review the biology of podocytes and their crucial role in regulating the glomerular filtration barrier, analyzing the main pathogenic pathways involved in podocyte injury, especially related to FD nephropathy. FD, , (FD) Xlinked X linked pattern Xq22.2, Xq222 Xq Xq22.2 Xq22 2 (Xq22.2) alphagalactosidase alpha galactosidase αGal, αGal α Gal (α-Gal) metabolism substrates Gb (Gb3 derivatives subsequently nephropathy process severely podocytopathy failure elucidated capillaries barrier nephropathies Furthermore progression (FD Xq22. Xq2 (Xq22.2 (α-Gal (Gb (Xq22. (Xq22 (Xq2 (Xq

Resumo O acometimento renal é uma das mais severas morbidades da doença de Fabry (DF), enfermidade multissistêmica de depósito lisossômico com padrão de herança ligada ao cromossomo X, decorrente de variantes patogênicas do gene GLA (Xq22.2), que codifica a produção de alfa-galactosidase A (α-Gal), responsável pelo metabolismo de glicoesfingolipídeos. A atividade insuficiente dessa enzima lisossômica gera depósitos de substratos intermediários não processados, especialmente do globotriaosilceramida (Gb3) e derivados, desencadeando injúria celular e, posteriormente, disfunção de múltiplos órgãos, incluindo a nefropatia crônica. A lesão renal na DF é classicamente atribuída aos depósitos de Gb3 nas células renais, sendo os podócitos o alvo principal do processo patológico, nos quais as alterações estruturais e funcionais são instaladas de forma precoce e severa, configurando uma podocitopatia metabólica hereditária típica, cujas manifestações clínicas são proteinúria e falência renal progressiva. Embora os desfechos clínicos tardios e as alterações morfológicas estejam bem estabelecidos nessa nefropatia, os mecanismos moleculares que deflagram e aceleram a injúria podocitária ainda não estão completamente elucidados. Podócitos são células altamente especializadas e diferenciadas que revestem a superfície externa dos capilares glomerulares, desempenhando papel essencial na preservação da estrutura e função da barreira de filtração glomerular, sendo alvos frequentes de injúria em muitas nefropatias. A disfunção e depleção dos podócitos glomerulares são, além disso, eventos cruciais implicados na patogênese da progressão da doença renal crônica. Revisaremos a biologia dos podócitos e seu papel na regulação da barreira de filtração glomerular, analisando as principais vias patogênicas envolvidas na lesão podocitária, especialmente relacionadas à nefropatia da DF. DF, , (DF) X Xq22.2, Xq222 Xq Xq22.2 Xq22 2 (Xq22.2) alfagalactosidase alfa galactosidase αGal, αGal α Gal (α-Gal) glicoesfingolipídeos processados Gb (Gb3 derivados posteriormente órgãos crônica renais patológico severa típica progressiva elucidados glomerular nefropatias disso (DF Xq22. Xq2 (Xq22.2 (α-Gal (Gb (Xq22. (Xq22 (Xq2 (Xq

Resumo O complexo da esclerose tuberosa (CET) é uma doença autossômica dominante caracterizada pelo desenvolvimento de hamartomas no sistema nervoso central, coração, pele, pulmões e rins e outras manifestações, incluindo convulsões, tubérculos corticais, linhas de migração radial, autismo e deficiência cognitiva. A doença está associada a variantes patogênicas nos genes TSC1 ou TSC2, resultando na hiperativação da via mTOR, um importante regulador do crescimento e metabolismo celular. Consequentemente, a hiperativação da via mTOR leva à proliferação anormal do tecido e ao desenvolvimento de tumores sólidos. O envolvimento renal no CET é caracterizado pelo desenvolvimento de lesões císticas, carcinoma de células renais e angiomiolipomas renais, que podem progredir e causar dor, sangramento e perda da função renal. Nos últimos anos, houve uma mudança notável na abordagem terapêutica do CET, especialmente no tratamento das manifestações renais. Os inibidores de mTOR surgiram como a principal opção terapêutica, enquanto intervenções cirúrgicas como nefrectomia e embolização são reservadas principalmente para complicações que não respondem ao tratamento clínico, como hemorragia renal grave. Esta revisão se concentra nas principais características clínicas do CET, nos mecanismos subjacentes ao envolvimento renal, nos recentes avanços na terapia para lesões renais e nas perspectivas futuras. (CET central coração pele convulsões corticais radial cognitiva TSC TSC2 celular Consequentemente sólidos císticas dor anos clínico grave futuras

Abstract Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by the development of hamartomas in the central nervous system, heart, skin, lungs, and kidneys and other manifestations including seizures, cortical tubers, radial migration lines, autism and cognitive disability. The disease is associated with pathogenic variants in the TSC1 or TSC2 genes, resulting in the hyperactivation of the mTOR pathway, a key regulator of cell growth and metabolism. Consequently, the hyperactivation of the mTOR pathway leads to abnormal tissue proliferation and the development of solid tumors. Kidney involvement in TSC is characterized by the development of cystic lesions, renal cell carcinoma and renal angiomyolipomas, which may progress and cause pain, bleeding, and loss of kidney function. Over the past years, there has been a notable shift in the therapeutic approach to TSC, particularly in addressing renal manifestations. mTOR inhibitors have emerged as the primary therapeutic option, whereas surgical interventions like nephrectomy and embolization being reserved primarily for complications unresponsive to clinical treatment, such as severe renal hemorrhage. This review focuses on the main clinical characteristics of TSC, the mechanisms underlying kidney involvement, the recent advances in therapy for kidney lesions, and the future perspectives. (TSC system heart skin lungs seizures tubers lines disability genes metabolism Consequently tumors lesions angiomyolipomas pain bleeding function years option treatment hemorrhage perspectives

ABSTRACT Objectives. To determine the requirement and time to mechanical ventilation and Intensive Care Unit (ICU), hospitalization and hospitalization time, death and disability of the axonal variants of Guillain-Barré Syndrome (GBS) in comparison with the acute demyelinating variant in patients of all the ages. Materials and methods. The systematic review that included patients with GBS. The exposure variable was the axonal variants and the comparator was acute inflammatory demyelinating polyneuropathy (AIDP). The outcomes were the requirement and time on mechanical ventilation (MV), requirement and time in the ICU, hospitalization time, disability and death. The NewCasttle-Ottawa Scale (NOS) was used to assess risk of bias. A meta-analysis was conducted to calculate mean differences and relative risks (RR) with their 95% confidence intervals (CI) using inverse variances and random effects models. Results. Of the 3116 articles found, 46 met the selection criteria. The time on MV was 7.42 days (95% CI: 0.36 to 1.48) and the hospitalization time was 3.11 (95% CI: 0.73 to 5.49) days for the axonal variants. The axonal variants had a RR of 0.47 (95% CI: 0.24 to 0.92) for the requirement of MV in adults, but it was 1.68 (95% CI: 1.25 to 2.25) in children. There was a high statistical heterogeneity. Conclusions. Axonal variants showed, on average, longer MV and hospitalization time, overall and by subgroups. A high MV requirement was found for axonal variants in children; it was lower for adults.

RESUMEN Objetivos. Determinar el requerimiento y tiempo para ventilación mecánica y Unidad de Cuidados Intensivos (UCI), hospitalización y tiempo de hospitalización, muerte y discapacidad de las variantes axonales del Síndrome de Guillain-Barré (SGB) en comparación con la variante aguda desmielinizante en pacientes de todas las edades. Materiales y métodos. Revisión sistemática que incluyó pacientes con SGB; la exposición fueron las variantes axonales y el comparador la polineuropatía desmielinizante inflamatoria aguda (AIDP) los desenlaces fueron el requerimiento y tiempo en ventilación mecánica (VM), requerimiento y tiempo en la UCI, tiempo de hospitalización, discapacidad y muerte. Se utilizó la escala NewCasttle-Ottawa (NOS) para evaluar el riesgo de sesgo. Se realizó un metaanálisis para calcular las diferencias de medias y los riesgos relativos (RR) con sus intervalos de confianza (IC) del 95% utilizando varianzas inversas y modelos de efectos aleatorios. Resultados. De los 3116 artículos encontrados, 46 cumplieron los criterios de selección. El tiempo en VM fue 7,42 días (IC95%: 0,36 a 1,48) y el tiempo de hospitalización fue 3,11 (IC95%: 0,73 a 5,49) días en las variantes axonales. Las variantes axonales tuvieron un RR de 0,47 (IC95%: 0,24 a 0,92) para el requerimiento de VM en adultos, pero en niños fue de 1,68 (IC95%: 1,25 a 2,25). Hubo una alta heterogeneidad estadística. Conclusiones. Las variantes axonales tienen en promedio mayor tiempo de VM y de hospitalización, en total y por subgrupos. Se observó un mayor requerimiento de VM para las variantes axonales en niños; mientras que en los adultos fue menor.

Resumen Presentamos un paciente con una rara enfermedad autoinflamatoria sistémica (deficiencia de mevalonato quinasa -DMQ-) con la identificación de dos variantes heterocigotas (c.1129G>A y c.32C>T) en el gen Meval onato Quinasa, detectadas por secuenciación masiva en paralelo y una glomerulonefritis de alta prevalencia (nefropatía por IgA). El paciente presentó un cuadro de fiebre periódica recurrente mensual desde los 12 días de vida, acompañada de lesiones mucocutáneas (rash maculopapular en extremidades, estomatitis aftosa), compromiso articular (artralgias en tobillos, muñecas y rodillas), linfoideo (linfoadenopatía cervical, esplenome galia), gastrointestinal (diarrea, dolor abdominal) y renal (hematuria y proteinuria) con repetidas biospias most rando nefropatía por IgA alternando actividad y cronic idad. Durante el seguimiento, tuvo una pobre respuesta terapéutica a múltiples esquemas inmunosupresores utilizados durante 7 años (corticoides, azatrioprina, micofenolato, ciclofosfamida, rituximab y tocilizumab), y buena respuesta finalmente a canakinumab. Cuatro años posteriores al inicio de canakinumab, durante el curso de una infección por un absceso muscular, el cuadro clínico se complica con un evento microvascular renal grave (necrosis cortical renal -NCR-) con fallo renal agudo y necesidad de diálisis. Los episodios recurrentes de inflamación por la DMQ podrían actuar como gatil los para la reactivación de su glomerulonefritis (lo que explicaría la escasa respuesta a inmunosupresores y la progresión rápida a cronicidad histológica) y para gen erar un microambiente que predisponga el desarrollo de una NCR ante una infección no grave. En la DMQ se ha descripto un defecto en las moléculas de IgA, fenómeno también observado en la nefropatía por IgA. Esto plantea la desafiante hipótesis de un vínculo patogénico común entre todas las manifestaciones clínicas del paciente.

Abstract We present a patient with a rare systemic autoinflam matory disease (mevalonate kinase deficiency -MKD-) with the identification of two heterozygous variants (c.1129G>A and c.32C>T) in the Mevalonate Kinase gene, detected by next generation sequencing and a highly prevalent glomerulonephritis (IgA nephropathy). The patient presents clinically with a monthly recurrent periodic fever from 12 days of age, accompanied by mucocutaneous lesions (maculopapular rash in ex tremities, aphthous stomatitis), joint (arthralgias in ankles, wrists and knees), lymphoid (cervical lymph adenopathy, splenomegaly), gastrointestinal (diarrhea, abdominal pain) and kidney (hematuria and protei-nuria) with repeated biopsies showing IgA nephropathy alternating activity with chronicity. During follow-up. The patients presented a poor therapeutic response to multiple immunosuppressive regimens used for 7 years (corticosteroids, azathioprine, mycophenolate, cyclo phosphamide, rituximab and tocilizumab), and finally a good response to canakinumab. Four years after starting canakinumab, during the course of an infection due to a muscle abscess, the clinical presentation is complicated by a severe renal microvascular event (renal cortical necrosis -RCN-) with acute kidney injury and dialysis requirement. Therecurrent episodes of inflammation due to MKD could act as triggers for the reactivation of glomerulonephritis (which would explain the poor response to immunosuppressants and the rapid pro gression to histological chronicity) and to generate a microenvironment that predisposes the development of RCN in the face of a non-serious infection. A defect in IgA molecules has been described in MKD, a phenom enon also observed in IgA nephropathy. This raises the challenging hypothesis of a common pathogenetic link between all the patient’s clinical manifestations.

Resumen Introducción: La neoplasia endocrina múltiple tipo 1 (NEM1) es una enfermedad hereditaria autosómica dominante con una prevalencia estimada de 2-10:100 000. Las localizaciones principales de los tumores son glándulas paratiroides (HPT), tracto gastroenteropan creático (TGEP) y glándula pituitaria (TP). El objetivo de nuestra investigación fue describir el fenotipo y genotipo de pacientes argentinos con NEM1. Métodos: Estudiamos 68 casos índices diagnostica dos por presentar al menos dos de los tres tumores principales, o un tumor y un pariente con NEM1, y 84 familiares de primer grado. Secuenciamos la región codificante (exones 2-10); el promotor, exón 1; y las re giones intrónicas flanqueantes del gen MEN1 siguiendo el método de Sanger. Utilizamos MLPA en pacientes índice sin mutación. Resultados: Prevalencia de tumores: HPT 87.5%, TGEP 49% (p < 0.001), sin diferencias estadísticas entre las prevalencias de HPT vs TP (68%). Prevalencia de variantes patogénicas: 90% en casos familiares y 51% en esporádi cos. Hallamos 36 variantes patogénicas, 7 (20%) fueron noveles. Fueron 13 (36.2%) microarreglos con cambio en el marco de lectura, 9 (25%) variantes sin sentido, 8 (22.2%) con cambio de sentido, 3 (8.3%) en sitio de unión de empalme, 2 (5.5%) grandes deleciones y 1 microarre glo sin cambio en el marco de lectura. El 39 % (n = 33) de los parientes de primer grado en 23 familias fueron portadores de mutaciones. Conclusión: El fenotipo y genotipo de los pacientes argentinos con NEM1 fue similar al de otras poblaciones. Destacamos una alta frecuencia de TP y de variaciones patogénicas noveles.

Abstract Introduction: Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant inherited disease with an estimated prevalence of 2-10:100 000. The main locations of tumors are parathyroid glands (HPT), gas troenteropancreatic tract (GEPT), and anterior pituitary gland (PT). The aim of our investigation was to describe the phe notype and genotype of Argentinian patients with MEN1. Methods: A total of 68 index patients diagnosed with at least two of the three main tumors or one tumor and a relative with MEN1, and 84 first-degree relatives were studied. We sequenced the coding region (exons 2-10); the promoter, exon 1; and the flanking intronic regions of the MEN1 gene, following the Sanger method. We used MLPA in index patients without mutation. Results: Prevalence of tumors: HPT 87.5%, GEPT 49% (p< 0.001). No statistical differences in the prevalence of HPT vs. PT (68%). Prevalence of pathogenic variants: 90% in familial cases and 51% in sporadic cases. Of the different 36 pathogenic variants, 13 (36.2%) were frameshift micro-rearrangement, 8 (22.2%) were mis sense, 9 (25%) were nonsense, 3 (8.3%) were mutations in splicing sites, 2 (5.5%) were large deletions and, 1 in-frame micro-rearrangement. We found 7 novel pathogenic variants. Thirty-nine percent (n = 33) of first-degree relatives of 23 families were found to be mutation carriers. Conclusion: The phenotype and genotype of Argen tinian patients was similar to other MEN1 populations. A high frequency of PT and the identification of seven novel mutations are underscored.

Abstract: In order to evaluate the physicochemical and microbiological composition of functional beverages obtained from chayote pulp (Sechium edule) with L-carnitine. A randomized design with four replicates per treatment was used to evaluate chemical (dry matter, crude protein, ethereal extract, fiber, and ash), physical (pH, °Brix, acidity), and microbiological (mesophilic aerobes and molds and yeasts) parameters. The treatments studied were: V1, Chayote 100% plus 500 mg of L-carnitine; V2, Chayote 75% + 500 mg of L-carnitine and 25% of distilled water; V3, Chayote 75% + 250 mg of L-carnitine and 25% of distilled water; V4, Chayote 50% + 500 mg of L-carnitine and 50% of distilled water; V5, Chayote 50% + 250 mg of L-carnitine and 50% of distilled water. The pH values at V3 gradually decreased until day 21. Crude protein and ash differed (p<0.05) in V1 and V2 compared to the other treatments. While dry matter, ethereal, and nitrogen-free extract did not differ between the variants, mesophilic aerobes, molds, and yeasts were within the ranges (<3) of acceptance according to NTE INEN 1529-6 standards. Treatment V3 showed the highest pH reduction (5.09) compared to other variants after 21 days of storage. It is concluded that including different amounts of chayote pulp with L-carnitine is a suitable alternative to obtain functional beverages for human consumption.

Resumen: Con el objetivo de evaluar la composición fisicoquímica y microbiológica de las bebidas funcionales obtenidas a partir pulpa de chayote (Sechium edule) con L-Carnitina, se empleó un diseño completamente aleatorizado con cuatro repeticiones por tratamiento se evaluaron parámetros químicos (materia seca, proteína cruda, extracto eterio, fibra y ceniza), físicos (pH, °Brix, acidez) y microbiológicos (aerobios mesófilos y mohos y levaduras). Los tratamientos estudiados fueron: V1, Chayote 100 % más 500 mg de L-carnitina; V2, Chayote 75% + 500 mg L-Carnitina y 25% agua destilada; V3, chayote 75% +250 mg L-Carnitina y 25% agua destilada; V4, Chayote 50% + 500 mg L-Carnitina y 50% agua destilada; V5, Chayote 50% + 250 mg L-Carnitina y 50% agua destilada. Los valores de pH en el V3 se redujeron gradualmente hasta el día 21. La proteína cruda y ceniza difirieron (p<0.05) en los V1 y V2 frente a los demás. Mientras que la materia seca, extracto etéreo y extracto libre de nitrógeno, no presentaron diferencia entre variantes. Los aerobios mesófilos, mohos y levaduras estuvieron dentro los rangos (<3) de aceptación según las normas NTE INEN 1529-6. El tratamiento V3 fue el que presentó mayor reducción de pH (5,09) con frente a otras variantes a los 21dias de conservado. Se concluye, que la inclusión de diferentes cantidades de pulpa de chayote con L-Carnitina es una alternativa apropiada para obtener bebidas funcionales aptos para consumo humano.

Abstract Background: Utricularia jamesoniana, a small epiphytic plant found in wet tropical forests, stands out for its carnivorous habit, intricate trap system, and small but beautiful and complex flowers. This species remains relatively understudied despite its wide geographical distribution and curious adaptations. Questions: Our aim is to elucidate the composition of bacterial and fungal communities inhabiting both the bladders and leaves of Utricularia jamesoniana, facilitating the comprehension of the physiology and ecological dynamics of this carnivorous species. Methods: In this study, we employed 16S rRNA and ITS sequencing to compare the prokaryotic and fungal communities within leaves and traps of U. jamesoniana. Results: The analysis of amplicon sequence variants (ASVs) unveiled notable differences in community composition depending on the plant tissue and type of microorganism. Prokaryotic communities predominantly comprised Proteobacteria and Actinobacteriota, featuring genera such as Acidocella, Bradyrhizobium, Ferritrophicum, and Ferrovum. Fungal communities were dominated by Ascomycota and Basidiomycota, encompassing representatives of Dothideomycetes, Sordariomycetes, Eurotiomycetes, and Agaricomycetes, as well as ASVs related to Mycosphaerellaceae, Colletotrichum, Aspergillus, and Thanatephorus. We determined that the prokaryotic diversity was higher in the bladders with respect to the leaves. Fungal communities, in turn, were more diverse in leaves than in bladders. Conclusions: This study sheds light on the microbial communities associated with this carnivorous epiphyte and provides valuable insights into the intricate relationships between the plant and its microbial inhabitants across different tissues.

Resumen Antecedentes: Utricularia jamesoniana es una pequeña planta epífita que se encuentra en bosques tropicales húmedos. Destaca por su hábito carnívoro, su intrincado sistema de trampas y sus pequeñas pero complejas flores. A pesar de su amplia distribución geográfica y sus curiosas adaptaciones, esta especie sigue estando relativamente poco estudiada. Objetivo: Nuestro objetivo es dilucidar la composición de las comunidades bacterianas y fúngicas asociadas tanto en los utrículos como en las hojas de Utricularia jamesoniana, facilitando la comprensión de la fisiología y la dinámica ecológica de esta especie carnívora. Métodos: Empleamos la secuenciación de los marcadores 16S ARNr e ITS para comparar las comunidades procariotas y fúngicas dentro de hojas y trampas de U. jamesoniana. Resultados: El análisis de las variantes de secuencia de amplicones (ASVs) reveló notables diferencias en la composición de la comunidad dependiendo del tejido vegetal y del tipo de microorganismo. Las comunidades procariotas estaban compuestas predominantemente por Proteobacteria y Actinobacteriota, incluyendo los géneros Acidocella, Bradyrhizobium, Ferritrophicum y Ferrovum. Las comunidades fúngicas estaban dominadas por Ascomycota y Basidiomycota, con representantes de Dothideomycetes, Sordariomycetes, Eurotiomycetes y Agaricomycetes; así como ASVs relacionados con Mycosphaerellaceae, Colletotrichum, Aspergillus y Thanatephorus. La diversidad procariota es más alta en los utrículos con respecto a las hojas, pero las comunidades fúngicas fueron más diversas en las hojas que en los utrículos Conclusiones: Este estudio arroja luz sobre las comunidades microbianas asociadas a esta epífita carnívora y proporciona valiosos conocimientos sobre las intrincadas relaciones entre la planta y los habitantes microbianos asociados a sus diferentes tejidos.

Abstract Very early onset inflammatory bowel disease (VEOI BD) is a rare entity in pediatrics. Its association with pri mary immunodeficiencies of monogenic origin is known. We present the case of a patient diagnosed with VEOIBD who underwent massive paralleled exome sequencing. The result of the study showed a pathogenic variant in the RET proto-oncogene, associated with multiple endo crine neoplasia type 2A disease. There are no previous reports of association of RET proto-oncogene variants with VEOIBD. The presence of these two clinical entities cannot be attributed to a single genetic cause.

Resumen La enfermedad inflamatoria intestinal de inicio muy temprano (VEOIBD) es una entidad rara en pediatría. Es conocida su asociación con inmunodeficiencias prima rias de origen monogénico. Presentamos el caso de una paciente con diagnóstico de VEOIBD a quien se le realizó una secuenciación masiva del exoma. El resultado del estudio permitió identificar una variante patogénica en el proto oncogen RET, asociada con enfermedad neoplasia endocrina múltiple tipo 2A. No hay reportes de asociación de variantes en el proto oncogen RET con VEOIBD. No se puede adjudicar la presencia de estas dos entidades clínicas a una única causa genética.