RESUMEN
Amyloidosis are a group of diseases in which soluble proteins aggregate and deposit in fibrillar conformation extracellularly in tissues. The effectiveness of therapeutic strategies depends on the specific protein involved, being crucial to accurately determine its nature. Moreover, following the diagnosis, the search for the mutation within relatives allows the clinical advice. Here we report the precise diagnosis and explored the possible reasons of the structural pathogenicity for a renal amyloidosis related to a fibrinogen Aα-chain variant. Whole-exome sequencing and GATK calling pipeline were leveraged to characterize the protein variant present in a patient with kidney failure. Bioinformatics strategies were applied to suggest potential explanations of the variants aggregation. Our pipeline allowed the identification of a single-point variant of fibrinogen Aα-chain, which opened the possibility of curative transplantation. In silico structural analysis suggested that the pathogenicity of the variant may be attributed to a heightened susceptibility to yield a peptide prone to deposit as an oligomer with a ß-sheet structure. Exploiting the comprehensive coverage of whole-genome sequencing, we managed to fill a vacant stage in the diagnosis of hereditary amyloidosis and to stimulate the advancement in biomedicine.
RESUMEN
Transition metal oxides are a great alternative to less expensive hydrogen evolution reaction (HER) catalysts. However, the lack of conductivity of these materials requires a conductor material to support them and improve the activity toward HER. On the other hand, carbon paste electrodes result in a versatile and cheap electrode with good activity and conductivity in electrocatalytic hydrogen production, especially when the carbonaceous material is agglomerated with ionic liquids. In the present work, an electrode composed of multi-walled carbon nanotubes (MWCNTs) and cobalt ferrite oxide (CoFe2O4) was prepared. These compounds were included on an electrode agglomerated with the ionic liquid N-octylpyridinium hexafluorophosphate (IL) to obtain the modified CoFe2O4/MWCNTs/IL nanocomposite electrode. To evaluate the behavior of each metal of the bimetallic oxide, this compound was compared to the behavior of MWCNTs/IL where a single monometallic iron or cobalt oxides were included (i.e., α-Fe2O3/MWCNTs/IL and Co3O4/MWCNTs/IL). The synthesis of the oxides has been characterized by X-ray diffraction (XRD), RAMAN spectroscopy, and field emission scanning electronic microscopy (FE-SEM), corroborating the nanometric character and the structure of the compounds. The CoFe2O4/MWCNTs/IL nanocomposite system presents excellent electrocatalytic activity toward HER with an onset potential of -270 mV vs. RHE, evidencing an increase in activity compared to monometallic oxides and exhibiting onset potentials of -530 mV and -540 mV for α-Fe2O3/MWCNTs/IL and Co3O4/MWCNTs/IL, respectively. Finally, the system studied presents excellent stability during the 5 h of electrolysis, producing 132 µmol cm-2 h-1 of hydrogen gas.
Asunto(s)
Cobalto , Compuestos Férricos , Hidrógeno , Líquidos Iónicos , Nanocompuestos , Nanotubos de Carbono , Óxidos , Cobalto/química , Nanotubos de Carbono/química , Líquidos Iónicos/química , Nanocompuestos/química , Catálisis , Hidrógeno/química , Compuestos Férricos/química , Óxidos/química , Electrodos , Técnicas Electroquímicas/métodos , Difracción de Rayos X , Espectrometría RamanRESUMEN
Objectives: Patients diagnosed with transthyretin amyloid cardiomyopathy (ATTR-CM) often experience poor outcomes due to the development of heart failure (HF). Tricuspid regurgitation (TR) has been found to be correlated with adverse outcomes in patients with HF. This study aims to assess whether the presence of significant TR is associated to adverse cardiac outcomes in patients diagnosed with ATTR-CM. Materials and methods: Retrospective study of ATTR-CM patients enrolled in the Institutional Registry of Amyloidosis (NCT01347047). Patients were categorized based on the presence of significant TR (moderate or severe according to current guidelines criteria) or absence of significant TR. All patients were followed up for 2 years to assess the incidence of the composite outcome of death or HF hospitalization. Results: A total of 93 ATTR-CM patients were included. The mean age at diagnosis was 82.5 [IQR 75 - 86] years, 86% were male, and the mean left ventricular ejection fraction was 52% [IQR 43 - 60]. Among them, 32.3% (n = 30) patients had significant TR. Patients with significant TR had higher NTpro-BNP values (5308 vs 2454, pg/mL, p = 0.004), and a lower left ventricular ejection fraction (44 vs. 56%, p = 0.0002) compared to patients without significant TR. The incidence of the primary outcome was higher in patients with significant TR (77% vs. 30%, p<0.001). In a multivariate Cox regression analysis, only NTpro-BNP, as a numerical variable (HR 1.00, 95% CI 1.00005-1.0002, p = 0.001), and significant TR (HR 2.23, 95% CI 1.12-4.42, p=0.021) were independently associated with the composite outcome of death or HF hospitalization. Conclusions: In patients diagnosed with ATTR-CM, the presence of significant TR was associated with worse outcomes.
Objetivos: Los pacientes con diagnóstico de miocardiopatía amiloidótica por transtiretina (ATTR) suelen presentar mal pronóstico, principalmente por el desarrollo de insuficiencia cardiaca (IC). Se ha descrito que la insuficiencia tricúspidea (IT) está relacionada con peor pronóstico en pacientes con IC. Este estudio tiene como objetivo evaluar el impacto pronóstico de la IT significativa en pacientes con diagnóstico de amiloidosis ATTR. Materiales y métodos: Estudio de cohorte retrospectiva. Se incluyeron pacientes con diagnóstico de amiloidosis ATTR pertenecientes al registro institucional de amiloidosis de nuestra institución (NCT01347047). Los pacientes fueron divididos según la presencia o no de IT significativa (moderada o severa, de acuerdo a las guías de práctica clínica actuales). Se realizó un seguimiento con censura a los 2 años para evaluar la incidencia del punto final primario combinado de muerte u hospitalizaciones por IC. Resultados: Se incluyeron 93 pacientes con diagnóstico de amiloidosis ATTR. La mediana de edad fue de 82,5 años [RIC 75-85], 86% fueron hombres. La mediana de fracción de eyección ventricular izquierda fue de 52% [RIC 43-60]. El 32,3% (n=30) de pacientes presentaron IT significativa al momento del diagnóstico de la amiloidosis ATTR. Aquellos con IT significativa tuvieron valores superiore de NT-proBNP (5308 vs. 2454, pg/mL, p=0.004) y menor mediana de fracción de eyección ventricular izquierda (44% vs. 56%, p=0,0002) comparado con los pacientes sin IT significativa. En el seguimiento a 2 años, la incidencia del punto final primario combinado fue mayor en pacientes con IT significativa (77% vs. 30%, p<0,001). En un modelo de regresión de Cox multivariada, solo el NT-proBNP (HR 1,00, 95% CI 1,00005-1,0002, p=0,001) y la IT significativa (HR 2.23, 95% CI 1.12-4.42, p=0.021) estuvieron asociadas de forma independiente con la ocurrencia del punto final primario combinado. Conclusiones: En pacientes con diagnóstico de miocardiopatía amiloidótica por ATTR, la presencia de IT significativa se asoció a peor pronóstico en el seguimiento.
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BACKGROUND: Persistent respiratory symptoms and lung abnormalities post-COVID-19 are public health problems. This study evaluated biomarkers to stratify high-risk patients to the development or persistence of post-COVID-19 interstitial lung disease. METHODS: One hundred eighteen patients discharged with residual lung abnormalities compatible with interstitial lung disease (COVID-ILD patients) after a severe COVID-19 were followed for 1 year (post-COVID-ILD patients). Physical examination, pulmonary function tests, and chest high-resolution computed tomography (HRCT) were performed. Soluble forms (s) of PD-L1, PD-L2, TIM-3, and GAL-9 were evaluated in serum and cell culture supernatant, as well as T-cells subsets and the transmembrane expression of PD-L1 and PD-L2 on the cell surface. RESULTS: Eighty percent of the post-COVID-ILD patients normalized their lung function at 1-year follow-up, 8% presented COVID-independent ILD, and 12% still showed functional and HRCT alterations. PD-L2 levels were heterogeneous during acute COVID-19 (aCOVID); patients who increased (at least 30%) their sPD-L2 levels at 1 year post-COVID-19 and exhibited altered CD4/CD8 ratio showed persistence of chest tomographic and functional alterations. By contrast, patients who decreased sPD-L2 displayed a complete lung recovery. sPD-L1, sTIM-3, and sGAL-9 increased significantly during aCOVID and decreased in all patients after 1-year follow-up. CONCLUSION: Increased sPD-L2 and an altered CD4/CD8 ratio after 12 months of aCOVID are associated with the persistence of lung lesions, suggesting that they may contribute to lung damage post-COVID-19.
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Relación CD4-CD8 , COVID-19 , Pulmón , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/sangre , COVID-19/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Anciano , Pulmón/inmunología , Pulmón/patología , Pulmón/diagnóstico por imagen , SARS-CoV-2/inmunología , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/sangre , Biomarcadores/sangre , Antígeno B7-H1/sangre , Pruebas de Función Respiratoria , Tomografía Computarizada por Rayos X , Estudios de Seguimiento , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , AdultoRESUMEN
In this study, a beverage made from a combination of Agave sap (AS) and prickly pear juice (PPJ) was analyzed for its nutrients and bioactive and potentially health-promoting compounds. The beverage was evaluated for its ability to act as an antioxidant, regulate glycemic properties, and undergo gut bacterial fermentation in vitro. The major mono- and oligosaccharides present in the beverage were galacturonic acid (217.74 ± 13.46 mg/100 mL), rhamnose (227.00 ± 1.58 mg/100 mL), and fructose (158.16 ± 8.86 mg/mL). The main phenolic compounds identified were protocatechuic acid (440.31 ± 3.06 mg/100 mL) and catechin (359.72 ± 7.56 mg/100 mL). It was observed that the beverage had a low glycemic index (<40) and could inhibit digestive carbohydrases. The combination of ingredients also helped to reduce gas production during AS fermentation from 56.77 cm3 to 15.67 cm3. The major SCFAs produced during fermentation were butyrate, acetate, and propionate, with valerate being produced only during the late fermentation of the AS. This beverage is rich in bioactive compounds, such as polyphenols and dietary fiber, which will bring health benefits when consumed.
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Agave , Antioxidantes , Jugos de Frutas y Vegetales , Agave/química , Jugos de Frutas y Vegetales/análisis , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/análisis , Fermentación , Hidroxibenzoatos/análisis , Polifenoles/análisis , Polifenoles/química , Pyrus/química , Fenoles/análisis , Fenoles/química , Ramnosa/análisis , Ramnosa/química , Catequina/análisis , Catequina/química , Catequina/análogos & derivados , Ácidos HexurónicosRESUMEN
Abstract Introduction : Chia and flax seeds are rich in alpha-linolenic acid (ALA), which is bioconverted into the active derivatives eicosapentaenoic (EPA) and doco sahexaenoic (DHA) having multiple beneficial effects. However, there is limited knowledge about the anti-inflammatory effects of chia and flax integral flours diets rich in ALA. Objective : The study aimed to evaluate the anti-inflammatory effect of dietary supplementation with integral chia and flax flours in a murine model of LPS-induced systemic inflammation. Methods : Balb/c mice were distributed into three groups: diet A (control), diet B (supplemented with inte gral chia flour), and diet C (supplemented with integral flax flour). Nutritional, hematological, and biochemical determinations were performed. ALA, EPA, and DHA were assessed by GC-MS in the liver, brain, cardiac and skeletal muscles. NF-kB immunoassays were per formed in kidney, liver, and peritoneal macrophages, respectively. The phagocytic capacity was determined in peritoneal macrophages and the expression of the pro- and anti-inflammatory cytokines was assessed by RT-qPCR in the kidney, liver, and spleen. Results : Diets B and C exhibited optimal nutritional adequacy and caused increased levels of ALA, EPA, and DHA in critical tissues compared to the control. The phagocytic capacity of murine peritoneal macrophages (p< 0.01) and IL-10 transcription increased, whereas the expression of NF-κB, IL-1β, IL-6, and TNF-α decreased in animals fed both experimental diets. Conclusions : This work contributes to the current knowledge of the anti-inflammatory effects of chia and flax integral flours rich in ALA and reinforces the health advantages of their consumption.
Resumen Introducción : Las semillas de chía y lino son ricas en ácido alfa-linolénico (ALA), sus derivados activos eico sapentaenoico (EPA) y docosahexaenoico (DHA) ejercen probados efectos beneficiosos. Existe un conocimiento limitado sobre los efectos protectores de ambas semillas bajo la forma de harinas integrales, siendo de particular interés el efecto antiinflamatorio. Objetivo : El objetivo de este trabajo fue evaluar el efecto antiinflamatorio de la suplementación dietaria con harinas integrales de semillas de chía y lino en un modelo murino de inflamación sistémica inducido por LPS. Métodos : Ratones de la cepa Balb/c fueron distribui dos en tres grupos: dieta A (control), dieta B (suplemen tada con harina integral de chía) y dieta C (suplementa da con harina integral de lino). Se efecturaron determi naciones nutricionales, hematológicas y bioquímicas. El contenido de ALA, EPA y DHA en hígado, cerebro, corazón y músculo esquelético se determinó por cromatografía GC-MS. Se realizó la inmunodetección de NF-kB en macrófagos peritoneales, riñón e hígado. Se determinó la capacidad fagocítica de macrófagos peritoneales y se evaluó la expresión de citoquinas pro y antiinflamatorias por RT-qPCR en riñón, hígado y bazo. Resultados : Las dietas B y C mostraron una adecua ción nutricional óptima y generaron niveles elevados de ALA, EPA y DHA en tejidos críticos. La capacidad fagocítica de los macrófagos peritoneales (p< 0.01) y la transcripción de IL-10 aumentó, mientras que la expre sión de NF-κB, IL-1β, IL-6 y TNF-α disminuyó en animales de los grupos B y C. Conclusiones : Este trabajo contribuye al conocimien to actual de los efectos antiinflamatorios de ambas hari nas integrales y refuerza los beneficios de su consumo.
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WRN helicase is a promising target for treatment of cancers with microsatellite instability (MSI) due to its essential role in resolving deleterious non-canonical DNA structures that accumulate in cells with faulty mismatch repair mechanisms1-5. Currently there are no approved drugs directly targeting human DNA or RNA helicases, in part owing to the challenging nature of developing potent and selective compounds to this class of proteins. Here we describe the chemoproteomics-enabled discovery of a clinical-stage, covalent allosteric inhibitor of WRN, VVD-133214. This compound selectively engages a cysteine (C727) located in a region of the helicase domain subject to interdomain movement during DNA unwinding. VVD-133214 binds WRN protein cooperatively with nucleotide and stabilizes compact conformations lacking the dynamic flexibility necessary for proper helicase function, resulting in widespread double-stranded DNA breaks, nuclear swelling and cell death in MSI-high (MSI-H), but not in microsatellite-stable, cells. The compound was well tolerated in mice and led to robust tumour regression in multiple MSI-H colorectal cancer cell lines and patient-derived xenograft models. Our work shows an allosteric approach for inhibition of WRN function that circumvents competition from an endogenous ATP cofactor in cancer cells, and designates VVD-133214 as a promising drug candidate for patients with MSI-H cancers.
Asunto(s)
Regulación Alostérica , Descubrimiento de Drogas , Inhibidores Enzimáticos , Proteómica , Helicasa del Síndrome de Werner , Animales , Femenino , Humanos , Masculino , Ratones , Regulación Alostérica/efectos de los fármacos , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/patología , Cisteína/efectos de los fármacos , Cisteína/metabolismo , Roturas del ADN de Doble Cadena/efectos de los fármacos , Descubrimiento de Drogas/métodos , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inestabilidad de Microsatélites , Modelos Moleculares , Helicasa del Síndrome de Werner/antagonistas & inhibidores , Helicasa del Síndrome de Werner/química , Helicasa del Síndrome de Werner/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Muerte Celular/efectos de los fármacos , Adenosina Trifosfato/metabolismoRESUMEN
INTRODUCTION: Chia and flax seeds are rich in alphalinolenic acid (ALA), which is bioconverted into the active derivatives eicosapentaenoic (EPA) and docosahexaenoic (DHA) having multiple beneficial effects. However, there is limited knowledge about the antiinflammatory effects of chia and flax integral flours diets rich in ALA. OBJECTIVE: The study aimed to evaluate the antiinflammatory effect of dietary supplementation with integral chia and flax flours in a murine model of LPSinduced systemic inflammation. METHODS: Balb/c mice were distributed into three groups: diet A (control), diet B (supplemented with integral chia flour), and diet C (supplemented with integral flax flour). Nutritional, hematological, and biochemical determinations were performed. ALA, EPA, and DHA were assessed by GC-MS in the liver, brain, cardiac and skeletal muscles. NF-kB immunoassays were performed in kidney, liver, and peritoneal macrophages, respectively. The phagocytic capacity was determined in peritoneal macrophages and the expression of the pro- and anti-inflammatory cytokines was assessed by RT-qPCR in the kidney, liver, and spleen. RESULTS: Diets B and C exhibited optimal nutritional adequacy and caused increased levels of ALA, EPA, and DHA in critical tissues compared to the control. The phagocytic capacity of murine peritoneal macrophages (p< 0.01) and IL-10 transcription increased, whereas the expression of NF-κB, IL-1Β, IL-6, and TNF-α decreased in animals fed both experimental diets. CONCLUSIONS: This work contributes to the current knowledge of the anti-inflammatory effects of chia and flax integral flours rich in ALA and reinforces the health advantages of their consumption.
Introducción: Las semillas de chía y lino son ricas en ácido alfa-linolénico (ALA), sus derivados activos eicosapentaenoico (EPA) y docosahexaenoico (DHA) ejercen probados efectos beneficiosos. Existe un conocimiento limitado sobre los efectos protectores de ambas semillas bajo la forma de harinas integrales, siendo de particular interés el efecto antiinflamatorio. OBJETIVO: El objetivo de este trabajo fue evaluar el efecto antiinflamatorio de la suplementación dietaria con harinas integrales de semillas de chía y lino en un modelo murino de inflamación sistémica inducido por LPS. Métodos: Ratones de la cepa Balb/c fueron distribuidos en tres grupos: dieta A (control), dieta B (suplementada con harina integral de chía) y dieta C (suplementada con harina integral de lino). Se efecturaron determinaciones nutricionales, hematológicas y bioquímicas. El contenido de ALA, EPA y DHA en hígado, cerebro, corazón y músculo esquelético se determinó por cromatografía GC-MS. Se realizó la inmunodetección de NF-kB en macrófagos peritoneales, riñón e hígado. Se determinó la capacidad fagocítica de macrófagos peritoneales y se evaluó la expresión de citoquinas pro y antiinflamatorias por RT-qPCR en riñón, hígado y bazo. RESULTADOS: Las dietas B y C mostraron una adecuación nutricional óptima y generaron niveles elevados de ALA, EPA y DHA en tejidos críticos. La capacidad fagocítica de los macrófagos peritoneales (p< 0.01) y la transcripción de IL-10 aumentó, mientras que la expresión de NF-κB, IL-1Β, IL-6 y TNF-α disminuyó en animales de los grupos B y C. CONCLUSIONES: Este trabajo contribuye al conocimiento actual de los efectos antiinflamatorios de ambas harinas integrales y refuerza los beneficios de su consumo.
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Suplementos Dietéticos , Lino , Inflamación , Ratones Endogámicos BALB C , Animales , Inflamación/dietoterapia , Ratones , Harina/análisis , Citocinas/análisis , Modelos Animales de Enfermedad , MasculinoRESUMEN
The objective of this study was to estimate the prevalence of diabetes mellitus (DM) and cardiovascular risk factors in a rural population in the province of San Luis, Argentina. Cross-sectional study developed between September and November 2017 with 18-year-old inhabitants and more than four towns in the Juan Martín de Pueyrredón department, San Luis. The participants answered questions by self-report on sociodemographic aspects, habits, psychosocial and risk factors for non-communicable diseases; physical measurements, FINDIRSC questionnaire and blood sample extraction were performed. Univariate estimates stratified by sex with their 95% confidence interval (95%CI) were obtained. We worked with sample expansion factors; crude and adjusted prevalences were calculated. The population consisted of 424 men (52.5%, 95%CI: 46.0-58.9) and 384 women (47.5%, 95%CI: 41.1-54.0). The adjusted prevalences for both sexes (by self-report) were: DM 11.8% (95%CI: 8.2-15.4); arterial hypertension (AHT): 35.5% (95% CI: 31.0-40.1); high cholesterol: 20.3% (CI 16.0-24.7). Males had significantly higher desirable HDL cholesterol and elevated blood pressure than females; women abdominal obesity in greater magnitude. 16.4% (95% CI: 11.0 - 23.6) had a high-very high risk of developing type 2 DM in the next 10 years. The adjusted prevalences of DM, hypertension, and high cholesterol were lower than those of the urban population of the province of San Luis. We highlight the pioneering contribution of this work to the knowledge of the health profile of rural communities in Argentina.
El objetivo de este estudio fue estimar la prevalencia de diabetes mellitus (DM) y factores de riesgo cardiovascular en una población rural de la provincia de San Luis, Argentina. Estudio transversal desarrollado entre septiembre y noviembre de 2017 con habitantes de 18 años y más de cuatro localidades del departamento Juan Martín de Pueyrredón, San Luis. Los participantes respondieron preguntas por autorreporte sobre aspectos sociodemográficos, hábitos, factores psicosociales y de riesgo para enfermedades no transmisibles; se realizaron mediciones físicas, cuestionario FINDIRSC y extracción de muestras de sangre. Se obtuvieron estimaciones univariadas estratificadas por sexo con su intervalo de confianza del 95% (IC95%). Se trabajó con factores de expansión de la muestra; se calcularon prevalencias crudas y ajustadas. La población estuvo constituida por 424 varones (52,5%, IC95%: 46,0-58,9) y 384 mujeres (47,5%, IC95%: 41,1-54,0). Las prevalencias ajustadas para ambos sexos (por autorreporte) fueron: DM 11,8% (IC95%: 8,2-15,4); hipertensión arterial (HTA): 35,5% (IC95%: 31,0-40,1); colesterol elevado: 20,3% (IC 16,0-24,7). Los varones tuvieron colesterol HDL deseable y tensión arterial elevada en una proporción significativamente superior a las mujeres; las mujeres obesidad abdominal en mayor magnitud. El 16,4 % (IC95%: 11,0 - 23,6) ostentó riesgo alto-muy alto de desarrollar DM tipo 2 en los próximos 10 años. Las prevalencias ajustadas de DM, HTA y colesterol elevado fueron inferiores a la de la población urbana de la provincia de San Luis. Destacamos la contribución pionera de este trabajo al conocimiento del perfil de salud de las comunidades rurales de Argentina.
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Enfermedades no Transmisibles , Humanos , Prevalencia , Población Rural , Argentina/epidemiología , Factores de Riesgo , Estudios RetrospectivosRESUMEN
Salinity is an increasing problem in coastal areas affected by saltwater intrusion, with deleterious effects on tree health and forest growth. Ectomycorrhizal (ECM) fungi may improve the salinity tolerance of host trees, but the impact of external potassium (K+ ) availability on these effects is still unclear. Here, we performed several experiments with the ECM fungus Paxillus ammoniavirescens and loblolly pine (Pinus taeda L.) in axenic and symbiotic conditions at limited or sufficient K+ and increasing sodium (Na+ ) concentrations. Growth rate, biomass, nutrient content, and K+ transporter expression levels were recorded for the fungus, and the colonization rate, root development parameters, biomass, and shoot nutrient accumulation were determined for mycorrhizal and non-mycorrhizal plants. P. ammoniavirescens was tolerant to high salinity, although growth and nutrient concentrations varied with K+ availability and increasing Na+ exposure. While loblolly pine root growth and development decreased with increasing salinity, ECM colonization was unaffected by pine response to salinity. The mycorrhizal influence on loblolly pine salinity response was strongly dependent on external K+ availability. This study reveals that P. ammoniavirescens can reduce Na+ accumulation of salt-exposed loblolly pine, but this effect depends on external K+ availability.
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Basidiomycota , Micorrizas , Pinus taeda/genética , Salinidad , PotasioRESUMEN
Functional response describes the number of hosts attacked by a parasitoid in relation to host densities and plays an important role by connecting behavioral-level processes with community-level processes. Most functional response studies were carried out using simple experimental designs where the insects were confined to a plain and small arena with different host densities during a fixed period of time. With these designs, other factors that might affect the functional response of parasitoids were not analyzed, such as fecundity, age, and experience. We proposed a series of latent-variables Markovian models that comprised an integrated approach of functional response and egg production models to estimate the realized lifetime reproductive success of parasitoids. As a case study, we used the parasitoids Anagyrus cachamai and A. lapachosus (Hymenoptera: Encyrtidae), two candidate agents for neoclassical biocontrol of the Puerto Rican cactus pest mealybug, Hypogeococcus sp. (Hemiptera: Pseudococcidae). The tested species were assessed according to their physiology and prior experience. We estimated the number of mature eggs after emergence, egg production on the first day, egg production rate, the proportion of eggs resorbed, egg resorption threshold, and egg storage capacity. Anagyrus cachamai and A. lapachosus both presented a type III functional response. However, the two parasitoids behaved differently; for A. cachamai, the number of parasitized hosts decreased with female age and depended on the number of mature eggs that were available for oviposition, whereas A. lapachosus host parasitism increased with female age and was modulated by its daily egg load and previous experience. The methodology presented may have large applicability in pest control, invasive species management, and conservation biology, as it has the potential to increase our understanding of the reproductive biology of a wide variety of species, ultimately leading to improved management strategies.
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Cactaceae , Hemípteros , Himenópteros , Avispas , Femenino , Animales , Himenópteros/fisiología , Oviposición , Hemípteros/fisiología , Control Biológico de Vectores , Óvulo , Avispas/fisiología , Interacciones Huésped-ParásitosRESUMEN
In birds, primordial germ cells (PGCs) use the bloodstream to travel to a specific region, where the cells undergo extravasation followed by intrastromal migration to the gonadal crest for further colonization. Currently, DDX4, SSEA1, and Oct4 are used to identify germ cells. Other germline cell-associated molecules are N-cadherin, GnRHR, and 3ß hydroxysteroid dehydrogenase (3ßHSD), which have been used in mice and birds during gonadal development; however, its role in early gonadogenesis in birds is poorly described. This study aimed to evaluate the differential immunodetection of N-cadherin binding molecule, Oct4 pluripotency protein, GnRHR receptor, and 3ßHSD enzyme in Columba livia embryos during migration colonization of PGCs in the gonadal crest and early gonadogenesis. These markers were revealed by immunohistochemistry in histological preparations of C. livia corresponding to stages (S)15 to S40. Immunodetection of N-cadherin, Oct4, GnRHR, and 3ßHSD in the germ line of C. livia allowed the identification of PGCs in the yolk sac membrane at the level of the splanchnic mesoderm during migration to the genital crest and its colonization. In the same way, it was possible to characterize and localize PGCs during early gonadogenesis. This study in C. livia demonstrates that Oct4, N-cadherin, GNRHR, and 3ßHSD are immunodetected in PGCs and could be used as potential germline cell markers during cell migration out of blood vessels, colonization in the genital crest, and early gonadogenesis. Furthermore, this study could be used as a novel general model to understand the early gonadogenesis in altricial species.
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Columbidae , Columbiformes , Animales , Ratones , Células Germinativas/metabolismo , Diferenciación Celular , Movimiento Celular , Cadherinas/metabolismoRESUMEN
INTRODUCCIÓN: La pandemia por COVID-19 condujo a la adopción de medidas de confinamiento con impacto en el control de la diabetes mellitus (DM). El objetivo fue evaluar el efecto de la pandemia en la atención de personas con DM del subsector público y privado de salud del Partido de General Pueyrredon (PGP). MÉTODOS: Se utilizó un diseño cuasiexperimental que comparó dos períodos: pandemia (3 de marzo de 2020 al 2 de marzo de 2021) y prepandemia (3 de marzo de 2019 al 2 de marzo de 2020). Se incluyó a personas de 18 años y más del PGP con diagnóstico de DM; se conformaron dos grupos según cobertura de salud. Los criterios de valoración principal fueron la hemoglobina glicosilada (HbA1c) y el control metabólico; los secundarios: glucemia basal, índice de masa corporal (IMC), triglicéridos, colesterol, consultas médicas, internación, fondo de ojo e índice albúmina/creatinina. Las diferencias con valor p<0,05 se consideraron estadísticamente significativas. Se ajustaron modelos multivariados. RESULTADOS: Se incluyeron 327 participantes (51,7% del subsector público). La mediana de HbA1c aumentó de 8,1% (rango intercuartílico [RIC] 2,7) a 8,8% (RIC 2,8). La pandemia, la atención en el subsector público y el tratamiento incompleto de la DM fueron predictores independientes del aumento de HbA1c; en tanto que el tratamiento con insulina lo fue del deterioro del control glucémico. DISCUSIÓN: La pandemia impactó negativamente en la atención de la DM, evidenciando desigualdades en los subsectores del sistema de salud.
Asunto(s)
Cobertura de los Servicios de Salud , Diabetes Mellitus , COVID-19 , Inequidades en SaludRESUMEN
Resumen La amiloidosis por depósito de cadenas livianas de inmunoglobulinas (AL) es una enfermedad poco frecuen te y subdiagnosticada. El mejor tratamiento disponible al momento es el trasplante autólogo de médula ósea (TMO). El compromiso cardíaco es el principal determi nante pronóstico en esta patología y en ocasiones un impedimento para recibir el TMO. Se presenta el caso de un varón de 44 años que consultó por signos y síntomas de insuficiencia cardiaca (IC) con biomarcadores cardia cos elevados. Se realizó un ecocardiograma transtorácico donde se objetivó aumento de espesores parietales con hipoquinesia global y fracción de eyección deteriorada en grado leve (50%). El paciente se internó en unidad coronaria para balance negativo y para estudio etiológico del cuadro. Ante la sospecha de enfermedad infiltrativa, se solicitaron un centellograma óseo con pirofosfato y cadenas livianas libres en suero. El centellograma óseo resultó no sugestivo para amiloidosis por transtiretina y las cadenas livianas libres mostraron una relación me nor a 0.26 con predominio lambda. Se realizó una biopsia de encía que confirmó el diagnóstico de amiloidosis AL. Posterior al diagnóstico comenzó tratamiento qui mioterápico específico con Ciclofosfamida, Bortezomib y Dexametasona (esquema CYBORD) y Daratumumab. Evolucionó con IC refractaria por lo que ingresó a lista de trasplante cardiaco, recibiendo el mismo al poco tiempo con buena evolución. Esto permitió reiniciar el esquema quimioterápico y en segundo término finalmente recibir el TMO, con buena evolución.
Abstract Light chain amyloidosis (AL) is a rare and underdi agnosed disease. The best treatment available is au tologous bone marrow transplantation (BMT). Cardiac involvement is the main prognostic determinant in this pathology and sometimes an impediment to re ceive BMT. We present a clinical case of a 44-year-old who consulted for signs and symptoms of heart failure (HF) with elevated cardiac biomarkers. A transthoracic echocardiogram showed increased wall thickness with global hypokinesia and mildly impaired ejection fraction (50%). The patient was admitted to the coronary unit for treatment with diuretics and for etiological study of the condition. In view of the suspicion of infiltrative disease, a bone scintigraphy with pyrophosphate and free light chains in serum were requested. The bone scintigraphy was not suggestive of transthyretin amyloidosis and the free light chains showed a ratio of less than 0.26 with lambda predominance. A gum biopsy was per formed and confirmed the diagnosis of AL amyloidosis. After diagnosis, specific chemotherapy treatment with Cyclophosphamide, Bortezomib and Dexamethasone (CYBORD scheme) and Daratumumab was started. He evolved with refractory HF so it was decided to admit him to the cardiac transplantation list, receiving the same soon after, with good evolution. This allowed the patient to restart the chemotherapy regimen and finally receive BMT, with good evolution.
RESUMEN
La amiloidosis siempre ha representado un desafío diagnóstico. En el año 2020, el Grupo de Estudio de Amiloidosis (GEA), confeccionó la Guía de Práctica Clínica para el Diagnóstico de Amiloidosis. Nuevas líneas de investigación se han desarrollado posteriormente. Esta revisión narrativa tiene como intención explorar el estado del arte en el diagnóstico de la amiloidosis. En pacientes con amiloidosis se recomienda la tipificación de la proteína mediante espectrometría de masa, técnica de difícil ejecución por requerir de microdisectores láser para la preparación de la muestra. Algunas publicaciones recientes proponen otros métodos para obtener la muestra de amiloide que se va a analizar, permitiendo prescindir de la microdisección. Por otra parte, en pacientes con Amiloidosis ATTR confirmada, la recomendación de secuenciar el gen amiloidogénico se encontraba destinada a los casos sospechosos de ATTR hereditaria (ATTRv,), pero actualmente esta se ha extendido a todos los pacientes sin importar la edad. En lo que respecta a los estudios complementarios orientados al diagnóstico de compromiso cardíaco, se ha propuesto el uso de la inteligencia artificial para su interpretación, permitiendo la detección temprana de la enfermedad y el correcto diagnóstico diferencial. Para el diagnóstico de neuropatía, las últimas publicaciones proponen el uso de la cadena ligera de neurofilamento sérica, que también podría resultar un indicador útil para seguimiento. Finalmente, con referencia a la amiloidosis AL, la comunidad científica se encuentra interesada en definir qué características determinan el carácter amiloidogénico de las cadenas livianas. La N-glicosilación de dichas proteínas impresiona ser uno de los determinantes en cuestión. (AU)
Amyloidosis has always represented a diagnostic challenge. In 2020, the Amyloidosis Study Group (ASG) developed the "Clinical Practice Guideline for the Diagnosis of Amyloidosis". New lines of research have subsequently emerged. This narrative review aims to explore the state of the art in the diagnosis of amyloidosis diagnosis. In patients with amyloidosis, protein typing by mass spectrometry is recommended, a technique hard to perform because it requires laser microdissection for sample preparation. Recent publications propose other methods to obtain the amyloid sample to be analyzed, making it possible to dispense with microdissection. On the other hand, in patients with confirmed TTR amyloidosis (aTTR), the recommendation to sequence the amyloidogenic gene was intended for suspected cases of hereditary aTTR but has now been extended to all patients regardless of age. (AU)
Asunto(s)
Humanos , Neuropatías Amiloides Familiares/diagnóstico , Diagnóstico Precoz , Amiloidosis/diagnóstico , Espectrometría de Masas , Biopsia , Glicosilación , Inteligencia Artificial , Imagen por Resonancia Magnética , Análisis de Secuencia de ADN , Guías de Práctica Clínica como Asunto , Diagnóstico Diferencial , Electrocardiografía , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
La amiloidosis AL es una enfermedad debida al depósito, en órganos y tejidos, de fibrillas formadas por cadenas livianas producidas de forma patológica por plasmocitos clonales. Su tratamiento actualmente está orientado a erradicar el clon de células plasmáticas; este históricamente se extrapoló de tratamientos disponibles y estudiados para otras discrasias sanguíneas. En el año 2020, el Grupo de Estudio de Amiloidosis (GEA) confeccionó distintas guías de práctica clínica para el tratamiento de la amiloidosis AL. Desde entonces se han publicado ensayos clínicos que arrojan contundencia al conocimiento disponible hasta el momento, y están en desarrollo nuevas líneas de investigación que robustecen y estimulan el estudio en el área. En esta revisión se realiza una actualización de las guías existentes en lo que respecta al tratamiento de la amiloidosis por cadenas livianas.Como evidencia de relevancia, en el último año estuvieron disponibles resultados de ensayos clínicos que respaldan el uso de esquemas basados en daratumumab (un anticuerpo monoclonal anti-CD38+) para pacientes con diagnóstico reciente de amiloidosis AL como primera línea. Además, para el tratamiento de la amiloidosis AL refractaria o recaída, la disponibilidad de bibliografía respaldatoria es escasa y extrapolada del tratamiento del mieloma múltiple; sin embargo, actualmente existe evidencia de calidad para recomendar el uso de ixazomib, un inhibidor de proteosoma reversible por vía oral disponible en la Argentina desde 2020. Por último, se mencionan algunas líneas de investigación con otros anticuerpos monoclonales y terapéuticas basadas en el uso de CAR-T cells. (AU)
AL amyloidosis is a disease caused by the deposit in different organs and tissues of protein fibrils formed by light chains synthetized by pathological clonal plasma cells. Its treatment is currently aimed at eradicating this plasma cell clone and it has been historically extrapolated from available and validated treatments for other blood dyscrasias. In 2020, the Amyloidosis Study Group prepared different clinical practice guidelines for the treatment of AL amyloidosis.Since then, clinical trials have been published that confirm and strengthen the knowledge available up to now, and new lines of research are being developed that stimulate study in the area. In this review, an update of the existing guidelines regarding the treatment of AL amyloidosis is made. As relevant evidence, in the last year, results of clinical trials have been made available that support the use of regimens based on Daratumumab (an anti-CD38+ monoclonal antibody) for patients with newly diagnosed AL amyloidosis as first line therapy. In addition, for the treatment of refractory or relapsed AL amyloidosis, where the availability of supporting literature is scant and extrapolated from the treatment of multiple myeloma, there is currently quality evidence to recommend the use of ixazomib, an oral reversible proteasome inhibitor, only available in Argentina since 2020. Finally, some research lines exploring the efficacy of other monoclonal antibodies and therapeutic experiments based on the use of CAR-T cells are mentioned. (AU)
Asunto(s)
Humanos , Antígeno de Maduración de Linfocitos B/uso terapéutico , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Recurrencia , Guías de Práctica Clínica como Asunto , Trasplante de Células Madre HematopoyéticasRESUMEN
Resumen Objetivo: Describir la evolución de las cadenas livianas libres séricas (CLL) en el período comprendido entre el trasplante cardíaco ortotópico (TCO) y el trasplante de células progenitoras hematopoyéticas (TCPH), la respuesta hematológica al año tras el TCPH y el tratamiento quimioterápico e inmunosupresor en pacientes con amiloidosis AL. Método: Serie de casos de pacientes consecutivos con diagnóstico de amiloidosis AL que recibieron TCO seguido de TCPH del Registro Institucional de Amiloidosis del Hospital Italiano de Buenos Aires, entre enero de 2010 y noviembre de 2021. Se reportaron los valores de CLL entre trasplantes y al año del TCPH. Las variables cuantitativas se describieron como mediana e intervalo intercuartil, y las variables categóricas como frecuencias absolutas y relativas. Resultados: De 106 pacientes con amiloidosis AL, seis tuvieron TCO seguido de TCPH. La mediana de edad fue de 55 años. La mayoría eran hombres (n = 5). En el período entre trasplantes, la CLL involucrada disminuyó en dos pacientes y se mantuvo estable en tres. Todos lograron la remisión hematológica completa al año del TCPH. Un solo paciente presentó recaída en el órgano sólido trasplantado. Tacrolimus, micofenolato de mofetilo y corticoides fue el esquema inmunosupresor utilizado después del TCO. Conclusiones: El TCO representa una opción de tratamiento en pacientes con falla cardíaca grave por amiloidosis, permitiendo luego un tratamiento intensivo con quimioterapia de inducción y TCPH. Si bien faltan estudios, la terapia inmunosupresora después del TCO podría tener algún efecto sobre las células plasmáticas clonales.
Abstract Objective: To describe the evolution of serum free light chains (FLC) in the period between orthotopic heart transplantation (OHT) and autologous stem cell transplantation (ASCT), the hematological response one year after ASCT and chemotherapy and immunosuppressive treatment in patients with AL amyloidosis. Method: Case series of consecutive patients diagnosed with AL amyloidosis who received OHT followed by ASCT from the Institutional Registry of Amyloidosis of the Italian Hospital of Buenos Aires, between January 2010 and November 2021. FLC values between transplants and at year post ASCT. Quantitative variables were described with their median and interquartile range. Categorical variables as absolute and relative frequencies. Results: Of 106 patients with AL amyloidosis, 6 had an OHT followed by ASCT. The median age was 55 years. Most were men (n = 5). In the period between transplants, the involved CLL decreased in two patients and remained stable in three. All achieved complete hematologic remission 1 year after ASCT. A single patient presented relapse in the transplanted solid organ. Tacrolimus, mycophenolate mofetil, and corticosteroids were the immunosuppressive regimen used after OHT. Conclusions: OHT represents a treatment option in patients with severe heart failure due to amyloidosis, allowing later intensive treatment with induction chemotherapy and ASCT. Although studies are lacking, immunosuppressive therapy after OHT might have some effect on clonal plasma cells.