Diferencias en la percepción del estrés en personas con diabetes mellitus de distinto sexo durante el confinamiento por COVID-19

Introducción: diversos estudios sugieren que existe una diferencia en el estrés percibido (EP) entre sexos en la población general. Sin embargo, hay escasas publicaciones que describan las diferencias de percepción del estrés entre sexos durante el confinamiento por COVID-19 en personas con diabetes mellitus (DM). Objetivos: evaluar las diferencias entre sexos relacionadas con el EP y la ansiedad en personas con DM durante el confinamiento por COVID-19 en Argentina. Materiales y métodos: estudio multicéntrico, observacional y transversal. Se incluyeron adultos con DM1 y DM2. El grado de estrés se evaluó por la escala de estrés percibido (perceived stress scale, PSS), y la ansiedad por el inventario de ansiedad de Beck (Beck anxiety inventory, BAI). Resultados: se incluyeron 2.273 pacientes (52,5% mujeres). En el análisis univariado, las puntuaciones de BAI y PSS fueron significativamente más altas en las mujeres con DM versus los hombres (BAI 8,9 versus 6,6; p<0,001 y PSS 14,3 versus 11,8; p<0,001). En el análisis multivariado, el sexo femenino se asoció significativamente con mayores puntuaciones de BAI y PSS después de ajustar por tipo de DM, edad, nivel de A1c, nivel educativo, condición de vivir solo/a, y presencia de comorbilidades o complicaciones (p<0,001). En la regresión lineal múltiple, las puntuaciones de BAI y PSS se asociaron significativamente con el sexo femenino (BAI p<0,0001 y PSS p<0,0013). Conclusiones: en los pacientes con DM, el sexo femenino se asoció con puntuaciones más altas de ansiedad y EP en el contexto de aislamiento durante la pandemia de COVID-19 en Argentina

NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy

Chronic myelomonocytic leukemia (CMML) is frequently associated with mutations in the rat sarcoma gene (RAS), leading to worse prognosis. RAS mutations result in active RAS-GTP proteins, favoring myeloid cell proliferation and survival and inducing the NLRP3 inflammasome together with the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which promote caspase-1 activation and interleukin (IL)-1(3 release. Here, we report, in a cohort of CMML patients with mutations in KRAS, a constitutive activation of the NLRP3 inflammasome in monocytes, evidenced by ASC oligomerization and IL-1(3 release, as well as a specific inflammatory cytokine signature. Treatment of a CMML patient with a KRASG12D mutation using the IL-1 receptor blocker anakinra inhibits NLRP3 inflammasome activation, reduces monocyte count, and improves the patient's clinical status, enabling a stem cell transplant. This reveals a basal inflammasome activation in RAS-mutated CMML patients and suggests potential therapeutic applications of NLRP3 and IL-1 blockers

Chronic myelomonocytic leukemia with ring sideroblasts/SF3B1 mutation presents with low monocyte count and resembles myelodysplastic syndromes with-RS/SF3B1 mutation in terms of phenotype and prognosis

IntroductionChronic myelomonocytic leukemia (CMML) and myelodysplastic syndromes (MDS) with ring sideroblasts (RS) or SF3B1 mutation (MDS-RS/SF3B1) differ in many clinical features, but share others, such as anemia. RS and SF3B1 mutation can also be found in CMML.MethodsWe compared CMML with and without RS/SF3B1 and MDS-RS/SF3B1 considering the criteria established by the 2022 World Health Organization classification.ResultsA total of 815 patients were included (CMML, n=319, CMML-RS/SF3B1, n=172 and MDS-RS/SF3B1, n=324). The percentage of RS was ≥15% in almost all CMML-RS/SF3B1 patients (169, 98.3%) and most (125, 72.7%) showed peripheral blood monocyte counts between 0.5 and 0.9 x109/L and low risk prognostic categories. CMML-RS/SF3B1 differed significantly from classical CMML in the main clinical characteristics, whereas it resembled MDS-RS/SF3B1. At a molecular level, CMML and CMML-RS/SF3B1 had a significantly higher frequency of mutations in TET2 (mostly multi-hit) and ASXL1 (p=0.013) and CMML had a significantly lower frequency of DNMT3A and SF3B1 mutations compared to CMML/MDS-RS/SF3B1. Differences in the median overall survival among the three groups were statistically significant: 6.75 years (95% confidence interval [CI] 5.41-8.09) for CMML-RS/SF3B1 vs. 3.17 years (95% CI 2.56-3.79) for CMML vs. 16.47 years (NA) for MDS-RS/SF3B1, p&lt;0.001. Regarding patients with CMML and MDS, both with SF3B1 mutation, survival did not significantly differ. CMML had a higher risk of transformation to acute myeloid leukemia (24% at 8 years, 95%CI 19%-30%).DiscussionCMML-RS/SF3B1 mutation resembles MDS-RS/SF3B1 in terms of phenotype and clearly differs from CMML. The presence of ≥15% RS and/or SF3B1 in CMML is associated with a low monocyte count. SF3B1 mutation clearly improves the prognosis of CMML

Genotype-stratified treatment for monogenic insulin resistance: a systematic review

This is the final version. Available from Nature Research via the DOI in this record. Data availability: All data used in this review is available from publicly available and herein referenced sources. A list of included studies is provided in Supplementary Data 1. All data generated or analyzed during this study are included in this published article and its supplementary information files. Source data for the figures are available as Supplementary Data 2.BACKGROUND: Monogenic insulin resistance (IR) includes lipodystrophy and disorders of insulin signalling. We sought to assess the effects of interventions in monogenic IR, stratified by genetic aetiology. METHODS: Systematic review using PubMed, MEDLINE and Embase (1 January 1987 to 23 June 2021). Studies reporting individual-level effects of pharmacologic and/or surgical interventions in monogenic IR were eligible. Individual data were extracted and duplicates were removed. Outcomes were analysed for each gene and intervention, and in aggregate for partial, generalised and all lipodystrophy. RESULTS: 10 non-randomised experimental studies, 8 case series, and 23 case reports meet inclusion criteria, all rated as having moderate or serious risk of bias. Metreleptin use is associated with the lowering of triglycerides and haemoglobin A1c (HbA1c) in all lipodystrophy (n = 111), partial (n = 71) and generalised lipodystrophy (n = 41), and in LMNA, PPARG, AGPAT2 or BSCL2 subgroups (n = 72,13,21 and 21 respectively). Body Mass Index (BMI) is lowered in partial and generalised lipodystrophy, and in LMNA or BSCL2, but not PPARG or AGPAT2 subgroups. Thiazolidinediones are associated with improved HbA1c and triglycerides in all lipodystrophy (n = 13), improved HbA1c in PPARG (n = 5), and improved triglycerides in LMNA (n = 7). In INSR-related IR, rhIGF-1, alone or with IGFBP3, is associated with improved HbA1c (n = 17). The small size or absence of other genotype-treatment combinations preclude firm conclusions. CONCLUSIONS: The evidence guiding genotype-specific treatment of monogenic IR is of low to very low quality. Metreleptin and Thiazolidinediones appear to improve metabolic markers in lipodystrophy, and rhIGF-1 appears to lower HbA1c in INSR-related IR. For other interventions, there is insufficient evidence to assess efficacy and risks in aggregated lipodystrophy or genetic subgroups.Wellcome TrustWellcome Trus

Matrix effect of aluminium, calcium and magnesium in axially viewing inductively coupled plasma atomic emission spectrometry

The matrix effect due to Al, Ca and Mg in axial view mode ICP-AES was investigated over analyte lines with total excitation energy from 1.62 to 16.51 eV. A global qualitative explanation of the action of the matrix is proposed. The energy is directly transferred between matrix and analyte specimens (atoms or ions) during inelastic collisions, which are particularly relevant in the 1.62-8 eV excitation energy range, where the direct action with argon specimens is less probable to occur. Concrete applications of this global qualitative explanation are given, taking into account the resonance energy effect and the spin conservation rule. The characteristic matrix effect of Al and Ca for lines excited by charge transference mechanism was observed. In the presence of Mg, other possible matrix-analyte interactions may reduce the efficiency of this mechanism. The particular behavior of the matrix effect for lines in the 10.5-11.5 eV energy range can be considered as experimental evidence of the Penning ionization-excitation mechanism, which probably actuates along other matrix-analyte interactions. © The Royal Society of Chemistry 2008

NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy

Chronic myelomonocytic leukemia (CMML) is frequently associated with mutations in the rat sarcoma gene (RAS), leading to worse prognosis. RAS mutations result in active RAS-GTP proteins, favoring myeloid cell proliferation and survival and inducing the NLRP3 inflammasome together with the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which promote caspase-1 activation and interleukin (IL)-1β release. Here, we report, in a cohort of CMML patients with mutations in KRAS, a constitutive activation of the NLRP3 inflammasome in monocytes, evidenced by ASC oligomerization and IL-1β release, as well as a specific inflammatory cytokine signature. Treatment of a CMML patient with a KRAS mutation using the IL-1 receptor blocker anakinra inhibits NLRP3 inflammasome activation, reduces monocyte count, and improves the patient's clinical status, enabling a stem cell transplant. This reveals a basal inflammasome activation in RAS-mutated CMML patients and suggests potential therapeutic applications of NLRP3 and IL-1 blockers

Lemat: libro electrónico de matemáticas

El proyecto LEMAT nació hace dos años, tomando como marco las nuevas propuestas educativas basadas en el aprendizaje y el uso de las NTICs, como propugna el Espacio Común Europeo de Enseñanza Superior, y dada la falta de consolidación de la base matemática del alumno en los diversos niveles educativos. Hasta este momento hemos elaborado material correspondiente a ciertos temas, y hemos llevado a cabo en el curso 03-04 una experimentación con los alumnos de Ingeniero Químico, Ingeniero Industrial, Ingeniero de Telecomunicación y Matemáticas, de la Universidad de Cantabria. El uso del material multimedia de LEMAT se basa en la puesta en práctica de un método de enseñanza basado en el proceso de aprendizaje del alumno, en el que se trata de reducir el tiempo de clase magistral a favor de una mayor participación del alumno en clases dirigidas. Este trabajo pretende presentar el material disponible hasta el momento y analizar esta primera experimentación realizada tanto en la Universidad como en varios Institutos de Bachillerato, intentando evaluar no sólo el material utilizado, sino también el proceso de enseñanza-aprendizaje.SIN FINANCIACIÓNNo data 200

El impacto de las experiencias infantiles adversas en el periodo perinatal y el desarrollo del primer año de vida del bebé: Un estudio longitudinal.

El proyecto que se plantea pretende conocer cómo afecta la adversidad sufrida en la infancia al proceso perinatal y al desarrollo del bebé en el primer año de vida. Este conocimiento es relevante para plantear estrategias de intervención y prevención que podrán mejorar la salud de las mujeres y las futuras generaciones. Por otra parte, supone un primer paso que idealmente debería extenderse también al estudio de los varones y futuros padres. Además de las implicaciones relacionadas con la salud, el proyecto es novedoso en nuestro país, ya que prácticamente no hay estudios sobre el impacto de la adversidad temprana en general y mucho menos en el ámbito perinatal. Por último, tampoco existe investigación que aborde el proceso perinatal completo a través de metodología cualitativa y cuantitativa. A continuación se presenta una breve justificación de los objetivos planteados considerando la investigación previa realizada, casi en su totalidad, en países anglosajones