Biological and Medicinal Properties of Natural Chromones and Chromanones.

Emerging threats to human health require a concerted effort to search for new treatment therapies. One of the biggest challenges is finding medicines with few or no side effects. Natural products have historically contributed to major advances in the field of pharmacotherapy, as they offer special characteristics compared to conventional synthetic molecules. Interest in natural products is being revitalized, in a continuous search for lead structures that can be used as models for the development of new medicines by the pharmaceutical industry. Chromone and chromanones are recognized as privileged structures and useful templates for the design of diversified therapeutic molecules with potential pharmacological interest. Chromones and chromanones are widely distributed in plants and fungi, and significant biological activities, namely antioxidant, anti-inflammatory, antimicrobial, antiviral, etc., have been reported for these compounds, suggesting their potential as lead drug candidates. This review aims to update the literature published over the last 6 years (2018-2023) regarding the natural occurrence and biological activity of chromones and chromanones, highlighting the recent findings and the perspectives that they hold for future research and applications namely in health, cosmetic, and food industries.

Mortality and cardiovascular risk in vasculitis ANCA. Importance of hypertension and renal function. Experience from southern Spain.

BACKGROUND: Cardiovascular disease (CVD) is one of the principal causes of death in antineutrophil cytoplasmic antibody-(ANCA)-associated vasculitis (AAV). OBJECTIVES: To evaluate the mortality and it's causes and CVD and its vascular risk factors (VRFs) in AAV patients in Andalusia. METHODS: A multicenter cohort of 220 AAV patients followed-up from 1979 until June 2020 was studied in Andalussia, south of Spain. The information, including socio-demographic and clinical data was recorded retrospectively through chart review. Data was analysed using Chi2, ANOVA and Cox proportional hazards regresion as uni and multivariate test with a 95% confidence interval (CI). RESULTS: During a mean ± standard deviation follow-up of 96.79 ± 75.83 months, 51 patients died and 30 presented at least one CVE. Independent prognostic factors of mortality were age (HR 1.083, p=0.001) and baseline creatinine (HR 4.41, p=0.01). Independent prognostic factors of CVE were age [hazard ratio (HR) 1.042, p=0.005] and the presence of hypertension (HTN) six months after diagnosis (HR 4.641, p=0.01). HTN, diabetes and renal failure, all of these important VRFs, are more prevalent in AAV patients than it is described in matched general population. CONCLUSIONS: Age and baseline renal function, but not CVEs, are predictors of mortality and age and early HTN are independent predictors for having a CVE. CVD screening in AAV patients is demanded.

Assessment of dosimetric sensitivity enhancement of xylenol orange Fricke gel by AuNPs: optical and MR imaging investigation.

Metallic nanoparticles, such as gold (Au, Z = 79) and silver (Ag, Z = 47) nanoparticles (AuNPs and AgNPs, respectively), possess strong surface plasmonic resonance (SPR) and high atomic number, which makes them ideal candidates for enhancing dosimeter sensitivity. In this study, we have inserted different mass percentages (from 0 to 0.015 wt%) of AuNPs into a gelatinous Fricke-xylenol-orange (FXO-f) gel matrix and irradiated it with doses ranging from 2 to 32 Gy, using a source of x-ray of low energy with an effective energy of 42 keV. Optical absorption increased significantly; sensitivity gains of up to 50% were achieved for the FXO-f gel matrix containing 0.011 wt% AuNPs. To elucidate the mechanism underlying this increased sensitivity, we also evaluated FXO-f gel matrixes containing AgNPs. AgNPs insertion into the FXO-f gel matrix did not enhance sensitivity, which suggested that the AgNPs plasmonic absorption band and the FXO-f gel matrix absorption band at 441 nm overlapped, to increase absorption even after the gel matrix was irradiated. To visualize the dose distribution, we recorded optical tomography and acquired 3D reconstruction maps. In addition, we analyzed the dose enhancement factor (DEF) by using magnetic resonance images. AuNPs insertion into the FXO-f gel matrix resulted in a DEF gain of 1.37, associated with the photoelectric effect originating from the increased number of free radicals.

Metastasis of the choroid plexuses: A systematic review of the literature and case illustration.

BACKGROUND: Choroid plexus (CP) metastases are an extremely rare condition accounting for less than 1% of brain metastases. Due to its scarcity, little is known about this pathology and its management. Herein, we propose a review of the current literature to help its diagnosis and management. METHODS: Through a literature review based on PubMed/MEDLINE database, we reviewed 94 cases of intraventricular metastasis of solid cancer in 28 full-text articles in English from 1980 to 2010. We have reported epidemiological, clinical, radiological, histological data, as well as management strategies and outcomes. A case report of fourth ventricular pulmonary metastasis illustrates this review. RESULTS: Intraventricular metastases are most often reported in patients in their 6th decade. The clinical presentation is marked by acute hydrocephalus, more rarely lesional bleeding. Three-quarters of intraventricular metastases develop in lateral ventricle, then respectively in the fourth and third ventricles. Kidney cancer accounts for 45% of the cases. The treatment modalities are surgical removal in case of a single lesion and adjuvant radiotherapy and chemotherapy depending on the primary cancer. The prognosis remains poor due to dissemination via the cerebrospinal fluid. CONCLUSION: Multiple choroid plexus metastasis is a rare diagnosis, affecting patients with a specific clinical presentation and a misleading radiological appearance. There is no standard of care for the management of these lesions and surgical approach can be challenging.

Gravedad de COVID-19 atribuible a obesidad según IMC y CUN-BAE / Severity of COVID-19 attributable to obesity according to BMI and CUN-BAE

Introducción La obesidad es considerada un factor de riesgo en casos graves de la COVID-19, habiendo sido analizada mediante el índice de masa corporal (IMC), estimador que no correlaciona adecuadamente con el porcentaje de grasa corporal (GC). El objetivo de este estudio ha sido analizar la fracción atribuible poblacional a la GC en formas graves de COVID-19 atendiendo al IMC y al CUN-BAE. Material y métodos Estudio multicéntrico observacional de prevalencia. Se recogió información sociodemográfica, antecedentes personales, IMC y CUN-BAE, de casos positivos SARS-CoV-2, de las provincias de León y La Rioja. Mediante modelos de regresión logística se calcularon odds ratio con sus respectivos intervalos de confianza del 95% ajustando por edad y antecedentes personales, así como la fracción atribuible poblacional a la GC. Resultados Participaron 785 pacientes, 123 (15,7%) fueron graves. Se detectaron como factores de riesgo la edad, la obesidad (tanto por IMC como por CUN-BAE) y los antecedentes personales. Un 51,6% de casos graves podrían ser atribuidos a un exceso de IMC y un 61,4% a exceso de GC estimada según CUN-BAE, observándose una mayor infraestimación del riesgo en mujeres. Conclusiones El exceso de GC es un factor de riesgo para formas graves de la COVID-19 junto con la edad avanzada y la presencia de enfermedades cardiovasculares, respiratorias crónicas u oncohematológicas. El IMC infraestima el riesgo, especialmente en mujeres, siendo el CUN-BAE el predictor seleccionado por su mejor estimación del porcentaje de GC (AU)

Introduction Obesity is considered a risk factor in severe cases of COVID-19, which has been analysed using body mass index (BMI), an estimator that does not correlate adequately with body fat (BF) percentage. The aim of this study was to analyse the population attributable fraction to BF in severe forms of COVID-19 based on BMI and CUN-BAE. Material and methods Multicentre observational prevalence study. Sociodemographic information, personal history, BMI and CUN-BAE were collected in SARS-CoV-2 positive cases from the provinces of León and La Rioja. Logistic regression models were used to calculate odds ratios with their respective 95% confidence intervals adjusting for age and personal history, as well as the population attributable fraction to BF. Results Seven hundred eighty-five patients participated, 123 (15.7%) were severe. Age, obesity (both by BMI and CUN-BAE) and personal history were detected as risk factors. 51.6% of severe cases could be attributed to excess BMI and 61.4% to excess BF estimated according to CUN-BAE, with a higher underestimation of risk in women. Conclusions Excess BF is a risk factor for severe forms of COVID-19 together with advanced age and the presence of cardiovascular, chronic respiratory or oncohematological diseases. BMI underestimates the risk especially in women, being CUN-BAE the predictor selected for its better estimation of the percentage of BF (AU)

Retinosquisis ligada al X en homocigosis: A propósito de un caso / X-linked retinoschisis: About a case

La retinosquisis ligada al cromosoma X (RLX) es una causa de degeneración retiniana que afecta a varones en edades tempranas. Los desórdenes ligados al cromosoma X clásicamente afectan sólo a varones. Presentamos el caso de una mujer de 10 años de edad, con el espectro completo de la patología. MAVC 0.7 AO. En la tomografía de coherencia óptica (TCO) presentaba alteración foveal bilateral de aspecto quístico. En el estudio genético se identifica la variante c.644A>T (p.Glu215Gly) en el gen RS1 en homocigosis, asociada a retinosquisis con modo de herencia recesiva ligada al X. La RXL es una condición que tiene una gran variedad en la severidad de la enfermedad y no existe correlación entre esta última y la progresión de la patología. La enfermedad ha sido descrita en un limitado número de mujeres principalmente en familias con alto grado de consanguinidad (AU)

X-linked retinoschisis (XLR) is a cause of retinal degeneration that affects males at an early age. X-linked disorders classically affect only males. We present the case of a 10-year-old female with the full spectrum of the pathology. BCVA 0.7 OU. Optical coherence tomography (OCT) showed bilateral foveal alteration with cystic appearance. The genetic study identified the variant c.644A>T (p.Glu215Gly) in the RS1 gene in homozygosis, associated with retinoschisis with X-linked recessive mode of inheritance. XLR is a condition that has a great variety in the severity of the disease and there is no correlation between the latter and the progression of the pathology. The disease has been described in a limited number of females mainly in families with high degree of consanguinity (AU)

X-linked retinoschisis: About a case.

X-linked retinoschisis (XLR) is a cause of retinal degeneration that affects males at an early age. X-linked disorders classically affect only males. We present the case of a 10-year-old female with the full spectrum of the pathology. BCVA 0.7 OU. Optical coherence tomography (OCT) showed bilateral foveal alteration with cystic appearance. The genetic study identified the variant c.644A>T (p.Glu215Gly) in the RS1 gene in homozygosis, associated with retinoschisis with X-linked recessive mode of inheritance. XLR is a condition that has a great variety in the severity of the disease and there is no correlation between the latter and the progression of the pathology. The disease has been described in a limited number of females mainly in families with high degree of consanguinity.

[Severity of COVID-19 attributable to obesity according to BMI and CUN-BAE]. / Gravedad de COVID-19 atribuible a obesidad según IMC y CUN-BAE.

INTRODUCTION: Obesity is considered a risk factor in severe cases of COVID-19, which has been analysed using body mass index (BMI), an estimator that does not correlate adequately with body fat (BF) percentage. The aim of this study was to analyse the population attributable fraction to BF in severe forms of COVID-19 based on BMI and CUN-BAE. MATERIAL AND METHODS: Multicentre observational prevalence study. Sociodemographic information, personal history, BMI and CUN-BAE were collected in SARS-CoV-2 positive cases from the provinces of León and La Rioja. Logistic regression models were used to calculate odds ratios with their respective 95% confidence intervals adjusting for age and personal history, as well as the population attributable fraction to BF. RESULTS: Seven hundred eighty-five patients participated, 123 (15.7%) were severe. Age, obesity (both by BMI and CUN-BAE) and personal history were detected as risk factors. 51.6% of severe cases could be attributed to excess BMI and 61.4% to excess BF estimated according to CUN-BAE, with a higher underestimation of risk in women. CONCLUSIONS: Excess BF is a risk factor for severe forms of COVID-19 together with advanced age and the presence of cardiovascular, chronic respiratory or oncohematological diseases. BMI underestimates the risk especially in women, being CUN-BAE the predictor selected for its better estimation of the percentage of BF.

Mal de montaña de tipo agudo, subagudo y crónico / Acute, subacute and chronic mountain sickness

Más de 100 millones de personas ascienden cada año a áreas montañosas elevadas en todo el planeta y en altitudes no extremas (< 5.500 m) entre el 10 y el 85% se ven afectados por el denominado mal agudo de montaña, la enfermedad más frecuentemente inducida por una hipoxia hipobárica ligera-moderada. Asimismo, unos 140 millones de seres humanos viven de forma permanente en cotas comprendidas entre 2.500-5.500 m y hasta un 10% de ellos padecen la forma subaguda del mal de montaña (hipertensión pulmonar de la gran altitud) o la forma crónica (enfermedad de Monge), esta última especialmente frecuente en etnias andinas. La presente revisión expone los conceptos generales más relevantes en torno a estas 3variantes clínicas, las cuales pueden ser incapacitantes, llegar a complicarse y ser potencialmente mortales, siendo esencial realizar una correcta prevención, diagnóstico, terapéutica y manejo de las mismas en un entorno hostil como es la alta montaña (AU)

More than 100 million people ascend to high mountainous areas worldwide every year. At nonextreme altitudes (<5500 m), 10–85% of these individuals are affected by acute mountain sickness, the most common disease induced by mild-moderate hypobaric hypoxia. Approximately 140 million individuals live permanently at heights of 2500–5500 m, and up to 10% of them are affected by the subacute form of mountain sickness (high-altitude pulmonary hypertension) or the chronic form (Monge's disease), the latter of which is especially common in Andean ethnicities. This review presents the most relevant general concepts of these 3 clinical variants, which can be incapacitating and can result in complications and become life-threatening. Proper prevention, diagnosis, treatment and management of these conditions in a hostile environment such as high mountains are therefore essential (AU)

Acute, subacute and chronic mountain sickness.

More than 100 million people ascend to high mountainous areas worldwide every year. At nonextreme altitudes (<5500m), 10-85% of these individuals are affected by acute mountain sickness, the most common disease induced by mild-moderate hypobaric hypoxia. Approximately 140 million individuals live permanently at heights of 2500-5500m, and up to 10% of them are affected by the subacute form of mountain sickness (high-altitude pulmonary hypertension) or the chronic form (Monge's disease), the latter of which is especially common in Andean ethnicities. This review presents the most relevant general concepts of these 3 clinical variants, which can be incapacitating and can result in complications and become life-threatening. Proper prevention, diagnosis, treatment and management of these conditions in a hostile environment such as high mountains are therefore essential.

Síndrome de Aicardi-Goutières: un caso familiar por alteración del gen RNASEH2B / Aicardi-Goutières syndrome: a family case due to alteration of the RNASEH2B gene

Introducción: El síndrome de Aicardi-Goutières es una encefalopatía progresiva de inicio en el primer año de vida que condiciona retraso psicomotor, microcefalia y disfunción piramidal. Tiene una prevalencia de 1-5 de cada 10.000 recién nacidos vivos. La mayoría de los casos tiene transmisión autosómica recesiva, por alteración en siete genes implicados en el metabolismo del interferón, lo cual condiciona un aumento de sus niveles en la sangre y el líquido cefalorraquídeo, y afecta al cerebro (leucodistrofia, atrofia corticosubcortical, calcificaciones en los núcleos basales…), la piel y el sistema inmunitario. Caso clínico: Se trata de dos hermanos que presentan la variante p.Ala177Thr en homocigosis en el gen RNASEH2B; ambos progenitores, consanguíneos, son portadores. El primer hermano comenzó a los 10 meses con hipotonía axial, hipertonía de las extremidades, regresión psicomotriz y movimientos distónicos. El segundo hermano presentó desde el nacimiento tono axial bajo con hipertonía de las extremidades, a los 4 meses se hallaron calcificaciones en los núcleos lenticuloestriados mediante ecografía transfontalar y a los 6 meses inició movimientos distónicos y nistagmo intermitente. Ambos han desarrollado tetraparesia espástica y permanecen estables con 8 y 10 años, pese a las complicaciones propias del síndrome. Conclusiones: El síndrome de Aicardi-Goutières es una entidad rara que debe tenerse presente ante situaciones que cursen con alteración del desarrollo psicomotor y calcificaciones intracraneales; destacamos la importancia del diagnóstico genético tanto para conocer el pronóstico de nuestros pacientes en función de su alteración genética como para ofrecer consejo genético a sus familias.(AU)

Introduction: Aicardi-Goutières syndrome is a progressive encephalopathy with onset in the first year of life that conditions psychomotor retardation, microcephaly and pyramidal dysfunction. It has a prevalence of 1-5 in 10,000 newly live births. Most cases have autosomal recessive transmission, due to alteration in seven genes involved in the metabolism of interferon, which causes an increase in its levels in the blood and cerebrospinal fluid, and affects the brain (leukodystrophy, corticosubcortical atrophy, calcifications in the basal ganglia…), the skin and the immune system. Clinical case: They are two brothers who present the homozygous p.Ala177Thr variant in the RNASEH2B gene; both of them parents, consanguineous, are carriers. The first sibling started at 10 months with axial hypotonia, hypertonia of the extremities, psychomotor regression and dystonic movements. The second brother presented from the birth low axial tone with hypertonia of the extremities, at 4 months calcifications were found in the nuclei lenticulostriated by transfontalar ultrasound and, at 6 months, she started dystonic movements and intermittent nystagmus. Both have developed spastic tetraparesis and remain stable at 8 and 10 years, despite complications typical of the syndrome. Conclusions: The Aicardi-Goutières syndrome is a rare entity that should be taken into account in situations that occur with altered psychomotor development and intracranial calcifications; we highlight the importance of diagnosis both to know the prognosis of our patients based on their genetic alteration and to offer genetic counseling to their families.(AU)

[Aicardi-Goutieres syndrome: a family case due to alteration of the RNASEH2B gene]. / Síndrome de Aicardi-Goutières: un caso familiar por alteración del gen RNASEH2B.

INTRODUCTION: Aicardi-Goutieres syndrome is a progressive encephalopathy with onset in the first year of life that conditions psychomotor retardation, microcephaly and pyramidal dysfunction. It has a prevalence of 1-5 in 10,000 newly live births. Most cases have autosomal recessive transmission, due to alteration in seven genes involved in the metabolism of interferon, which causes an increase in its levels in the blood and cerebrospinal fluid, and affects the brain (leukodystrophy, corticosubcortical atrophy, calcifications in the basal ganglia…), the skin and the immune system. CLINICAL CASE: They are two brothers who present the homozygous p.Ala177Thr variant in the RNASEH2B gene; both of them parents, consanguineous, are carriers. The first sibling started at 10 months with axial hypotonia, hypertonia of the extremities, psychomotor regression and dystonic movements. The second brother presented from the birth low axial tone with hypertonia of the extremities, at 4 months calcifications were found in the nuclei lenticulostriated by transfontalar ultrasound and, at 6 months, she started dystonic movements and intermittent nystagmus. Both have developed spastic tetraparesis and remain stable at 8 and 10 years, despite complications typical of the syndrome. CONCLUSIONS: The Aicardi-Goutieres syndrome is a rare entity that should be taken into account in situations that occur with altered psychomotor development and intracranial calcifications; we highlight the importance of diagnosis both to know the prognosis of our patients based on their genetic alteration and to offer genetic counseling to their families.

TITLE: Síndrome de Aicardi-Goutières: un caso familiar por alteración del gen RNASEH2B.Introducción. El síndrome de Aicardi-Goutières es una encefalopatía progresiva de inicio en el primer año de vida que condiciona retraso psicomotor, microcefalia y disfunción piramidal. Tiene una prevalencia de 1-5 de cada 10.000 recién nacidos vivos. La mayoría de los casos tiene transmisión autosómica recesiva, por alteración en siete genes implicados en el metabolismo del interferón, lo cual condiciona un aumento de sus niveles en la sangre y el líquido cefalorraquídeo, y afecta al cerebro (leucodistrofia, atrofia corticosubcortical, calcificaciones en los núcleos basales…), la piel y el sistema inmunitario. Caso clínico. Se trata de dos hermanos que presentan la variante p.Ala177Thr en homocigosis en el gen RNASEH2B; ambos progenitores, consanguíneos, son portadores. El primer hermano comenzó a los 10 meses con hipotonía axial, hipertonía de las extremidades, regresión psicomotriz y movimientos distónicos. El segundo hermano presentó desde el nacimiento tono axial bajo con hipertonía de las extremidades, a los 4 meses se hallaron calcificaciones en los núcleos lenticuloestriados mediante ecografía transfontalar y a los 6 meses inició movimientos distónicos y nistagmo intermitente. Ambos han desarrollado tetraparesia espástica y permanecen estables con 8 y 10 años, pese a las complicaciones propias del síndrome. Conclusiones. El síndrome de Aicardi-Goutières es una entidad rara que debe tenerse presente ante situaciones que cursen con alteración del desarrollo psicomotor y calcificaciones intracraneales; destacamos la importancia del diagnóstico genético tanto para conocer el pronóstico de nuestros pacientes en función de su alteración genética como para ofrecer consejo genético a sus familias.