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The use of z-drugs has increased worldwide since its introduction. Although the prescribing patterns of hypnotics differ among countries, zolpidem is the most widely used z-drug in the world. Zolpidem may be involved in poisoning and deaths. A simple and fast HPLC-PDA method was developed and validated. Zolpidem and the internal standard chloramphenicol were extracted from plasma using a sonication-assisted dispersive liquid-liquid microextraction procedure. The method was validated including selectivity, linearity, precision, accuracy, and recovery. The calibration range (0.15-0.6 µg/mL) covers therapeutic and toxic levels of zolpidem in plasma. The limit of quantification was set at 0.15 µg/mL. Intra- and interday accuracy and precision values were lower than 15% at the concentration levels studied. Excellent recovery results were obtained for all concentrations. The proposed method was successfully applied to ten real postmortem plasma samples. In our series, multiple substances (alcohol and/or other drugs) were detected in most cases of death involving zolpidem. Our analytical method is suitable for routine toxicological analysis.
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Microextracción en Fase Líquida , Zolpidem , Zolpidem/sangre , Humanos , Microextracción en Fase Líquida/métodos , Cromatografía Líquida de Alta Presión/métodos , Sonicación/métodos , Reproducibilidad de los Resultados , Hipnóticos y Sedantes/sangre , Límite de Detección , Piridinas/sangreRESUMEN
PURPOSE OF REVIEW: Familial Hypercholesterolemia is associated with an increased risk of cardiovascular disease. The current international guidelines of the main scientific societies consider that all people with familial hypercholesterolemia have a high or very high cardiovascular risk. However, the occurrence of atherosclerotic cardiovascular disease is very heterogeneous in this population. Stratifying risk within people with familial hypercholesterolemia is essential to identify individuals who require intensive cholesterol-lowering therapies. RECENT FINDINGS: In the last year, several studies have been published focusing on the contribution of diabetes to familial hypercholesterolemia, the role of stroke, as a manifestation of atherosclerotic disease, and the external validation of the SAFEHEART risk equation in the English population diagnosed with Familial Hypercholesterolemia. SUMMARY: It is necessary the development of a tool that allows us to identify, in a simple, reproducible, and universal way, patients who may have a high risk of suffering a cardiovascular event and who are susceptible to more intensive treatments to reduce cholesterol levels.
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Enfermedades Cardiovasculares , Factores de Riesgo de Enfermedad Cardiaca , Hiperlipoproteinemia Tipo II , Humanos , Hiperlipoproteinemia Tipo II/complicaciones , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Medición de Riesgo/métodos , Factores de RiesgoRESUMEN
Arthrospira platensis, known as spirulina, is a cyanobacterium with multiple nutritional benefits, as it contains substantial amounts of proteins, fatty acids, and pigments. However, the production of this microalga has faced significant challenges, primarily related to the cost and composition of the required culture medium for its optimal growth. This study focused on optimizing two nitrogen sources (urea and potassium nitrate) to maximize the growth of A. platensis and the production of phycocyanin, a photosynthetic pigment of significant commercial value. Optimization was performed using the response surface methodology (RSM) with a central composite design (CCD). Analysis of variance (ANOVA) was employed to validate the model, which revealed that the different concentrations of urea were statistically significant (p < 0.05) for biomass and phycocyanin production. However, potassium nitrate (KNO3) showed no significant influence (p > 0.05) on the response variables. The RSM analysis indicated that the optimal concentrations of KNO3 and urea to maximize the response variables were 3.5 g L-1 and 0.098 g L-1, respectively. This study offers valuable perspectives for the efficient production of A. platensis while reducing production costs for its cultivation on a larger scale.
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PURPOSE OF REVIEW: Familial hypercholesterolemia is associated with an increased risk of cardiovascular disease. The current international guidelines of the main scientific societies consider that, all people with Familial Hypercholesterolemia have a high or very high cardiovascular risk. However, the occurrence of atherosclerotic cardiovascular disease is very heterogeneous in this population. Stratifying risk within people with familial hypercholesterolemia is essential to identify individuals who require intensive cholesterol-lowering therapies. RECENT FINDINGS: In the last year, several studies have been published focusing on the contribution of diabetes to Familial Hypercholesterolemia, the role of stroke, as a manifestation of atherosclerotic disease, and the external validation of the SAFEHEART risk equation in the English population diagnosed with Familial Hypercholesterolemia. SUMMARY: It is necessary the development of a tool that allows us to identify, in a simple, reproducible, and universal way, patients who may have a high risk of suffering a cardiovascular event and who are susceptible to more intensive treatments to reduce cholesterol levels.
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Aterosclerosis , Enfermedades Cardiovasculares , Hiperlipoproteinemia Tipo II , Humanos , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/epidemiología , Factores de Riesgo , Hiperlipoproteinemia Tipo II/epidemiología , LDL-Colesterol , Aterosclerosis/complicaciones , Aterosclerosis/epidemiología , Aterosclerosis/diagnóstico , Factores de Riesgo de Enfermedad CardiacaRESUMEN
Introduction: Policymakers, health practitioners, and other key partners are increasingly focused on ensuring that clients of food assistance programs have positive experiences, a key aspect of high-quality programming. The objectives of this review are to describe the experiences of clients participating in food assistance programs in the United States (US) and to identify ways that these programs promote or hinder positive experiences. Methods and analysis: We will conduct a qualitative evidence synthesis with partners from food security organizations and community members. Peer-reviewed literature will be systematically searched in Scopus, CINAHL, and AGRICOLA. To identify grey literature, we will use Google's programmable search engine. This review will consider sources that present results of primary qualitative studies that focus on at least one food assistance program in the US and explore the perspectives of adult clients. Only sources published in English or Spanish from 2007 onward will be included. Multiple reviewers will screen articles for inclusion and extract data from articles that meet the inclusion criteria, using a structured data extraction tool. Thematic synthesis or meta-ethnography may be appropriate approaches for synthesizing the extracted data. The final selection of synthesis method will be determined once the set of primary qualitative studies to be included in the review is complete and the type of data presented in these studies is known. We will assess the methodological quality of the included studies using the CASP (Critical Appraisal Skills Programme) tool for qualitative studies and assess the confidence in the review findings using the GRADE-CERQual (Confidence in Evidence from Reviews of Qualitative research) approach. Discussion: The findings of this review will inform the development of measures to assess client experience and quality improvement efforts.
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Asistencia Alimentaria , Humanos , Estados Unidos , Adulto , Investigación Cualitativa , Mejoramiento de la Calidad , Motor de Búsqueda , Revisiones Sistemáticas como AsuntoRESUMEN
Oxidative stress (OS) is a relevant intermediate mechanism involved in Type 2 Diabetes Mellitus (T2D) development. To date, the interaction between OS parameters and variations in genes related to T2D has not been analyzed. AIMS: To study the genetic interaction of genes potentially related to OS levels (redox homeostasis, renin-angiotensin-aldosterone system, endoplasmic stress response, dyslipidemia, obesity and metal transport) and OS and T2D risk in a general population from Spain (the Hortega Study) in relation to the risk of suffering from T2D. MATERIALS AND METHODS: One thousand five hundred and two adults from the University Hospital Rio Hortega area were studied and 900 single nucleotide polymorphisms (SNPs) from 272 candidate genes were analyzed. RESULTS: There were no differences in OS levels between cases and controls. Some polymorphisms were associated with T2D and with OS levels. Significant interactions were observed between OS levels and two polymorphisms in relation to T2D presence: rs196904 (ERN1 gene) and rs2410718 (COX7C gene); and between OS levels and haplotypes of the genes: SP2, HFF1A, ILI8R1, EIF2AK2, TXNRD2, PPARA, NDUFS2 and ERN1. CONCLUSIONS: Our results indicate that genetic variations of the studied genes are associated with OS levels and that their interaction with OS parameters may contribute to the risk of developing T2D in the Spanish general population. These data support the importance of analyzing the influence of OS levels and their interaction with genetic variations in order to establish their real impact in T2D risk. Further studies are required to identify the real relevance of interactions between genetic variations and OS levels and the mechanisms involved in them.
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Diabetes Mellitus Tipo 2 , Adulto , Humanos , Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad , Haplotipos , Obesidad/genética , Alelos , Polimorfismo de Nucleótido Simple , Estudios de Casos y ControlesRESUMEN
INTRODUCTION: Heterozygous familial hypercholesterolaemia (heFH) is the most common monogenic cause of premature atherosclerotic cardiovascular disease. The precise diagnosis of heFH is established by genetic testing. This systematic review will investigate the risk factors that predict cardiovascular events in patients with a genetic diagnosis of heFH. METHODS AND ANALYSIS: Our literature search will cover publications from database inception until June 2023. We will undertake a search of CINAHL (trial), clinicalKey, Cochrane Library, DynaMed, Embase, Espacenet, Experiments (trial), Fisterra, ÍnDICEs CSIC, LILACS, LISTA, Medline, Micromedex, NEJM Resident 360, OpenDissertations, PEDro, Trip Database, PubPsych, Scopus, TESEO, UpToDate, Web of Science and the grey literature for eligible studies. We will screen the title, abstract and full-text papers for potential inclusion and assess the risk of bias. We will employ the Cochrane tool for randomised controlled trials and non-randomised clinical studies and the Newcastle-Ottawa Scale for assessing the risk of bias in observational studies. We will include full-text peer-reviewed publications, reports of a cohort/registry, case-control and cross-sectional studies, case report/series and surveys related to adults (≥18 years of age) with a genetic diagnostic heFH. The language of the searched studies will be restricted to English or Spanish. The Grading of Recommendations, Assessment, Development and Evaluation approach will be used to assess the quality of the evidence. Based on the data available, the authors will determine whether the data can be pooled in meta-analyses. ETHICS AND DISSEMINATION: All data will be extracted from published literature. Hence, ethical approval and patient informed consent are not required. The findings of the systematic review will be submitted for publication in a peer-reviewed journal and presentation at international conferences. PROSPERO REGISTRATION NUMBER: CRD42022304273.
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Enfermedades Cardiovasculares , Hiperlipoproteinemia Tipo II , Humanos , Estudios Transversales , Factores de Riesgo , Enfermedades Cardiovasculares/genética , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/genética , Revisiones Sistemáticas como AsuntoRESUMEN
Ventricular fibrillation (VF) is a leading immediate cause of sudden cardiac death. There is a strong association between aging and VF, although the mechanisms are unclear, limiting the availability of targeted therapeutic interventions. Here we found that the stress kinases p38γ and p38δ are activated in the ventricles of old mice and mice with genetic or drug-induced arrhythmogenic conditions. We discovered that, upon activation, p38γ and p38δ cooperatively increase the susceptibility to stress-induced VF. Mechanistically, our data indicate that activated p38γ and p38δ phosphorylate ryanodine receptor 2 (RyR2) disrupt Kv4.3 channel localization, promoting sarcoplasmic reticulum calcium leak, Ito current reduction and action potential duration prolongation. In turn, this led to aberrant intracellular calcium handling, premature ventricular complexes and enhanced susceptibility to VF. Blocking this pathway protected genetically modified animals from VF development and reduced the VF duration in aged animals. These results indicate that p38γ and p38δ are a potential therapeutic target for sustained VF prevention.
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Proteína Quinasa 12 Activada por Mitógenos , Canal Liberador de Calcio Receptor de Rianodina , Fibrilación Ventricular , Animales , Proteína Quinasa 12 Activada por Mitógenos/metabolismo , Proteína Quinasa 12 Activada por Mitógenos/genética , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Canal Liberador de Calcio Receptor de Rianodina/genética , Fibrilación Ventricular/fisiopatología , Fibrilación Ventricular/metabolismo , Fibrilación Ventricular/genética , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Proteína Quinasa 13 Activada por Mitógenos/metabolismo , Proteína Quinasa 13 Activada por Mitógenos/genética , Fosforilación , Miocitos Cardíacos/metabolismo , Masculino , Activación Enzimática , Ratones , Complejos Prematuros Ventriculares/fisiopatología , Complejos Prematuros Ventriculares/genética , Complejos Prematuros Ventriculares/metabolismo , Retículo Sarcoplasmático/metabolismo , Ratones Noqueados , Humanos , Señalización del Calcio , Factores de EdadRESUMEN
BACKGROUND: Pediatric early warning systems (PEWS) aid in the early identification of deterioration in hospitalized children with cancer; however, they are under-used in resource-limited settings. The authors use the knowledge-to-action framework to describe the implementation strategy for Proyecto Escala de Valoracion de Alerta Temprana (EVAT), a multicenter quality-improvement collaborative, to scale-up PEWS in pediatric oncology centers in Latin America. METHODS: Proyecto EVAT mentored participating centers through an adaptable implementation strategy to: (1) monitor clinical deterioration in children with cancer, (2) contextually adapt PEWS, (3) assess barriers to using PEWS, (4) pilot and implement PEWS, (5) monitor the use of PEWS, (6) evaluate outcomes, and (7) sustain PEWS. The implementation outcomes assessed included the quality of PEWS use, the time required for implementation, and global program impact. RESULTS: From April 2017 to October 2021, 36 diverse Proyecto EVAT hospitals from 13 countries in Latin America collectively managing more than 4100 annual new pediatric cancer diagnoses successfully implemented PEWS. The time to complete all program phases varied among centers, averaging 7 months (range, 3-13 months) from PEWS pilot to implementation completion. All centers ultimately implemented PEWS and maintained high-quality PEWS use for up to 18 months after implementation. Across the 36 centers, more than 11,100 clinicians were trained in PEWS, and more than 41,000 pediatric hospital admissions had PEWS used in their care. CONCLUSIONS: Evidence-based interventions like PEWS can be successfully scaled-up regionally basis using a systematic approach that includes a collaborative network, an adaptable implementation strategy, and regional mentorship. Lessons learned can guide future programs to promote the widespread adoption of effective interventions and reduce global disparities in childhood cancer outcomes. LAY SUMMARY: Pediatric early warning systems (PEWS) are clinical tools used to identify deterioration in hospitalized children with cancer; however, implementation challenges limit their use in resource-limited settings. Proyecto EVAT is a multicenter quality-improvement collaborative to implement PEWS in 36 pediatric oncology centers in Latin America. This is the first multicenter, multinational study reporting a successful implementation strategy (Proyecto EVAT) to regionally scale-up PEWS. The lessons learned from Proyecto EVAT can inform future programs to promote the adoption of clinical interventions to globally improve childhood cancer outcomes.
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Oncología Médica , Neoplasias , Niño , Humanos , América Latina , Hospitales Pediátricos , HospitalizaciónRESUMEN
Las pacientes embarazadas con diabetes mellitus (DM) pregestacional y complicaciones micro y macroangiopáticas tienen mayor riesgo de empeoramiento de las mismas y de presentar otros trastornos asociados al embarazo. La progresión de la retinopatía diabética ocurre durante el embarazo y el posparto. La nefropatía se asocia con un mayor riesgo de preeclampsia, parto prematuro, restricción del crecimiento fetal y mortalidad perinatal. Cuando hay enfermedad de arterias coronarias o gastroparesia se observa un aumento de la morbilidad materna y fetal. El parto prematuro es una condición prevalente en pacientes con DM. La maduración pulmonar fetal con corticosteroides fue extensamente estudiada, con numerosas pruebas controladas, hasta convertirse en una de las más importantes terapias prenatales basadas en evidencias para reducir la mortalidad perinatal y el síndrome de dificultad respiratoria, la hemorragia intraventricular y la enterocolitis necrosante en los niños prematuros. Sin embargo, en dicha evidencia no se han incluido a embarazadas con DM, por lo cual no se conocen resultados perinatales en este grupo de pacientes.
Pregnant patients with pregestational diabetes mellitus (DM) and micro and macroangiopathic complications have a higher risk of their worsening and of presenting other pregnancyassociated disorders. The progression of diabetic retinopathy occurs during pregnancy and postpartum. Nephropathy is associated with an increased risk of preeclampsia, preterm delivery, fetal growth restriction, and perinatal mortality. When there is coronary artery disease or gastroparesis, an increase in maternal and fetal morbidity is observed Preterm delivery is a prevalent condition in diabetic patients. Corticosteroid fetal lung maturation has been extensively studied, with numerous controlled trials, to become one of the most important evidence-based prenatal therapies to reduce perinatal mortality and decrease respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis, in premature infants. Nevertheless, this evidence did not include patients with DM, for this reason perinatal results are not known in this group of patients.
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Diabetes Mellitus , Recien Nacido Prematuro , Corticoesteroides , Mujeres Embarazadas , Mortalidad Perinatal , PulmónRESUMEN
Las pacientes embarazadas con diabetes mellitus (DM) pregestacional y complicaciones micro y macroangiopáticas tienen mayor riesgo de empeoramiento de las mismas y de presentar otros trastornos asociados al embarazo. La progresión de la retinopatía diabética ocurre durante el embarazo y el posparto. La nefropatía se asocia con un mayor riesgo de preeclampsia, parto prematuro, restricción del crecimiento fetal y mortalidad perinatal. Cuando hay enfermedad de arterias coronarias o gastroparesia se observa un aumento de la morbilidad materna y fetal. El parto prematuro es una condición prevalente en pacientes con DM. La maduración pulmonar fetal con corticosteroides fue extensamente estudiada, con numerosas pruebas controladas, hasta convertirse en una de las más importantes terapias prenatales basadas en evidencias para reducir la mortalidad perinatal y el síndrome de dificultad respiratoria, la hemorragia intraventricular y la enterocolitis necrosante en los niños prematuros. Sin embargo, en dicha evidencia no se han incluido a embarazadas con DM, por lo cual no se conocen resultados perinatales en este grupo de pacientes.
Pregnant patients with pregestational diabetes mellitus (DM) and micro and macroangiopathic complications have a higher risk of their worsening and of presenting other pregnancyassociated disorders. The progression of diabetic retinopathy occurs during pregnancy and postpartum. Nephropathy is associated with an increased risk of preeclampsia, preterm delivery, fetal growth restriction, and perinatal mortality. When there is coronary artery disease or gastroparesis, an increase in maternal and fetal morbidity is observed Preterm delivery is a prevalent condition in diabetic patients. Corticosteroid fetal lung maturation has been extensively studied, with numerous controlled trials, to become one of the most important evidence-based prenatal therapies to reduce perinatal mortality and decrease respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis, in premature infants. Nevertheless, this evidence did not include patients with DM, for this reason perinatal results are not known in this group of patients.
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BACKGROUND: Familial Hypercholesterolemia is the most frequent genetic cause of premature coronary heart disease. The delay in the diagnosis prevents the correct early treatment. There are no effective screening strategies at the national level that ensure a correct diagnosis. OBJECTIVE: To determine the capacity of a centralized laboratory for the diagnosis of Familial Hypercholesterolemia through the creation of a health program for population screening in the province of Huelva. METHOD: Active search of patients with primary hypercholesterolemia through the blood tests carried out in the reference laboratories with results of low-density lipoprotein cholesterol greater than 200â¯mg/dl and assessment in the Lipid Unit of Huelva to identify index cases, with subsequent family cascade screening. RESULTS: 37,440 laboratory tests with lipid profile were examined. After screening, 846 individuals were seen in the Lipid Unit, of which they were diagnosed according to criteria of the Dutch Lipid Clinic Network as possible 654 and probable/definitive 192 individuals, representing 1.74% and 0.51% of the general population examined respectively. CONCLUSIONS: The point prevalence of Familial Hypercholesterolemia in patients submitted to laboratory lipid profile tests was 1:195, higher compared to the prevalence of Familial Hypercholesterolemia in the general population (based on 1 in 200-300). The opportunistic search strategy of the index case through a laboratory alert and centralized screening is an efficient strategy to implement a national screening for the diagnosis of Familial Hypercholesterolemia.
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Hiperlipoproteinemia Tipo II , LDL-Colesterol , Enfermedad de la Arteria Coronaria , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Tamizaje Masivo , Prevalencia , EspañaRESUMEN
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) introduced in the 1960s and widely used as an analgesic, anti-inflammatory, and antipyretic. In its acid form, the solubility of 21 mg/L greatly limits its bioavailability. Since the bioavailability of a drug product plays a critical role in the design of oral administration dosage, this study investigated the enzymatic esterification of ibuprofen as a strategy for hydrophilization. This work proposes an enzymatic strategy for the covalent attack of highly hydrophilic molecules using acidic functions of commercially available bioactive compounds. The poorly water-soluble drug ibuprofen was esterified in a hexane/water biphasic system by direct esterification with sorbitol using the cheap biocatalyst porcine pancreas lipase (PPL), which demonstrated itself to be a suitable enzyme for the effective production of the IBU-sorbitol ester. This work reports the optimization of the esterification reaction.
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Biocatálisis , Medios de Cultivo/química , Ibuprofeno/química , Sorbitol/química , Animales , Esterificación , Hidrólisis , Ibuprofeno/síntesis química , Lipasa/metabolismo , Solventes , Especificidad por Sustrato , Porcinos , Temperatura , Factores de Tiempo , Agua/químicaRESUMEN
RESUMEN Fundamento: El carcinoma basocelular periocular es una lesión tumoral que surge de las células basales de la epidermis y los folículos pilosos, con un alto potencial de destrucción local, pueden ser desfigurantes e invaden el tejido que los rodea dando lugar a deformidades o pérdida de la función del órgano afectado. En orden de aparición es más común en el párpado inferior, el canto medial, el párpado superior y el canto temporal. Objetivo: Describir los resultados de la aplicación del HeberFERON en una serie de casos con carcinoma basocelular periocular que acudieron a consulta de dermatología del Policlínico Centro, de enero de 2017 a diciembre del 2020. Metodología: Se realizó un estudio de serie de casos clínicos con carcinoma basocelular periocular que acudieron a la consulta de dermatología del Policlínico Centro. Se incluyeron 17 casos con diagnóstico clínico, dermatoscópico e histopatológico. Se realizó una evaluación inicial, durante y 16 semanas después del tratamiento; se administró 10.5 UI de HeberFERON 3 veces por semana perilesional e intradérmica hasta completar 9 dosis. Las variables principales fueron la respuesta al tratamiento y la presencia o no de eventos adversos. Resultados: Predominó el sexo masculino, el fototipocutáneo II, la localización en párpado inferior, el subtipo clínico nódulo ulcerativo y el histológico sólido, se logró respuesta completa en la mayoría de los pacientes. Como eventos adversos se presentaron dolor en el sitio de inyección, fiebre, mal estar general, edema y eritema perilesional. Conclusiones: La respuesta al tratamiento fue favorable en la mayoría de los pacientes tratados con HeberFERON.
ABSTRACT Background: Periocular basal cell carcinoma is a tumor lesion arising from the epidermis and hair follicles basal cells, with a high potential local destruction, can be disfiguring and invade the surrounding tissue leading to deformities or loss of function of the affected organ. In order of appearance it is most common in the lower eyelid, medial edge, upper eyelid and temporal edge. Objective: To describe the results of the application of HeberFERON in a case series with periocular basal cell carcinoma who attended dermatology appointment at the Policlínico Centro, from January 2017 to December 2020. Methodology: A series study of clinical cases with periocular basal cell carcinoma who attended the dermatology appointment at the Policlínico Centro was conducted. 17 cases with clinical, dermatoscopic and histopathological diagnosis were included. A baseline evaluation was conducted, during and 16 weeks after treatment; 10.5 IU of HeberFERON was administered 3 times a week perilesional and intradermally until completing 9 doses. The main variables were the treatment response and the presence or absence of adverse events. Results: Male sex, phototypocutaneous II, lower eyelid location, clinical subtype ulcerative nodule and solid histological subtype predominated, complete response was achieved in most patients. Adverse events were pain at the injection site, fever, general malaise, edema and perilesional erythema. Conclusions: Treatment response was favorable in most patients treated with HeberFERON.
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Neoplasias Cutáneas/terapia , Carcinoma Basocelular/terapia , Interferón alfa-2/uso terapéutico , Dermatitis Perioral/terapiaRESUMEN
Metabolic stress causes activation of the cJun NH2-terminal kinase (JNK) signal transduction pathway. It is established that one consequence of JNK activation is the development of insulin resistance and hepatic steatosis through inhibition of the transcription factor PPARα. Indeed, JNK1/2 deficiency in hepatocytes protects against the development of steatosis, suggesting that JNK inhibition represents a possible treatment for this disease. However, the long-term consequences of JNK inhibition have not been evaluated. Here we demonstrate that hepatic JNK controls bile acid production. We found that hepatic JNK deficiency alters cholesterol metabolism and bile acid synthesis, conjugation, and transport, resulting in cholestasis, increased cholangiocyte proliferation, and intrahepatic cholangiocarcinoma. Gene ablation studies confirmed that PPARα mediated these effects of JNK in hepatocytes. This analysis highlights potential consequences of long-term use of JNK inhibitors for the treatment of metabolic syndrome.
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Ácidos y Sales Biliares/metabolismo , Colangiocarcinoma/enzimología , Proteína Quinasa 8 Activada por Mitógenos/metabolismo , Proteína Quinasa 9 Activada por Mitógenos/metabolismo , Animales , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Colangiocarcinoma/fisiopatología , Homeostasis , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína Quinasa 8 Activada por Mitógenos/genética , Proteína Quinasa 9 Activada por Mitógenos/genética , PPAR alfa/genética , PPAR alfa/metabolismoRESUMEN
To ascertain the relationship between the perimetric differences obtained between the limbs and the type of fluoroscopic pattern observed by Indocyanine green (ICG) lymphography in patients with upper limb lymphedema.A correlational descriptive study was carried out in 19 patients with upper limb lymphedema secondary to breast cancer. The perimetric increase was recorded in 11 anatomical regions after ICG injection, fluoroscopic patterns were identified using an infrared camera. The ICG patterns were categorized into worse (stardust, diffuse) or better (linear, splash) patterns.The pattern coincidence between the anterior and posterior regions of the edematous extremities was 45%. At the wrist level, a difference of 2âcm was associated with the presence of a worse fluoroscopic pattern, whereas perimeter differences of 4.25âcm in the elbow and 2.25âcm in the arm (12âcm from the epicondyle) were associated with the presence of a better fluoroscopic pattern.The perimetric differences observed between the healthy and affected upper limbs in 4 specific anatomical areas allowed us to predict the type of fluoroscopic pattern. ICG lymphography has facilitated the study of the posterior regions of edema, which are difficult to visualize using other imaging techniques.
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Verde de Indocianina/administración & dosificación , Vasos Linfáticos/diagnóstico por imagen , Linfedema/etiología , Linfografía/métodos , Pruebas del Campo Visual/métodos , Adulto , Anciano , Neoplasias de la Mama/complicaciones , Estudios de Casos y Controles , Estudios de Evaluación como Asunto , Femenino , Fluoroscopía/métodos , Fluoroscopía/estadística & datos numéricos , Humanos , Vasos Linfáticos/patología , Linfedema/clasificación , Linfedema/patología , Persona de Mediana Edad , España/epidemiología , Extremidad Superior/anatomía & histología , Extremidad Superior/diagnóstico por imagenRESUMEN
RESUMEN Introducción: La causa común de dolor en la región subcalcánea es la fascitis plantar. Por su efecto analgésico y antiinflamatorio, el empleo de la radiación electromagnética en su tratamiento constituye una opción terapéutica. Objetivos: Evaluar la utilidad de la radiación electromagnética en pacientes que presentaban síndrome doloroso en la región subcalcánea y relacionar la mejoría clínica con los grupos de edades y sexos. Métodos: Se realizó un estudio descriptivo de corte transversal a dos grupos de pacientes con dolor en la región subcalcánea. Para el análisis estadístico, al final del tratamiento se utilizó la prueba de homogeneidad λ2 con un nivel de significación de ά 0,05. Resultados: A las 20 sesiones de tratamiento, el 93,33 por ciento de los pacientes tratados con la radiación electromagnética no presentaron dolor, el 94,44 por ciento de ellos pertenecían al grupo de edades de 25-59 años y el 90,90 por ciento eran del sexo femenino. Conclusiones: Se evalúa de positiva la utilidad de la radiación electromagnética en el tratamiento del dolor en la región subcalcánea, con una diferencia significativa en relación con el tratamiento médico convencional. El mayor número de pacientes correspondió al grupo de edades entre 25 y 59 años, con predominio del sexo femenino(AU)
ABSTRACT Introduction: The common cause of pain in the subcalcaneal region is plantar fasciitis. The electromagnetic radiation in its treatment constitutes a therapeutic option due to its analgesic and anti-inflammatory effect. Objectives: To assess the value electromagnetic radiation in patients who suffered pain syndrome in the subcalcaneal region and to relate the clinical improvement with age and gender groups. Methods: A descriptive cross-sectional study was conducted in two groups of patients with pain in the subcalcaneal region. For the statistical analysis, the λ2 homogeneity test was used at the end of the treatment with a significance level of ά 0.05. Results: After a treatment of 20 electromagnetic radiation sessions, 93.33 percent did not had pain, 94.44 percent were in the 25-to-59-year-olds group and 90.90 percent were women. Conclusions: The value of electromagnetic radiation in the treatment of pain in the subcalcaneal region is positively assessed, showing significant difference in relation to conventional medical treatment. The largest number of patients corresponded to the 25-to-59-year-olds group, with a predominance of women(AU)