The liver is an important integrator of nutrient metabolism, yet no liver-derived factors regulating nutrient preference or carbohydrate appetite have been identified. Here we show that the liver ...regulates carbohydrate intake through production of the hepatokine fibroblast growth factor 21 (FGF21), which markedly suppresses consumption of simple sugars, but not complex carbohydrates, proteins, or lipids. Genetic loss of FGF21 in mice increases sucrose consumption, whereas acute administration or overexpression of FGF21 suppresses the intake of both sugar and non-caloric sweeteners. FGF21 does not affect chorda tympani nerve responses to sweet tastants, instead reducing sweet-seeking behavior and meal size via neurons in the hypothalamus. This liver-to-brain hormonal axis likely represents a negative feedback loop as hepatic FGF21 production is elevated by sucrose ingestion. We conclude that the liver functions to regulate macronutrient-specific intake by producing an endocrine satiety signal that acts centrally to suppress the intake of “sweets.”
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•The liver functions as a post-ingestive regulator of macronutrient preference•Carbohydrate activates hepatic ChREBP increasing production of FGF21 from the liver•FGF21 acts on the paraventricular nucleus of the hypothalamus to suppress sugar intake
Cravings for sweet foods are common, yet the mechanisms that influence the “sweet tooth” are not well-defined. von Holstein-Rathlou et al. show that in response to carbohydrate intake, the liver produces FGF21 to selectively suppress sugar appetite by acting on the PVN of the hypothalamus.
The ancestry of the Colombian population comprises a large number of well differentiated Native communities belonging to diverse linguistic groups. In the late fifteenth century, a process of ...admixture was initiated with the arrival of the Europeans, and several years later, Africans also became part of the Colombian population. Therefore, the genepool of the current Colombian population results from the admixture of Native Americans, Europeans and Africans. This admixture occurred differently in each region of the country, producing a clearly stratified population. Considering the importance of population substructure in both clinical and forensic genetics, we sought to investigate and compare patterns of genetic ancestry in Colombia by studying samples from Native and non-Native populations living in its 5 continental regions: the Andes, Caribe, Amazonia, Orinoquía, and Pacific regions. For this purpose, 46 AIM-Indels were genotyped in 761 non-related individuals from current populations. Previously published genotype data from 214 Colombian Natives from five communities were used for population comparisons. Significant differences were observed between Native and non-Native populations, among non-Native populations from different regions and among Native populations from different ethnic groups. The Pacific was the region with the highest African ancestry, Amazonia harboured the highest Native ancestry and the Andean and Orinoquían regions showed the highest proportion of European ancestry. The Andean region was further sub-divided into 6 sub-regions: North East, Central West, Central East, West, South West and South East. Among these regions, the South West region showed a significantly lower European admixture than the other regions. Hardy-Weinberg equilibrium and variance values of ancestry among individuals within populations showed a potential stratification of the Pacific population.
La circunferencia de cuello es una medida de fácil acceso y bajo costo, que podría ayudar a la identificación del sobrepeso u obesidad. Objetivo. Determinar la precisión diagnóstica de la ...circunferencia de cuello para la predicción de sobrepeso y obesidad en estudiantes universitarios mexicanos y analizar la correlación entre la circunferencia de cuello con otros indicadores antropométricos y la presión arterial como factor de riesgo cardiovascular. Materiales y métodos. Estudio transversal, analítico en 236 universitarios. Se realizaron mediciones antropométricas y presión arterial. Se realizaron análisis de las curvas ROC para obtener la sensibilidad y especificidad de los puntos de corte para la predicción de sobrepeso u obesidad y correlaciones de Pearson de circunferencia de cuello vs variables antropométricas. Resultados. Se observó, en hombres y mujeres, una correlación fuerte entre circunferencia de cuello y peso r= 0,74 y r= 0,82 (p<0,01), respectivamente, seguida por IMC r= 0,77 y r= 0,75 (p<0,01), respectivamente, circunferencia de cintura r= 0,73 y r= 0,77 (p<0,01), respectivamente e ICT r= 0,71 y r= 0,73 (p<0,01), respectivamente; se encontraron correlaciones moderadas para porcentaje de masa grasa y tensión arterial. La circunferencia de cuello vs circunferencia de cintura fue la mejor prueba de predicción para asociar el sobrepeso u obesidad tanto en hombres (AUC= 0,93; 89,3% sensibilidad y 82,3% especificidad) como mujeres (AUC= 0,95: 94,3% sensibilidad y 82,3% especificidad). Conclusiones. Los puntos de corte de la circunferencia de cuello presentan una adecuada capacidad para predecir el sobrepeso y obesidad en jóvenes adultos mexicanos.
Introduction Long QT syndrome (LQTS) is an autosomal dominant inherited cardiac condition characterized by a QT interval prolongation and risk of sudden death. There are 17 subtypes of this syndrome ...associated with genetic variants in 11 genes. The second most common is type 2, caused by a mutation in the KCNH2 gene, which is part of the potassium channel and influences the final repolarization of the ventricular action potential. This case report presents an Ecuadorian teen with congenital Long QT Syndrome type 2 (OMIM ID: 613688), from a family without cardiac diseases or sudden cardiac death backgrounds. Case presentation A 14-year-old girl with syncope, normal echocardiogram, and an irregular electrocardiogram was diagnosed with LQTS. Moreover, by performing Next-Generation Sequencing, a pathogenic variant in the KCNH2 gene p.(Ala614Val) (ClinVar ID: VCV000029777.14) associated with LQTS type 2, and two variants of uncertain significance in the AKAP9 p.(Arg1654GlyfsTer23) (rs779447911), and TTN p. (Arg34653Cys) (ClinVar ID: VCV001475968.4) genes were identified. Furthermore, ancestry analysis showed a mainly Native American proportion. Conclusion Based on the genomic results, the patient was identified to have a high-risk profile, and an implantable cardioverter defibrillator was selected as the best treatment option, highlighting the importance of including both the clinical and genomics aspects for an integral diagnosis.
Our aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose ...tolerance.
Our animal model was the Wistar rat, fed a chow diet, with or without experimentally induced diabetes. Diabetic males were fed control, low, or high-iron diets, the latter, with or without capsaicin. Healthy rats were fed identical diets, but without the capsaicin supplement. We then measured the parameters listed above, using the Student t-test and ANOVA, to compare groups.
Healthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats) further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable for the treatment of elevated hemoglobin, in patients.
Objectives
The appearance of characteristic pulmonary lesions has been noted after COVID-19, being described as post-COVID-19 pneumo-hematocele. The aim of this study is to describe the clinical, ...histopathologic, and imaging features of pneumo-hematocele and to suggest a treatment algorithm for these patients.
Methods
A retrospective study was performed in patients admitted with a diagnosis of SARS-CoV2 infection from March 2020 to September 2021 who presented a pneumo-hematocele on imaging studies. Clinical and demographic variables were recorded, and CT scans were analyzed. A secondary analysis was performed to estimate the risk provided by the pneumo-hematocele diameter of developing pneumothorax.
Results
37 patients were diagnosed with pneumo-hematoceles, 97.3% were males with a median age of 41 ± 13 years and 51% were smokers. The mean diameter of the pneumatocele was 6.3 ± 2.8 cm; they were more common on the subpleural surface and in the inferior lobe. Thirty patients had ruptured pneumo-hematoceles and developed pneumothorax (81.1%); a total of 26 patients required surgery (70.3%). Lesions measuring 5 cm had a high risk of rupture (OR 6.8, CI 95% 1.1–42); those measuring 3 cm were prone to this complication. For each centimeter that the pneumo-hematocele diameter increases, the OR for rupture increases 1.5.
Conclusions
It appears that post-COVID-19 pneumo-hematocele occurs secondary to encapsulation of blood accumulation inside the lung, as a result of micro-capillary bleeding, with partial reabsorption of blood and subsequent air filling. We recommend surgery for patients with pneumo-hematoceles of 5 cm and those with persistent lesions of 3 cm.
Trial registration
Clinical Trial Registration: NCT05067881.
Objetivo: Determinar la relación entre la circunferencia de cuello y variables antropométricas; comparar dicha circunferencia con valores de percentiles propuestos en 2021.
Material y métodos: ...Estudio transversal, analítico en una muestra de 392 escolares entre 6 y 12 años residentes de Ciudad Obregón, Sonora, México. Se realizaron correlaciones de Pearson; y se contrastaron los datos de circunferencia de cuello de 331 niños, con los percentiles de referencia de un estudio realizado en el centro México.
Resultados: Se encontró que el 44.64% tenían normopeso,14.29% bajo peso, 22.19% sobrepeso y 18.88% obesidad. La media de circunferencia de cuello fue de 27.36±2.80 en niñas y 28.44±2.78 en niños. En el subanálisis, la circunferencia de cuello fue mayor en niños vs niñas (28.04±2.62 vs 26.89±2.54). El 21.91% de las niñas y el 20.92% de los niños están por arriba del percentil 97 de referencia, y en el percentil 25 está el 19.66% de las niñas y el 18.15% de los niños. No se detectaron niñas en los percentiles 3, 85, 95 y 97; y en los niños en los percentiles 3 y 97. La circunferencia de cuello se correlacionó con todas las medidas antropométricas (circunferencia de cadera, peso, circunferencia cintura, IMC, ICT, y talla).
Conclusiones: la circunferencia de cuello se relaciona con el IMC, por lo tanto, podría ser un indicador secundario de sobrepeso u obesidad.
Palabras clave: Cuello; Índice de Masa Corporal; Obesidad; Niños.
Insufficient insulin secretion is a hallmark of type 2 diabetes and has been attributed to beta cell identity loss characterized by decreased expression of several key beta cell genes. The ...pro-inflammatory factor BMP-2 is upregulated in islets of Langerhans from individuals with diabetes and acts as an inhibitor of beta cell function and proliferation. Exposure to BMP-2 induces expression of Id1-4, Hes-1, and Hey-1 which are transcriptional regulators associated with loss of differentiation. The aim of this study was to investigate the mechanism by which BMP-2 induces beta cell dysfunction and loss of cell maturity. Mouse islets exposed to BMP-2 for 10 days showed impaired glucose-stimulated insulin secretion and beta cell proliferation. BMP-2-induced beta cell dysfunction was associated with decreased expression of cell maturity and proliferation markers specific to the beta cell such as Ins1, Ucn3, and Ki67 and increased expression of Id1-4, Hes-1, and Hey-1. The top 30 most regulated proteins significantly correlated with corresponding mRNA expression. BMP-2-induced gene expression changes were associated with a predominant reduction in acetylation of H3K27 and a decrease in NeuroD1 chromatin binding activity. These results show that BMP-2 induces loss of beta cell maturity and suggest that remodeling of H3K27ac and decreased NeuroD1 DNA binding activity participate in the effect of BMP-2 on beta cell dysfunction.
Bariatric surgery is the most efficacious treatment for obesity, though it is not free from complications. Preoperative conditioning has proved beneficial in various clinical contexts, but the ...evidence is scarce on the role of prehabilitation in bariatric surgery. We describe the protocol and pilot study of a randomized (ratio 1:1), parallel, controlled trial assessing the effect of a physical conditioning and respiratory muscle training programme, added to a standard 8-week group intervention based on therapeutical education and cognitive-behavioural therapy, in patients awaiting bariatric surgery. The primary outcome is preoperative weight-loss. Secondary outcomes include associated comorbidity, eating behaviour, physical activity, quality of life, and short-term postoperative complications. A pilot sample of 15 participants has been randomized to the intervention or control groups and their baseline features and results are described. Only 5 patients completed the group programme and returned for assessment. Measures to improve adherence will be implemented and once the COVID-19 pandemic allows, the clinical trial will start. This is the first randomized, clinical trial assessing the effect of physical and respiratory prehabilitation, added to standard group education and cognitive-behavioural intervention in obese patients on the waiting list for bariatric surgery. Clinical Trial Registration: NCT0404636.
Hearing loss is the most common sensory disability, and it is estimated that 50% of cases are caused by genetic factors. One of the genes associated with deafness is the eyes absent homolog 4 (
) ...gene, a transcription factor related to the development and function of the inner ear. Emery-Dreifuss muscular dystrophy is a rare inherited disease characterized by atrophy and weakness of the humeroperoneal muscles, multi-joint contractures, and cardiac manifestations. It is inherited in an autosomal-dominant, X-linked, or less frequently autosomal recessive manner; one of the genes associated with EDMD is the emerin (
gene.
A total of two Ecuadorian siblings aged 57 (Subject A) and 55 (Subject B) were diagnosed with deafness and an unspecified type of muscular dystrophy based on family history and clinical findings. Next-generation sequencing (NGS) using the TruSight Cardio and Inherited Disease kits at the Centro de Investigación Genética y Genómica CIGG, Universidad UTE, was performed. The genetic analyses showed two mutations: a stop mutation in exon 11/20 (NM_004100.4:c.940G>T) of the
gene and a missense mutation in exon 6 (NM_000117.2:c.548C>G) of the
gene.
The
predictions described the
variant as likely pathogenic and the
variant as a variant of uncertain significance (VUS). Moreover, an ancestry analysis was performed using 46 Ancestry Informative Insertion/Deletion Markers (AIM-InDels), and the ancestral composition of subject A was 46% African, 26.1% European, and 27.9% American Indian ancestry, whereas the ancestral composition of subject B was 41.3% African, 38.2% European, and 20.5% American Indian ancestry. The present case report describes two Ecuadorian siblings with a mainly African ancestral component, muscular dystrophy, and deafness phenotypes. Moreover, using next-generation sequencing (NGS), a mutation in the
and a novel mutation in
genes possibly associated with the subjects' phenotype were identified and discussed.
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