A Prospective, Observational Study of the Effect of a High-Calorie, High-Protein Oral Nutritional Supplement with HMB in an Old and Malnourished or at-Risk-of-Malnutrition Population with Hip Fractures: A FracNut Study.

BACKGROUND: Hip fractures are prevalent among older people, often leading to reduced mobility, muscle loss, and bone density decline. Malnutrition exacerbates the prognosis post surgery. This study aimed to evaluate the impact of a 12-week regimen of a high-calorie, high-protein oral supplement with ß-hydroxy-ß-methylbutyrate (HC-HP-HMB-ONS) on nutritional status, daily activities, and compliance in malnourished or at-risk older patients with hip fractures receiving standard care. SUBJECTS AND METHODS: A total of 270 subjects ≥75 years of age, residing at home or in nursing homes, malnourished or at risk of malnutrition, and post hip fracture surgery, received HC-HP-HMB-ONS for 12 weeks. Various scales and questionnaires assessed outcomes. RESULTS: During the 12 weeks of follow-up, 82.8% consumed ≥75% of HC-HP-HMB-ONS. By week 12, 62.4% gained or maintained weight (+0.3 kg), 29.2% achieved normal nutritional status (mean MNA score +2.8), and 46.8% improved nutritional status. Biochemical parameters improved significantly. Subjects reported good tolerability (mean score 8.5/10), with 87.1% of healthcare providers concurring. CONCLUSIONS: The administration of HC-HP-HMB-ONS markedly enhanced nutritional status and biochemical parameters in older hip-fracture patients, with high compliance and tolerability. Both patients and healthcare professionals expressed satisfaction with HC-HP-HMB-ONS.

Mechanistic Insights about Sorafenib-, Valproic Acid- and Metformin-Induced Cell Death in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is among the main causes of death by cancer worldwide, representing about 80-90% of all liver cancers. Treatments available for advanced HCC include atezolizumab, bevacizumab, sorafenib, among others. Atezolizumab and bevacizumab are immunological options recently incorporated into first-line treatments, along with sorafenib, for which great treatment achievements have been reached. However, sorafenib resistance is developed in most patients, and therapeutical combinations targeting cancer hallmark mechanisms and intracellular signaling have been proposed. In this review, we compiled evidence of the mechanisms of cell death caused by sorafenib administered alone or in combination with valproic acid and metformin and discussed them from a molecular perspective.

Single anastomosis duodeno-ileal bypass with sleeve gastrectomy generates sustained improvement of glycemic control compared with sleeve gastrectomy in the diet-induced obese rat model.

Bariatric surgery has become a recognized and effective procedure for treating obesity and type 2 diabetes (T2D). Our objective was to directly compare the caloric intake-independent effects of sleeve gastrectomy (SG) and single anastomosis duodenoileal bypass with SG (SADI-S) on glucose tolerance in rats with diet-induced obesity (DIO) and to elucidate the differences between bariatric surgery and caloric restriction.A total of 120 adult male Wistar rats with DIO and insulin resistance were randomly assigned to surgical (sham operation, SG, and SADI-S) and dietary (pair-feeding the amount of food eaten by animals undergoing the SG or SADI-S surgeries) interventions. Body weight and food intake were weekly monitored, and 6 weeks after interventions, fasting plasma glucose, oral glucose and insulin tolerance tests, plasma insulin, adiponectin, GIP, GLP-1, and ghrelin levels were determined.The body weight of SADI-S rats was significantly (p < 0.001) lower as compared to the sham-operated, SG, and pair-fed groups. Furthermore, SADI-S rats exhibited decreased whole body fat mass (p < 0.001), lower food efficiency rates (p < 0.001), and increased insulin sensitivity, as well as improved glucose and lipid metabolism compared to that of the SG and pair-fed rats.SADI-S was more effective than SG, or caloric restriction, in improving glycemic control and metabolic profile, with a higher remission of insulin resistance as well as long-term weight loss.

La adaptación transcultural, confiabilidad y validez del instrumento actitudes y conocimientos de seguridad del paciente / The cross-cultural adaptation, reliability and validity of the instrument attitudes and knowledge of patient safety

Resumen Objetivo: La seguridad del paciente busca reducir los riesgos y ocurrencia de daño evitable, y que los errores sean menos probables en la población que recibe atención sanitaria. La formación de recursos humanos en salud es considerada como un elemento fundamental para generar cambios en la práctica sanitaria y contribuir a disminuir o limitar los errores, así como tener procesos más seguros. El objetivo de esta investigación es adaptar y validar el "Cuestionario para medir actitudes y conocimientos de seguridad del paciente" para su aplicación con estudiantes de enfermería y medicina de una Universidad Pública de Medicina y Enfermería del Caribe Mexicano. Materiales y Métodos: Estudio transversal, observacional, con aplicación de encuesta anónima y voluntaria. La muestra incluyó a 220 estudiantes (120 mujeres y 100 hombres) con una edad promedio de 24 años (DE=2) matriculados en una Universidad Pública de medicina y enfermería del Caribe Mexicano. 46% se encontraban realizando Internado de pregrado y 54% en prácticas de Servicio Social. El instrumento presentó 1 ficha de identificación y 21 reactivos tipo Likert. Resultados: A través del Análisis Factorial Exploratorio (AFE) se fijó a cinco factores con el método de Máxima Verosimilitud y rotación Varimax sobre los 21 reactivos del cuestionario de seguridad del paciente para estudiantes mexicanos, resultando una escala de cinco factores que explican el 63.59% de la varianza total y un índice de consistencia interna de la escala total aceptable (α=.87). Conclusiones: El cuestionario para medir actitudes y conocimientos sobre seguridad del paciente adaptado en los estudiantes de medicina y enfermería es válido, confiable y útil para medir las acciones de seguridad del paciente para la prevención del error en la atención sanitaria.

Abstract Objective: Patient safety seeks to reduce the risk and occurrence of avoidable harm, and to make errors less common in the population that receive health care. The training of human resources in health is considered a fundamental element to generate changes in health practices and contribute to reducing errors, furthermore safer processes. The objective of the present study is adapt and validate the "Questionnaire to measure attitudes and knowledge of patient safety" for its application with nursing and medical students of Public University of Medicine and Nursing in the Mexican Caribbean. Materials and methods: A cross-sectional, observational study, with the application of an anonymous and voluntary survey. The sample included 220 students (120 women and 100 men) with an average age of 24 years (SD=2) a Public University of Medicine and Nursing in the Mexican Caribbean. The 46% were undergraduate internship and 54% in Social Service practices. The instrument presented one identification card and 21 Likert-type items. Results: Through the Exploratory Factor Analysis (EFA), five factors were set with the Maximum Likelihood method and Varimax rotation on the 21 items of the patient safety questionnaire for Mexican students, resulting five factors that explain 63.59% of the total variance and an internal consistency index of the acceptable total scale (α=.87). Conclusions: The questionnaire to measure attitudes and knowledge about patient safety translated and adapted to medical and nursing students is valid, reliable and useful to measure patient safety actions for the prevention of errors in health care.

Increased Expression Levels of Netrin-1 in Visceral Adipose Tissue during Obesity Favour Colon Cancer Cell Migration.

Netrin (NTN)-1, an extracellular matrix protein with a crucial role in inflammation, is dysregulated during obesity (OB) and influences colon cancer (CC) progression. To decipher the mechanisms underlying CC development during obesity, we examined the expression of NTN1 and its receptors in the visceral adipose tissue (VAT) of 74 (25 normal weight (NW)) (16 with CC) and 49 patients with OB (12 with CC). We also evaluated the effect of caloric restriction (CR) on the gene expression levels of Ntn1 and its receptors in the colon from a rat model fed a normal diet. The impact of adipocyte-conditioned media (ACM) from patients with OB and NTN-1 was assessed on the expression levels of neogenin 1(NEO1), deleted in colorectal carcinomas (DCC) and uncoordinated-5 homolog B (UNC5B) in Caco-2 and HT-29 human colorectal cell lines, as well as on Caco-2 cell migration. Increased NTN1 and NEO1 mRNA levels in VAT were due to OB (p < 0.05) and CC (p < 0.001). In addition, an upregulation in the expression levels of DCC and UNC5B in patients with CC (p < 0.01 and p < 0.05, respectively) was observed. Decreased (p < 0.01) Ntn1 levels in the colon from rats submitted to CR were found. In vitro experiments showed that ACM increased DCC (p < 0.05) and NEO1 (p < 0.01) mRNA levels in HT-29 and Caco-2 cell lines, respectively, while UNC5B decreased (p < 0.01) in HT-29. The treatment with NTN-1 increased (p < 0.05) NEO1 mRNA levels in HT-29 cells and DCC (p < 0.05) in both cell lines. Finally, we revealed a potent migratory effect of ACM and NTN-1 on Caco-2 cells. Collectively, these findings point to increased NTN-1 during OB and CC fuelling cancer progression and exerting a strong migratory effect on colon cancer cells.

Increased Aquaporin-7 Expression Is Associated with Changes in Rat Brown Adipose Tissue Whitening in Obesity: Impact of Cold Exposure and Bariatric Surgery.

Glycerol is a key metabolite for lipid accumulation in insulin-sensitive tissues. We examined the role of aquaporin-7 (AQP7), the main glycerol channel in adipocytes, in the improvement of brown adipose tissue (BAT) whitening, a process whereby brown adipocytes differentiate into white-like unilocular cells, after cold exposure or bariatric surgery in male Wistar rats with diet-induced obesity (DIO) (n = 229). DIO promoted BAT whitening, evidenced by increased BAT hypertrophy, steatosis and upregulation of the lipogenic factors Pparg2, Mogat2 and Dgat1. AQP7 was detected in BAT capillary endothelial cells and brown adipocytes, and its expression was upregulated by DIO. Interestingly, AQP7 gene and protein expressions were downregulated after cold exposure (4 °C) for 1 week or one month after sleeve gastrectomy in parallel to the improvement of BAT whitening. Moreover, Aqp7 mRNA expression was positively associated with transcripts of the lipogenic factors Pparg2, Mogat2 and Dgat1 and regulated by lipogenic (ghrelin) and lipolytic (isoproterenol and leptin) signals. Together, the upregulation of AQP7 in DIO might contribute to glycerol influx used for triacylglycerol synthesis in brown adipocytes, and hence, BAT whitening. This process is reversible by cold exposure and bariatric surgery, thereby suggesting the potential of targeting BAT AQP7 as an anti-obesity therapy.

Fear and Coping with Death in Intensive Care Nurses: a Structural Model Predictor of Compassion Fatigue / Miedo y afrontamiento ante la muerte del usuario: un modelo estructural predictor de la fatiga por compasión en enfermeros de cuidados intensivos / Medo e enfrentamento da morte do usuário: um modelo estrutural preditivo da fadiga por compaixão em enfermeiros de terapia intensiva

Objective. To determine the effect of fear and coping with death on compassion fatigue in nurses working in the intensive care unit. Methods. Correlational-predictive design, applied in 245 nurses working in the intensive care unit through intentional sampling. The study applied a personal data card, the Collet-Lester Fear of Death Scale (α=0.72), the Bugen Fell of Death Scale (α=0.82), and the Empathy Exhaustion Scale (α=0.80). Descriptive and inferential statistics were performed, such as Spearman's test and a structural equation model. Results. The work had 255 nurses who participated, finding a relationship among fear and coping toward death and compassion fatigue (p<0.01), together with the equation model showing that fear and coping toward death have a positive effect in 43.6% on compassion fatigue. Conclusion. Fear and coping with death have an effect on compassion fatigue in nurses working in the intensive care unit, so that when working in a critical area it can cause health effects

Objetivo. Determinar el efecto del miedo y afrontamiento ante la muerte sobre la fatiga por compasión en enfermeros que laboran en la unidad cuidados intensivos. Método. Diseño correlacional-predictivo. A través de un muestreo intencional se seleccionaron 255 enfermeros que laboraban en Unidades de Cuidados Intensivos de Adultos de hospitales de la Península de Yucatán (México). Se aplicó una cédula de datos personales, la escala de miedo a la muerte de Collet-Lester (α=0.72), la escala de Bugen de afrontamiento de la muerte (α=0.82) y la escala de agotamiento por empatía (α=0.80). Se realizó estadística descriptiva e inferencial como prueba de Spearman y un modelo de ecuación estructural. Resultados. Se encontró relación del miedo y el afrontamiento hacia la muerte con la fatiga por compasión (p<0.01). Adicionalmente, el modelo de ecuaciones muestra que el miedo y el afrontamiento hacia la muerte predice en un 43.6% sobre la fatiga por compasión. Conclusión. El miedo y el afrontamiento hacia la muerte tienen efecto sobre la fatiga por compasión en los enfermeros que laboran en la unidad de cuidados intensivos, por lo que al estar laborando en esta área crítica puede provocar afectaciones en su estado de salud.

Objetivo. Determinar o efeito do medo e enfrentamento da morte na fadiga por compaixão em enfermeiros que atuam em Unidade de Terapia Intensiva (UTI). Métodos. Desenho preditivo correlacional. Por meio de amostragem intencional, foram selecionados 255 enfermeiros que trabalhavam em Unidades de Terapia Intensiva de Adultos de hospitais da Península de Yucatán (México). Foi aplicada uma ficha de dados pessoais, a escala de medo da morte de Collet -Lester (α=0.72), a escala de Bugen de enfrentamento da morte (α=0.82) e a escala de exaustão por empatia (α=0.80). Foram realizadas estatísticas descritivas e inferenciais como o teste de Spearman e um modelo de equação estrutural. Resultados. Encontrou-se relação entre medo e enfrentamento da morte e fadiga por compaixão (p<0.01). Além disso, o modelo de equação mostra que o medo e o enfrentamento da morte preveem 43.6% da fadiga por compaixão. Conclusão. O medo e o enfrentamento da morte afetam a fadiga por compaixão em enfermeiros que atuam em UTI, portanto, trabalhar nessa área crítica pode afetar seu estado de saúde.

Improved Adipose Tissue Function after Single Anastomosis Duodeno-Ileal Bypass with Sleeve-Gastrectomy (SADI-S) in Diet-Induced Obesity.

Bariatric surgery has been recognized as the safest and most effective procedure for controlling type 2 diabetes (T2D) and obesity in carefully selected patients. The aim of the present study was to compare the effects of Sleeve Gastrectomy (SG) and Single Anastomosis Duodenoileal Bypass with SG (SADI-S) on the metabolic profile of diet-induced obese rats. A total of 35 four-week-old male Wistar rats were submitted to surgical interventions (sham operation, SG and SADI-S) after 4 months of being fed a high-fat diet. Body weight, metabolic profile and the expression of molecules involved in the control of subcutaneous white (SCWAT), brown (BAT) and beige (BeAT) adipose tissue function were analyzed. SADI-S surgery was associated with significantly decreased amounts of total fat pads (p < 0.001) as well as better control of lipid and glucose metabolism compared to the SG counterparts. An improved expression of molecules involved in fat browning in SCWAT and in the control of BAT and BeAT differentiation and function was observed following SADI-S. Together, our findings provide evidence that the enhanced metabolic improvement and their continued durability after SADI-S compared to SG rely, at least in part, on the improvement of the BeAT phenotype and function.

Netrin-1 Promotes Visceral Adipose Tissue Inflammation in Obesity and Is Associated with Insulin Resistance.

Netrin (NTN)-1 exhibits pro- and anti-inflammatory roles in different settings, playing important roles in the obesity-associated low-grade chronic inflammation. We aimed to determine the impact of NTN-1 on obesity and obesity-associated type 2 diabetes, as well as its role in visceral adipose tissue (VAT) inflammation. A total of 91 subjects were enrolled in this case-control study. Circulating levels of NTN-1 and its receptor neogenin (NEO)-1 were determined before and after weight loss achieved by caloric restriction and bariatric surgery. mRNA levels of NTN1 and NEO1 were assessed in human VAT, liver, and peripheral blood mononuclear cells. In vitro studies in human visceral adipocytes and human monocytic leukemia cells (THP-1)-derived macrophages were performed to analyze the impact of inflammation-related mediators on the gene expression levels of NTN1 and its receptor NEO1 as well as the effect of NTN-1 on inflammation. Increased (p < 0.001) circulating concentrations of NTN-1 in obesity decreased (p < 0.05) after diet-induced weight loss being also associated with a reduction in glucose (p < 0.01) and insulin levels (p < 0.05). Gene expression levels of NTN1 and NEO1 were upregulated (p < 0.05) in the VAT from patients with obesity with the highest expression in the stromovascular fraction cells compared with mature adipocytes (p < 0.01). NTN1 expression levels were enhanced (p < 0.01) under hypoxia and by inflammatory factors in both adipocytes and macrophages. Adipocyte-conditioned media strongly upregulated (p < 0.001) the mRNA levels of NTN1 in macrophages. The treatment of adipocytes with NTN-1 promoted the upregulation (p < 0.05) of pro-inflammatory and chemotactic molecules as well as its receptor NEO1. Collectively, these findings suggest that NTN-1 regulates VAT chronic inflammation and insulin resistance in obesity.

Caracterización de pacientes con traumatismos torácicos atendidos en el servicio de Cirugía General. Cienfuegos, 2019-2020 / Characterization of patients with thoracic trauma treated in the General Surgery Service. Cienfuegos, 2019-2020

RESUMEN Fundamento el traumatismo torácico es un cuadro clínico complejo que puede comprometer la vida del paciente. Por ello es de interés su estudio y análisis. Objetivo caracterizar los pacientes con traumatismo torácico en el servicio de Cirugía General. Métodos estudio descriptivo, prospectivo, de serie de casos, que incluyó a pacientes que ingresaron con el diagnóstico de traumatismo torácico, en el servicio de Cirugía General del Hospital General Universitario Dr. Gustavo Aldereguía Lima, de Cienfuegos, en el período enero/2019 a diciembre/2020. Las variables analizadas fueron: edad, sexo, comorbilidades, exámenes imagenológicos, agente causal, lesión torácica, tipo de tratamiento, tipo de traumatismo torácico y estado al egreso. Resultados el trauma de tórax fue más frecuente en el sexo masculino, a partir de la cuarta década de vida en pacientes sanos. El examen imagenológico más usado fue la radiografía simple de tórax; y el agente causal predominante, la herida por arma blanca. Las lesiones torácicas más frecuentes resultaron el enfisema subcutáneo y el hemoneumotorax, así como la pleurostomía fue el tipo de tratamiento más usado. Predominó el traumatismo torácico aislado, siendo las lesiones abdominales las más asociadas. La mayoría de los pacientes egresaron vivos. Conclusión el trauma torácico constituye una patología altamente desafiante, por lo complejas que pueden llegar a ser las lesiones derivadas de él; se presenta con mayor frecuencia en hombres sanos. Cuando se asocia a otras lesiones aumenta la mortalidad.

Background chest trauma is a complex clinical picture that can compromise the patient's life. Therefore, its study and analysis is of interest. Objective to characterize patients with chest trauma in the General Surgery service. Methods descriptive, prospective, case series study which included patients admitted with a diagnosis of chest trauma, in the General Surgery Service at the Dr. Gustavo Aldereguía Lima General University Hospital, Cienfuegos, from January 2019 to December2020. The analyzed variables were: age, sex, comorbidities, imaging tests, causal agent, chest injury, type of treatment, type of chest trauma, and discharge status. Results chest trauma was more frequent in males, from the fourth decade of life in healthy patients. The most used imaging test was the simple chest X-ray; and the predominant causal agent, the stab wound. The most frequent chest injuries were subcutaneous emphysema and hemopneumothorax, and pleurostomy was the most used type of treatment. Isolated chest trauma prevailed, with abdominal injuries being the most associated. Most of the patients were discharged alive. Conclusion thoracic trauma constitutes a highly challenging pathology, due to how complex the injuries derived from it can become; It occurs more frequently in healthy men. When associated with other injuries, mortality increases.

Dermatopontin Influences the Development of Obesity-Associated Colon Cancer by Changes in the Expression of Extracellular Matrix Proteins.

Dysfunctional adipose tissue (AT) in the context of obesity leads to chronic inflammation together with an altered extracellular matrix (ECM) remodelling, favouring cancer development and progression. Recently, the influence of dermatopontin (DPT) in AT remodelling and inflammation has been proposed. We aimed to evaluate the role of DPT in the development of obesity-associated colon cancer (CC). Samples obtained from 73 subjects [26 lean (LN) and 47 with obesity (OB)] were used in a case-control study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (42 without CC and 31 with CC). In vitro studies in the adenocarcinoma HT-29 cell line were performed to analyse the impact of pro- and anti-inflammatory mediators on the transcript levels of DPT as well as the effect of DPT on ECM remodelling and inflammation. Although obesity increased (p < 0.05) the circulating levels of DPT, its concentrations were significantly decreased (p < 0.05) in patients with CC. Gene expression levels of DPT in the colon from patients with CC were downregulated and, oppositely, a tendency towards increased mRNA levels in visceral AT was found. We further showed that DPT expression levels in HT-29 cells were enhanced (p < 0.05) by inflammatory factors (LPS, TNF-α and TGF-ß), whereas the anti-inflammatory IL-4 decreased (p < 0.05) its expression levels. We also demonstrated that DPT upregulated (p < 0.05) the mRNA of key molecules involved in ECM remodelling (COL1A1, COL5A3, TNC and VEGFA) whereas decorin (DCN) expression was downregulated (p < 0.05) in HT-29 cells. Finally, we revealed that the adipocyte-conditioned medium obtained from volunteers with OB enhanced (p < 0.01) the expression of DPT in HT-29 and Caco-2 cells. The decreased circulating and expression levels of DPT in the colon together with the tendency towards increased levels in visceral AT in patients with CC and its influence on the expression of ECM proteins suggest a possible role of DPT in the OB-associated CC.

Serum Levels of IL-1 RA Increase with Obesity and Type 2 Diabetes in Relation to Adipose Tissue Dysfunction and are Reduced After Bariatric Surgery in Parallel to Adiposity.

BACKGROUND: Excess adiposity leads to a dysfunctional adipose tissue that contributes to the development of obesity-associated comorbidities such as type 2 diabetes (T2D). Interleukin-1 receptor antagonist (IL-1RA) is a naturally occurring antagonist of the IL-1 receptor with anti-inflammatory properties. The aim of the present study was to compare the circulating concentrations of IL-1RA and its mRNA expression in visceral adipose tissue (VAT) in subjects with normal weight (NW), obesity with normoglycemia (OB-NG), or obesity with impaired glucose tolerance or T2D (OB-IGT&T2D) and to analyze the effect of changes in body fat percentage (BF%) on IL-1RA levels. METHODS: Serum concentrations of IL-1RA were measured in 156 volunteers. Expression of IL1RN mRNA in VAT obtained from 36 individuals was determined. In addition, the concentrations of IL-1RA were measured before and after weight gain as well as weight loss following a dietetic program or Roux-en-Y gastric bypass (RYGB). RESULTS: Serum levels of IL-1RA were significantly increased in individuals with obesity, being further increased in the OB-IGT&T2D group (NW 440 ± 316, OB-NG 899 ± 562, OB-IGT&T2D 1265 ± 739 pg/mL; P<0.001) and associated with markers of inflammation and fatty liver. IL1RN mRNA expression in VAT was significantly increased in the OB-IGT&T2D group and correlated in the global cohort with the mRNA expression of SPP1, CCL2, CD68, and MMP9. Levels of IL-1RA were not modified after modest changes in BF%, but RYGB-induced weight loss significantly decreased IL-1RA concentrations from 1233 ± 1009 to 660 ± 538 pg/mL (P<0.001). CONCLUSION: Serum IL-1RA concentrations are increased in patients with obesity being further elevated in obesity-associated IGT and T2D in association with markers of adipose tissue dysfunction. The mRNA expression of IL1RN is markedly increased in VAT of subjects with obesity and T2D in relation with genes involved in macrophage recruitment, inflammation and matrix remodeling. Serum IL-1RA concentrations are reduced when a notable amount of BF% is loss. Measurement of IL-1RA is an excellent biomarker of adipose tissue dysfunction in obesity-associated metabolic alterations.

Increased Levels of Interleukin-36 in Obesity and Type 2 Diabetes Fuel Adipose Tissue Inflammation by Inducing Its Own Expression and Release by Adipocytes and Macrophages.

Interleukin (IL)-36 is a recently described cytokine with well-known functions in the regulation of multiple inflammatory diseases. Since no data exists on how this cytokine regulates adipose tissue (AT) homeostasis, we aimed to explore the function of a specific isoform, IL-36γ, an agonist, in human obesity and obesity-associated type 2 diabetes as well as in AT inflammation and fibrosis. Plasma IL-36γ was measured in 91 participants in a case-control study and the effect of weight loss was evaluated in 31 patients with severe obesity undergoing bariatric surgery. Gene expression levels of IL36G and its receptor were analyzed in relevant human metabolic tissues. The effect of inflammatory factors and IL-36γ was determined in vitro in human adipocytes and macrophages. We found, for the first time, that the increased (P<0.05) circulating levels of IL-36γ in patients with obesity decreased (P<0.001) after weight and fat loss achieved by Roux-en-Y gastric bypass and that gene expression levels of IL36G were upregulated in the visceral AT (P<0.05) and in the peripheral blood mononuclear cells (P<0.01) from patients with obesity. We also demonstrated increased (P<0.05) expression levels of Il36g in the epididymal AT from diet-induced obese mice. IL36G was significantly enhanced (P<0.001) by LPS in human adipocytes and monocyte-derived macrophages, while no changes were found after the incubation with anti-inflammatory cytokines. The addition of IL-36γ for 24 h strongly induced (P<0.01) its own expression as well as key inflammatory and chemoattractant factors with no changes in genes associated with fibrosis. Furthermore, adipocyte-conditioned media obtained from patients with obesity increased (P<0.01) the release of IL-36γ and the expression (P<0.05) of cathepsin G (CTSG) in monocyte-derived macrophages. These findings provide, for the first time, evidence about the properties of IL-36γ in the regulation of AT-chronic inflammation, emerging as a link between AT biology and the obesity-associated comorbidities.

Changes in mechanical properties of adipose tissue after bariatric surgery driven by extracellular matrix remodelling and neovascularization are associated with metabolic improvements.

Biomechanical properties of adipose tissue (AT) are closely involved in the development of obesity-associated comorbidities. Bariatric surgery (BS) constitutes the most effective option for a sustained weight loss in addition to improving obesity-associated metabolic diseases including type 2 diabetes (T2D). We aimed to determine the impact of weight loss achieved by BS and caloric restriction (CR) on the biomechanical properties of AT. BS but not CR changed the biomechanical properties of epididymal white AT (EWAT) from a diet-induced obesity rat model, which were associated with metabolic improvements. We found decreased gene expression levels of collagens and Lox together with increased elastin and Mmps mRNA levels in EWAT after BS, which were also associated with the biomechanical properties. Moreover, an increased blood vessel density was observed in EWAT after surgery, confirmed by an upregulation of Acta2 and Antxr1 gene expression levels, which was also correlated with the biomechanical properties. Visceral AT from patients with obesity showed increased stiffness after tensile tests compared to the EWAT from the animal model. This study uncovers new insights into EWAT adaptation after BS with decreased collagen crosslink and synthesis as well as an increased degradation together with enhanced blood vessel density providing, simultaneously, higher stiffness and more ductility. STATEMENT OF SIGNIFICANCE: Biomechanical properties of the adipose tissue (AT) are closely involved in the development of obesity-associated comorbidities. In this study, we show for the first time that biomechanical properties of AT determined by E, UTS and strain at UTS are decreased in obesity, being increased after bariatric surgery by the promotion of ECM remodelling and neovascularization. Moreover, these changes in biomechanical properties are associated with improvements in metabolic homeostasis. Consistently, a better characterization of the plasticity and biomechanical properties of the AT after bariatric surgery opens up a new field for the development of innovative strategies for the reduction of fibrosis and inflammation in AT as well as to better understand obesity and its associated comorbidities.

High plasma and lingual uroguanylin as potential contributors to changes in food preference after sleeve gastrectomy.

BACKGROUND: The biological mediators supporting long-term weight loss and changes in dietary choice behaviour after sleeve gastrectomy remain unclear. Guanylin and uroguanylin are gut hormones involved in the regulation of satiety, food preference and adiposity. Thus, we sought to analyze whether the guanylin system is involved in changes in food preference after sleeve gastrectomy in obesity. METHODS: Proguanylin (GUCA2A) and prouroguanylin (GUCA2B) were determined in patients with severe obesity (n = 41) as well as in rats with diet-induced obesity (n = 48), monogenic obesity (Zucker fa/fa) (n = 18) or in a food choice paradigm (normal diet vs high-fat diet) (n = 16) submitted to sleeve gastrectomy. Lingual distribution and expression of guanylins (GUCA2A and GUCA2B) and their receptor GUCY2C as well as the fatty acid receptor CD36 were evaluated in the preclinical models. RESULTS: Circulating concentrations of GUCA2A and GUCA2B were increased after sleeve gastrectomy in patients with severe obesity as well as in rats with diet-induced and monogenic (fa/fa) obesity. Interestingly, the lower dietary fat preference observed in obese rats under the food choice paradigm as well as in patients with obesity after sleeve gastrectomy were negatively associated with post-surgical GUCA2B levels. Moreover, sleeve gastrectomy upregulated the low expression of GUCA2A and GUCA2B in taste bud cells of tongues from rats with diet-induced and monogenic (fa/fa) obesity in parallel to a downregulation of the lingual lipid sensor CD36. CONCLUSIONS: The increased circulating and lingual GUCA2B after sleeve gastrectomy suggest an association between the uroguanylin-GUCY2C endocrine axis and food preference through the regulation of gustatory responses.

Pulmonary Cystic Disease Associated With COVID 19 Pneumonia: An Emerging Atypical Manifestation.

Chest tomography has played an essential role during the coronavirus disease 2019 (COVID-19) pandemic since it has allowed to suspect and diagnose the disease early and to assess the severity of lung involvement, predict the disease's course, and detect the complications associated with it. Certain chest CT findings have been reported in more than 70% of reverse transcription polymerase chain reaction (RT-PCR) test-proven COVID-19 cases, including ground-glass opacities, vascular enlargement, bilateral abnormalities, lower lobe involvement, and posterior predilection. In COVID-19-endemic regions, observing these chest CT findings should raise the suspicion of a possible COVID-19 diagnosis. Rare reported CT findings in RT-PCR test-proven COVID-19 cases include pleural effusion, lymphadenopathy, tree-in-bud sign, central lesion distribution, pericardial effusion, and cavitating lung lesions. The observation of one or more of these findings suggests an alternative diagnosis, although COVID-19 cannot be excluded from the differential diagnosis. Here, we report an interesting case of a patient with no relevant history presenting a COVID-19 infection which, as a complication, presented cystic lesions; we discuss its etiology briefly.

The Differential Expression of the Inflammasomes in Adipose Tissue and Colon Influences the Development of Colon Cancer in a Context of Obesity by Regulating Intestinal Inflammation.

BACKGROUND: Inflammasomes maintain tissue homeostasis and their altered regulation in the colon, and the adipose tissue (AT) leads to chronic activation of inflammatory pathways promoting colon cancer (CC) development. We aimed to analyze the potential involvement of inflammasomes in obesity-associated CC. METHODS: Ninety-nine volunteers [61 with obesity (OB) and 38 normoponderal (NP)] further subclassified according to the approved protocol for the diagnosis of CC (58 without CC and 41 with CC) were included in the case-control study. RESULTS: CC (P<0.01) and obesity (P<0.01) were accompanied by increased mRNA levels of NLRP3, NLRP6, ASC, IL1B and NOD2 in VAT. Contrarily, patients with CC exhibited a downregulation of NLRP6 and IL18 in their colon. Additionally, we revealed that the decreased Nlrp1 (P<0.05), Nlrp3 (P<0.01) and Nlrp6 (P<0.01) mRNA levels in the colon from obese rats significantly increase (P<0.05) after caloric restriction. Adipocyte-conditioned media obtained from subjects with obesity reduced (P<0.01) the mRNA of NLRP3 as well as molecules involved in maintaining the intestinal integrity (MUC2, CLDN1 and TJP1) and the anti-inflammatory factors FGF21, KLF4, and IL33 and in HT-29 cells. We also found that the knockdown of NLRP6 in HT-29 cells significantly upregulated (P<0.05) the mRNA of NLRP1 and NLRP3 and inhibited (P<0.05) the expression levels of MUC2. Finally, we showed that the incubation of HT-29 with Akkermansia muciniphila influence (P<0.05) the inflammasome expression profile as well as intestinal integrity-related genes and aberrant inflammation. CONCLUSIONS: These findings provide evidence that the downregulated levels of NLRP6 and IL18 in the colon from patients with CC may be responsible for a reduced intestinal-barrier integrity, triggering local inflammation, which in turn acts on the dysfunctional AT in obesity, increasing the expression of different inflammasome components and flaring up a vicious cycle of uncontrollable inflammatory cascades that favours a pro-tumorigenic microenvironment.

Isotretinoin and Thalidomide Down-Regulate c-MYC Gene Expression and Modify Proteins Associated with Cancer in Hepatic Cells.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer. The number of cases is increasing and the trend for the next few years is not encouraging. HCC is usually detected in the advanced stages of the disease, and pharmacological therapies are not entirely effective. For this reason, it is necessary to search for new therapeutic options. The objective of this work was to evaluate the effect of the drugs isotretinoin and thalidomide on c-MYC expression and cancer-related proteins in an HCC cellular model. The expression of c-MYC was measured using RT-qPCR and western blot assays. In addition, luciferase activity assays were performed for the c-MYC promoters P1 and P2 using recombinant plasmids. Dose-response-time analyses were performed for isotretinoin or thalidomide in cells transfected with the c-MYC promoters. Finally, a proteome profile analysis of cells exposed to these two drugs was performed and the results were validated by western blot. We demonstrated that in HepG2 cells, isotretinoin and thalidomide reduced c-MYC mRNA expression levels, but this decrease in expression was linked to the regulation of P1 and P1-P2 c-MYC promoter activity in isotretinoin only. Thalidomide did not exert any effect on c-MYC promoters. Also, isotretinoin and thalidomide were capable of inducing and repressing proteins associated with cancer. In conclusion, isotretinoin and thalidomide down-regulate c-MYC mRNA expression and this is partially due to P1 or P2 promoter activity, suggesting that these drugs could be promising options for modulating the expression of oncogenes and tumor suppressor genes in HCC.

Decreased Levels of Microfibril-Associated Glycoprotein (MAGP)-1 in Patients with Colon Cancer and Obesity Are Associated with Changes in Extracellular Matrix Remodelling.

OBJECTIVE: The protein microfibril-associated glycoprotein (MAGP)-1 constitutes a crucial extracellular matrix protein. We aimed to determine its impact on visceral adipose tissue (VAT) remodelling during obesity-associated colon cancer (CC). METHODS: Samples obtained from 79 subjects (29 normoponderal (NP) (17 with CC) and 50 patients with obesity (OB) (19 with CC)) were used in the study. Circulating concentrations of MAGP-1 and its gene expression levels (MFAP2) in VAT were analysed. The impact of inflammation-related factors and adipocyte-conditioned media (ACM) on MFAP2 mRNA levels in colon adenocarcinoma HT-29 cells were further analysed. The effects of MAGP-1 in the expression of genes involved in the extracellular matrix (ECM) remodelling and tumorigenesis in HT-29 cells was also explored. RESULTS: Obesity (p < 0.01) and CC (p < 0.001) significantly decreased MFAP2 gene expression levels in VAT whereas an opposite trend in TGFB1 mRNA levels was observed. Increased mRNA levels of MFAP2 after the stimulation of HT-29 cells with lipopolysaccharide (LPS) (p < 0.01) and interleukin (IL)-4 (p < 0.01) together with a downregulation (p < 0.05) after hypoxia mimicked by CoCl2 treatment was observed. MAGP-1 treatment significantly enhanced the mRNA levels of the ECM-remodelling genes collagen type 6 α3 chain (COL6A3) (p < 0.05), decorin (DCN) (p < 0.01), osteopontin (SPP1) (p < 0.05) and TGFB1 (p < 0.05). Furthermore, MAGP-1 significantly reduced (p < 0.05) the gene expression levels of prostaglandin-endoperoxide synthase 2 (COX2/PTGS2), a key gene controlling cell proliferation, growth and adhesion in CC. Interestingly, a significant decrease (p < 0.01) in the mRNA levels of MFAP2 in HT-29 cells preincubated with ACM from volunteers with obesity compared with control media was observed. Conclusion: The decreased levels of MAGP-1 in patients with obesity and CC together with its capacity to modulate key genes involved in ECM remodelling and tumorigenesis suggest MAGP-1 as a link between AT excess and obesity-associated CC development.

Dermatopontin, A Novel Adipokine Promoting Adipose Tissue Extracellular Matrix Remodelling and Inflammation in Obesity.

Compelling evidence suggests that dermatopontin (DPT) regulates collagen and fibronectin fibril formation, the induction of cell adhesion and the prompting of wound healing. We aimed to evaluate the role of DPT on obesity and its associated metabolic alterations as well as its impact in visceral adipose tissue (VAT) inflammation and extracellular matrix (ECM) remodelling. Samples obtained from 54 subjects were used in a case-control study. Circulating and VAT expression levels of DPT as well as key ECM remodelling- and inflammation-related genes were analysed. The effect of pro- and anti-inflammatory mediators on the transcript levels of DPT in visceral adipocytes was explored. The impact of DPT on ECM remodelling and inflammation pathways was also evaluated in cultured adipocytes. We show that obesity and obesity-associated type 2 diabetes (T2D) increased (p < 0.05) circulating levels of DPT. In this line, DPT mRNA in VAT was increased (p < 0.05) in obese patients with and without T2D. Gene expression levels of DPT were enhanced (p < 0.05) in human visceral adipocytes after the treatment with lipopolysaccharide, tumour growth factor (TGF)- and palmitic acid, whereas a downregulation (p < 0.05) was detected after the stimulation with interleukin (IL)-4 and IL-13, critical cytokines mediating anti-inflammatory pathways. Additionally, we revealed that DPT increased (p < 0.05) the expression of ECM- (COL6A3, ELN, MMP9, TNMD) and inflammation-related factors (IL6, IL8, TNF) in human visceral adipocytes. These findings provide, for the first time, evidence of a novel role of DPT in obesity and its associated comorbidities by influencing AT remodelling and inflammation.