[Impact of bariatric surgery on maternal-fetal outcomes during pregnancy compared to non-operated obese women]. / Impacto de la cirugía bariátrica en los resultados materno-fetales de la gestación en comparación con mujeres con obesidad no operadas.

OBJECTIVE: the aim of our study was to assess the effect of bariatric surgery on obstetric outcomes. MATERIAL AND METHODS: a retrospective cohort study was conducted, including 54 pregnancies post-bariatric surgery and 219 pregnancies in non-operated obese women, from December 2018 to January 2023. Various maternal and obstetric characteristics were evaluated, ranging from baseline data to antepartum, intrapartum, postpartum, and neonatal outcomes. RESULTS: bariatric surgery showed a significant 69 % reduction in the risk of gestational diabetes (GDM) (p = 0.045) and a 63.1 % reduction in cesarean sections (p = 0.014), but also a notable increase in the risk of miscarriage (3.5 times more, p = 0.046) and intrauterine growth restriction (35 times more, p = 0.009). Bariatric surgery was associated with a significant prolongation of postpartum hospital stay (7.5 times more, p = 0.001) and a decrease in the average weight of the newborn (213.71 g, p = 0.006). CONCLUSION: pregnancy after bariatric surgery presents benefits, such as a reduced risk of gestational diabetes (GDM) and cesarean section, but also presents challenges, such as an increased risk of miscarriage and intrauterine growth restriction (IUGR). These results highlight the importance of specialized obstetric care to optimize maternal-fetal outcomes in pregnant women with a history of bariatric surgery.

Improving inpatient hyperglycaemia in non-critically ill adults in resident wards through audit and feedback.

Inpatient hyperglycaemia is associated with an increase in morbidity and mortality, number of rehospitalisations and length of hospitalisation. Although the advantages of proper glycaemic control in hospitalised patients with diabetes are well established, a variety of barriers limit accomplishment of blood glucose targets. Our primary aim was to decrease the number of glucose values above 180 mg/dL in non-critical care hospitalised patients using an audit and feedback intervention with pharmacy and internal medicine residents. A resident-led multidisciplinary team implemented the quality improvement (QI) project including conception, literature review, educating residents, iterative development of audit and feedback tools and data analysis. The multidisciplinary team met every 5 weeks and undertook three 'plan-do-study-act' cycles over an 8-month intervention period (August 2022 to March 2023) to educate residents on inpatient hyperglycaemia management, develop and implement an audit and feedback process and assess areas for improvement. We performed 1045 audits analysing 16 095 accu-checks on 395 non-duplicated patients. Most audits showed compliance with guidelines. The monthly run-on chart shows per cent of glucose values above 180 mg/dL in our non-ICU hospitalised patients and an overall pre-to-post comparison of 25.1%-23.0% (p value<0.05). The intervention was well accepted by residents evidenced by survey results. We did not meet our primary aim to reduce hyperglycaemia by 30% and this combined with the audits showing mostly compliance with guidelines suggests that prescribing behaviour was not a key driver of inpatient hyperglycaemia in our population. This internal medicine resident and pharmacy interprofessional collaboration with audit and feedback for inpatient hyperglycaemia was feasible, well accepted and had a statistically significant yet small improvement in inpatient hyperglycaemia. The project may be helpful to others wishing to explore inpatient hyperglycaemia, interprofessional QI with pharmacists, resident-led QI and audit and feedback.

[Effectiveness of immunonutrition in the perioperative nutritional management of gastric cancer]. / Efectividad de la inmunonutrición en el manejo nutricional perioperatorio del cáncer gástrico.

Introduction: Objective: to assess the effectiveness of immunonutrition (IN) compared to standard nutritional formulas in patients undergoing gastric cancer surgery. Material and methods: this is a real-life, observational retrospective cohort study. It included 134 patients, all of whom underwent gastrectomy at Montecelo Hospital between December 2019 and December 2022. Group A (N = 79 patients) received standard nutrition, and Group B (N = 55 patients) received formulas containing arginine, nucleotides, omega-3 fatty acids, and extra virgin olive oil. This protocol was carried out both pre and postoperatively for an average period of 10 days. The study evaluated hospital stay, the need for parenteral nutrition (PN), postoperative complications, as well as anthropometric and laboratory variables. Statistical analyses were performed using Stata 16.1.® Results: in the IN group compared to the standard nutrition group, the hospital stay was reduced by 34 % (p < 0.001). The number of patients requiring PN decreased by 21.1 % (p = 0.022), and its duration also decreased by 33.2 % (p < 0.001). The risk of infectious complications was lower with IN, specifically 70.1 % less (p < 0.001). As for other postoperative complications, IN reduced the risk of intestinal obstruction by 84 % (p < 0.002), suture dehiscence by 90.9 % (p < 0.001), blood transfusion by 99.8 % (p < 0.001), pleural effusion by 90.9 % (p = 0.021), acute renal failure by 84.02 % (p = 0.047), and surgical re-intervention by 69.93 % (p < 0.011). In the IN group, there was less weight loss (p = 0.048) and a smaller decrease in postoperative albumin (p = 0.005) and cholesterol (p < 0.001). Conclusion: immunonutrition reduces postoperative complications, decreases hospital stay, and optimizes nutritional outcomes.

Introducción: Objetivo: valorar la efectividad de la inmunonutrición (IN) frente a las fórmulas nutricionales estándar en pacientes operados de cáncer gástrico. Material y métodos: se trata de un estudio de vida real, de tipo observacional, retrospectivo y de cohortes. Para este estudio se incluyeron 134 pacientes, todos ellos sometidos a gastrectomía en en el Hospital Montecelo, entre diciembre de 2019 y diciembre de 2022. El grupo A (N = 79 pacientes) recibió nutrición estándar y el grupo B (N = 55 pacientes) recibió fórmulas con arginina, nucleótidos, ácidos grasos omega-3 y aceite de oliva virgen extra. Este protocolo se ha realizado de forma pre y postoperatoria por un periodo medio de 10 días. Se evaluaron el tiempo de estancia hospitalaria, la necesidad de nutrición parenteral (NPT), las complicaciones postoperatorias y las variables antropométricas y analíticas. Los análisis estadísticos se realizaron con el programa Stata 16.1.® Resultados: en el grupo de IN respecto al grupo de nutrición estándar: la estancia hospitalaria se reduce un 34 % (p < 0,001). La cantidad de pacientes que precisan NPT se reduce un 21,1 % (p = 0,022) y su duración también se reduce un 33,2 % (p < 0,001). El riesgo de complicaciones infecciosas es menor con la IN, concretamente un 70,1 % menos (p < 0,001). En cuanto a las otras complicaciones postoperatorias, la IN disminuye el riesgo de oclusión intestinal en un 84 % (p < 0,002), la dehiscencia de suturas en un 90,9 % (p < 0,001), la transfusión sanguínea en un 99,8 % (p < 0,001), el derrame pleural en un 90,9 % (p = 0,021), la insuficiencia renal aguda en un 84,02 % (p = 0,047) y la reintervención quirúrgica en un 69,93 % (p < 0,011). En el grupo de IN se observa una menor pérdida ponderal (p = 0,048) y una menor disminución de la albúmina (p = 0,005) y el colesterol postoperatorios (p < 0,001). Conclusión: la inmunonutrición reduce las complicaciones postoperatorias, disminuye la estancia hospitalaria y optimiza los resultados nutricionales.

Conocimientos, percepciones y prácticas de médicos de atención primaria en Ecuador sobre la infección por Angiostrongylus cantonensis / Knowledge, perceptions and practice of primary healthcare doctors in Ecuador on Angiostrongylus cantonensis infection

Introducción: La angiostrongiliasis humana presenta un amplio espectro clínico: desde una infección asintomática a meningitis eosinofílica, meningoencefalitis eosinofílica y angiostrongiliasis ocular. Objetivo: Determinar los conocimientos, percepciones y prácticas en relación con la infección por Angiostrongylus cantonensis que poseen médicos de atención primaria de la República del Ecuador. Métodos: Se realizó un estudio observacional descriptivo. Se diseñó, validó y aplicó una encuesta sobre conocimientos, percepciones y prácticas a 163 médicos de atención primaria de las provincias Napo y Guayas, entre los meses de noviembre y diciembre de 2017. La información obtenida se almacenó en una base de datos Microsoft Access y se realizó un análisis de frecuencias a las respuestas dadas a cada una de las preguntas. Resultados: Se encontraron conocimientos insuficientes, percepciones inadecuadas y prácticas incorrectas en relación con la angiostrongiliasis. Conclusiones: Estos resultados orientan hacia la implementación de un programa de intervención educativa en médicos de atención primaria con el fin de atenuar las deficiencias encontradas, para incidir de forma positiva en comunidades donde existe la presencia de hospederos intermediarios y definitivos infectados y un riesgo potencial de infección.

Introduction: Human angiostrongyliasis presents a broad clinical spectrum, which ranges from asymptomatic infection to eosinophilic meningitis, eosinophilic meningoencephalitis, and ocular angiostrongyliasis. Objective: To determine the knowledge, perceptions, and practice of primary healthcare doctors in the Republic of Ecuador regarding Angiostrongylus cantonensis infection. Methods: It was conducted a descriptive observational study. A survey on knowledge, perceptions, and practice was designed, validated, and applied to 163 primary healthcare doctors from Napo and Guayas provinces between November and December 2017. The information obtained was stored in a Microsoft Access 2016 database, and a frequency analysis was performed to the answers provided to every question. Results: Insufficient knowledge, inadequate perceptions, and incorrect practice regarding angiostrongyliasis were found. Conclusions: The results evidenced the need to implement an educational intervention program to primary healthcare doctors aimed at reducing the deficiencies found to have a positive impact on the communities where the intermediate and definitive hosts and a potential infection risk exist.

Role of adropin in arterial stiffening associated with obesity and type 2 diabetes.

Adropin is a peptide largely secreted by the liver and known to regulate energy homeostasis; however, it also exerts cardiovascular effects. Herein, we tested the hypothesis that low circulating levels of adropin in obesity and type 2 diabetes (T2D) contribute to arterial stiffening. In support of this hypothesis, we report that obesity and T2D are associated with reduced levels of adropin (in liver and plasma) and increased arterial stiffness in mice and humans. Establishing causation, we show that mesenteric arteries from adropin knockout mice are also stiffer, relative to arteries from wild-type counterparts, thus recapitulating the stiffening phenotype observed in T2D db/db mice. Given the above, we performed a set of follow-up experiments, in which we found that 1) exposure of endothelial cells or isolated mesenteric arteries from db/db mice to adropin reduces filamentous actin (F-actin) stress fibers and stiffness, 2) adropin-induced reduction of F-actin and stiffness in endothelial cells and db/db mesenteric arteries is abrogated by inhibition of nitric oxide (NO) synthase, and 3) stimulation of smooth muscle cells or db/db mesenteric arteries with a NO mimetic reduces stiffness. Lastly, we demonstrated that in vivo treatment of db/db mice with adropin for 4 wk reduces stiffness in mesenteric arteries. Collectively, these findings indicate that adropin can regulate arterial stiffness, likely via endothelium-derived NO, and thus support the notion that "hypoadropinemia" should be considered as a putative target for the prevention and treatment of arterial stiffening in obesity and T2D.NEW & NOTEWORTHY Arterial stiffening, a characteristic feature of obesity and type 2 diabetes (T2D), contributes to the development and progression of cardiovascular diseases. Herein we establish that adropin is decreased in obese and T2D models and furthermore provide evidence that reduced adropin may directly contribute to arterial stiffening. Collectively, findings from this work support the notion that "hypoadropinemia" should be considered as a putative target for the prevention and treatment of arterial stiffening in obesity and T2D.

ADAM17 cleaves the insulin receptor ectodomain on endothelial cells and causes vascular insulin resistance.

Inflammation and vascular insulin resistance are hallmarks of type 2 diabetes (T2D). However, several potential mechanisms causing abnormal endothelial insulin signaling in T2D need further investigation. Evidence indicates that the activity of ADAM17 (a disintegrin and metalloproteinase-17) and the presence of insulin receptor (IR) in plasma are increased in subjects with T2D. Accordingly, we hypothesized that in T2D, increased ADAM17 activity sheds the IR ectodomain from endothelial cells and impairs insulin-induced vasodilation. We used small visceral arteries isolated from a cross-sectional study of subjects with and without T2D undergoing bariatric surgery, human cultured endothelial cells, and recombinant proteins to test our hypothesis. Here, we demonstrate that arteries from subjects with T2D had increased ADAM17 expression, reduced presence of tissue inhibitor of metalloproteinase-3 (TIMP3), decreased extracellular IRα, and impaired insulin-induced vasodilation versus those from subjects without T2D. In vitro, active ADAM17 cleaved the ectodomain of the IRß subunit. Endothelial cells with ADAM17 overexpression or exposed to the protein kinase-C activator, PMA, had increased ADAM17 activity, decreased IRα presence on the cell surface, and increased IR shedding. Moreover, pharmacological inhibition of ADAM17 with TAPI-0 rescued PMA-induced IR shedding and insulin-signaling impairments in endothelial cells and insulin-stimulated vasodilation in human arteries. In aggregate, our findings suggest that ADAM17-mediated shedding of IR from the endothelial surface impairs insulin-mediated vasodilation. Thus, we propose that inhibition of ADAM17 sheddase activity should be considered a strategy to restore vascular insulin sensitivity in T2D.NEW & NOTEWORTHY To our knowledge, this is the first study to investigate the involvement of ADAM17 in causing impaired insulin-induced vasodilation in T2D. We provide evidence that ADAM17 activity is increased in the vasculature of patients with T2D and support the notion that ADAM17-mediated shedding of endothelial IRα ectodomains is a novel mechanism causing vascular insulin resistance. Our results highlight that targeting ADAM17 activity may be a potential therapeutic strategy to correct vascular insulin resistance in T2D.

Cryptosporidium spp. en muestras de lavado broncoalveolar de pacientes VIH/sida en un hospital de Guayaquil, Ecuador / Cryptosporidium spp. in bronchoalveolar lavage samples of HIV/AIDS patients in a hospital in Guayaquil, Ecuador

Introducción: Cryptosporidium spp. son parásitos que causan infecciones respiratorias principalmente en pacientes inmunocomprometidos. Objetivo: Detectar Cryptosporidium spp. en el lavado broncoalveolar (BAL) de pacientes VIH positivos y con síndrome respiratorio. Métodos: Se seleccionaron 60 muestras de BAL y se analizaron mediante microscopía óptica con tinción de Ziehl-Neelsen y PCR de punto final; esta última es una técnica eficiente para el diagnóstico de patógenos oportunistas. Se recolectaron datos clínicos y epidemiológicos de cada paciente. Resultados: La prevalencia hallada en este estudio mediante PCR de punto final fue del 5 %. Los signos y síntomas que se presentaron con mayor frecuencia, sobre todo en el grupo etario de 31 a 40 años, fueron fiebre, tos y disnea; sin embargo, no se obtuvieron asociaciones estadísticamente significativas a ninguna de las variables y no se pudo visualizar parásitos mediante la tinción de Ziehl-Neelsen. Conclusión: Cryptosporidium spp. puede causar infecciones pulmonares de difícil reconocimiento clínico, pues se confunde con otras infecciones oportunistas. En el presente estudio no puede establecerse si la detección del ADN parasitario correspondió a una verdadera infección o solamente a colonización, lo que es importante para implementar técnicas con mayor sensibilidad para el diagnóstico. Se debe considerar relevante la prevalencia encontrada en Ecuador, al ser inusualmente alta en comparación con países cercanos como Brasil(AU)

Introduction: Cryptosporidium spp. are parasites that cause respiratory infections mainly in immunocompromised patients. Objective: To detect Cryptosporidium spp. in bronchoalveolar lavage (BAL) of HIV-positive patients with respiratory syndrome. Methods: Sixty samples of BAL were selected and analyzed by optical microscopy with Ziehl-Neelsen staining and end-point PCR. The latter is an efficient technique for the diagnosis of opportunistic pathogens. Clinical and epidemiological data were collected from every patient. Results: In this study, the prevalence by end-point PCR was 5%. The most frequent signs and symptoms, mainly in the age group 31-40 years old, were fever, cough, and dyspnea. However, no significant statistical associations to any variable were obtained, and no parasites were observed with the Ziehl-Neelsen staining technique. Conclusions: Cryptosporidium spp. can cause pulmonary infections that are difficult to identify clinically, since they are confused with other opportunistic diseases. The current study could not establish whether the detection of parasitic DNA corresponded to a real infection or only to colonization, which is important to implement diagnostic techniques with greater sensitivity. The prevalence found in Ecuador should be considered relevant, as it is unusually high in comparison with nearby countries such as Brazil(AU)

Endothelial HSP72 is not reduced in type 2 diabetes nor is it a key determinant of endothelial insulin sensitivity.

Impaired endothelial insulin signaling and consequent blunting of insulin-induced vasodilation is a feature of type 2 diabetes (T2D) that contributes to vascular disease and glycemic dysregulation. However, the molecular mechanisms underlying endothelial insulin resistance remain poorly known. Herein, we tested the hypothesis that endothelial insulin resistance in T2D is attributed to reduced expression of heat shock protein 72 (HSP72). HSP72 is a cytoprotective chaperone protein that can be upregulated with heating and is reported to promote insulin sensitivity in metabolically active tissues, in part via inhibition of JNK activity. Accordingly, we further hypothesized that, in individuals with T2D, 7 days of passive heat treatment via hot water immersion to waist level would improve leg blood flow responses to an oral glucose load (i.e., endogenous insulin stimulation) via induction of endothelial HSP72. In contrast, we found that: 1) endothelial insulin resistance in T2D mice and humans was not associated with reduced HSP72 in aortas and venous endothelial cells, respectively; 2) after passive heat treatment, improved leg blood flow responses to an oral glucose load did not parallel with increased endothelial HSP72; and 3) downregulation of HSP72 (via small-interfering RNA) or upregulation of HSP72 (via heating) in cultured endothelial cells did not impair or enhance insulin signaling, respectively, nor was JNK activity altered. Collectively, these findings do not support the hypothesis that reduced HSP72 is a key driver of endothelial insulin resistance in T2D but provide novel evidence that lower-body heating may be an effective strategy for improving leg blood flow responses to glucose ingestion-induced hyperinsulinemia.

SGLT2 inhibition attenuates arterial dysfunction and decreases vascular F-actin content and expression of proteins associated with oxidative stress in aged mice.

Aging of the vasculature is characterized by endothelial dysfunction and arterial stiffening, two key events in the pathogenesis of cardiovascular disease (CVD). Treatment with sodium glucose transporter 2 (SGLT2) inhibitors is now known to decrease cardiovascular morbidity and mortality in type 2 diabetes. However, whether SGLT2 inhibition attenuates vascular aging is unknown. We first confirmed in a cohort of adult subjects that aging is associated with impaired endothelial function and increased arterial stiffness and that these two variables are inversely correlated. Next, we investigated whether SGLT2 inhibition with empagliflozin (Empa) ameliorates endothelial dysfunction and reduces arterial stiffness in aged mice with confirmed vascular dysfunction. Specifically, we assessed mesenteric artery endothelial function and stiffness (via flow-mediated dilation and pressure myography mechanical responses, respectively) and aortic stiffness (in vivo via pulse wave velocity and ex vivo via atomic force microscopy) in Empa-treated (14 mg/kg/day for 6 weeks) and control 80-week-old C57BL/6 J male mice. We report that Empa-treated mice exhibited improved mesenteric endothelial function compared with control, in parallel with reduced mesenteric artery and aortic stiffness. Additionally, Empa-treated mice had greater vascular endothelial nitric oxide synthase activation, lower phosphorylated cofilin, and filamentous actin content, with downregulation of pathways involved in production of reactive oxygen species. Our findings demonstrate that Empa improves endothelial function and reduces arterial stiffness in a preclinical model of aging, making SGLT2 inhibition a potential therapeutic alternative to reduce the progression of CVD in older individuals.

Cystamine reduces vascular stiffness in Western diet-fed female mice.

Consumption of diets high in fat, sugar, and salt (Western diet, WD) is associated with accelerated arterial stiffening, a major independent risk factor for cardiovascular disease (CVD). Women with obesity are more prone to develop arterial stiffening leading to more frequent and severe CVD compared with men. As tissue transglutaminase (TG2) has been implicated in vascular stiffening, our goal herein was to determine the efficacy of cystamine, a nonspecific TG2 inhibitor, at reducing vascular stiffness in female mice chronically fed a WD. Three experimental groups of female mice were created. One was fed regular chow diet (CD) for 43 wk starting at 4 wk of age. The second was fed a WD for the same 43 wk, whereas a third cohort was fed WD, but also received cystamine (216 mg/kg/day) in the drinking water during the last 8 wk on the diet (WD + C). All vascular stiffness parameters assessed, including aortic pulse wave velocity and the incremental modulus of elasticity of isolated femoral and mesenteric arteries, were significantly increased in WD- versus CD-fed mice, and reduced in WD + C versus WD-fed mice. These changes coincided with respectively augmented and diminished vascular wall collagen and F-actin content, with no associated effect in blood pressure. In cultured human vascular smooth muscle cells, cystamine reduced TG2 activity, F-actin:G-actin ratio, collagen compaction capacity, and cellular stiffness. We conclude that cystamine treatment represents an effective approach to reduce vascular stiffness in female mice in the setting of WD consumption, likely because of its TG2 inhibitory capacity.NEW & NOTEWORTHY This study evaluates the novel role of transglutaminase 2 (TG2) inhibition to directly treat vascular stiffness. Our data demonstrate that cystamine, a nonspecific TG2 inhibitor, improves vascular stiffness induced by a diet rich in fat, fructose, and salt. This research suggests that TG2 inhibition might bear therapeutic potential to reduce the disproportionate burden of cardiovascular disease in females in conditions of chronic overnutrition.

Angiostrongylus cantonensis en Achatina fulica en la provincia del Napo, Ecuador y el riesgo incrementado de angiostrongiliasis / Angiostrongylus cantonensis in Achatina fulica in Napo province, Ecuador and the increased risk of angiostrongyliasis

Introducción: Angiostrongylus cantonensis es reconocido como uno de los principales patógenos causantes de la meningoencefalitis eosinofílica, fue identificado en Ecuador por primera vez en 2008. Métodos: se recolectaron 1476 ejemplares de Achatina fulica con el método de captura por unidad de esfuerzo durante 30 minutos, en 3 cantones de la provincia del Napo, con el fin de establecer la prevalencia de infección por A. cantonensis Resultados: el porcentaje total de caracoles infectados fue de 46,5% (687/1476). Conclusiones: Los resultados revelan una amplia distribución de A. fulica infectado con A. cantonensis, lo que, sumado a la gran cantidad de hospederos definitivos presentes, indica que un número considerable de personas tiene riesgo de adquirir angiostrongiliasis. Se necesita intervenciones educativas comunitaria orientadas a formación sanitaria, recalcando el riesgo de adquirir la infección parasitaria, principalmente por el consumo de A. fulica, crudos y/o con cocción inadecuada, principal forma de contagio. Además, se recomienda vigilancia rigurosa y control de los hospedadores involucrados, saneamiento ambiental, haciendo insistencia en factores relacionados con los hábitos biológico del caracol gigante africano, entre ello alimentos (vegetales), suelos y derivados del caracol de uso artesanal; para prevenir la aparición de casos esporádicos y de brotes de la enfermedad(AU)

Introduction: Angiostrongylus cantonensis is recognized as one of the main pathogens that cause eosinophilic meningoencephalitis, it was identified in Ecuador for the first time in 2008. Methods: 1476 specimens of Achatina fulica were collected using the capture method per unit of effort for 30 minutes, in 3 cantons of the Napo province, in order to establish the prevalence of infection by A. cantonensis Results: the total percentage of infected snails was 46.5% (687/1476). Conclusions: The results reveal a wide distribution of A. fulica infected with A. cantonensis, which, added to the large number of definitive hosts present, indicates that a considerable number of people are at risk of acquiring angiostrongyliasis. Community educational interventions aimed at health training are needed, emphasizing the risk of acquiring parasitic infection, mainly due to the consumption of A. fulica, raw and/or inadequately cooked, the main form of contagion. In addition, rigorous surveillance and control of the hosts involved, environmental sanitation, insisting on factors related to the biological habits of the giant African snail, including food (vegetables), soil and snail derivatives for artisanal use; to prevent the appearance of sporadic cases and outbreaks of the disease(AU)

Mutation of the 5'-untranslated region stem-loop mRNA structure reduces type I collagen deposition and arterial stiffness in male obese mice.

Arterial stiffening, a characteristic feature of obesity and type 2 diabetes, contributes to the development and progression of cardiovascular diseases (CVD). Currently, no effective prophylaxis or therapeutics is available to prevent or treat arterial stiffening. A better understanding of the molecular mechanisms underlying arterial stiffening is vital to identify newer targets and strategies to reduce CVD burden. A major contributor to arterial stiffening is increased collagen deposition. In the 5'-untranslated regions of mRNAs encoding for type I collagen, an evolutionally conserved stem-loop (SL) structure plays an essential role in its stability and post-transcriptional regulation. Here, we show that feeding a high-fat/high-sucrose (HFHS) diet for 28 wk increases adiposity, insulin resistance, and blood pressure in male wild-type littermates. Moreover, arterial stiffness, assessed in vivo via aortic pulse wave velocity, and ex vivo using atomic force microscopy in aortic explants or pressure myography in isolated femoral and mesenteric arteries, was also increased in those mice. Notably, all these indices of arterial stiffness, along with collagen type I levels in the vasculature, were reduced in HFHS-fed mice harboring a mutation in the 5'SL structure, relative to wild-type littermates. This protective vascular phenotype in 5'SL-mutant mice did not associate with a reduction in insulin resistance or blood pressure. These findings implicate the 5'SL structure as a putative therapeutic target to prevent or reverse arterial stiffening and CVD associated with obesity and type 2 diabetes.NEW & NOTEWORTHY In the 5'-untranslated (UTR) regions of mRNAs encoding for type I collagen, an evolutionally conserved SL structure plays an essential role in its stability and posttranscriptional regulation. We demonstrate that a mutation of the SL mRNA structure in the 5'-UTR decreases collagen type I deposition and arterial stiffness in obese mice. Targeting this evolutionarily conserved SL structure may hold promise in the management of arterial stiffening and CVD associated with obesity and type 2 diabetes.

Mineralocorticoid Receptor in Myeloid Cells Mediates Angiotensin II-Induced Vascular Dysfunction in Female Mice.

Enhanced mineralocorticoid receptor (MR) signaling is critical to the development of endothelial dysfunction and arterial stiffening. However, there is a lack of knowledge about the role of MR-induced adipose tissue inflammation in the genesis of vascular dysfunction in women. In this study, we hypothesize that MR activation in myeloid cells contributes to angiotensin II (Ang II)-induced aortic stiffening and endothelial dysfunction in females via increased pro-inflammatory (M1) macrophage polarization. Female mice lacking MR in myeloid cells (MyMRKO) were infused with Ang II (500 ng/kg/min) for 4 weeks. This was followed by determinations of aortic stiffness and vasomotor responses, as well as measurements of markers of inflammation and macrophage infiltration/polarization in different adipose tissue compartments. MyMRKO mice were protected against Ang II-induced aortic endothelial stiffening, as assessed via atomic force microscopy in aortic explants, and vasorelaxation dysfunction, as measured by aortic wire myography. In alignment, MyMRKO mice were protected against Ang II-induced macrophage infiltration and M1 polarization in visceral adipose tissue (VAT) and thoracic perivascular adipose tissue (tPVAT). Collectively, this study demonstrates a critical role of MR activation in myeloid cells in the pathogenesis of vascular dysfunction in females associated with pro-inflammatory macrophage polarization in VAT and tPVAT. Our data have potential clinical implications for the prevention and management of cardiovascular disease in women, who are disproportionally at higher risk for poor outcomes.

Effects of Elevated Blood Alcohol Levels on Burn Patient Outcomes.

Background: Alcohol use has been associated with poor wound healing in traumatic injuries as it impairs immune function and lowers leukocyte production. The aim of this study is to describe the association of alcohol use on the outcomes of patients with burn injuries. It is proposed that the use of alcohol can have a detrimental effect on burn patient outcomes. Methods: A retrospective review of the American Burn Association Burn Registry from 2002 through 2011 was conducted. Patients were stratified into 2 groups: burn patients with a blood alcohol level above the legal limit 0.08 mg/dl on admission (group 1) vs burn patients with a blood alcohol level below the legal limit of 0.08 mg/dl on admission (group 2). The outcome measures included in-hospital mortality rate, hospital length of stay (LOS), intensive care unit (ICU) LOS, and total days on a ventilator. Results: A total of 11,286 burn patients met the inclusion criteria. There were a total of 1,544 patients in group 1 and a total of 9,742 patients in group 2. The percentage of total body surface area (TBSA) involvement of the burns was statistically similar in both groups, with an average of 2.08% in group 1 and 2.32% in group 2. There was a significantly higher ICU LOS at 5.91 days in group 1 compared to 3.66 in group 2. The days on a ventilator were significantly higher in group 1 at 5.67 days versus group 2 at 3.06 days. The in-hospital mortality was also significantly higher in group 1 at 4.86% compared to group 2 at 3.91%. Conclusion: Burn patients who tested above the legal limit for alcohol on admission were associated with increased inpatient mortality, as well as increased ICU LOS and total days on a ventilator. An elevated admission blood alcohol level may be an independent predictor of worse outcome in patients with burn injury, leading to an increase in resource needs and health care costs.

The Outcomes of Inhalation Injuries in Lesser Burns: Still a Deadly Injury.

Background: Although it has been widely proposed that inhalation injuries worsen burn outcomes, large-scale studies have yet to demonstrate the exact relationship. This study proposes inhalation injuries as an independent risk factor that worsens burn outcomes. Methods: A retrospective review of the American Burn Association Registry from 2002 to 2011 was conducted. Inclusion criteria included burn patients with a total body surface area (TBSA) of less than 15% and adequate data recording of the inhalation injury within the registry. Patients were stratified into 2 groups: inhalation injuries (group 1) vs non-inhalation injuries (group 2). Outcome measures included in-hospital mortality rate, hospital length of stay (LOS), intensive care unit (ICU) LOS, and days on a ventilator. Results: A total of 93781 burn patients met the inclusion criteria. There were 4204 patients in group 1 and 89577 patients in group 2. There was no statistically significant difference between the 2 groups in terms of TBSA, with 3.50% in group 1 and 3.58% in group 2. There was a significantly higher ICU LOS at 8.55 days in group 1 compared to 6.27 days in group 2. There was a significantly higher hospital LOS at 11.48 days in group 1 compared to 6.27 days in group 2. The in-hospital mortality was significantly higher in group 1 at 8.54% vs group 2 at 1.42%. Conclusion: The presence of inhalation injury may be a predictor of increased mortality and poor outcome in burn patients, even in those with small sized burns.

Admission Carboxyhemoglobin: Is It a Marker for Burn Patient Outcomes?

BACKGROUND: Carbon monoxide is a gas produced by the combustion of hydrocarbon products that binds to heme molecules, 240 times more than oxygen, producing carboxyhemoglobin (COHb). As a result of its high affinity, there is shift of the oxyhemoglobin dissociation curve, compromising oxygen transport and delivery to tissues. Our study aim was to evaluate COHb elevation on admission as a predictor of worse outcomes in burn patients. METHODS: This is a 10-year retrospective review of the American Burn Association Burn Registry from 2002 to 2011. We stratified the patients into 2 groups: adult patients with normal COHb on admission (group 1) versus elevated COHb (group 2). Elevated COHb levels were defined as greater than 10% on the first arterial blood gas. Outcome measures included in-hospital mortality rate, hospital length of stay (LOS), intensive care unit LOS (ICU-LOS), and ventilator days. χ and t test analyses were used with significance defined as a P value of less than 0.05. RESULTS: A total of 6365 burn patients meet our inclusion criteria. There were 5775 patients in group 1 and 590 patients in group 2. Group 1 had an average age of 39.29 years compared with 42.62 years in group 2. The total body surface area was higher in group 1 compared with group 2 (6.24 vs 4.65) and with a statistically significant increase in partial thickness burns at 4.97 in group 1 compared with 3.27 in group 2. There was no statistically significant difference between the 2 groups in terms of full thickness total body surface area. The hospital LOS was significantly higher in group 2 compared with group 1 (15.34 vs 9.66). There was a significantly higher ICU-LOS at 12.89 days in group 2 compared with 4.01 in the group 1 (P = 0.0001, t test). There were higher ventilator days in group 2 at 9.23 than those in group 1 at 2.05 (P < 0.0001, t test). The in-hospital mortality was also significantly higher in group 2 at 15.59% than in group 1 at 1.33% (P = 0.0001, χ). CONCLUSIONS: Elevated COHb on admission was associated with an increased hospital and ICU-LOS, average ventilator days, and in-hospital mortality. The presence of elevated COHb of greater than 10% on an initial arterial blood gas suggests worse outcomes and increased need of resource utilization during the index hospital admission.

Angiostrongylus (Parastrongylus) cantonensis on intermediate and definitive hosts in Ecuador, 2014-2017 / Angiostrongylus (Parastrongylus) cantonensis en huéspedes intermediarios y definitivos en Ecuador, 2014-2017

Introduction: Angiostrongylus cantonensis is a serious public health problem and is widely distributed in the country. When the parasite infects the snails, it becomes deeply embedded in their interior and accidentally, it can infect people and other mammals. Objective: To establish the geographical distribution of A. cantonensis intermediate hosts (Achatina fulica) and definitive hosts (Rattus spp.) in Ecuador from 2014 to 2017. Materials and methods: We collected 2,908 A. fulica specimens in 16 provinces using the capture method per unit of effort for 30 minutes. We captured 211 hosts of which 20 were Rattus rattus and 191 R. norvegicus. The specimens were transported to the Instituto Nacional de Salud Pública e Investigación in Guayaquil where the larvae L3 were identified and counted in the tissues of the snail, which were then inoculated in laboratory rats to reproduce the life cycle. In the rodents, the brains, hearts, lung arteries and lungs were dissected, and the parasites were identified by taxonomic morphology. Results: Of the snails harvested, 441 were positive for A. cantonensis (15.2%) and a total of 6,166 L3 larvae were found; 77 (36.5%) specimens of Rattus spp., were infected with A. cantonensis and a total of 220 parasites (L4-L5 larvae and adult worms) were collected. Conclusions: We confirmed the presence of A. cantonensis in several provinces, which ratifies the endemic nature of this zoonosis in the national territory. Rattus spp. specimens constitute the definitive hosts of the parasite, which together with the presence of intermediate hosts, indicates the zoonotic potential of this parasitic infection.

Introducción. Angiostrongylus cantonensis es un serio problema de salud pública y está ampliamente distribuido en el país. Cuando el parásito infecta a los caracoles terrestres Achatina, se enquista en su interior y puede infectar accidentalmente a las personas y otros mamíferos. Objetivo. Establecer la distribución geográfica de A. cantonensis en huéspedes intermediarios (Achatina fulica) y definitivos (Rattus spp.) en Ecuador entre el 2014 y el 2017. Materiales y métodos. Se recolectaron 2.908 ejemplares de A. fulica en 16 provincias utilizando el método de captura por unidad de esfuerzo durante 30 minutos. Se capturaron 211 ejemplares de las especies huéspedes, de los cuales 20 eran Rattus rattus y 191 R. norvegicus. Los ejemplares fueron transportados para su análisis al Instituto Nacional de Salud Pública e Investigación en Guayaquil. En los tejidos del caracol se identificaron y se contabilizaron larvas L3 que luego se inocularon en ratas de laboratorio para reproducir el ciclo de vida. En los roedores se disecaron los cerebros, los corazones, las arterias pulmonares y los pulmones, y se identificaron los parásitos por morfología taxonómica. Resultados. De los caracoles recolectados se encontraron 441 positivos para A. cantonensis (15,2 %) y un total de 6.166 larvas L3. En los ejemplares Rattus spp. capturados (211), 77 (36,5 %) estaban infectados con A. cantonensis, con un total de 220 parásitos (larvas L4-L5 y adultos). Conclusiones. Se constató la presencia de A. cantonensis en varias provincias, lo que confirma el carácter endémico de esta zoonosis en el territorio nacional. La presencia de Rattus spp., huésped definitivo del parásito, y de huéspedes intermediarios, indica el potencial zoonótico de esta infección parasitaria.

Angiostrongylus (Parastrongylus) cantonensis en huéspedes intermediarios y definitivos en Ecuador, 2014-2017 / Angiostrongylus (Parastrongylus) cantonensis on intermediate and definitive hosts in Ecuador, 2014-2017

Resumen Introducción. Angiostrongylus cantonensis es un serio problema de salud pública y está ampliamente distribuido en el país. Cuando el parásito infecta a los caracoles terrestres Achatina, se enquista en su interior y puede infectar accidentalmente a las personas y otros mamíferos. Objetivo. Establecer la distribución geográfica de A. cantonensis en huéspedes intermediarios (Achatina fulica) y definitivos (Rattus spp.) en Ecuador entre el 2014 y el 2017. Materiales y métodos. Se recolectaron 2.908 ejemplares de A. fulica en 16 provincias utilizando el método de captura por unidad de esfuerzo durante 30 minutos. Se capturaron 211 ejemplares de las especies huéspedes, de los cuales 20 eran Rattus rattus y 191 R. norvegicus. Los ejemplares fueron transportados para su análisis al Instituto Nacional de Salud Pública e Investigación en Guayaquil. En los tejidos del caracol se identificaron y se contabilizaron larvas L3 que luego se inocularon en ratas de laboratorio para reproducir el ciclo de vida. En los roedores se disecaron los cerebros, los corazones, las arterias pulmonares y los pulmones, y se identificaron los parásitos por morfología taxonómica. Resultados. De los caracoles recolectados se encontraron 441 positivos para A. cantonensis (15,2 %) y un total de 6.166 larvas L3. En los ejemplaresRattus spp. capturados (211), 77 (36,5 %) estaban infectados con A. cantonensis, con un total de 220 parásitos (larvas L4-L5 y adultos). Conclusiones. Se constató la presencia de A. cantonensis en varias provincias, lo que confirma el carácter endémico de esta zoonosis en el territorio nacional. La presencia de Rattus spp., huésped definitivo del parásito, y de huéspedes intermediarios, indica el potencial zoonótico de esta infección parasitaria.

Abstract Introduction: Angiostrongylus cantonensis is a serious public health problem and is widely distributed in the country. When the parasite infects the snails, it becomes deeply embedded in their interior and accidentally, it can infect people and other mammals. Objective: To establish the geographical distribution of A. cantonensis intermediate hosts (Achatina fulica) and definitive hosts (Rattus spp.) in Ecuador from 2014 to 2017. Materials and methods: We collected 2,908 A. fulica specimens in 16 provinces using the capture method per unit of effort for 30 minutes. We captured 211 hosts of which 20 were Rattus rattus and 191 R. norvegicus. The specimens were transported to the Instituto Nacional de Salud Pública e Investigación in Guayaquil where the larvae L3 were identified and counted in the tissues of the snail, which were then inoculated in laboratory rats to reproduce the life cycle. In the rodents, the brains, hearts, lung arteries and lungs were dissected, and the parasites were identified by taxonomic morphology. Results: Of the snails harvested, 441 were positive for A. cantonensis (15.2%) and a total of 6,166 L3 larvae were found; 77 (36.5%) specimens of Rattus spp., were infected with A. cantonensis and a total of 220 parasites (L4-L5 larvae and adult worms) were collected. Conclusions: We confirmed the presence of A. cantonensis in several provinces, which ratifies the endemic nature of this zoonosis in the national territory. Rattus spp. specimens constitute the definitive hosts of the parasite, which together with the presence of intermediate hosts, indicates the zoonotic potential of this parasitic infection.

Efecto de la adenosina sobre la P50 y su relación con el 2, 3-difosfoglicerato / The efect of adenosin on the P50 and its relationship with the 2, 3 diphosphoglyceric acid

En 17 perros anestesiados mantenidos en condiciones estables de ventilación, temperatura y equilibrio ácido base, estudiamos los efectos de dosis crecientes de adenosina administrada por infusión continua, sobre la posición de la curva de disociación de la hemoglobina (CDH) y su relación con los niveles intraeritrocíticos de 2,3 difosfo glicerato (2,3 DPG). en todos los perros la CDH (en sangre arterial y venosa) se desplazó a la izquierda en forma significativa, excepto a la dosis de 120 ug/kg/min, en que la CDH se desplazó a la derecha, y a partir de 240 ug/kg/minla CDH se estabilizó en un nivel inferior al control. Estos cambios fueron paralelos con los experimentos, la frecuencia cardiaca y la presión arterial disminuyeron significativamente. Concluimos que la adenosina modifica la CDH desplazándola en general hacia la izquierda, y que ésto parece estar en relación con un cambio en los niveles intraeritrocíticos de 2,3-DPG