Estrategias de afrontamiento centradas en las emociones de enfermeros de un hospital de Corrientes en el año 2022 / Coping strategies focused on emotions in nurses from a hospital in Corrientes in the year 2022

Introducción: el personal de enfermería enfrenta a diario jornadas extendidas de trabajo, tiene muchos pacientes a su cargo, dificultades en las relaciones interpersonales, que podrían desencadenar en estrés, para lo cual el individuo desarrolla un proceso de adaptación o desequilibrio y es por esta razón la importancia de contar con estrategias para afrontar las situaciones. Objetivos: el objetivo de este estudio fue analizar las estrategias de afrontamiento ante situaciones de estrés utilizadas por los profesionales de enfermería de un Hospital Público de la ciudad de Corrientes capital, así como su asociación con variables socio demográficas. Metodología: estudio de tipo cuantitativo, descriptivo, transversal y observacional. La población incluyó enfermeros de un hospital público de la ciudad de Corrientes en el período 2022. Se consideró como criterios de inclusión personal de enfermería que cumpla funciones asistenciales y su tiempo de labor fuera de 1 año o más; como criterios de exclusión, personal que tuviera dos o más puestos de trabajo y de criterios de eliminación aquellos enfermeros que no se encuentren presentes al momento de la encuesta. El cálculo del tamaño muestral se realizó a través del método probabilístico aleatorio simple resultando de éste 120 profesionales de enfermería. Para la recolección de datos, se aplicó una encuesta adaptada del cuestionario Ways of Coping Questionnaire de Lazarus y Folkman. Resultados: se evidenció que la estrategia de afrontamiento más utilizada por los enfermeros fue la reinterpretación positiva. Conclusión: a través de este estudio se logró reconocer las estrategias de afrontamiento que el personal de enfermería utilizó al momento de enfrentar situaciones o experiencias estresantes[AU]

Introduction: nursing staff face extended work days daily, have many patients under their care, difficulties in interpersonal relationships, which could trigger stress, for which the individual develops a process of adaptation or imbalance and it is for this reason the importance of having strategies to deal with situations. Objectives: the objective of this study was to analyze coping strategies in stressful situations used by nursing professionals from a Public Hospital in the capital city of Corrientes, as well as their association with sociodemographic variables. Methodology: quantitative, descriptive, cross-sectional and observational study. The population included nurses from a public hospital in the city of Corrientes in the period 2022. Inclusion criteria were considered nursing personnel who perform care functions and their time of work was 1 year or more; as exclusion criteria, personnel who had two or more jobs and as elimination criteria those nurses who were not present at the time of the survey. The calculation of the sample size was carried out through the simple random probabilistic method, resulting in 120 nursing professionals. For data collection, a survey adapted from the Ways of Coping Questionnaire by Lazarus and Folkman was applied. Results: it was evidenced that the coping strategy most used by nurses was positive reinterpretation. Conclusion: through this study, it was possible to recognize the coping strategies that the nursing staff used when facing stressful situations or experiences[AU]

Introdução: a equipe de enfermagem enfrenta diariamente jorna-das de trabalho extensas, tem muitos pacientes sob seus cuidados, dificuldades no relacionamento interpessoal, podendo desenca-dear estresse, para o qual o indivíduo desenvolve um processo de adaptação ou desequilíbrio e por isso a importância de se ter estra-tégias para lidar com as situações. Objetivos: o objetivo deste estudo foi analisar as estratégias de enfrentamento em situações estressan-tes utilizadas por profissionais de enfermagem de um Hospital Pú-blico da capital Corrientes, bem como sua associação com variáveis sociodemográficas. Metodologia: estudo quantitativo, descritivo, transversal e observacional. A população incluiu enfermeiros de um hospital público da cidade de Corrientes no período de 2022. Os critérios de inclusão foram considerados pessoal de enfermagem que desempenha funções assistenciais e seu tempo de trabalho foi de 1 ano ou mais; como critérios de exclusão, pessoal que exercesse dois ou mais vínculos empregatícios e como critérios de eliminação os enfermeiros que não estivessem presentes no momento da pes-quisa. O cálculo do tamanho da amostra foi realizado pelo método probabilístico aleatório simples, resultando em 120 profissionais de enfermagem. Para a coleta de dados, foi aplicado um questionário adaptado do Questionário de Modos de Enfrentamento de Lazarus e Folkman. Resultados: evidenciou-se que a estratégia de enfrenta-mento mais utilizada pelos enfermeiros foi a reinterpretação posi-tiva. Conclusão: Por meio deste estudo, foi possível reconhecer as estratégias de enfrentamento que a equipe de enfermagem utiliza diante de situações ou experiências estressantes[AU]

Effect of a pescetarian and vegan diet on fatty acid composition in blood and spermatozoa in young healthy men.

INTRODUCTION: There is a growing interest in vegetarian and vegan diets, but both can potentially affect tissue fatty acids (FA) composition. We aimed to evaluate the effect of vegetarian diets on plasma, erythrocytes, and sperm n-3 polyunsaturated fatty acids (n-3 PUFA) status in healthy young men. METHODS: Four groups were studied: i) men consuming a regular omnivore diet (OMV-1, n = 35); ii) men consuming an omnivore diet but excluding fish and seafood (OMV-2, n = 34); iii) men consuming a pescetarian diet (including dairy, eggs, fish, and seafood) (PESC, n = 36); and iv) men following a strict vegan diet (VEG, n = 35). Participants in each group should follow their diet for at least the previous 12 months. Diet evaluation used a structured validated food frequency questionnaire. FA composition was measured in plasma, erythrocyte phospho-lipids, and spermatozoa by gas-liquid chromatography, expressed as a mole percentage of the total FA content. RESULTS: Main findings showed higher alpha-linolenic fatty acid (ALA) and total n-3 PUFA dietary intake in the VEG group. In plasma, arachidonic and eicosapentaenoic acids were higher in OMV and PESC groups, whereas docosahexaenoic acid (DHA) level was lower in VEG. Higher ALA, but reduced DHA and total n-3 PUFA levels were found in erythrocytes and spermatozoa in the VEG group. CONCLUSION: Higher dietary ALA intake was found in pescetarians and vegan men. However, the higher ALA intake was not reflected in higher DHA content in the evaluated tissues. PUFA assessment, with particular emphasis in DHA, are necessary to improve PUFA status in vegan men.

Acyl-CoA thioesterase 12 suppresses YAP-mediated hepatocarcinogenesis by limiting glycerolipid biosynthesis.

Cancer cells use acetate to support the higher demand for energy and lipid biosynthesis during uncontrolled cell proliferation, as well as for acetylation of regulatory proteins. Acyl-CoA thioesterase 12 (Acot12) is the enzyme that hydrolyzes acetyl-CoA to acetate in liver cytosol and is downregulated in hepatocellular carcinoma (HCC). A mechanistic role for Acot12 in hepatocarcinogenesis was assessed in mice in response to treatment with diethylnitrosamine(DEN)/carbon tetrachloride (CCl4) administration or prolonged feeding of a diet that promotes non-alcoholic steatohepatitis (NASH). Relative to controls, Acot12-/- mice exhibited accelerated liver tumor formation that was characterized by the hepatic accumulation of glycerolipids, including lysophosphatidic acid (LPA), and that was associated with reduced Hippo signaling and increased yes-associated protein (YAP)-mediated transcriptional activity. In Acot12-/- mice, restoration of hepatic Acot12 expression inhibited hepatocarcinogenesis and YAP activation, as did knockdown of hepatic YAP expression. Excess LPA produced due to deletion of Acot12 signaled through LPA receptors (LPARs) coupled to Gα12/13 subunits to suppress YAP phosphorylation, thereby promoting its nuclear localization and transcriptional activity. These findings identify a protective role for Acot12 in suppressing hepatocarcinogenesis by limiting biosynthesis of glycerolipids including LPA, which preserves Hippo signaling.

High-throughput screening identifies small molecule inhibitors of thioesterase superfamily member 1: Implications for the management of non-alcoholic fatty liver disease.

OBJECTIVE: Thioesterase superfamily member 1 (Them1) is a long chain acyl-CoA thioesterase comprising two N-terminal HotDog fold enzymatic domains linked to a C-terminal lipid-sensing steroidogenic acute regulatory transfer-related (START) domain, which allosterically modulates enzymatic activity. Them1 is highly expressed in thermogenic adipose tissue, where it functions to suppress energy expenditure by limiting rates of fatty acid oxidation, and is induced markedly in liver in response to high fat feeding, where it suppresses fatty acid oxidation and promotes glucose production. Them1-/- mice are protected against non-alcoholic fatty liver disease (NAFLD), suggesting Them1 as a therapeutic target. METHODS: A high-throughput small molecule screen was performed to identify promising inhibitors targeting the fatty acyl-CoA thioesterase activity of purified recombinant Them1.Counter screening was used to determine specificity for Them1 relative to other acyl-CoA thioesterase isoforms. Inhibitor binding and enzyme inhibition were quantified by biophysical and biochemical approaches, respectively. Following structure-based optimization, lead compounds were tested in cell culture. RESULTS: Two lead allosteric inhibitors were identified that selectively inhibited Them1 by binding the START domain. In mouse brown adipocytes, these inhibitors promoted fatty acid oxidation, as evidenced by increased oxygen consumption rates. In mouse hepatocytes, they promoted fatty acid oxidation, but also reduced glucose production. CONCLUSION: Them1 inhibitors could prove attractive for the pharmacologic management of NAFLD.

c-Abl Activation Linked to Autophagy-Lysosomal Dysfunction Contributes to Neurological Impairment in Niemann-Pick Type A Disease.

Niemann-Pick type A (NPA) disease is a fatal lysosomal neurodegenerative disorder caused by the deficiency in acid sphingomyelinase (ASM) activity. NPA patients present severe and progressive neurodegeneration starting at an early age. Currently, there is no effective treatment for this disease and NPA patients die between 2 and 3 years of age. NPA is characterized by an accumulation of sphingomyelin in lysosomes and dysfunction in the autophagy-lysosomal pathway. Recent studies show that c-Abl tyrosine kinase activity downregulates autophagy and the lysosomal pathway. Interestingly, this kinase is also activated in other lysosomal neurodegenerative disorders. Here, we describe that c-Abl activation contributes to the mechanisms of neuronal damage and death in NPA disease. Our data demonstrate that: 1) c-Abl is activated in-vitro as well as in-vivo NPA models; 2) imatinib, a clinical c-Abl inhibitor, reduces autophagy-lysosomal pathway alterations, restores autophagy flux, and lowers sphingomyelin accumulation in NPA patient fibroblasts and NPA neuronal models and 3) chronic treatment with nilotinib and neurotinib, two c-Abl inhibitors with differences in blood-brain barrier penetrance and target binding mode, show further benefits. While nilotinib treatment reduces neuronal death in the cerebellum and improves locomotor functions, neurotinib decreases glial activation, neuronal disorganization, and loss in hippocampus and cortex, as well as the cognitive decline of NPA mice. Our results support the participation of c-Abl signaling in NPA neurodegeneration and autophagy-lysosomal alterations, supporting the potential use of c-Abl inhibitors for the clinical treatment of NPA patients.

Thyroid hormone signaling promotes hepatic lipogenesis through the transcription factor ChREBP.

Thyroid hormone (TH) action is essential for hepatic lipid synthesis and oxidation. Analysis of hepatocyte-specific thyroid receptor ß1 (TRß1) knockout mice confirmed a role for TH in stimulating de novo lipogenesis and fatty acid oxidation through its nuclear receptor. Specifically, TRß1 and its principal corepressor NCoR1 in hepatocytes repressed de novo lipogenesis, whereas the TH-mediated induction of lipogenic genes depended on the transcription factor ChREBP. Mice with a hepatocyte-specific deficiency in ChREBP lost TH-mediated stimulation of the lipogenic program, which, in turn, impaired the regulation of fatty acid oxidation. TH regulated ChREBP activation and recruitment to DNA, revealing a mechanism by which TH regulates specific signaling pathways. Regulation of the lipogenic pathway by TH through ChREBP was conserved in hepatocytes derived from human induced pluripotent stem cells. These results demonstrate that TH signaling in the liver acts simultaneously to enhance both lipogenesis and fatty acid oxidation.

Biosensors for the Detection of Bacterial and Viral Clinical Pathogens.

Biosensors are measurement devices that can sense several biomolecules, and are widely used for the detection of relevant clinical pathogens such as bacteria and viruses, showing outstanding results. Because of the latent existing risk of facing another pandemic like the one we are living through due to COVID-19, researchers are constantly looking forward to developing new technologies for diagnosis and treatment of infections caused by different bacteria and viruses. Regarding that, nanotechnology has improved biosensors' design and performance through the development of materials and nanoparticles that enhance their affinity, selectivity, and efficacy in detecting these pathogens, such as employing nanoparticles, graphene quantum dots, and electrospun nanofibers. Therefore, this work aims to present a comprehensive review that exposes how biosensors work in terms of bacterial and viral detection, and the nanotechnological features that are contributing to achieving a faster yet still efficient COVID-19 diagnosis at the point-of-care.

Estrogen Activation of G-Protein-Coupled Estrogen Receptor 1 Regulates Phosphoinositide 3-Kinase and mTOR Signaling to Promote Liver Growth in Zebrafish and Proliferation of Human Hepatocytes.

BACKGROUND & AIMS: Patients with cirrhosis are at high risk for hepatocellular carcinoma (HCC) and often have increased serum levels of estrogen. It is not clear how estrogen promotes hepatic growth. We investigated the effects of estrogen on hepatocyte proliferation during zebrafish development, liver regeneration, and carcinogenesis. We also studied human hepatocytes and liver tissues. METHODS: Zebrafish were exposed to selective modifiers of estrogen signaling at larval and adult stages. Liver growth was assessed by gene expression, fluorescent imaging, and histologic analyses. We monitored liver regeneration after hepatocyte ablation and HCC development after administration of chemical carcinogens (dimethylbenzanthrazene). Proliferation of human hepatocytes was measured in a coculture system. We measured levels of G-protein-coupled estrogen receptor (GPER1) in HCC and nontumor liver tissues from 68 patients by immunohistochemistry. RESULTS: Exposure to 17ß-estradiol (E2) increased proliferation of hepatocytes and liver volume and mass in larval and adult zebrafish. Chemical genetic and epistasis experiments showed that GPER1 mediates the effects of E2 via the phosphoinositide 3-kinase-protein kinase B-mechanistic target of rapamycin pathway: gper1-knockout and mtor-knockout zebrafish did not increase liver growth in response to E2. HCC samples from patients had increased levels of GPER1 compared with nontumor tissue samples; estrogen promoted proliferation of human primary hepatocytes. Estrogen accelerated hepatocarcinogenesis specifically in male zebrafish. Chemical inhibition or genetic loss of GPER1 significantly reduced tumor development in the zebrafish. CONCLUSIONS: In an analysis of zebrafish and human liver cells and tissues, we found GPER1 to be a hepatic estrogen sensor that regulates liver growth during development, regeneration, and tumorigenesis. Inhibitors of GPER1 might be developed for liver cancer prevention or treatment. TRANSCRIPT PROFILING: The accession number in the Gene Expression Omnibus is GSE92544.

Thioesterase Superfamily Member 2 Promotes Hepatic VLDL Secretion by Channeling Fatty Acids Into Triglyceride Biosynthesis.

In nonalcoholic fatty liver disease (NAFLD), triglycerides accumulate within the liver because the rates of fatty acid accrual by uptake from plasma and de novo synthesis exceed elimination by mitochondrial oxidation and secretion as very low-density lipoprotein (VLDL) triglycerides. Thioesterase superfamily member 2 (Them2) is an acyl-coenzyme A (CoA) thioesterase that catalyzes the hydrolysis of fatty acyl-CoAs into free fatty acids plus CoASH. Them2 is highly expressed in the liver, as well as other oxidative tissues. Mice globally lacking Them2 are resistant to diet-induced obesity and hepatic steatosis, and exhibit improved glucose homeostasis. These phenotypes are attributable, at least in part, to roles of Them2 in the suppression of thermogenesis in brown adipose tissue and insulin signaling in skeletal muscle. To elucidate the hepatic function of Them2, we created mice with liver-specific deletion of Them2 (L-Them2-/- ). Although L-Them2-/- mice were not protected against excess weight gain, hepatic steatosis or glucose intolerance, they exhibited marked decreases in plasma triglyceride and apolipoprotein B100 concentrations. These were attributable to reduced rates of VLDL secretion owing to decreased incorporation of plasma-derived fatty acids into triglycerides. The absence of hepatic steatosis in L-Them2-/- mice fed chow was explained by compensatory increases in rates of fatty acid oxidation and by decreased de novo lipogenesis in high fat-fed mice. Consistent with a role for Them2 in hepatic VLDL secretion, THEM2 levels were increased in livers of obese patients with NAFLD characterized by simple steatosis. Conclusion: Them2 functions in the liver to direct fatty acids toward triglyceride synthesis for incorporation into VLDL particles. When taken together with its functions in brown adipose and muscle, these findings suggest that Them2 is a target for the management of NAFLD and dyslipidemia.

Structural and functional analysis of the ASM p.Ala359Asp mutant that causes acid sphingomyelinase deficiency.

Niemann-Pick disease (NPD) type A and B are recessive hereditary disorders caused by deficiency in acid sphingomyelinase (ASM). The p.Ala359Asp mutation has been described in several patients but its functional and structural effects in the protein are unknown. In order to characterize this mutation, we modeled the three-dimensional ASM structure using the recent available crystal of the mammalian ASM as a template. We found that the p.Ala359Asp mutation is localized in the hydrophobic core and far from the sphingomyelin binding site. However, energy function calculations using statistical potentials indicate that the mutation causes a decrease in ASM stability. Therefore, we investigated the functional effect of the p.Ala359Asp mutation in ASM expression, secretion, localization and activity in human fibroblasts. We found a 3.8% residual ASM activity compared to the wild-type enzyme, without changes in the other parameters evaluated. These results support the hypothesis that the p.Ala359Asp mutation causes structural alterations in the hydrophobic environment where ASM is located, decreasing its enzymatic activity. A similar effect was observed in other previously described NPDB mutations located outside the active site of the enzyme. This work shows the first full size ASM mutant model describe at date, providing a complete analysis of the structural and functional effects of the p.Ala359Asp mutation over the stability and activity of the enzyme.

CAPACIDAD DE CARGA ASIGNABLE AL AGROECOTURISMO EN ÁREAS PROTEGIDAS DE BOLIVIA / ALLOCABLE CAPACITY TO AGROECOTOURISM IN BOLIVIAN PROTECTED AREAS

Este documento tiene como objetivo valorar la capacidad de carga asignable al agroturismo en áreas protegidas de Bolivia en el marco de la economía ecológica. En esta nación, el agroturismo puede constituirse en una práctica novedosa para hacer que los visitantes de áreas protegidas sean partícipes de las actividades de desarrollo económico local. Además, permite determinar la cantidad de personas que pueden visitar un sitio protegido sin alterar el equilibrio de los ecosistemas que alberga. Metodológicamente se empleó un enfoque mixto (cuantitativo y cualitativo) apoyado con la medición tradicional de carga turística física, real y efectiva. En el caso de los agroecosistemas de las áreas protegidas de Bolivia se puede observar que existe capacidad de carga suficiente para su operación que actualmente que alcanza el 96 %. También, es posible mejorarla e incrementarla en función de las características ecológicas, físicas y sociales de estos sitios. Por otra parte es importante resaltar la importancia de los ingresos económicos obtenidos diarios de un área protegida individual que corresponde a 404 Bs. en promedio. Finalmente, el empleo de la economía ecológica permite establecer el valor y aprovechamiento de los recursos existentes en las áreas protegidas de interés nacional de Bolivia. De esta manera, es posible mejorar la gestión de sitios protegidas a nivel ambiental y financiero.

This document has the objective to value the allocable capacity assigned to agrotourism in Bolivian protected areas within the framework of ecological economy, Agroecotourism in this nation can become an innovating alternative to enhance the participation of protected areas visitors in local economic activities development. Furthermore, it allows quantifying the amount of people who can visit a protected site without disturbing the ecosystems equilibrium in the area. Methodologically, a mixed approach (quantitative and qualitative) was applied based on the traditional measuring of physical, real and effective tourism allocable capacity. In the case of the Bolivian agroecosystems protected areas it is possible to observe that there is enough allocable capacity for its operation, which is currently reaching 96%. In addition, it is possible to improve it and increase it according to the ecological, physical and social characteristics of these sites. On the other hand, it is possible to highlight the importance of the economical revenues obtained daily in an individual protected area that corresponds to an average of 404 Bs. Finally, the application of ecological economy allows establishing the value and use of existing resources in the protected areas of national interest in Bolivia. In this way, it is possible to improve protected sites management in financial and environmental terms.

Epidemiological, clinical and biochemical characterization of the p.(Ala359Asp) SMPD1 variant causing Niemann-Pick disease type B.

Niemann-Pick disease type B (NPDB) is a rare, inherited lysosomal storage disorder that occurs due to variants in the sphingomyelin phosphodiesterase 1 (SMPD1) gene and the resultant deficiency of acid sphingomyelinase (ASM) activity. While numerous variants causing NPDB have been described, only a small number have been studied in any detail. Herein, we describe the frequency of the p.(Ala359Asp) variant in the healthy Chilean population, and determine the haplotype background of homozygous patients to establish if this variant originated from a common founder. Genomic DNA samples from 1691 healthy individuals were analyzed for the p.(Ala359Asp) variant. The frequency of p.(Ala359Asp) was found to be 1/105.7, predicting a disease incidence of 1/44 960 in Chile, higher than the incidence estimated by the number of confirmed NPDB cases. We also describe the clinical characteristics of 13 patients homozygous for p.(Ala359Asp) and all of them had moderate to severe NPDB disease. In addition, a conserved haplotype and shared 280 Kb region around the SMPD1 gene was observed in the patients analyzed, indicating that the variant originated from a common ancestor. The haplotype frequency and mitochondrial DNA analysis suggest an Amerindian origin for the variant. To assess the effect of the p.(Ala359Asp) variant, we transfected cells with the ASM-p.(Ala359Asp) cDNA and the activity was only 4.2% compared with the wild-type cDNA, definitively demonstrating the causative effect of the variant on ASM function. Information on common variants such as p.(Ala359Asp) is essential to guide the successful implementation for future therapies and benefit to patients.

Transgenic overexpression of Niemann-Pick C2 protein promotes cholesterol gallstone formation in mice.

BACKGROUND & AIMS: Niemann-Pick C2 (NPC2) is a lysosomal protein involved in the egress of low-density lipoprotein-derived cholesterol from lysosomes to other intracellular compartments. NPC2 has been detected in several tissues and is also secreted from the liver into bile. We have previously shown that NPC2-deficient mice fed a lithogenic diet showed reduced biliary cholesterol secretion as well as cholesterol crystal and gallstone formation. This study aimed to investigate the consequences of NPC2 hepatic overexpression on liver cholesterol metabolism, biliary lipid secretion, gallstone formation and the effect of NPC2 on cholesterol crystallization in model bile. METHODS: We generated NPC2 transgenic mice (Npc2.Tg) and fed them either chow or lithogenic diets. We studied liver cholesterol metabolism, biliary lipid secretion, bile acid composition and gallstone formation. We performed cholesterol crystallization studies in model bile using a recombinant NPC2 protein. RESULTS: No differences were observed in biliary cholesterol content or secretion between wild-type and Npc2.Tg mice fed the chow or lithogenic diets. Interestingly, Npc2.Tg mice showed an increased susceptibility to the lithogenic diet, developing more cholesterol gallstones at early times, but did not show differences in the bile acid hydrophobicity and gallbladder cholesterol saturation indices compared to wild-type mice. Finally, recombinant NPC2 decreased nucleation time in model bile. CONCLUSIONS: These results suggest that NPC2 promotes cholesterol gallstone formation by decreasing the cholesterol nucleation time, indicating a pro-nucleating function of NPC2 in bile.

Deficiency of Niemann-Pick C1 protein protects against diet-induced gallstone formation in mice.

BACKGROUND/AIMS: Receptor-mediated endocytosis is a critical cellular mechanism for the uptake of lipoprotein cholesterol in the liver. Because Niemann-Pick C1 (NPC1) protein is a key component for the intracellular distribution of cholesterol originating from lipoprotein endocytosis, it may play an important role in controlling biliary cholesterol secretion and gallstone formation induced by a lithogenic diet. METHODS: We studied biliary cholesterol secretion, gallbladder lipid composition and gallstone formation in NPC1-deficient mice fed a low-fat lithogenic diet (1.5% cholesterol and 0.5% cholic acid) compared with control animals under the same diet. RESULTS: The lipid secretion response to the lithogenic diet was impaired in NPC1 (-/-) mice, leading to a decreased cholesterol output and an increased hepatic cholesterol concentration compared with the lithogenic diet-fed wild-type mice. A decreased cholesterol saturation index was found in the gallbladder bile of NPC1 (+/-) and (-/-) mice after lithogenic diet feeding. Consequently, mice with a partial or a total deficiency of NPC1 had a drastically lower frequency of gallbladder cholesterol crystals and a reduced prevalence of gallstones. CONCLUSION: Hepatic NPC1 expression is an important factor for regulating the biliary secretion of diet-derived cholesterol as well as for diet-induced cholesterol gallstone formation in mice.

Mutational screening of the APC gene in Chilean families with familial adenomatous polyposis: nine novel truncating mutations.

PURPOSE: Familial adenomatous polyposis is characterized by the development of hundreds of adenomatous polyps located mainly in the colon and rectum. Patients with familial adenomatous polyposis who do not receive treatment will develop cancer before aged 40 years. This disease is caused by germline mutations in the adenomatous polyposis coli gene. Different studies have shown a correlation between the location of the mutation and the clinical phenotype, such as the grade of severity and/or the presence of extracolonic manifestations, such as desmoid tumors. This study was designed to identify germline mutation in the adenomatous polyposis coli gene in Chilean families with familial adenomatous polyposis. METHODS: We examined the adenomatous polyposis coli gene in 24 Chilean families with familial adenomatous polyposis. The adenomatous polyposis coli gene was screened for mutations combining single strand conformation polymorphism technique, protein truncation test, and DNA sequencing. RESULTS: We detected 17 different truncating mutations in 21 of 24 families (87.5 percent); 9 of these were novel. Fourteen mutations were detected in exon 15, being the most frequent c.3,927_3,931delAAAGA, found in 3 of 21 families (14 percent). Eight families (33 percent) showed at least one patient affected with desmoid tumors, presenting mutations between codons 849 and 1,533. Interestingly, two mutations, c.3,632dupA and c.3,783_3,784delTT, leading into a truncating protein at codons 1,216 and 1,274, were associated with almost 100 percent penetrance for desmoid tumors among relatives. CONCLUSIONS: We achieved 87 percent mutation detection rate in adenomatous polyposis coli gene; more than 50 percent of them were novel. The high percentage of novel mutations found may be because of the genetic composition of the Chilean population, which is an admixture of Amerindian and Spaniards, and the scarce information in the literature about similar populations.

Trypanosoma cruzi detection in blood by xenodiagnosis and polymerase chain reaction in the wild rodent Octodon degus.

We detected Trypanosoma cruzi in blood samples of the wild rodent Octodon degus by xenodiagnosis and a polymerase chain reaction (PCR) using the domestic and wild vectors of Chagas disease, Triatoma infestans and Mepraia spinolai, respectively. We captured 35 rodents and extracted DNA from blood samples and intestinal contents of vectors fed on O. degus. Our results indicate that the percentage of rodents naturally infected with T. cruzi depends on the biologic sample used for PCR and on the vector species for xenodiagnosis. The PCR with blood samples did not detect T. cruzi DNA, but the PCR with intestinal contents showed that both vectors were positive for T. cruzi. The PCR performed with M. spinolai intestinal contents detected four times more T. cruzi-positive O. degus than the PCR with Triatoma infestans intestinal contents (22.9% and 5.7%, respectively). We report the improvement of T. cruzi detection in sylvatic animals by a combination of PCR and xenodiagnosis using sylvatic vectors, especially in disease-endemic areas with low parasitemias in mammals.

Seasonal variation in the home range and host availability of the blood-sucking insect Mepraia Spinolai in wild environment.

In this study, we quantify the home range of Mepraia spinolai, a wild vector of Trypanosoma cruzi, and the abundance of wild mammals during summer and winter seasons in a protected area of north-central Chile. Results revealed significant differences between seasons for home range size and host availability. M. spinolai presented larger home range sizes, and mammal hosts were more abundant in summer, indicating that T. cruzi would have a higher probability of being transmitted during warmer months.

Abundance of Mepraia spinolai in a Periurban zone of Chile.

Mepraia spinolai is a silvatic species of Triatominae which prefers microhabitats near to or in rock piles. It is also able to maintain similar or higher size populations near houses. The density of bugs in quarries near Santiago, Chile, differed within microhabitats and varied significantly within sites according to season. M. spinolai was not found in sites characterized by human perturbation of quarries. Our results confirm M. spinolai as a silvatic triatomine whose importance as a vector of Chagas disease will depend on contact with humans. This could occur if the habitats where populations of this species are found become exploited for the building of urban areas.