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Hemostatic powders (HP) are increasingly used to address limitations in conventional endoscopic techniques for gastrointestinal bleeding. HP is a relatively recent addition to the arsenal of hemostatic endoscopic procedures (HEPs) for gastrointestinal bleeding (GIB) due to benign and malignant lesions, which all life-threatening conditions. HP acts as a mechanical barrier and/or promotes platelet activation and coagulation cascade. Malignancy causes comprise 1-5% of all non-variceal upper gastrointestinal bleeding (NVUGIB). UI-EWD (NexPowder) is composed of oxidized dextran and succinic anhydride, which is converted to an adhesive hydrogel upon contact with moisture. The resulting hydrogel cross-links within itself and with adjacent tissue to create a mechanical barrier to promote hemostasis. As it does not require clot formation to achieve hemostasis, UI-EWD does not require active bleeding. This provides it a potential role in prophylaxis, such as post-procedure or following primary hemostasis achieved with conventional endoscopic techniques. While UI-EWD is the newest development in hemostatic powders for clinical use, initial results are promising. We report the case of a 51-year-old male with epidermoid esophageal stenosing carcinoma recently diagnosed and locally advanced. Started treatment concurrent chemotherapy and radiotherapy, being necessary a nasogastric tube for parenteral nutrition. Our patient came to the emergency unit due to hematemesis which came from a pressure ulcer with active bleeding shown in gastroscopy exploration, withdrawing the tube and spraying onto the surface of the bleeding site UI-EWD until the bleeding lesion was completely covered with the powder, doing successful hemostasis confirmed by hemostasis until 5 minutes after the endoscopic treatment. HP is highly effective in patients with NVUGIB when used either in combination with or as rescue therapy. Rapid development of hemostatic powders and growing clinical expertise has established these agents as a valuable strategy in gastrointestinal bleeding.
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BACKGROUND AND AIMS: Extracellular vesicles (EVs) have emerged as a potential source of circulating biomarkers in liver disease. We evaluated circulating AV+ EpCAM+ CD133+ EVs as a potential biomarker of the transition from simple steatosis to steatohepatitis. METHODS: EpCAM and CD133 liver proteins and EpCAM+ CD133+ EVs levels were analysed in 31 C57BL/6J mice fed with a chow or high fat, high cholesterol and carbohydrates diet (HFHCC) for 52 weeks. The hepatic origin of MVs was addressed using AlbCrexmT/mG mice fed a Western (WD) or Dual diet for 23 weeks. Besides, we assessed plasma MVs in 130 biopsy-proven NAFLD patients. RESULTS: Hepatic expression of EpCAM and CD133 and EpCAM+ CD133+ EVs increased during disease progression in HFHCC mice. GFP+ MVs were higher in AlbCrexmT/mG mice fed a WD (5.2% vs 12.1%) or a Dual diet (0.5% vs 7.3%). Most GFP+ MVs were also positive for EpCAM and CD133 (98.3% and 92.9% respectively), suggesting their hepatic origin. In 71 biopsy-proven NAFLD patients, EpCAM+ CD133+ EVs were significantly higher in those with steatohepatitis compare to those with simple steatosis (286.4 ± 61.9 vs 758.4 ± 82.3; p < 0.001). Patients with ballooning 367 ± 40.6 vs 532.0 ± 45.1; p = 0.01 and lobular inflammation (321.1 ± 74.1 vs 721.4 ± 80.1; p = 0.001), showed higher levels of these EVs. These findings were replicated in an independent cohort. CONCLUSIONS: Circulating levels of EpCAM+ CD133+ MVs in clinical and experimental NAFLD were increased in the presence of steatohepatitis, showing high potential as a non-invasive biomarker for the evaluation and management of these patients.
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Vesículas Extracelulares , Enfermedad del Hígado Graso no Alcohólico , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Molécula de Adhesión Celular Epitelial/metabolismo , Ratones Endogámicos C57BL , Hígado/metabolismo , Vesículas Extracelulares/metabolismo , Biomarcadores , Modelos Animales de Enfermedad , Dieta Alta en GrasaRESUMEN
Near-infrared (NIR) emitting phosphors are currently receiving considerable attention owing to their high demand in various applications, such as light detection and ranging (LiDAR), short-range communications, security, biosensing and night vision lighting applications. The miniaturization of photonic components demands the integration of thin films into exploitable devices. In this context, NIR emitting ZnAl2O4:Ce/Nd films of hundreds of nanometer thickness are synthesized using a scalable and cost-efficient approach to screen printing. Cerium co-doping is responsible for the Nd emission in the NIR through energy transfer by exciting the films under UV excitation at around 360 nm. Through the proper design of ink, dense Nd/Ce doped ZnAl2O4 ceramic films were produced using polycrystalline alumina. The use of polycrystalline alumina substrates opens up new opportunities because this ceramic is a cheap and well-known substrate for optoelectronic packaging. During manufacturing, as a direct effect of predominant crystal growth over the polycrystalline alumina substrate, an increase in emission intensity is achieved. The results obtained by X-ray photoelectron (XPS) and X-ray absorption near edge spectroscopy (XANES) serve to determine the oxidation state of Ce. The findings of this study indicate that a higher concentration of Ce4+ promotes NIR emission. This study may contribute to a better understanding of film production processes of films based on the ZnAl2O4 matrix and guide future studies on films for NIR emitters.
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The function of the α1B-adrenergic receptor phosphorylation sites previously detected by mass spectrometry was evaluated by employing mutants, substituting them with non-phosphorylatable amino acids. Substitution of the intracellular loop 3 (IL3) sites did not alter baseline or stimulated receptor phosphorylation, whereas substitution of phosphorylation sites in the carboxyl terminus (Ctail) or both domains (IL3/Ctail) markedly decreased receptor phosphorylation. Cells expressing the IL3 or Ctail receptor mutants exhibited a noradrenaline-induced calcium-maximal response similar to those expressing the wild-type receptor, and a shift to the left in the concentration-response curve to noradrenaline was also noticed. Cells expressing the IL3/Ctail mutant exhibited higher apparent potency and increased maximal response to noradrenaline than those expressing the wild-type receptor. Phorbol ester-induced desensitization of the calcium response to noradrenaline was reduced in cells expressing the IL3 mutant and abolished in cells in which the Ctail or the IL3/Ctail were modified. In contrast, desensitization in response to preincubation with noradrenaline was unaffected in cells expressing the distinct receptor mutants. Noradrenaline-induced ERK phosphorylation was surprisingly increased in cells expressing IL3-modified receptors but not in those expressing receptors with the Ctail or IL3/Ctail substitutions. Our data indicate that phosphorylation sites in the IL3 and Ctail domains mediate and regulate α1B-adrenergic receptor function. Phorbol ester-induced desensitization seems to be closely associated with receptor phosphorylation, whereas noradrenaline-induced desensitization likely involves other elements.
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Calcio , Norepinefrina , Fosforilación , Calcio/metabolismo , Norepinefrina/farmacología , Ésteres del Forbol , Receptores Adrenérgicos/metabolismoRESUMEN
Due to the high concentration of pollutants, swine wastewater needs to be treated prior to disposal. The combination of anaerobic and aerobic technologies in one hybrid system allows to obtain higher removal efficiencies compared to those achieved via conventional biological treatment, and the performance of a hybrid system depends on the microbial community in the bioreactor. Here, we evaluated the community assembly of an anaerobic-aerobic hybrid reactor for swine wastewater treatment. Sequencing of partial 16S rRNA coding genes was performed using Illumina from DNA and retrotranscribed RNA templates (cDNA) extracted from samples from both sections of the hybrid system and from a UASB bioreactor fed with the same swine wastewater influent. Proteobacteria and Firmicutes were the dominant phyla and play a key role in anaerobic fermentation, followed by Methanosaeta and Methanobacterium. Several differences were found in the relative abundances of some genera between the DNA and cDNA samples, indicating an increase in the diversity of the metabolically active community, highlighting Chlorobaculum, Cladimonas, Turicibacter and Clostridium senso stricto. Nitrifying bacteria were more abundant in the hybrid bioreactor. Beta diversity analysis revealed that the microbial community structure significantly differed among the samples (p < 0.05) and between both anaerobic treatments. The main predicted metabolic pathways were the biosynthesis of amino acids and the formation of antibiotics. Also, the metabolism of C5-branched dibasic acid, Vit B5 and CoA, exhibited an important relationship with the main nitrogen-removing microorganisms. The anaerobic-aerobic hybrid bioreactor showed a higher ammonia removal rate compared to the conventional UASB system. However, further research and adjustments are needed to completely remove nitrogen from wastewater.
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Chlorobi , Microbiota , Purificación del Agua , Animales , Porcinos , Aguas Residuales , Aguas del Alcantarillado/química , Eliminación de Residuos Líquidos , Anaerobiosis , Chlorobi/genética , ARN Ribosómico 16S/genética , ADN Complementario , Reactores Biológicos/microbiologíaRESUMEN
Infectious diseases are extremely important in the global health landscape, specifically dengue and its severe forms. Clinical characterization is very variable due to the wide spectrum of manifestations the virus induces. Dengue is a viral infection caused by the dengue virus and is transmitted to humans by mosquitos of the Aedes family. Dengue is the most important arthropod-borne disease and if symptoms occur, could appear suddenly, characterized by biphasic fever, headache, retroocular pain, pain in various parts of the body, prostration and rash. It has also been described that the Dengue virus can also cause liver dysfunction that could vary from mild injury to severe hepatocyte injury, commonly in tropical and subtropical climates. We report the case of a 24-year-old female who came to the emergency room due to fever and myalgia, in the context of a recent trip to Cuba. Physical examination included positive tourniquet test and laboratory findings showed anaemia and thrombocytopenia, as well as elevated transaminase levels. Serologic tests for dengue virus are requested and a positive result of specific antibodies-IgM classified the patient as presumptive being necessary to confirm authorities the outbreak and explain the patient it requires a close monitoring. Abdominal ultrasound showed mild splenomegaly. Because of progressive analytical normalization, the patient asked for outpatient care.
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Schistosomiasis is a parasitic infection caused by trematode species of the genus Schistosoma. It is prevalent in tropical regions of Africa, Asia and South America, being rare in Europe, where it is usually diagnosed in immigrants and tourists from endemic areas. It has different clinical forms of presentation. Hepatosplenic schistosomiasis produces periportal fibrosis, which can progress to presinusoidal portal hypertension, with all its associated complications. We present the case of a 43-year-old female patient from the Philippines who was referred to gastroenterology consultation due to liver enzyme alteration with a predominantly cholestatic pattern. An aetiological study was performed, with negative results. An abdominal ultrasound revealed signs of chronic liver disease, with transient elastography of 9.5 kPa. A percutaneous liver biopsy was performed, with histological findings consistent with infestation by schistosome eggs, receiving treatment with praziquantel and subsequently verifying its eradication with a stool test.
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Cullen´s sign and Grey Turner sign are, respectively, the cutaneous ecchymoses located in periumbilical region and tissues flanks along the lower portion of the abdomen. Both have been observed in <1% of individuals with acute pancreatitis, suggesting poor prognosis in terms of gravity and mortality. However, these signs are not exclusive for acute pancreatitis, as they can appear in other identities such as: ruptured ectopic pregnancy, aortic aneurysm, rectus abdominis muscle hematoma, perforated duodenal ulcer, common bile duct rupture and biliary peritonitis, idiopathic perirenal hemorrhage, infectious mononucleosis with splenic rupture, metastatic esophageal and thyroid cancer, non-Hodgkin lymphoma, amoebic liver abscess, portal hypertension, and liver tumor disease. Based on the review of the literature, it is patent that Cullen´s sign and Grey Turner sign are neither sensitive nor specific for acute pancreatitis, therefore it may be best to relate these findings in the physical examination to conditions associated with abdominal pathology and retroperitoneal hemorrhage. We report the case of a 60-year-old Spanish female, with previous history of squamous small cell neuroendocrine lung carcinoma with hepatic extension in follow-up by palliative care services. Due to disease progression after two palliative chemotherapy sessions, the patient came to the emergency room with jaundice and abdominal pain in superior regions. On physical examination, notable findings included ecchymoses in the right flank and periumbilical region. Laboratory findings showed elevated bilirubin and transaminase levels, as well as a small increase in the serum amylase and lipase levels. Cholangioresonance was performed to discard acute biliary pancreatitis. The imaging revealed no enlargement of the pancreas, dilatation of the common bile duct without visible stone, and a liver full of new cancerous liver implants. These findings were consistent with diffuse distribution metastases lesions, concluding the progression of liver disease.
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BACKGROUND AND AIMS: Liver cancer stem cells (CSCs) could be involved in the carcinogenesis, recurrence, metastasis and chemoresistance of hepatocellular carcinoma (HCC). The aim of this study was to explore the role of lncRNA-H19 as a biomarker for liver cancer. METHODS: LncRNA-H19 expression levels and the functional assays were conducted in EpCAM+ CD133+ CSCs and C57BL/6J mice fed with a high-fat high-cholesterol carbohydrate (HFHCC) or standard diet for 52 weeks. Liver tissue and plasma samples from patients with cirrhosis, with or without HCC, were used for the analyses of gene expression and circulating lncRNA-H19 levels in an estimation and validation cohort. RESULTS: EpCAM+ CD133+ cells showed a stem cell-like phenotype, self-renewal capacity, upregulation of pluripotent gene expression and overexpressed lncRNA-H19 (p < .001). Suppression of lncRNA-H19 by antisense oligonucleotide treatment significantly reduced the self-renewal capacity (p < .001). EpCAM, CD133 and lncRNA-h19 expression increased accordingly with disease progression in HFHCC-fed mice (p < .05) and also in liver tissue from HCC patients (p = .0082). Circulating lncRNA-H19 levels were significantly increased in HCC patients in both cohorts (p = .013; p < .0001). In addition, lncRNA-H19 levels increased accordingly with BCLC staging (p < .0001) and decreased after a partial and complete therapeutic response (p < .05). In addition, patients with cirrhosis who developed HCC during follow-up showed higher lncRNA-H19 levels (p = .0025). CONCLUSION: LncRNA-H19 expression was increased in CSCs, in liver tissue and plasma of patients with HCC and decreased after partial/complete therapeutic response. Those patients who developed HCC during the follow-up showed higher levels of lncRNA-H19. LncRNA-H19 could constitute a new biomarker of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , ARN Largo no Codificante , Animales , Biomarcadores de Tumor , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Molécula de Adhesión Celular Epitelial/genética , Molécula de Adhesión Celular Epitelial/metabolismo , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/genética , Cirrosis Hepática/metabolismo , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Ratones , Ratones Endogámicos C57BL , Células Madre Neoplásicas , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
The "El Chichón" crater-lake in Mexico is a thermo-acidic environment whose microorganisms have been scarcely studied. In this study, we surveyed the prokaryotic communities by amplicon sequencing of the 16S rRNA gene considering samples of sediment and water collected within a pH/temperature gradient (pH 1.9-5.1, 38-89 °C). Further, we interpreted these results within a physicochemical context. The composition of the microbial assemblage differed significantly between the sediments and water. Sediment communities were different in the site with the highest temperature and lower pH value compared to the other ones sampled, while those in the water were relatively similar at all points. Most of the genera found were related to Alicyclobacillus, Acinetobacter, Bacillus, Mesoaciditoga, Methanothermobacter, Desulfitobacterium, Therminicanus, Kyrpidia, Paenibacillus, Thermoanaerobacterium, and Gelria. Some of these genera are known by their thermo-acidic tolerant capacities with flexible metabolisms to use diverse electron donor/acceptors (S or Fe), while others are thermo(acid)philes that mainly occur in the most extreme sites of the lake. These results show the presence of a microbial community adapted to the changing conditions of a very dynamic crater-lake, that include chemoorganotrophs and chemolithotrophs.
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Sedimentos Geológicos , Lagos , Filogenia , Fuerza Protón-Motriz , ARN Ribosómico 16S/genéticaRESUMEN
Deep-UV (180-280 nm) phosphors have attracted tremendous interest in tri-band-based white light-emitting diode (LED) technology, bio- and photochemistry, as well as various medical fields. However, the application of many UV-emitting materials has been hindered due to their poor thermal or chemical stability, complex synthesis, and environmental harmfulness. A particular concern is posed by the utilization of rare earths affected by rising price and depletion of natural resources. As a consequence, the development of phosphors without rare-earth elements represents an important challenge. In this work, as a potential UV-C phosphor, undoped ZnAl2O4 fibers have been synthesized by a cost-efficient wet chemical route. The rare-earth-free ZnAl2O4 nanofibers exhibit a strong UV emission with two bands peaking at 5.4 eV (230 nm) and 4.75 eV (261 nm). The emission intensity can be controlled by tuning the Zn/Al ratio. A structure-property relationship has been thoroughly studied to understand the origin of the UV emission. For this reason, ZnAl2O4 nanofibers have been analyzed by X-ray absorption near-edge structure (XANES), extended X-ray absorption fine structure (EXAFS), X-ray diffraction (XRD), and Raman spectroscopy techniques showing that a normal spinel structure of the synthesized material is preserved within a wide range of Zn/Al ratios. The experimental evidence of a strong and narrow band at 7.04 eV in the excitation spectrum of the 5.4 eV emission suggests its excitonic nature. Moreover, the 4.75 eV emission is shown to be related to excitons perturbed by lattice defects, presumably oxygen or cation vacancies. These findings shed light on the design of UV-C emission devices for sterilization based on a rare-earth-free phosphor, providing a feasible alternative to the conventional phosphors doped with rare-earth elements.
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Extracellular vesicles (EVs) are membrane-derived vesicles released by a variety of cell types, including hepatocytes, hepatic stellate cells, and immune cells in normal and pathological conditions. Depending on their biogenesis, there is a complex repertoire of EVs that differ in size and origin. EVs can carry lipids, proteins, coding and non-coding RNAs, and mitochondrial DNA causing alterations to the recipient cells, functioning as intercellular mediators of cell-cell communication (auto-, para-, juxta-, or even endocrine). Nevertheless, many questions remain unanswered in relation to the function of EVs under physiological and pathological conditions. The development and optimization of methods for EV isolation are crucial for characterizing their biological functions, as well as their potential as a treatment option in the clinic. In this manuscript, we will comprehensively review the results from different studies that investigated the role of hepatic EVs during liver diseases, including non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, alcoholic liver disease, fibrosis, and hepatocellular carcinoma. In general, the identification of patients with early-stage liver disease leads to better therapeutic interventions and optimal management. Although more light needs to be shed on the mechanisms of EVs, their use for early diagnosis, follow-up, and prognosis has come into the focus of research as a high-potential source of 'liquid biopsies', since they can be found in almost all biological fluids. The use of EVs as new targets or nanovectors in drug delivery systems for liver disease therapy is also summarized.
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Vesículas Extracelulares , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Vesículas Extracelulares/metabolismo , Biomarcadores/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Neoplasias Hepáticas/metabolismoRESUMEN
A common splice variant in HSD17B13 (rs72613567:TA) was recently found to be associated with a reduced risk of developing chronic liver disease in NAFLD patients and a reduced risk of progression to advanced fibrosis and cirrhosis. In this study, we aimed to evaluate the prognosis of cirrhotic patients harboring this variant. We performed a retrospective analysis on 483 prospectively recruited patients from four different hospitals in Spain, followed-up for at least 5 years. We collected clinical, demographic, and biochemical data, and we performed a genotyping analysis for common variants previously associated with liver disease risk (HSD17B13 rs72613567:TA and PNPLA3 rs738409). Patients homozygous for the TA allele showed a higher MELD score (p = 0.047), Child−Turcotte−Pugh score (p = 0.014), and INR levels (p = 0.046), as well as decreased albumin (p = 0.004) at baseline. After multivariate analysis, patients with the "protective" variant indeed had an increased risk of hepatic decompensation [aHR 2.37 (1.09−5.06); p = 0.029] and liver-related mortality [aHR 2.32 (1.20−4.46); p = 0.012]. Specifically, these patients had an increased risk of developing ascites (Log-R 11.6; p < 0.001), hepatic encephalopathy (Log-R 10.2; p < 0.01), and higher mortality (Log-R 14.1; p < 0.001) at 5 years of follow-up. Interactions with the etiology of the cirrhosis and with the variant rs738409 in PNPLA3 are also described. These findings suggest that the variant rs72613567:TA in HSD17B13 has no protective effect, but indeed increases the risk of decompensation and death in patients with advanced chronic liver disease.
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17-Hidroxiesteroide Deshidrogenasas , Enfermedad del Hígado Graso no Alcohólico , Polimorfismo de Nucleótido Simple , 17-Hidroxiesteroide Deshidrogenasas/genética , Albúminas , Humanos , Cirrosis Hepática/etiología , Cirrosis Hepática/mortalidad , Mutación con Pérdida de Función , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/mortalidad , Estudios RetrospectivosRESUMEN
This article aims to conduct a techno-economic feasibility assessment of producing energy by waste incineration and methane capture in the central region of Mexico. Three scenarios at different efficiency rates were considered: 50, 80 and 100%. For the methane project, yields and power capacity were determined using the potential generation rate and the degradable organic carbon content through the LandGEM model. For incineration, the waste calorific potential and the average moisture content were used to estimate the achievable electrical performance. The estimated annual energy was 35,018 GWh for methane, compared to 537.71 GWh for incineration. Both projects reported financial economic feasibilities when evaluated at a discount rate of 12%. Incineration reported an net present value of US$49,942,534 and an internal rate of return of 26% in contrast to US$4,054,109 and 17% for the methane project. Although the payback period for incineration was lower than for methane, its levelized cost of energy was significantly higher. These results are intended to assist the decision-making process when planning and developing waste management strategies under principles of circular economy in Mexico and similar regions worldwide.
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Incineración , Eliminación de Residuos , Incineración/métodos , Metano , Eliminación de Residuos/métodos , México , Instalaciones de Eliminación de Residuos , Carbono , Residuos Sólidos/análisisRESUMEN
Receptors are proteins coded by DNA, some of which have already been crystalized, thus allowing the details of their structure at the atomic level and some aspects of their function to be known. This review focuses on the most diverse and abundant family of receptors, G protein-coupled receptors. This family of receptors recognizes and mediates the action of several endogenous ligands (hormones, neurotransmitters, growth factors and local hormones) and also intervenes in the pathogenesis of various diseases, which is why they are targeted by approximately 30 to 40% of medications that are used in daily clinical practice and of various illegal drugs as well. X-ray crystallography is one of the essential tools that has allowed to observe the structure of these receptors in the amino acids that participate in this interaction, which allows to know the binding site of the endogenous ligand and of synthetic molecules that act on them to modulate their action. Molecular modeling or "docking" is also a computational bioinformatics tool that supports research on receptor-ligand binding, which allows the design and development of increasingly specific drugs. These developments have brought along significant changes in fundamental pharmacodynamic concepts.
Los receptores son proteínas codificadas por el ADN, algunos de los cuales ya han sido cristalizados, lo que permite conocer los detalles de su estructura a nivel atómico y algunos aspectos de su función. Esta revisión se enfoca en los más diversos y abundantes, los receptores acoplados a la proteína G. Esta familia de receptores reconoce y media la acción de varios ligandos endógenos (hormonas, neurotransmisores, factores de crecimiento y hormonas locales) y también interviene en la patogenia de diversas enfermedades, por lo que son el blanco terapéutico de aproximadamente 30 a 40 % de los medicamentos que se emplean en la práctica clínica cotidiana y de diversas drogas ilegales. La cristalografía de rayos X es una de las herramientas clave que ha permitido observar la estructura de estos receptores en los aminoácidos que participan en esta interacción, lo que posibilita conocer el sitio de unión del ligando endógeno y de moléculas sintéticas que actúan sobre ellos para modular su acción. El modelado molecular es también una herramienta bioinformática computacional que apoya la investigación sobre la unión receptor-ligando, que hace posible el diseño y desarrollo de fármacos cada vez más específicos. A estos desarrollos se suman importantes cambios en los conceptos farmacodinámicos fundamentales.
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Aminoácidos , Receptores Acoplados a Proteínas G , Hormonas , Humanos , Ligandos , Modelos MolecularesRESUMEN
INTRODUCTION: We aimed to define the impact of the genetic background on overt hepatic encephalopathy (HE) in patients with liver cirrhosis by developing a combined clinical-genetic risk score. METHODS: Patients suffering from liver cirrhosis from the outpatient clinics of 4 hospitals (n = 600) were included and followed up for at least 5 years until HE bouts, liver transplant, or death. Patients were genotyped for 60 candidate single nucleotide polymorphisms together with the microsatellite in the promoter region of the gene GLS. RESULTS: Single nucleotide polymorphisms rs601338 (FUT2), rs5743836 (TRL9), rs2562582 (SLC1A3), rs313853 (SLC1A5), and GLS microsatellite did predict independently the incidence and severity of overt HE and were included as genetic score. Competing risk analysis revealed that bilirubin (subhazard ratio [sHR] 1.30 [1.15-1.48], P < 0.001), albumin (sHR 0.90 [0.86-0.93], P < 0.001), genetic score (sHR 1.90 [1.57-2.30], P < 0.001), and previous episodes of overt HE (sHR 2.60 [1.57-4.29], P < 0.001) were independently associated to HE bouts during the follow-up with an internal (C-index 0.83) and external validation (C-index 0.74). Patients in the low-risk group had 5% and 12% risk of HE at 1 (log-rank 92.1; P < 0.001) and 5 (log-rank 124.1; P < 0.001) years, respectively, whereas 36% and 48% in the high-risk group. DISCUSSION: The genetic background influenced overt HE risk and severity. The clinical-genetic HE Risk score, which combined genetic background together with albumin, bilirubin, and previous episodes of overt HE, could be a useful tool to predict overt HE in patients with cirrhosis.
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Encefalopatía Hepática/genética , Cirrosis Hepática/complicaciones , Medición de Riesgo/métodos , Anciano , Femenino , Genotipo , Encefalopatía Hepática/epidemiología , Humanos , Incidencia , Cirrosis Hepática/etiología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , España/epidemiologíaRESUMEN
This study investigates the community composition, structure, and abundance of sulfate-reducing microorganisms (SRM) in surficial sediments of the Northwestern Gulf of Mexico (NWGoM) along a bathymetric gradient. For these purposes, Illumina sequencing and quantitative PCR (qPCR) of the dissimilatory sulfite reductase gene beta subunit (dsrB gene) were performed. Bioinformatic analyses indicated that SRM community was predominantly composed by members of Proteobacteria and Firmicutes across all the samples. However, Actinobacteria, Thermodesulfobacteria, and Chlorobi were also detected. Phylogenetic analysis indicated that unassigned dsrB sequences were related to Deltaproteobacteria and Nitrospirota superclusters, Euryarchaeota, and to environmental clusters. PCoA ordination revealed that samples clustered in three different groups. PERMANOVA indicated that water depth, temperature, redox, and nickel and cadmium content were the main environmental drivers for the SRM communities in the studied sites. Alpha diversity and abundance of SRM were lower for deeper sites, suggesting decreasing sulfate reduction activity with respect to water depth. This study contributes with the understanding of distribution and composition of dsrAB-containing microorganisms involved in sulfur transformations that may contribute to the resilience and stability of the benthic microbial communities facing metal and hydrocarbon pollution in the NWGoM, a region of recent development for oil and gas drilling.
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Bacterias , Sulfatos , Bacterias/genética , Sedimentos Geológicos , Golfo de México , Secuenciación de Nucleótidos de Alto Rendimiento , FilogeniaRESUMEN
Latent tuberculosis infection (LTBI) affects one-fourth of the world´s population. Hematopoietic stem cell transplantation (HSCT) recipients are at an elevated risk of developing active tuberculosis infection (ATBI). In this retrospective study of donors and HSCT recipients who underwent transplantation between February 2000 and June 2018, our aim was to determine the prevalence of LTBI and ATBI and to describe diagnostic and therapeutic strategies in an HSCT population in an endemic region. The cohort of 409 participants included 125 allogeneic HSCT (allo-HSCT) recipients, 165 autologous HSCT (auto-HSCT) recipients, and 119 HSCT donors. Patients were evaluated pre-HSCT with tuberculin skin test and thoracic imaging. LTBI was diagnosed in 26.2% of the cohort. Cases represented 20% of the auto-HSCT population, 20% of the allo-HSCT population, and 41.2% of the donor population. Pre-HSCT evaluation to rule out ATBI was performed in 62.6% of the cohort; all results were negative. Isoniazid was administered to 73.3% of those with LTBI. Within subgroups, 91.7% of HSCT recipients and 51% of donors received treatment. The median duration of therapy pre-HSCT was 70 days in recipients and 48 days in donors. The incidence of post-HSCT ATBI was 0 at 1-year follow-up. The incidence of LTBI in our population was higher than expected and still might have been underestimated owing to diagnostic test limitations. The absence of incident ATBI suggests that recipients, as opposed to donors, must receive LTBI treatment. Prevention of infectious complications in the HSCT population should be prioritized to improve clinical outcomes. Prospective data from collaborative working groups is needed to determine the best diagnostic and therapeutic approaches in this vulnerable patient population.
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Trasplante de Células Madre Hematopoyéticas , Tuberculosis Latente , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Tuberculosis Latente/terapia , Estudios Prospectivos , Estudios Retrospectivos , Trasplante HomólogoRESUMEN
There is increasing recognition that ecosystems and their services need to be managed at landscape scale and greater. The development of landscape-scale conservation strategies need to incorporate information from multiple sources. In this study, we combine various research tools to link landscape patterns with production units and systems in the Usumacinta River Basin, and inform the discussion of key questions around decision-making related to conservation action and policy in Southern Mexico. A typology based on policy-relevant farmer characteristics (land tenure, farm size, source of income, farming system) differentiated between farmers (traditional vs. cattle ranching) with different motivations that determine how management affects landscape configuration. Five main types of traditional farming systems were identified that combine different forms of land use and vary in their degree of land intensification. Major fragmentation and decrease in connectivity coincided spatially with floodplains dominated by large-scale commercial farms that specialize in livestock production. Traditional practices within large units with low-sloped high quality land were also seen to be intensive; however the presence of trees was notable throughout these units. Policies that promote livestock farming are among the principle causes motivating deforestation. Land intensification by traditional farmers decreased as the landscape became increasingly rugged. Traditional farmers are the focus of initiatives developed by the Biological Corridor project which seeks to increase forest cover and landscape connectivity. These initiatives have shown high levels of rural participation (10,010 farmers benefited from 27,778 projects involving 95,374â¯ha of land) and acceptance (producers carried out more than one project and several types of projects during the first eight years of work). Strong action is still required to take on the segment of large-scale ranchers. Changes in the structure of land tenure over the past decade are highlighted that could have a profound impact on conservation policies and programs.
Asunto(s)
Agricultura , Ríos , Agricultura/métodos , Animales , Bovinos , Conservación de los Recursos Naturales , Ecosistema , Agricultores , Granjas , Renta , México , ÁrbolesRESUMEN
INTRODUCTION: non-alcoholic fatty liver disease is one of the most prevalent liver disorders in the developed world. Currently, there is no approved pharmacological therapy except for lifestyle intervention. Therefore, there is a need to increase the knowledge of preclinical models in order to boost novel discoveries that could lead to a better therapeutic management. MATERIAL AND METHODS: this study characterized the effects of two different diets, a long-term high-fat high-fructose diet (HF-HFD) and a choline-deficient, methionine supplemented high-fat diet (CDA-HFD) in C57BL/6J mice for 52 weeks or 16 weeks, respectively. Body weight, lipid and hepatic profile were analyzed and liver histology was subsequently evaluated. RESULTS: HF-HFD animals had an increased body weight and total cholesterol levels, whereas the opposite occurred in CDA-HFD. Both HF-HFD and CDA-HFD animals had higher ALT and AST levels. With regard to histology findings, HF-HFD and CDA-HFD diets induced an increased collagen deposit and intrahepatic steatosis accumulation. CONCLUSION: in conclusion, the comparison of these models aided in the selection of a long-term, more physiological model for physiopathology studies or a more rapid NASH model for novel molecule testing.