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Unknown factors regulate mitochondrial U-insertion/deletion (U-indel) RNA editing in procyclic-form (PCF) and bloodstream-form (BSF) T. brucei. This editing, directed by anti-sense gRNAs, creates canonical protein-encoding mRNAs and may developmentally control respiration. Canonical editing by gRNAs that specify protein-encoding mRNA sequences occurs amid massive non-canonical editing of unclear sources and biological significance. We found PCF-specific repression at a major early checkpoint in mRNA ND7, involving helicase KREH2-dependent opposite modulation of canonical and non-canonical 'terminator' gRNA utilization. Terminator-programmed editing derails canonical editing and installs proposed repressive structure in 30% of the ND7 transcriptome. BSF-to-PCF differentiation in vitro recreated this negative control. Remarkably, KREH2-RNAi knockdown relieved repression and increased editing progression by reverting canonical/terminator gRNA utilization. ND7 transcripts lacking early terminator-directed editing in PCF exhibited similar negative editing control along the mRNA sequence, suggesting global modulation of gRNA utilization fidelity. The terminator is a 'moonlighting' gRNA also associated with mRNA COX3 canonical editing, so the gRNA transcriptome seems multifunctional. Thus, KREH2 is the first identified repressor in developmental editing control. This and our prior work support a model whereby KREH2 activates or represses editing in a stage and substrate-specific manner. KREH2's novel dual role tunes mitochondrial gene expression in either direction during development.
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Multiple organ failure (MOF) is a common and deadly condition. Patients with liver cirrhosis with acute-on-chronic liver failure (AOCLF) are particularly susceptible. Excess fluid accumulation in tissues makes routine hemodialysis generally ineffective because of cardiovascular instability. Patients with three or more organ failures face a mortality rate of more than 90%. Many cannot survive liver transplantation. Extracorporeal support systems like MARS (Baxter, Deerfield, IL) and Prometheus (Bad Homburg, Germany) have shown promise but fall short in bridging patients to transplantation. A novel Artificial Multi-organ Replacement System (AMOR) was developed at the University of Washington Medical Center. AMOR removes protein-bound toxins through a combination of albumin dialysis, a charcoal sorbent column, and a novel rinsing method to prevent sorbent column saturation. It removes excess fluid through hemodialysis. Ten AOCLF patients with over three organ failures were treated by the AMOR system. All patients showed significant clinical improvement. Fifty percent of the cohort received liver transplants or recovered liver function. AMOR was successful in removing large amounts of excess body fluid, which regular hemodialysis could not. AMOR is cost-effective and user-friendly. It removes excess fluid, supporting the other vital organs such as liver, kidneys, lungs, and heart. This pilot study's results encourage further exploration of AMOR for treating MOF patients.
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Insuficiencia Hepática Crónica Agudizada , Humanos , Insuficiencia Hepática Crónica Agudizada/terapia , Persona de Mediana Edad , Masculino , Femenino , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/terapia , Anciano , Adulto , Diálisis Renal/métodos , Diálisis Renal/instrumentaciónRESUMEN
Objective: To examine the association of left atrial (LA) function with incident chronic kidney disease (CKD) and assess the clinical utility of adding LA function to a CKD risk prediction equation. Patients and Methods: We included 4002 Atherosclerosis Risk in Communities study participants without prevalent CKD (mean ± SD age, 75±5 years; 58% female, 18% Black). Left atrial function (reservoir, conduit, and contractile strain) was evaluated by 2D-echocardiograms on 2011 to 2013. Chronic kidney disease was defined as greater than 25% decline in estimated glomerular filtration rate of less than 60 mL/min/1.73 m2, end-stage kidney disease, or hospital records. Cox proportional hazards models were used. Risk prediction and decision curve analyses evaluated 5-year CKD risk by diabetes status. Results: Median follow-up was 7.2 years, and 598 participants developed incident CKD. Incidence rate for CKD was 2.29 per 100 person-years. After multivariable adjustments, the lowest quintile of LA reservoir, conduit, and contractile strain (vs highest quintile) had a higher risk of CKD (hazard ratios [95% CIs]: 1.94 [1.42-2.64], 1.62 [1.19-2.20], and 1.49 [1.12-1.99]). Adding LA reservoir strain to the CKD risk prediction equation variables increased the C-index by 0.026 (95% CI: 0.005-0.051) and 0.031 (95% CI: 0.006-0.058) in participants without and with diabetes, respectively. Decision curve analysis found the model with LA reservoir strain had a higher net benefit than the model with CKD risk prediction equation variables alone. Conclusion: Lower LA function is independently associated with incident CKD. Adding LA function to the CKD risk prediction enhances prediction and yields a higher clinical net benefit. These findings suggest that impaired LA function may be a novel risk factor for CKD.
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AIMS: To assess the association between sociodemographic and clinical factors with body mass index (BMI) in a population at risk of type 2 diabetes (T2D) in Bogotá and Barranquilla, Colombia. METHODS: This cross-sectional study used data from the PREDICOL Study. Participants with a FINDRISC ≥ 12 who underwent an Oral Glucose Tolerance Test (OGTT) were included in the study (n=1166). The final analytical sample size was 1101 participants. Those with missing data were excluded from the analysis (n=65). The main outcome was body mass index (BMI), which was categorized as normal, overweight, and obese. We utilized unadjusted and adjusted ordinal logistic regression analysis to calculate odds ratios (OR) and 95â¯% confidence intervals (CI). RESULTS: The prevalence of overweight and obesity was 41â¯% (n=449) and 47â¯% (n=517), respectively. Participants with a 2-hour glucose ≥139â¯mg/dl had 1.71 times higher odds of being overweight or obese (regarding normal weight) than participants with normal 2-hour glucose values. In addition, being a woman, waist circumference altered, and blood pressure >120/80â¯mmHg were statistically significantly associated with a higher BMI. CONCLUSION: Strategies to control glycemia, blood pressure, and central adiposity are needed in people at risk of T2D. Future studies should be considered with a territorial and gender focus, considering behavioral, and sociocultural patterns.
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Biomarcadores , Glucemia , Índice de Masa Corporal , Diabetes Mellitus Tipo 2 , Obesidad , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangre , Colombia/epidemiología , Estudios Transversales , Femenino , Masculino , Factores de Riesgo , Persona de Mediana Edad , Prevalencia , Glucemia/metabolismo , Obesidad/epidemiología , Obesidad/diagnóstico , Adulto , Biomarcadores/sangre , Salud Urbana , Medición de Riesgo , Prueba de Tolerancia a la Glucosa , Anciano , Oportunidad Relativa , Factores Sexuales , Presión Sanguínea , Factores Sociodemográficos , Modelos Logísticos , Circunferencia de la CinturaRESUMEN
Carbapenem-resistant Acinetobacter spp. is associated with nosocomial infections in intensive care unit patients, resulting in high mortality. Although Acinetobacter spp. represent a serious public health problem worldwide, there are a few studies related to the presence of carbapenemases in health care facilities and other environmental settings in Ecuador. The main aim of this study was to characterize the carbapenem-resistant Acinetobacter spp. isolates obtained from four hospitals (52) and from five rivers (27) close to Quito. We used the disc diffusion and EDTA sinergy tests to determine the antimicrobial susceptibility and the production of metallo ß-lactamases, respectively. We carried out a multiplex PCR of gyrB gene and the sequencing of partial rpoB gene to bacterial species identification. We performed molecular screening of nine carbapenem-resistant genes (blaSPM, blaSIM, blaGIM, blaGES, blaOXA-23, blaOXA-24, blaOXA-51, blaOXA-58, and blaOXA-143) by multiplex PCR, followed by identification using sequencing of blaOXA genes. Our findings showed that carbapenem-resistant A. baumannii were the main species found in health care facilities and rivers. Most of the clinical isolates came from respiratory tract samples and harbored blaOXA-23, blaOXA-366, blaOXA-72, blaOXA-65, blaOXA-70, and blaOXA-143-like genes. The river isolates harbored only the blaOXA-51 and probably blaOXA-259 genes. We concluded that the most predominant type of carbapenem genes among isolates were both blaOXA-23 and blaOXA-65 among A. baumannii clinical isolates.
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Infecciones por Acinetobacter , Acinetobacter , Proteínas Bacterianas , beta-Lactamasas , Ecuador/epidemiología , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Humanos , Infecciones por Acinetobacter/microbiología , Infecciones por Acinetobacter/tratamiento farmacológico , Acinetobacter/genética , Acinetobacter/aislamiento & purificación , Acinetobacter/efectos de los fármacos , Acinetobacter/enzimología , Pruebas de Sensibilidad Microbiana , Infección Hospitalaria/microbiología , Antibacterianos/farmacología , Carbapenémicos/farmacología , Ríos/microbiología , Acinetobacter baumannii/genética , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/aislamiento & purificación , Acinetobacter baumannii/enzimología , Reacción en Cadena de la Polimerasa MultiplexRESUMEN
Phthalates may be associated with an increased risk of cardiometabolic diseases by interfering with glucose and lipid metabolism and by promoting adipogenesis. This study aimed to perform a systematic review and meta-analysis of the association between phthalate exposure and subclinical carotid atherosclerosis, using surrogate markers such as carotid intima-media thickness (IMT) and carotid plaques. The literature search was performed using four databases (Web of Science, Medline, PubMed, and Scopus), and this systematic review includes all available observational studies until July 6th, 2023. The Joanna Briggs Institute critical appraisal tool was used to assess the risk of bias. Meta-analyses were performed, and random effects models were used. Six high-quality cross-sectional studies and 2570 participants aged 12 to 70 were included. Six phthalate metabolites showed significant associations with subclinical carotid atherosclerosis. Exposure to MBzP, ΣDEHP, and MnBP was associated with increased carotid IMT. Exposure to MEP was associated with a higher prevalence of carotid plaques, and MiBP was associated with a lower prevalence. Mixed results were observed for MMP in older adults. The meta-analyses showed a high degree of heterogeneity, and the results are based on single studies. This study accurately describes the evidence of this association to date, suggesting that phthalates are associated with increased carotid IMT and a higher prevalence of carotid plaques. Further research is needed to elucidate this association, as phthalates are still used in the manufacture of everyday products, humans continue to be exposed to them, and atherosclerosis is a public health concern.
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Enfermedades de las Arterias Carótidas , Grosor Intima-Media Carotídeo , Exposición a Riesgos Ambientales , Ácidos Ftálicos , Humanos , Enfermedades de las Arterias Carótidas/inducido químicamente , Exposición a Riesgos Ambientales/estadística & datos numéricos , Contaminantes Ambientales , Adulto , Anciano , Persona de Mediana Edad , Niño , Adolescente , Adulto Joven , Estudios TransversalesAsunto(s)
Prótesis Valvulares Cardíacas , Indoles , Válvula Mitral , Trombosis , Anciano , Femenino , Humanos , Antineoplásicos/efectos adversos , Ecocardiografía Transesofágica/métodos , Prótesis Valvulares Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Indoles/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Trombosis/diagnóstico por imagen , Trombosis/etiologíaRESUMEN
Systemic lupus erythematosus (SLE) is a multisystem disease considered a prototype of the main autoimmune disease and presents serious complications, such as lupus nephritis (LN), which generates a significant impact on morbidity and mortality. The SPP1 gene encodes the osteopontin (OPN) protein, which plays a crucial role in the regulation of inflammation and immunity. The variants rs1126616 and rs9138 of this gene have been associated with the inflammatory response. The study aims to analyze the association of the rs1126616 and rs9138 variants of the SPP1 gene in SLE Mexican-Mestizo patients without LN (SLE-LN). In this cross-sectional study, a total of 171 genomic DNA samples from SLE patients were clinically confirmed, of which 111 were SLE without LN, 60 were SLE with LN, and 100 healthy individuals were included as reference group. The rs1126616 variant was genotyped using PCR-RFLPs, and the rs9138 variant was genotyped using qPCR TaqMan. The TT genotype, the recessive model [OR 2.76 (95% CI 1.31-5.82), p = 0.011], and the T allele [OR 2.0 (95% CI 1.26-3.16), p = 0.003] of the rs1126616 variant are risk factors for SLE with LN. By contrast, the rs9138 variant did not show statistically significant differences among SLE patients stratified by LN. In our study of SLE Mexican-Mestizo patients with and without NL, demographic and clinical characteristics do not differ from other SLE populations, and the TT genotype of the rs1126616 variant of the SPP1 gene confers a risk factor for the presentation of LN. Otherwise, the rs9138 variant did not show association with NL.
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Lupus Eritematoso Sistémico , Nefritis Lúpica , Humanos , Nefritis Lúpica/genética , Estudios Transversales , Lupus Eritematoso Sistémico/genética , Alelos , Genotipo , OsteopontinaRESUMEN
The Area Deprivation Index is a granular measure of neighborhood socioeconomic deprivation. The relationship between neighborhood socioeconomic deprivation and recipient survival following liver transplantation (LT) is unclear. To investigate this, the authors performed a retrospective cohort study of adults who underwent LT at the University of Washington Medical Center from January 1, 2004, to December 31, 2020. The primary exposure was a degree of neighborhood socioeconomic deprivation as determined by the Area Deprivation Index score. The primary outcome was posttransplant recipient mortality. In a multivariable Cox proportional analysis, LT recipients from high-deprivation areas had a higher risk of mortality than those from low-deprivation areas (HR: 1.81; 95% CI: 1.03-3.18, p =0.04). Notably, the difference in mortality between area deprivation groups did not become statistically significant until 6 years after transplantation. In summary, LT recipients experiencing high socioeconomic deprivation tended to have worse posttransplant survival. Further research is needed to elucidate the extent to which neighborhood socioeconomic deprivation contributes to mortality risk and identify effective measures to improve survival in more socioeconomically disadvantaged LT recipients.
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Trasplante de Hígado , Características de la Residencia , Factores Socioeconómicos , Humanos , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/estadística & datos numéricos , Trasplante de Hígado/mortalidad , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Características de la Residencia/estadística & datos numéricos , Adulto , Enfermedad Hepática en Estado Terminal/cirugía , Enfermedad Hepática en Estado Terminal/mortalidad , Enfermedad Hepática en Estado Terminal/diagnóstico , Factores de Riesgo , Modelos de Riesgos Proporcionales , Anciano , Washingtón/epidemiologíaRESUMEN
Artificial intelligence (AI) is a technology that is evolving rapidly and is changing the world and medicine as we know it. After reviewing the PROSPERO database of systematic reviews, there is no article related to this topic in facial plastic and reconstructive surgery. The objective of this article was to review the literature regarding AI applications in facial plastic and reconstructive surgery.A systematic review of the literature about AI in facial plastic and reconstructive surgery using the following keywords: Artificial Intelligence, robotics, plastic surgery procedures, and surgery plastic and the following databases: PubMed, SCOPUS, Embase, BVS, and LILACS. The inclusion criteria were articles about AI in facial plastic and reconstructive surgery. Articles written in a language other than English and Spanish were excluded. In total, 17 articles about AI in facial plastic met the inclusion criteria; after eliminating the duplicated papers and applying the exclusion criteria, these articles were reviewed thoroughly. The leading type of AI used in these articles was computer vision, explicitly using models of convolutional neural networks to objectively compare the preoperative with the postoperative state in multiple interventions such as facial lifting and facial transgender surgery.In conclusion, AI is a rapidly evolving technology, and it could significantly impact the treatment of patients in facial plastic and reconstructive surgery. Legislation and regulations are developing slower than this technology. It is imperative to learn about this topic as soon as possible and that all stakeholders proactively promote discussions about ethical and regulatory dilemmas.
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Nitric oxide (NO) is an essential reactive oxygen species and a signal molecule in plants. Although several studies have proposed the occurrence of oxidative NO production, only reductive routes for NO production, such as the nitrate (NO-3) -upper-reductase pathway, have been evidenced to date in land plants. However, plants grown axenically with ammonium as the sole source of nitrogen exhibit contents of nitrite and NO3-, evidencing the existence of a metabolic pathway for oxidative production of NO. We hypothesized that oximes, such as indole-3-acetaldoxime (IAOx), a precursor to indole-3-acetic acid, are intermediate oxidation products in NO synthesis. We detected the production of NO from IAOx and other oximes catalyzed by peroxidase (POD) enzyme using both 4-amino-5-methylamino-2',7'-difluorescein fluorescence and chemiluminescence. Flavins stimulated the reaction, while superoxide dismutase inhibited it. Interestingly, mouse NO synthase can also use IAOx to produce NO at a lower rate than POD. We provided a full mechanism for POD-dependent NO production from IAOx consistent with the experimental data and supported by density functional theory calculations. We showed that the addition of IAOx to extracts from Medicago truncatula increased the in vitro production of NO, while in vivo supplementation of IAOx and other oximes increased the number of lateral roots, as shown for NO donors, and a more than 10-fold increase in IAOx dehydratase expression. Furthermore, we found that in vivo supplementation of IAOx increased NO production in Arabidopsis thaliana wild-type plants, while prx33-34 mutant plants, defective in POD33-34, had reduced production. Our data show that the release of NO by IAOx, as well as its auxinic effect, explain the superroot phenotype. Collectively, our study reveals that plants produce NO utilizing diverse molecules such as oximes, POD, and flavins, which are widely distributed in the plant kingdom, thus introducing a long-awaited oxidative pathway to NO production in plants. This knowledge has essential implications for understanding signaling in biological systems.
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Arabidopsis , Óxido Nítrico , Animales , Ratones , Óxido Nítrico/metabolismo , Arabidopsis/metabolismo , Oximas/farmacología , Oximas/metabolismo , Flavinas/metabolismo , Estrés OxidativoRESUMEN
It has been shown that while feature selection algorithms are able to distinguish between relevant and irrelevant features, they fail to differentiate between relevant and redundant and correlated features. To address this issue, we propose a highly effective approach, called Nested Ensemble Selection (NES), that is based on a combination of filter and wrapper methods. The proposed feature selection algorithm differs from the existing filter-wrapper hybrid methods in its simplicity and efficiency as well as precision. The new algorithm is able to separate the relevant variables from the irrelevant as well as the redundant and correlated features. Furthermore, we provide a robust heuristic for identifying the optimal number of selected features which remains one of the greatest challenges in feature selection. Numerical experiments on synthetic and real-life data demonstrate the effectiveness of the proposed method. The NES algorithm achieves perfect precision on the synthetic data and near optimal accuracy on the real-life data. The proposed method is compared against several popular algorithms including mRMR, Boruta, genetic, recursive feature elimination, Lasso, and Elastic Net. The results show that NES significantly outperforms the benchmarks algorithms especially on multi-class datasets.
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Hemodialysis deteriorates patients' physical, metabolic, and mental status. Clinical outcomes derived from inflammation determine a worse status but are less frequently identified. The objective of the study was to identify inflammatory determinants and the effect of SNP-related serum IL-6 and IL-10 levels on associated morbidity in hemodialysis. A sample of hemodialysis patients at IMSS Regional Hospital No.46 in Guadalajara (n = 85) were tested using the Malnutrition Inflammation Score (MIS) and Patient Health Questionnaire-9 (PHQ-9) to assess the associated morbidity. Serum cytokine levels were quantified by enzyme-linked immunosorbent assay (ELISA). The restriction fragment length polymorphism (RFLP) technique was used for analysis of IL-6-572C/G and IL-10-1082A/G. Using data visualization methods, we identified relevant determinants of inflammation. A simple regression model was constructed between predictors and targets with genotypes as covariates. Results showed malnutrition in 85.9% of patients and depressive symptoms in 50.6%. IL-10 was the most relevant inflammatory determinant, with regression coefficients (R2) between 0.05 and 0.11. The GG genotype of IL-10-1082 A/G evinced small effect on both clinical outcomes (δ of 0.35 and 0.37, respectively). Hemodialysis increases the associated morbidity, cytokines act as inflammatory determinants, and genetic variability contributes to the severity of clinical outcomes. Further studies need to refine the causal relationship between inflammation and CKD.
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Purpose: The purpose of this study was to highlight the clinical and molecular features of 13 Raoultella ornithinolytica strains isolated from clinical environments in Ecuador, and to perform comparative genomics with previously published genomes of Raoultella spp. As Raoultella is primarily found in environmental, clinical settings, we focused our work on identifying mechanisms of resistance that can provide this bacterium an advantage to establish and persist in hospital environments. Methods: We analyzed 13 strains of Raoultella ornithinolytica isolated from patients with healthcare associated infections (HAI) in three hospitals in Quito and one in Santo Domingo de Los Tsáchilas, Ecuador, between November 2017 and April 2018. These isolates were subjected to phenotypic antimicrobial susceptibility testing, end-point polymerase chain reaction (PCR) to detect the presence of carbapenemases and whole-genome sequencing. Results: Polymerase chain reaction revealed that seven isolates were positive isolates for blaOXA-48 and one for blaKPC-2 gene. Of the seven strains that presented the blaOXA-48 gene, six harbored it on an IncFII plasmid, one was inserted into the bacterial chromosome. The blaKPC gene was detected in an IncM2/IncR plasmid. From the bioinformatics analysis, nine genomes had the gene blaOXA-48, originating from Ecuador. Moreover, all R. ornithinolytica strains contained the ORN-1 gene, which confers resistance for ß-lactams, such as penicillins and cephalosporins. Comparative genome analysis of the strains showed that the pangenome of R. ornithinolytica is considered an open pangenome, with 27.77% of core genes, which could be explained by the fact that the antibiotic resistance genes in the ancestral reconstruction are relatively new, suggesting that this genome is constantly incorporating new genes. Conclusion: These results reveal the genome plasticity of R. ornithinolytica, particularly in acquiring antibiotic-resistance genes. The genomic surveillance and infectious control of these uncommon species are important since they may contribute to the burden of antimicrobial resistance and human health.
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Background: Unlike other solid organs, no standardized treatment algorithms exist for intestinal transplantation (ITx). We established a consortium of American ITx centers to evaluate current practices. Methods: All American centers performing ITx during the past 3 y were invited to participate. As a consortium, we generated questions to evaluate and collect data from each institution. The data were compiled and analyzed. Results: Ten centers participated, performing 211 ITx during the past 3 y (range, 3-46; mean 21.1). Induction regimens varied widely. Thymoglobulin was the most common, used in the plurality of patients (85/211; 40.3%), but there was no consensus regimen. Similarly, regimens for the treatment of acute cellular rejection, antibody-mediated rejection, and graft-versus-host disease varied significantly between centers. We also evaluated differences in maintenance immunosuppression protocols, desensitization regimens, mammalian target of rapamycin use, antimetabolite use, and posttransplantation surveillance practices. Maintenance tacrolimus levels, stoma presence, and scoping frequency were not associated with differences in rejection events. Definitive association between treatments and outcomes, including graft and patient survival, was not the intention of this initial collaboration and is prevented by the lack of patient-level data and the presence of confounders. However, we identified trends regarding rejection episodes after various induction strategies that require further investigation in our subsequent collaborations. Conclusions: This initial collaboration reveals the extreme heterogeneity of practices among American ITx centers. Future collaboration will explore patient-level data, stratified by age and transplant type (isolated intestine versus multivisceral), to explore the association between treatment regimens and outcomes.
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Introduction: The hepatitis C virus (HCV) is responsible for 1.5 million new infections, and around 290 thousand deaths worldwide. 15 to 30% of the patients that go into a chronic phase of the disease will develop cirrhosis or hepatocellular carcinoma within 20 years and is the leading etiology for liver transplantation. HCV genetic characteristics display a remarkable genetic diversity, which divides HCV into 8 genotypes and 67 subgenotypes; the treatment and probability of chronic HCV depend on these genotypes and subgenotypes. In Ecuador, there is no available information regarding HCV genotypes and subgenotypes; therefore, this study aims to provide an overview of the main genotypes circulating in Ecuador. Methods: In a cross-sectional and descriptive study using the Ecuadorian Ministry of Health (MSP) registry of patients already diagnosed with Hepatitis C (HCV) between 2017 and 2019. From 51 patients identified by health ministry, blood samples from a total of 15 subjects (named HCV1 to HCV15) were collected using an appropriate venipuncture technique. Pandemic-related circumstances avoid reaching all patients identified by health ministry. Results: After the amplification of 11 samples from patients living in the Ecuadorian territory, the genotypes of HCV obtained were distributed as follows: 6 samples corresponding to subgenotype 2b (54.5%), 2 samples corresponding to subgenotype 1a (18.2%), 2 samples corresponding to subgenotype 4d (18.2%) and 1 corresponding to sample 1b (9.1%). Conclusion: These results represent the first epidemiological approach to genotype distribution in Ecuador, and it contributes to better management of patients. We emphasize the importance of the development of better strategies from the Healthcare Ministry of Ecuador (MSP) for the identification, treatment and tracking of HCV patients.
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Objective: There is an unmet need for optimizing hepatic allograft allocation from nondirected living liver donors (ND-LLD). Materials and method: Using OPTN living donor liver transplant (LDLT) data (1/1/2000-12/31/2019), we identified 6328 LDLTs (4621 right, 644 left, 1063 left-lateral grafts). Random forest survival models were constructed to predict 10-year graft survival for each of the 3 graft types. Results: Donor-to-recipient body surface area ratio was an important predictor in all 3 models. Other predictors in all 3 models were: malignant diagnosis, medical location at LDLT (inpatient/ICU), and moderate ascites. Biliary atresia was important in left and left-lateral graft models. Re-transplant was important in right graft models. C-index for 10-year graft survival predictions for the 3 models were: 0.70 (left-lateral); 0.63 (left); 0.61 (right). Similar C-indices were found for 1-, 3-, and 5-year graft survivals. Comparison of model predictions to actual 10-year graft survivals demonstrated that the predicted upper quartile survival group in each model had significantly better actual 10-year graft survival compared to the lower quartiles (p<0.005). Conclusion: When applied in clinical context, our models assist with the identification and stratification of potential recipients for hepatic grafts from ND-LLD based on predicted graft survivals, while accounting for complex donor-recipient interactions. These analyses highlight the unmet need for granular data collection and machine learning modeling to identify potential recipients who have the best predicted transplant outcomes with ND-LLD grafts.
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Fallo Hepático , Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Donadores Vivos , Estudios RetrospectivosRESUMEN
Background: Carbapenem-resistant Klebsiella pneumoniae, particularly isolates classified as sequence-type 258 (ST258), are multidrug-resistant strains that are strongly associated with poor-prognosis nosocomial infections, as current therapeutic options are limited and ineffective. In recent years, phage therapy has emerged as a promising treatment option for these scenarios. Methodology and Results: We report the isolation and characterization of three new phages against Klebsiella pneumoniae ST258 strains recovered from Machángara river wastewater. These new members of the Ackermannviridae family showed stability over a wide temperature and pH range and burst sizes ranging from 6 to 44 plaque-forming units per bacteria. Their genomes were about 157 kilobases, with an average guanine-cytosine content of 46.4% and showed presence of several transfer RNAs, which also allowed us to predict in silico a lytic replicative cycle due to the presence of endolysins and lysozymes. Conclusion: Three lytic phages of Ackermannviridae family were recovered against Klebsiella pneumoniae ST258 strains from sewage; however, further characterization is needed for future consideration as therapeutic alternatives.
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U-insertion/deletion (U-indel) RNA editing in trypanosome mitochondria is directed by guide RNAs (gRNAs). This editing may developmentally control respiration in bloodstream forms (BSF) and insect procyclic forms (PCF). Holo-editosomes include the accessory RNA Editing Substrate Binding Complex (RESC) and RNA Editing Helicase 2 Complex (REH2C), but the specific proteins controlling differential editing remain unknown. Also, RNA editing appears highly error prone because most U-indels do not match the canonical pattern. However, despite extensive non-canonical editing of unknown functions, accurate canonical editing is required for normal cell growth. In PCF, REH2C controls editing fidelity in RESC-bound mRNAs. Here, we report that KREH2, a REH2C-associated helicase, developmentally controls programmed non-canonical editing, including an abundant 3' element in ATPase subunit 6 (A6) mRNA. The 3' element sequence is directed by a proposed novel regulatory gRNA. In PCF, KREH2 RNAi-knockdown up-regulates the 3' element, which establishes a stable structure hindering element removal by canonical initiator-gRNA-directed editing. In BSF, KREH2-knockdown does not up-regulate the 3' element but reduces its high abundance. Thus, KREH2 differentially controls extensive non-canonical editing and associated RNA structure via a novel regulatory gRNA, potentially hijacking factors as a 'molecular sponge'. Furthermore, this gRNA is bifunctional, serving in canonical CR4 mRNA editing whilst installing a structural element in A6 mRNA.
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Trypanosoma brucei brucei , Trypanosoma , ARN Mensajero/metabolismo , ARN Helicasas/genética , ARN Helicasas/metabolismo , Trypanosoma brucei brucei/genética , Trypanosoma brucei brucei/metabolismo , Trypanosoma/genética , ARN/genética , ARN Protozoario/genética , ARN Protozoario/metabolismoRESUMEN
PURPOSE OF REVIEW: Type 2 diabetes mellitus (T2DM) is one of the leading causes of death and disability in the world. The majority of diabetes deaths (> 80%) occur in low- and middle-income countries, which are predominant in Latin America. Therefore, the purpose of this article is to compare the clinical practice guideline (CPG) for the pharmacological management of T2DM in Latin America (LA) with international reference guidelines. RECENT FINDINGS: Several LA countries have recently developed CPGs. However, the quality of these guidelines is unknown according to the AGREE II tool and taking as reference three CPGs of international impact: American Diabetes Association (ADA), European Diabetes Association (EASD), and Latin American Diabetes Association (ALAD). Ten CPGs were selected for analysis. The ADA scored > 80% on the AGREE II domains and was selected as the main comparator. Eighty percent of LA CPGs were developed before 2018. Only one was not recommended (all domains < 60%). The CPGs in LA have good quality but are outdated. They have significant gaps compared to the reference. There is a need for improvement, as proposing updates every three years to maintain the best available clinical evidence in all guidelines.