Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria.

Linear nitramines (R-N(R')NO2; R' = H or alkyl) are toxic compounds, some with environmental relevance, while others are rare natural product nitramines. One of these natural product nitramines is N-nitroglycine (NNG), which is produced by some Streptomyces strains and exhibits antibiotic activity towards Gram-negative bacteria. An NNG degrading heme enzyme, called NnlA, has recently been discovered in the genome of Variovorax sp. strain JS1663 (Vs NnlA). Evidence is presented that NnlA and therefore, NNG degradation activity is widespread. To achieve this objective, we characterized and tested the NNG degradation activity of five Vs NnlA homologs originating from bacteria spanning several classes and isolated from geographically distinct locations. E. coli transformants containing all five homologs converted NNG to nitrite. Four of these five homologs were isolated and characterized. Each isolated homolog exhibited similar oligomerization and heme occupancy as Vs NnlA. Reduction of this heme was shown to be required for NnlA activity in each homolog, and each homolog degraded NNG to glyoxylate, NO2- and NH4+ in accordance with observations of Vs NnlA. It was also shown that NnlA cannot degrade the NNG analog 2-nitroaminoethanol. The combined data strongly suggest that NnlA enzymes specifically degrade NNG and are found in diverse bacteria and environments. These results imply that NNG is also produced in diverse environments and NnlA may act as a detoxification enzyme to protect bacteria from exposure to NNG.

Infection due to Aspergillus flavus and Rhizopus oryzae complex in a patient with diabetes mellitus / Infección por Aspergillus flavus y Rhizopus oryzae complex en paciente con diabetes mellitus

Fungal sinusitis is a pathology that can occur in patients with diabetes mellitus and be associated with a hyperglycemic crisis. It is an aggressive entity with local complications that include involvement of the orbit or the central nervous system, and vascular involvement. Despite surgical and antifungal treatment, mortality raises up to 75%. We report the case of a female patient with a diagnosis of diabetic ketoacidosis and signs of unilateral ophthalmoplegia, which led to the study with magnetic resonance imaging of the central nervous system, finding signs of sinusitis, meningitis, and cerebritis. Initial microbiological studies were negative, and biomarkers such as serum galactomannan and Cryptococcus antigen were also negative. After surgical management and the identification of Aspergillus flavus and Rhizopus spp. in sinus tissue, the patient received treatment with posaconazole and after two months of follow-up she presented clinical improvement. Dual fungal infection and infection by A. flavus are uncommon and clinically relevant entities, with no cases previously reported in our country, therefore this corresponds to a case of clinical interest.

La sinusitis micótica es una condición patológica que puede presentarse en pacientes con diabetes mellitus y estar asociada a una crisis hiperglucémica. Es una entidad agresiva con complicaciones locales que incluyen afectación de la órbita y el sistema nervioso central, y compromiso vascular. A pesar del tratamiento quirúrgico y antimicótico, la mortalidad es de hasta el 75 %. Se describe el caso de una paciente con diagnóstico de cetoacidosis diabética y signos de oftalmoplejía unilateral que llevaron al estudio con resonancia magnética del sistema nervioso central; se encontraron signos de sinusitis, meningitis y cerebritis. Los estudios microbiológicos iniciales fueron negativos, y los biomarcadores galactomanano sérico y el antígeno de Cryptococcus también fueron negativos. Tras el manejo quirúrgico, se llegó a la identificación de Aspergillus flavus y Rhizopus spp. en el tejido de los senos paranasales. La paciente recibió tratamiento con posaconazol y, tras dos meses de seguimiento, había presentado mejoría clínica. La infección fúngica dual y la infección por A. flavus son entidades poco frecuentes y de relevancia clínica, sin casos presentados previamente en nuestro país por lo que este corresponde a un caso de interés clínico.

Infección por Aspergillus flavus y Rhizopus oryzae complex en paciente con diabetes mellitus / Infection due to Aspergillus flavus and Rhizopus oryzae complex in a patient with diabetes mellitus

La sinusitis micótica es una condición patológica que puede presentarse en pacientes con diabetes mellitus y estar asociada a una crisis hiperglucémica. Es una entidad agresiva con complicaciones locales que incluyen afectación de la órbita y el sistema nervioso central, y compromiso vascular. A pesar del tratamiento quirúrgico y antimicótico, la mortalidad es de hasta el 75 %. Se describe el caso de una paciente con diagnóstico de cetoacidosis diabética y signos de oftalmoplejía unilateral que llevaron al estudio con resonancia magnética del sistema nervioso central; se encontraron signos de sinusitis, meningitis y cerebritis. Los estudios microbiológicos iniciales fueron negativos, y los biomarcadores galactomanano sérico y el antígeno de Cryptococcus también fueron negativos. Tras el manejo quirúrgico, se llegó a la identificación de Aspergillus flavus y Rhizopus spp. en el tejido de los senos paranasales. La paciente recibió tratamiento con posaconazol y, tras dos meses de seguimiento, había presentado mejoría clínica. La infección fúngica dual y la infección por A. flavus son entidades poco frecuentes y de relevancia clínica, sin casos presentados previamente en nuestro país por lo que este corresponde a un caso de interés clínico.

Fungal sinusitis is a pathology that can occur in patients with diabetes mellitus and be associated with a hyperglycemic crisis. It is an aggressive entity with local complications that include involvement of the orbit or the central nervous system, and vascular involvement. Despite surgical and antifungal treatment, mortality raises up to 75%. We report the case of a female patient with a diagnosis of diabetic ketoacidosis and signs of unilateral ophthalmoplegia, which led to the study with magnetic resonance imaging of the central nervous system, finding signs of sinusitis, meningitis, and cerebritis. Initial microbiological studies were negative, and biomarkers such as serum galactomannan and Cryptococcus antigen were also negative. After surgical management and the identification of Aspergillus flavus and Rhizopus spp. in sinus tissue, the patient received treatment with posaconazole and after two months of follow-up she presented clinical improvement. Dual fungal infection and infection by A. flavus are uncommon and clinically relevant entities, with no cases previously reported in our country, therefore this corresponds to a case of clinical interest.

Highly Educated Black Americans Report Higher than Expected Perceived Job Demands.

Background: Educational attainment has well established and widely recognized the effects on employment conditions and job demands. However, the way in which educational attainment correlates with perceived job demands may be inconsistent across racial groups as suggested by Minorities' Diminished Returns (MDRs). The aim was to test the moderating effect of race on the association between educational attainment and perceived job demands, particularly for Black and White individuals. Methods: This study was a cross-sectional analysis of MIDUS Refresher 1, including 1,232 Black and White adults over the age of 25 in the United States. Education attainment was the independent variable and perceived job demands was the dependent variable covariates. Linear regression was used for multivariate models. Results-: We observed positive association between education and perceived job demands, however, statistical interaction between race and education suggested stronger positive associations for Black than White individuals. Conclusion: Being a highly educated Black professional in the United States equals high demand such increase stress is a risk factor of being a middle class black American. Innovated and bold market policies are required to solve this unfair dilemma.

The Rise and Fall of the HyFlex Approach in Mexico.

During the Covid-19 pandemic, the world turned to online tools as a means of ensuring continued access to education, highlighting possibilities for innovation, particularly in contexts like Mexico, where the use of edtech was not previously prevalent. When educational institutions reopened their physical campuses, many schools and universities considered a hybrid, flexible (HyFlex) approach as a way of catering for different needs. While research findings on students' perspectives tend to be positive, the implementation of HyFlex courses has shown some challenges. Issues reported by teachers relate to poor technical infrastructure, work overload and lack of guidance. The initial excitement for the HyFlex approach has subdued. However, an openness to innovation is still there, ready to be exploited.

Development of functional hybrid scaffolds for wound healing applications.

Hybrid hydrogels composed of chitosan (CS) and hyaluronic acid (HA) and collagen (Coll) were prepared by polyelectrolyte complex self-assembly. These scaffolds displayed a good intermingling of the polymeric chains, with porosities above 80% and good interconnected structures with pore sizes lying between 30-115 µm. The ionic interactions between CS and HA make the scaffolds have larger storage modulus and longer LVR regions than their pure counterparts. Both quantities progressively decrease as the HA and Coll concentrations in the formulation rise. These hybrid hydrogels showed good swelling extents from ca. 420 to ca. 690% and suitable resistance to enzymatic degradation, which was slightly lower for scaffolds containing CS to larger extents or Coll in the formulation. All scaffolds were largely cytocompatible and allowed the proliferation of both mouse fibroblast and human keratinocytes with their infiltration inside, thus becoming optimal matrices for intended tissue engineering applications as well as transdermal drug delivery depots.

The utility of the Edmonton Obesity Staging System for the prediction of COVID-19 outcomes: a multi-centre study.

BACKGROUND: Patients with obesity have an increased risk for adverse COVID-19 outcomes. Body mass index (BMI) does not acknowledge the health burden associated this disease. The performance of the Edmonton Obesity Staging System (EOSS), a clinical classification tool that assesses obesity-related comorbidity, is compared with BMI, with respect to adverse COVID-19 outcomes. METHODS: 1071 patients were evaluated in 11 COVID-19 hospitals in Mexico. Patients were classified into EOSS stages. Adjusted risk factors for COVID-19 outcomes were calculated and survival analysis for mechanical ventilation and death was carried out according to EOSS stage and BMI category. RESULTS: The risk for intubation was higher in patients with EOSS stages 2 and 4 (HR 1.42, 95% CI 1.02-1.97 and 2.78, 95% CI 1.83-4.24), and in patients with BMI classes II and III (HR 1.71, 95% CI 1.06-2.74, and 2.62, 95% CI 1.65-4.17). Mortality rates were significantly lower in patients with EOSS stages 0 and 1 (HR 0.62, 95% CI 0.42-0.92) and higher in patients with BMI class III (HR 1.58, 95% CI 1.03-2.42). In patients with a BMI ≥ 25 kg/m2, the risk for intubation increased with progressive EOSS stages. Only individuals in BMI class III showed an increased risk for intubation (HR 2.24, 95% CI 1.50-3.34). Mortality risk was increased in EOSS stages 2 and 4 compared to EOSS 0 and 1, and in patients with BMI class II and III, compared to patients with overweight. CONCLUSIONS: EOSS was associated with adverse COVID-19 outcomes, and it distinguished risks beyond BMI. Patients with overweight and obesity in EOSS stages 0 and 1 had a lower risk than patients with normal weight. BMI does not adequately reflect adipose tissue-associated disease, it is not ideal for guiding chronic-disease management.

Prevalence of protective haplotypes of the SLCO1B1 gene for statin transport in Mexican populations.

Aim: To evaluate the genetic distribution of the rs4149056 and rs2306283 variants in the SLCO1B1 gene in Mexican Mestizo (admixed) and Native American groups. Materials & methods: We recruited 360 volunteers who were qPCR-genotyped with TaqMan probes. Results: Allele and genotype frequencies are reported. Among the expected rs4149056-rs2306283 haplotypes, T-A (42.35-58.47%) was the most prevalent which relates to the normal activity of the OATP1B1 transporter. This was followed by the T-G haplotype associated with further statin transport and cholesterol reduction (32.49-43.76%). Conclusion: Based on these SLCO1B1 gene variants, we confirmed that a minimum fraction of the Mexican study populations would be at risk from decreasing simvastatin transport and the development of statin-induced myopathy.

Lay abstract The clinical response to statins, mainly atorvastatin and simvastatin, can be modified by interindividual variability including variations in the SLCO1B1 gene. This gene, that encodes the statin transporter OATP1B1, helps to regulate the cholesterol levels in the blood and is responsible for the presence of adverse drug reactions related to the statin consumption, such as muscular sickness. This study analyzes the distribution of the SLCO1B1 gene variants rs4149056 and rs2306283 in geographically dispersed samples of the two main populations in Mexico: two Mestizo (admixed) populations and three Native American groups. We found that the genetic combinations of T­A and T­G for the two SLCO1B1 gene variants ­ associated with normal or efficient activity of the transporter OATP1B ­ were predominant in all of the study population. Therefore, the SLCO1B1 gene variability suggests that a majority of the Mexican population will respond favorably to simvastatin and have a low risk of developing associated muscular complications.

Urocortin-3 neurons in the mouse perifornical area promote infant-directed neglect and aggression.

While recent studies have uncovered dedicated neural pathways mediating the positive control of parenting, the regulation of infant-directed aggression and how it relates to adult-adult aggression is poorly understood. Here we show that urocortin-3 (Ucn3)-expressing neurons in the hypothalamic perifornical area (PeFAUcn3) are activated during infant-directed attacks in males and females, but not other behaviors. Functional manipulations of PeFAUcn3 neurons demonstrate the role of this population in the negative control of parenting in both sexes. PeFAUcn3 neurons receive input from areas associated with vomeronasal sensing, stress, and parenting, and send projections to hypothalamic and limbic areas. Optogenetic activation of PeFAUcn3 axon terminals in these regions triggers various aspects of infant-directed agonistic responses, such as neglect, repulsion, and aggression. Thus, PeFAUcn3 neurons emerge as a dedicated circuit component controlling infant-directed neglect and aggression, providing a new framework to understand the positive and negative regulation of parenting in health and disease.

Pseudomicroangiopatía trombótica por deficiencia de vitamina B12 en un lactante / Pseudo-thrombotic microangiopathy due to vitamin B12 deficiency in an infant

La seudomicroangiopatía trombótica o síndrome de Moschcowitz es una manifestación infrecuente del déficit de vitamina B12. Se caracteriza por anemia hemolítica con características microangiopáticas, reticulocitos e índices hematimétricos normales o con ligera megaloblastosis, asociados a manifestaciones neurológicas. La vitamina B12 está presente en alimentos proteicos de origen animal. La lactancia materna es una fuente adecuada para los niños cuando los niveles maternos son normales. Se presenta a una paciente de 16 meses que se internó por anemia hemolítica con requerimiento transfusional, plaquetopenia, mal progreso pondoestatural y retraso neuromadurativo. Durante su internación se arribó al diagnóstico de seudomicroangiopatía trombótica secundaria a déficit de vitamina B12.

Pseudo-thrombotic microangiopathy, or Moschcowitz syndrome, is a rare manifestation of vitamin B12 deficiency. It is characterized by microangiopathic hemolytic anemia, reticulocytes, and hematimetric indices that can be normal or that might present a mild megaloblastosis, and which are associated with neurological manifestations. Vitamin B12 can be found in animal-based protein foods. Breastfeeding is an adequate source of this vitamin for children, when maternal serum levels are normal. The case of a 16-month-old infant is presented. She was admitted for hemolytic anemia with transfusion requirement, thrombocytopenia, failure to thrive and developmental delay. During her hospitalization, she was diagnosed with pseudothrombotic microangiopathy caused by vitamin B12 deficiency.

[Pseudo-thrombotic microangiopathy due to vitamin B12 deficiency in an infant]. / Pseudomicroangiopatía trombótica por deficiencia de vitamina B12 en un lactante.

Pseudo-thrombotic microangiopathy, or Moschcowitz syndrome, is a rare manifestation of vitamin B12 deficiency. It is characterized by microangiopathic hemolytic anemia, reticulocytes, and hematimetric indices that can be normal or that might present a mild megaloblastosis, and which are associated with neurological manifestations. Vitamin B12 can be found in animal-based protein foods. Breastfeeding is an adequate source of this vitamin for children, when maternal serum levels are normal. The case of a 16-month-old infant is presented. She was admitted for hemolytic anemia with transfusion requirement, thrombocytopenia, failure to thrive and developmental delay. During her hospitalization, she was diagnosed with pseudothrombotic microangiopathy caused by vitamin B12 deficiency.

La seudomicroangiopatía trombótica o síndrome de Moschcowitz es una manifestación infrecuente del déficit de vitamina B12. Se caracteriza por anemia hemolítica con características microangiopáticas, reticulocitos e índices hematimétricos normales o con ligera megaloblastosis, asociados a manifestaciones neurológicas. La vitamina B12 está presente en alimentos proteicos de origen animal. La lactancia materna es una fuente adecuada para los niños cuando los niveles maternos son normales. Se presenta a una paciente de 16 meses que se internó por anemia hemolítica con requerimiento transfusional, plaquetopenia, mal progreso pondoestatural y retraso neuromadurativo. Durante su internación se arribó al diagnóstico de seudomicroangiopatía trombótica secundaria a déficit de vitamina B12.

Machine-Learning-Based In-Hospital Mortality Prediction for Transcatheter Mitral Valve Repair in the United States.

BACKGROUND: Transcatheter mitral valve repair (TMVR) utilization has increased significantly in the United States over the last years. Yet, a risk-prediction tool for adverse events has not been developed. We aimed to generate a machine-learning-based algorithm to predict in-hospital mortality after TMVR. METHODS: Patients who underwent TMVR from 2012 through 2015 were identified using the National Inpatient Sample database. The study population was randomly divided into a training set (n = 636) and a testing set (n = 213). Prediction models for in-hospital mortality were obtained using five supervised machine-learning classifiers. RESULTS: A total of 849 TMVRs were analyzed in our study. The overall in-hospital mortality was 3.1%. A naïve Bayes (NB) model had the best discrimination for fifteen variables, with an area under the receiver-operating curve (AUC) of 0.83 (95% CI, 0.80-0.87), compared to 0.77 for logistic regression (95% CI, 0.58-0.95), 0.73 for an artificial neural network (95% CI, 0.55-0.91), and 0.67 for both a random forest and a support-vector machine (95% CI, 0.47-0.87). History of coronary artery disease, of chronic kidney disease, and smoking were the three most significant predictors of in-hospital mortality. CONCLUSIONS: We developed a robust machine-learning-derived model to predict in-hospital mortality in patients undergoing TMVR. This model is promising for decision-making and deserves further clinical validation.

Adsorption and Interaction of Bovine Serum Albumin and Pluronic P103 Triblock Copolymer on a Gold Electrode: Double-Layer Capacitance Measurements.

The interactions of proteins and other molecules and their adsorption onto substrates is a fascinating topic that has been applied to surface technologies, biosensors, corrosion studies, biotechnologies, and other fields. The success of these applications requires a previous characterization using some analytical techniques that, ordinarily, are not electrochemical. This work proposes analyzing the variation of the double-layer capacitance obtained through impedance electrochemical spectroscopy as an alternative strategy to show evidence of the interactions between proteins and triblock copolymers. The proposal is supported through the study of the interaction and adsorption of bovine serum albumin (BSA) and a commercial triblock copolymer (P103) in phosphate buffer on a gold electrode. The double-layer capacitance and the apparent interface thickness vs polarization potential curves as well as the potential of zero charge for pure P103 (0.6 wt %, corresponding to 6 g L-1), pure BSA (3 mg mL-1), and P103-BSA solutions (0.6 wt % and 3 mg mL-1, respectively) are sensitive enough to show not only the interaction and the adsorption of the species but also the polarization potential where these interactions are taking place. A qualitative and quantitative analysis concerning the double-layer capacitance behavior is given. The significance and impact of this work is also presented.

Gestantes con enfermedad por coronavirus 2019 y transmisión vertical intrauterina: una revisión sistemática / Pregnant women with coronavirus disease 2019 and intrauterine vertical transmission: a systematic review

Resumen Introducción . La enfermedad por coronavirus 2019 (COVID-19) es una enfermedad de las vías respiratorias potencialmente severa, producida por el coronavirus tipo 2 causante del síndrome respiratorio agudo grave (SARS-CoV-2). La transmisión intrauterina de la madre al feto es un motivo de debate. Objetivo. Identificar la evidencia disponible de transmisión vertical intrauterina en la gestante con COVID-19. Metodología. Revisión sistemática utilizando los términos: "Vertical transmission" AND "COVID-19" OR "SARS-CoV-2". Las bases de datos consultadas fueron MEDLINE/PubMed, Science Direct, Clinical Key, LILACS, SciELO, Google Scholar, medRxiv y SciELO Preprints. Resultados . Se identificaron 30 estudios que cumplieron los criterios de selección e incluían 476 gestantes. La infección se encontró en 9 neonatos (1,9%), el hisopado faríngeo en ellos se hizo dentro de las 48 horas del nacimiento. En 4 de ellos no se buscó la presencia del virus en otros tejidos y fluidos maternos, mientras que en los 5 casos restantes se identificó el ARN en la placenta de tres de ellos, en dos se encontró en el líquido amniótico y en uno en el canal vaginal. Los estudios fueron muy heterogéneos; así podemos mencionar la variedad de la población reportada, el número de muestras y momento de la toma en los neonatos, la falta de muestreo en los tejidos y fluidos maternos. Conclusiones . La transmisión vertical intrauterina del SARS-CoV-2 no ha sido demostrada de forma contundente debido a que la mayoría de las gestantes con la enfermedad ha tenido neonatos con la prueba molecular negativa (98,1%). Sin embargo, la heterogeneidad de los estudios tampoco permite descartar esta posibilidad.

ABSTRACT Introduction: Coronavirus disease 2019, also called COVID-19, is a potentially severe respiratory disease originated by the type 2 coronavirus that causes severe acute respiratory syndrome (SARS-CoV-2). Intrauterine transmission from mother to fetus is a matter of debate. Objective: To identify the available evidence of vertical intrauterine transmission in pregnant women with COVID-19. Methodology: A systematic review was performed using the terms: "Vertical transmission" AND "COVID-19" OR "SARSCoV-2" NOT "Review *". The databases consulted were MEDLINE/PubMed, Science Direct, Clinical Key, LILACS, SciELO, Google Scholar, medRxiv and SciELO Preprints. Results: Thirty primary studies met the selection criteria and included 476 pregnant women. Infection was found in 9 neonates (1.9%) in whom pharyngeal swabs were done within 48 hours of birth. In four of them the presence of the virus was not looked for in other maternal tissues and fluids; in the remaining 5 cases, the virus RNA was identified in the placenta of three of them, in two it was found in the amniotic fluid and in one in vaginal secretion. Studies were very heterogeneous, with great variety of the reported population, the number of samples and time of collection in neonates, the lack of sampling in maternal tissues and fluids. Conclusions: Vertical intrauterine transmission of SARS-CoV-2 has not been conclusively demonstrated in pregnant women with COVID-19 as the majority of patients with the disease had newborns with negative molecular test (98,1%). The heterogeneity of the studies does not allow to rule out this possibility either.

Shaking Table Test of U-Shaped Walls Made of Fiber-Reinforced Foamed Concrete.

Fiber-reinforced foamed concrete (FRFC) is a lightweight material that has the potential to perform well in seismic applications due to its low density and improved mechanical properties. However, studies focused on the seismic assessment of this material are limited. In this work, U-shaped wall specimens, made of FRFC reinforced with henequen fibers and plain foamed concrete (PFC) with a density of 900 kg/m3, were subjected to shaking table tests. PFC and FRFC were characterized using compression and tension tests. FRFC exhibited enhanced mechanical properties, which were attributed to the fibers. The dynamic tests showed that U-shaped walls made of FRFC performed better than those made of PFC. The time period prior to the collapse of the FRFC U-shaped walls was longer than that of the PFC specimens, which was attributed to the enhanced specimen integrity by the fibers. Finite element simulations of the shaking table test allowed for the prediction of the stress concentration and plastic strain that may lead to the failure of the U-shaped wall. These results showed that U-shaped walls made of FRFC have the potential to perform well in seismic applications, however, these results are preliminary and further studies are needed to support the findings of this work.

Candida glabrata peroxiredoxins, Tsa1 and Tsa2, and sulfiredoxin, Srx1, protect against oxidative damage and are necessary for virulence.

Candida glabrata is an opportunistic fungal pathogen that can cause life-threatening infections in immunocompromised patients. To ensure a successful infection, C. glabrata has evolved a variety of strategies to avoid killing within the host. One of these strategies is the resistance to oxidative stress. Here we show that the sulfiredoxin Srx1 and the peroxiredoxins, Tsa1 and Tsa2, are implicated in the oxidative stress response (OSR) and required for virulence. We analyzed null mutations in SRX1, TSA1 and TSA2 and showed that TSA2 and SRX1 are required to respond to oxidative stress. While TSA1 expression is constitutive, SRX1 and TSA2 are induced in the presence of H2O2 in a process dependent on H2O2 concentration and on both transcription factors Yap1 and Skn7. Msn2 and Msn4 are not necessary for the regulation of SRX1, TSA1 and TSA2. Interestingly, TSA1 and TSA2, which are localized in the cytoplasm, are induced in the presence of neutrophils and required for survival in these phagocytic cells.

Machine Learning Prediction Models for In-Hospital Mortality After Transcatheter Aortic Valve Replacement.

OBJECTIVES: This study sought to develop and compare an array of machine learning methods to predict in-hospital mortality after transcatheter aortic valve replacement (TAVR) in the United States. BACKGROUND: Existing risk prediction tools for in-hospital complications in patients undergoing TAVR have been designed using statistical modeling approaches and have certain limitations. METHODS: Patient data were obtained from the National Inpatient Sample database from 2012 to 2015. The data were randomly divided into a development cohort (n = 7,615) and a validation cohort (n = 3,268). Logistic regression, artificial neural network, naive Bayes, and random forest machine learning algorithms were applied to obtain in-hospital mortality prediction models. RESULTS: A total of 10,883 TAVRs were analyzed in our study. The overall in-hospital mortality was 3.6%. Overall, prediction models' performance measured by area under the curve were good (>0.80). The best model was obtained by logistic regression (area under the curve: 0.92; 95% confidence interval: 0.89 to 0.95). Most obtained models plateaued after introducing 10 variables. Acute kidney injury was the main predictor of in-hospital mortality ranked with the highest mean importance in all the models. The National Inpatient Sample TAVR score showed the best discrimination among available TAVR prediction scores. CONCLUSIONS: Machine learning methods can generate robust models to predict in-hospital mortality for TAVR. The National Inpatient Sample TAVR score should be considered for prognosis and shared decision making in TAVR patients.

Racial/Ethnic Disparities in Patients Undergoing Transcatheter Aortic Valve Replacement: Insights from the Healthcare Cost and Utilization Project's National Inpatient Sample.

PURPOSE: To identify racial/ethnic disparities in utilization rates, in-hospital outcomes and health care resource use among Non-Hispanic Whites (NHW), African Americans (AA) and Hispanics undergoing transcatheter aortic valve replacement (TAVR) in the United States (US). METHODS AND RESULTS: The National Inpatient Sample database was queried for patients ≥18 years of age who underwent TAVR from 2012 to 2014. The primary outcome was all-cause in hospital mortality. A total of 36,270 individuals were included in the study. The number of TAVR performed per million population increased in all study groups over the three years [38.8 to 103.8 (NHW); 9.1 to 26.4 (AA) and 9.4 to 18.2 (Hispanics)]. The overall in-hospital mortality was 4.2% for the entire cohort. Race/ethnicity showed no association with in-hospital mortality (P > .05). Though no significant difference were found between AA and NHW in any secondary outcome, being Hispanic was associated with higher incidence of acute myocardial infarction (aOR = 2.02; 95% CI, 1.06-3.85; P = .03), stroke/transient ischemic attack (aOR = 1.81; 95% CI, 1.04-3.14; P = .04), acute kidney injury (aOR = 1.65; 95% CI, 1.23-2.21; P < .01), prolonged length of stay (aOR = 1.18; 95% CI, 1.08-1.29; P < .01) and higher hospital costs (aOR = 1.27; 95% CI, 1.18-1.36; P < .01). CONCLUSION: There are significant racial disparities in patients undergoing TAVR in the US. Though in-hospital mortality was not associated with race/ethnicity, Hispanic patients had less TAVR utilization, higher in-hospital complications, prolonged length of stay and increased hospital costs.

Machine Learning Algorithm for Predicting Warfarin Dose in Caribbean Hispanics Using Pharmacogenetic Data.

Despite some previous examples of successful application to the field of pharmacogenomics, the utility of machine learning (ML) techniques for warfarin dose predictions in Caribbean Hispanic patients has yet to be fully evaluated. This study compares seven ML methods to predict warfarin dosing in Caribbean Hispanics. This is a secondary analysis of genetic and non-genetic clinical data from 190 cardiovascular Hispanic patients. Seven ML algorithms were applied to the data. Data was divided into 80 and 20% to be used as training and test sets. ML algorithms were trained with the training set to obtain the models. Model performance was determined by computing the corresponding mean absolute error (MAE) and % patients whose predicted optimal dose were within ±20% of the actual stabilization dose, and then compared between groups of patients with "normal" (i.e., > 21 but <49 mg/week), low (i.e., ≤21 mg/week, "sensitive"), and high (i.e., ≥49 mg/week, "resistant") dose requirements. Random forest regression (RFR) significantly outperform all other methods, with a MAE of 4.73 mg/week and 80.56% of cases within ±20% of the actual stabilization dose. Among those with "normal" dose requirements, RFR performance is also better than the rest of models (MAE = 2.91 mg/week). In the "sensitive" group, support vector regression (SVR) shows superiority over the others with lower MAE of 4.79 mg/week. Finally, multivariate adaptive splines (MARS) shows the best performance in the resistant group (MAE = 7.22 mg/week) and 66.7% of predictions within ±20%. Models generated by using RFR, MARS, and SVR algorithms showed significantly better predictions of weekly warfarin dosing in the studied cohorts than other algorithms. Better performance of the ML models for patients with "normal," "sensitive," and "resistant" to warfarin were obtained when compared to other populations and previous statistical models.

El raro caso de una joven con colitis ulcerativa crónica inespecífica grave y atrofia cerebral / The rare case of a young girl with ulcerative colitis and cerebral atrophy

Resumen La enfermedad inflamatoria intestinal es un grupo de enfermedades caracterizadas por inflamación crónica gastrointestinal y en ocasiones con repercusión extraintestinal. Las manifestaciones neurológicas y psiquiátricas corresponden a menos de 3%. Se comunica el caso de una mujer joven con colitis ulcerativa y atrofia cerebral como inicio.

Abstract Inflammatory bowel disease is a group of diseases characterized by chronic gastrointestinal inflammation and occasionally with extraintestinal repercussion. The neurological and psychiatric manifestations correspond to less than 3%. This paper reports the case of a young woman with ulcerative colitis and cerebral atrophy as debut.