Asymmetric Lipid Vesicles: Techniques, Applications, and Future Perspectives as an Innovative Drug Delivery System.

Novel lipid-based nanosystems have been of interest in improving conventional drug release methods. Liposomes are the most studied nanostructures, consisting of lipid bilayers ideal for drug delivery, thanks to their resemblance to the cell plasma membrane. Asymmetric liposomes are vesicles with different lipids in their inner and outer layers; because of this, they can be configured to be compatible with the therapeutic drug while achieving biocompatibility and stability. Throughout this review, topics such as the applications, advantages, and synthesis techniques of asymmetric liposomes will be discussed. Further, an in silico analysis by computational tools will be examined as a helpful tool for designing and understanding asymmetric liposome mechanisms in pharmaceutical applications. The dual-engineered design of asymmetric liposomes makes them an ideal alternative for transdermal drug delivery because of the improved protection of pharmaceuticals without lowering adsorption rates and system biocompatibility.

An Equilibrium State Diagram for Storage Stability and Conservation of Active Ingredients in a Functional Food Based on Polysaccharides Blends.

A functional food as a matrix based on a blend of carbohydrate polymers (25% maltodextrin and 75% inulin) with quercetin and Bacillus claussi to supply antioxidant and probiotic properties was prepared by spray drying. The powders were characterized physiochemically, including by moisture adsorption isotherms, X-ray diffraction (XRD), scanning electron microscopy (SEM), and modulated differential scanning calorimetry (MDSC). The type III adsorption isotherm developed at 35 °C presented a monolayer content of 2.79 g of water for every 100 g of dry sample. The microstructure determined by XRD presented three regions identified as amorphous, semicrystalline, and crystalline-rubbery states. SEM micrographs showed variations in the morphology according to the microstructural regions as (i) spherical particles with smooth surfaces, (ii) a mixture of spherical particles and irregular particles with heterogeneous surfaces, and (iii) agglomerated irregular-shape particles. The blend's functional performance demonstrated antioxidant activities of approximately 50% of DPPH scavenging capacity and viability values of 6.5 Log10 CFU/g. These results demonstrated that the blend displayed functional food behavior over the complete interval of water activities. The equilibrium state diagram was significant for identifying the storage conditions that promote the preservation of functional food properties and those where the collapse of the microstructure occurs.

Maternal control of triploid seed development by the TRANSPARENT TESTA 8 (TT8) transcription factor in Arabidopsis thaliana.

The balance between parental genome dosage is critical to offspring development in both animals and plants. In some angiosperm species, despite the imbalance between maternally and paternally inherited chromosome sets, crosses between parental lines of different ploidy may result in viable offspring. However, many plant species, like Arabidopsis thaliana, present a post-zygotic reproductive barrier, known as triploid block which results in the inability of crosses between individuals of different ploidy to generate viable seeds but also, in defective development of the seed. Several paternal regulators have been proposed as active players in establishing the triploid block. Maternal regulators known to be involved in this process are some flavonoid biosynthetic (FB) genes, expressed in the innermost layer of the seed coat. Here we explore the role of selected flavonoid pathway genes in triploid block, including TRANSPARENT TESTA 4 (TT4), TRANSPARENT TESTA 7 (TT7), SEEDSTICK (STK), TRANSPARENT TESTA 16 (TT16), TT8 and TRANSPARENT TESTA 13 (TT13). This approach allowed us to detect that TT8, a bHLH transcription factor, member of this FB pathway is required for the paternal genome dosage, as loss of function tt8, leads to complete rescue of the triploid block to seed development.

Brain transcriptomic profiling reveals common alterations across neurodegenerative and psychiatric disorders.

Neurodegenerative and neuropsychiatric disorders (ND-NPs) are multifactorial, polygenic and complex behavioral phenotypes caused by brain abnormalities. Large-scale collaborative efforts have tried to identify the genetic architecture of these conditions. However, the specific and shared underlying molecular pathobiology of brain illnesses is not clear. Here, we examine transcriptome-wide characterization of eight conditions, using a total of 2,633 post-mortem brain samples from patients with Alzheimer's disease (AD), Parkinson's disease (PD), Progressive Supranuclear Palsy (PSP), Pathological Aging (PA), Autism Spectrum Disorder (ASD), Schizophrenia (Scz), Major Depressive Disorder (MDD), and Bipolar Disorder (BP)-in comparison with 2,078 brain samples from matched control subjects. Similar transcriptome alterations were observed between NDs and NPs with the top correlations obtained between Scz-BP, ASD-PD, AD-PD, and Scz-ASD. Region-specific comparisons also revealed shared transcriptome alterations in frontal and temporal lobes across NPs and NDs. Co-expression network analysis identified coordinated dysregulations of cell-type-specific modules across NDs and NPs. This study provides a transcriptomic framework to understand the molecular alterations of NPs and NDs through their shared- and specific gene expression in the brain.

Caracterización de los pacientes con enfermedades vasculares periféricas fallecidos en un período de cuatro años / Characterization of patients with peripheral vascular diseases who died in a period of four years

Introducción: Las enfermedades vasculares periféricas constituyen un problema de salud en el ámbito mundial por resultar causa importante de discapacidad y de invalidez. Objetivo: Caracterizar a los pacientes con enfermedades vasculares periféricas fallecidos en un período de cuatro años. Método: Se realizó un estudio descriptivo y analítico en los pacientes fallecidos entre enero de 2015 y diciembre de 2018. Se estudiaron variables sociodemográficas y clínicas. Se estimaron las frecuencias absolutas y relativas, así como la tasa de mortalidad. Se identificó la asociación entre las variables con la causa directa de muerte. Resultados: El 42,7 por ciento de los diabéticos fallecieron; de estos, el 57,5 por ciento estaban descompensados. La hipertensión arterial, el tabaquismo y la diabetes mellitus fueron los factores de riesgo más frecuentes. La tasa de mortalidad total resultó 0,171/1000 ingresos. Como enfermedades arteriales más frecuente aparecieron los AAA (28,1 por ciento ) y la angiopatía diabética (25 por ciento ); y, como parte de esta última, el pie (25,7 por ciento ). La aneurismectomía con injerto por sustitución representó la cirugía revascularizadora más realizada (58,8 por ciento ). El shock hipovolémico y el tromboembolismo pulmonar predominaron como complicaciones posquirúrgicas (15,7 por ciento ). El shock séptico (31,6 por ciento ) y la bronconeumonía bacteriana (25,7 por ciento) fueron las causas directas de muerte. Conclusiones: Se logró caracterizar a los pacientes con enfermedades vasculares periféricas fallecidos en los últimos cuatro años, por lo que estimaron la tasa de prevalencia y la tendencia anual de la mortalidad en el Instituto Nacional de Angiología y Cirugía Vascular en ese período; asimismo, las variables asociadas a las causas directas de muerte(AU)

Introduction: Peripheral vascular diseases are a global health problem because they are a major cause of disability. Objective: Characterize patients with peripheral vascular diseases who died over a period of four years. Method: A descriptive and analytical study was conducted in patients who died between January 2015 and December 2018. Socio-demographic and clinical variables were studied. Absolute and relative frequencies were estimated, as well as the mortality rate. The association between the variables with the direct cause of death was identified. Results: 42.7 percent of diabetic patients died; of these, 57.5 percent were decompensated. High blood pressure, smoking and diabetes mellitus were the most frequent risk factors. The total mortality rate was 0.171/1000 admissions. The most frequent arterial diseases were AAA (28.1 percent) and diabetic angiopathy (25 percent); and, as part of the latter, foot angiopathy (25.7 percent). Aneurysmectomy with graft substitution represented the most performed revascularizing surgery (58.8 percent). Hypovolemic shock and pulmonary thromboembolism predominated as post-surgical complications (15.7 percent). Septic shock (31.6 percent) and bacterial bronchopneumonia (25.7 percent) were the direct causes of death. Conclusions: It was possible to characterize patients with peripheral vascular diseases who died in the last four years, so they estimated the prevalence rate and the annual trend of mortality at the National Institute of Angiology and Vascular Surgery in that period; also, the variables associated with direct causes of death(AU)

Blends of Carbohydrate Polymers for the Co-Microencapsulation of Bacillus clausii and Quercetin as Active Ingredients of a Functional Food.

A functional food based on blends of carbohydrate polymers and active ingredients was prepared by spray drying. Inulin (IN) and maltodextrin (MX) were used as carrying agents to co-microencapsulate quercetin as an antioxidant and Bacillus clausii (Bc) as a probiotic. Through a reduced design of experiments, eleven runs were conducted and characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and modulated differential scanning calorimetry (MDSC). The physical characterizations showed fine and non-aggregated powders, composed of pseudo-spherical particles with micrometric sizes. The observation of rod-like particles suggested that microorganisms were microencapsulated in these particles. The microstructure of the powders was amorphous, observing diffraction peaks attributed to the crystallization of the antioxidant. The glass transition temperature (Tg) of the blends was above the room temperature, which may promote a higher stability during storage. The antioxidant activity (AA) values increased for the IN-MX blends, while the viability of the microorganisms increased with the addition of MX. By a surface response plot (SRP) the yield showed a major dependency with the drying temperature and then with the concentration of IN. The work contributes to the use of carbohydrate polymers blends, and to the co-microencapsulation of active ingredients.

Comparison of Polysaccharides as Coatings for Quercetin-Loaded Liposomes (QLL) and Their Effect as Antioxidants on Radical Scavenging Activity.

Liposomes are microstructures containing lipid and aqueous phases employed in the encapsulation and delivery of bioactive agents. Quercetin-loaded liposomes (QLLs) were coated with three different polysaccharides and then tested as radical scavengers. Lactose (LCQLL), chitosan (CCQLL), and inulin (ICQLL) were employed as coating materials. Particle size determined by light scattering, showed primary size of 200 nm for all samples, while a secondary particle size of 600 nm was observed for CCQLL. Scanning electron microscopy (SEM) evidenced particle aggregation with the addition of the polysaccharide coating. Transmission electron microscopy (TEM) revealed the layered microstructure of liposomes composed of at least two layers, and primary particle size below 100 nm. QLL showed higher antioxidant activity than the coated liposomes. This behavior was attributed to the chemical interaction between quercetin and the corresponding coating polysaccharide in the layered structure, which traps the quercetin and keeps it unavailable for radical scavenging. From the three polysaccharides, lactose showed a better performance as coating material in the antioxidant activity, which suggested that the smaller size of the disaccharide molecule resulted in a faster releasing of the quercetin in the solution. Thus, LCQLL is an advantageous way to deliver quercetin for antioxidant purposes, where the low stability in delivered media of quercetin loaded liposomes is commonly compromised.

PyHIST: A Histological Image Segmentation Tool.

The development of increasingly sophisticated methods to acquire high-resolution images has led to the generation of large collections of biomedical imaging data, including images of tissues and organs. Many of the current machine learning methods that aim to extract biological knowledge from histopathological images require several data preprocessing stages, creating an overhead before the proper analysis. Here we present PyHIST (https://github.com/manuel-munoz-aguirre/PyHIST), an easy-to-use, open source whole slide histological image tissue segmentation and preprocessing command-line tool aimed at tile generation for machine learning applications. From a given input image, the PyHIST pipeline i) optionally rescales the image to a different resolution, ii) produces a mask for the input image which separates the background from the tissue, and iii) generates individual image tiles with tissue content.

The impact of sex on gene expression across human tissues.

Many complex human phenotypes exhibit sex-differentiated characteristics. However, the molecular mechanisms underlying these differences remain largely unknown. We generated a catalog of sex differences in gene expression and in the genetic regulation of gene expression across 44 human tissue sources surveyed by the Genotype-Tissue Expression project (GTEx, v8 release). We demonstrate that sex influences gene expression levels and cellular composition of tissue samples across the human body. A total of 37% of all genes exhibit sex-biased expression in at least one tissue. We identify cis expression quantitative trait loci (eQTLs) with sex-differentiated effects and characterize their cellular origin. By integrating sex-biased eQTLs with genome-wide association study data, we identify 58 gene-trait associations that are driven by genetic regulation of gene expression in a single sex. These findings provide an extensive characterization of sex differences in the human transcriptome and its genetic regulation.

Cell type-specific genetic regulation of gene expression across human tissues.

The Genotype-Tissue Expression (GTEx) project has identified expression and splicing quantitative trait loci in cis (QTLs) for the majority of genes across a wide range of human tissues. However, the functional characterization of these QTLs has been limited by the heterogeneous cellular composition of GTEx tissue samples. We mapped interactions between computational estimates of cell type abundance and genotype to identify cell type-interaction QTLs for seven cell types and show that cell type-interaction expression QTLs (eQTLs) provide finer resolution to tissue specificity than bulk tissue cis-eQTLs. Analyses of genetic associations with 87 complex traits show a contribution from cell type-interaction QTLs and enables the discovery of hundreds of previously unidentified colocalized loci that are masked in bulk tissue.

A limited set of transcriptional programs define major cell types.

We have produced RNA sequencing data for 53 primary cells from different locations in the human body. The clustering of these primary cells reveals that most cells in the human body share a few broad transcriptional programs, which define five major cell types: epithelial, endothelial, mesenchymal, neural, and blood cells. These act as basic components of many tissues and organs. Based on gene expression, these cell types redefine the basic histological types by which tissues have been traditionally classified. We identified genes whose expression is specific to these cell types, and from these genes, we estimated the contribution of the major cell types to the composition of human tissues. We found this cellular composition to be a characteristic signature of tissues and to reflect tissue morphological heterogeneity and histology. We identified changes in cellular composition in different tissues associated with age and sex, and found that departures from the normal cellular composition correlate with histological phenotypes associated with disease.

Carbohydrate reserves and seed development: an overview.

Seeds are one of the most important food sources, providing humans and animals with essential nutrients. These nutrients include carbohydrates, lipids, proteins, vitamins and minerals. Carbohydrates are one of the main energy sources for both plant and animal cells and play a fundamental role in seed development, human nutrition and the food industry. Many studies have focused on the molecular pathways that control carbohydrate flow during seed development in monocot and dicot species. For this reason, an overview of seed biodiversity focused on the multiple metabolic and physiological mechanisms that govern seed carbohydrate storage function in the plant kingdom is required. A large number of mutants affecting carbohydrate metabolism, which display defective seed development, are currently available for many plant species. The physiological, biochemical and biomolecular study of such mutants has led researchers to understand better how metabolism of carbohydrates works in plants and the critical role that these carbohydrates, and especially starch, play during seed development. In this review, we summarize and analyze the newest findings related to carbohydrate metabolism's effects on seed development, pointing out key regulatory genes and enzymes that influence seed sugar import and metabolism. Our review also aims to provide guidelines for future research in the field and in this way to assist seed quality optimization by targeted genetic engineering and classical breeding programs.

The effects of death and post-mortem cold ischemia on human tissue transcriptomes.

Post-mortem tissues samples are a key resource for investigating patterns of gene expression. However, the processes triggered by death and the post-mortem interval (PMI) can significantly alter physiologically normal RNA levels. We investigate the impact of PMI on gene expression using data from multiple tissues of post-mortem donors obtained from the GTEx project. We find that many genes change expression over relatively short PMIs in a tissue-specific manner, but this potentially confounding effect in a biological analysis can be minimized by taking into account appropriate covariates. By comparing ante- and post-mortem blood samples, we identify the cascade of transcriptional events triggered by death of the organism. These events do not appear to simply reflect stochastic variation resulting from mRNA degradation, but active and ongoing regulation of transcription. Finally, we develop a model to predict the time since death from the analysis of the transcriptome of a few readily accessible tissues.

Lung Injury Prediction Score in Hospitalized Patients at Risk of Acute Respiratory Distress Syndrome.

OBJECTIVE: The Lung Injury Prediction Score identifies patients at risk for acute respiratory distress syndrome in the emergency department, but it has not been validated in non-emergency department hospitalized patients. We aimed to evaluate whether Lung Injury Prediction Score identifies non-emergency department hospitalized patients at risk of developing acute respiratory distress syndrome at the time of critical care contact. DESIGN: Retrospective study. SETTING: Five academic medical centers. PATIENTS: Nine hundred consecutive patients (≥ 18 yr old) with at least one acute respiratory distress syndrome risk factor at the time of critical care contact. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Lung Injury Prediction Score was calculated using the worst values within the 12 hours before initial critical care contact. Patients with acute respiratory distress syndrome at the time of initial contact were excluded. Acute respiratory distress syndrome developed in 124 patients (13.7%) a median of 2 days (interquartile range, 2-3) after critical care contact. Hospital mortality was 22% and was significantly higher in acute respiratory distress syndrome than non-acute respiratory distress syndrome patients (48% vs 18%; p < 0.001). Increasing Lung Injury Prediction Score was significantly associated with development of acute respiratory distress syndrome (odds ratio, 1.31; 95% CI, 1.21-1.42) and the composite outcome of acute respiratory distress syndrome or death (odds ratio, 1.26; 95% CI, 1.18-1.34). A Lung Injury Prediction Score greater than or equal to 4 was associated with the development of acute respiratory distress syndrome (odds ratio, 4.17; 95% CI, 2.26-7.72), composite outcome of acute respiratory distress syndrome or death (odds ratio, 2.43; 95% CI, 1.68-3.49), and acute respiratory distress syndrome after accounting for the competing risk of death (hazard ratio, 3.71; 95% CI, 2.05-6.72). For acute respiratory distress syndrome development, the Lung Injury Prediction Score has an area under the receiver operating characteristic curve of 0.70 and a Lung Injury Prediction Score greater than or equal to 4 has 90% sensitivity (misses only 10% of acute respiratory distress syndrome cases), 31% specificity, 17% positive predictive value, and 95% negative predictive value. CONCLUSIONS: In a cohort of non-emergency department hospitalized patients, the Lung Injury Prediction Score and Lung Injury Prediction Score greater than or equal to 4 can identify patients at increased risk of acute respiratory distress syndrome and/or death at the time of critical care contact but it does not perform as well as in the original emergency department cohort.

Sustainable application of pecan nutshell waste: Greener synthesis of Pd-based nanocatalysts for electro-oxidation of methanol.

Palladium-based electrocatalysts are widely used in alkaline direct alcohol fuel cells. The synthesis and characterization of carbon-supported bimetallic nanoparticles (NP) of AuPd and AgPd is described using pecan nutshell extract (Carya illinoinensis) which serves as both, reducing and the stabilizing agent. This environmentally friendly route generates bimetallic NP for a wide range of applications, including electrocatalysis; since particularly AuPd NP proved to be a potentially suitable electrode material for alkaline direct methanol fuel cells. The electrocatalytic activity of these nanomaterials was comparable to commercially available Pd/C 1% in the electro-oxidation of methanol in alkaline media.

Enterococcus hirae Bacteremia Associated with Acute Pancreatitis and Septic Shock.

Infection with Enterococcus hirae has rarely been reported in humans but is not uncommon in mammals and birds. We describe a case of Enterococcus hirae bacteremia associated with acute pancreatitis, acute cholecystitis, and septic shock responsive to antibiotic therapy and supportive critical care management. Unique aspects of this case of Enterococcus hirae bacteremia are its association with acute pancreatitis and its geographical origin. To our knowledge, this is the first report of Enterococcus hirae bacteremia occurring in a patient in the United States. Although human infection with this organism appears to be rare, all cases reported to date describe bacteremia associated with severe and life-threatening illness. Thus, physicians need to be cognizant of the clinical significance of this heretofore little recognized pathogen.

Ventilator Settings Can Substantially Impact Patients' Comfort.

BACKGROUND: With increasing realization that sedatives may complicate care of mechanically ventilated patients, greater emphasis might turn to promoting comfort by titration of ventilator settings. HYPOTHESIS: Patients with acute on chronic respiratory failure (ACRF) with underlying chronic obstructive pulmonary disease (COPD) demonstrate different levels of comfort in response to varying ventilator settings compared to those with underlying obesity hypoventilation syndrome (OHS). METHODS: Patients recovering from ACRF with underlying COPD or OHS were randomized to varying combinations of ventilator modes (assist control and pressure support), tidal volumes, and inspiratory flows for 3 minutes/setting. For each ventilator setting, physiologic variables were recorded and patients indicated their level of comfort using a 10-point Borg scale. RESULTS: In all, 20 patients, aged 68 ± 13 years (standard deviation) and ventilated for 4.9 days, were enrolled. Of 20 patients, 13 had COPD and 7 had OHS. No ventilator mode, flow, or tidal volume provided consistently greater comfort between the groups, but patients reported substantial ranges of comfort (up to 8 Borg points) across the ventilator settings studied. There were no significant differences in heart rate, blood pressure, or airway pressures within patients across ventilator settings or between the groups, but patients with OHS were more tachypneic compared to patients with COPD while breathing on assist control of 6 mL/kg (constant flow 60 L/min) and 8 mL/kg (decelerating flow 40 L/min). There was no correlation between comfort and systolic blood pressure, heart rate, or respiratory rate. CONCLUSION: Ventilator parameters may impact patients' comfort substantially. Future studies may help identify evidence-based methodology for gauging comfort following changes in ventilator settings and the settings that are most likely to positively impact various groups of patients.

Perseverant, non-indicated treatment of obese patients for obstructive lung disease.

BACKGROUND: Bronchodilators are a mainstay of treatment for patients with airflow obstruction. We hypothesized that patients with obesity and no objective documentation of airflow obstruction are inappropriately treated with bronchodilators. METHODS: Spirometric results and medical records of all patients with body mass index >30 kg/m2 who were referred for testing between March 2010 and August 2011 were analyzed. RESULTS: 155 patients with mean age of 52.6 ± (SE)1.1 y and BMI of 38.7 ± 0.7 kg/m2 were studied. Spirometry showed normal respiratory mechanics in 62 (40%), irreversible airflow obstruction in 36 (23.2%), flows suggestive of restriction in 35 (22.6%), reversible obstruction, suggestive of asthma in 11 (7.1%), and mixed pattern (obstructive and restrictive) in 6 (3.9%). Prior to testing, 45.2% (28 of 62) of patients with normal spirometry were being treated with medications for obstructive lung diseases and 33.9% (21 of 62) continued them despite absence of airflow obstruction on spirometry. 60% (21 of 35) of patients with a restrictive pattern in their spirometry received treatment for obstruction prior to spirometry and 51.4% (18 of 35) continued bronchodilator therapy after spirometric testing. There was no independent association of non-indicated treatment with spirometric results, age, BMI, co-morbidities or smoking history. All patients with airflow obstruction on testing who were receiving bronchodilators before spirometry continued to receive them after testing. CONCLUSION: A substantial proportion of patients with obesity referred for pulmonary function testing did not have obstructive lung disease, but were treated nonetheless, before and after spirometry demonstrating absence of airway obstruction.

Factores determinantes de la salud: Importancia de la prevención

La prevención, dentro de los conocimientos relacionados con la atención de la salud, pertenecen al ámbito de la doctrina de la Salud Pública, que es la disciplina que orienta la atención de la salud de la población.