Assessing human exposure to pesticides and mycotoxins: optimization and validation of a method for multianalyte determination in urine samples.

Humans are exposed to an increasing number of contaminants, with diet being one of the most important exposure routes. In this framework, human biomonitoring is considered the gold standard for evaluating human exposure to chemicals. Pesticides and mycotoxins are chemicals of special concern due to their health implications. They constitute the predominant border rejection notifications for food and feed in Europe and the USA. However, current biomonitoring studies are focused on a limited number of compounds and do not evaluate mycotoxins and pesticides together. In this study, an analytical method has been developed for the determination of 30 pesticides and 23 mycotoxins of concern in urine samples. A salting-out liquid-liquid extraction (SALLE) procedure was optimized achieving recoveries between 70 and 120% for almost all the compounds and limits as lower as when QuEChERS was applied. The compounds were then determined by liquid chromatography coupled to triple quadrupole mass spectrometry. Different chromatographic conditions and analytical columns were tested, selecting a Hypersild gold aQ column as the best option. Finally, the method was applied to the analysis of 45 urine samples, in which organophosphate and pyrethroid pesticides (detection rates (DR) of 82% and 42%, respectively) and ochratoxin A and deoxynivalenol (DR of 51% and 33%, respectively) were the most detected compounds. The proposed analytical method involves the simultaneous determination of a diverse set of pesticides and mycotoxins, including their most relevant metabolites, in human urine. It serves as an essential tool for biomonitoring the presence of highly prevalent contaminants in modern society.

Machine Learning Classification of Event-Related Brain Potentials during a Visual Go/NoGo Task.

Machine learning (ML) methods are increasingly being applied to analyze biological signals. For example, ML methods have been successfully applied to the human electroencephalogram (EEG) to classify neural signals as pathological or non-pathological and to predict working memory performance in healthy and psychiatric patients. ML approaches can quickly process large volumes of data to reveal patterns that may be missed by humans. This study investigated the accuracy of ML methods at classifying the brain's electrical activity to cognitive events, i.e., event-related brain potentials (ERPs). ERPs are extracted from the ongoing EEG and represent electrical potentials in response to specific events. ERPs were evoked during a visual Go/NoGo task. The Go/NoGo task requires a button press on Go trials and response withholding on NoGo trials. NoGo trials elicit neural activity associated with inhibitory control processes. We compared the accuracy of six ML algorithms at classifying the ERPs associated with each trial type. The raw electrical signals were fed to all ML algorithms to build predictive models. The same raw data were then truncated in length and fitted to multiple dynamic state space models of order nx using a continuous-time subspace-based system identification algorithm. The 4nx numerator and denominator parameters of the transfer function of the state space model were then used as substitutes for the data. Dimensionality reduction simplifies classification, reduces noise, and may ultimately improve the predictive power of ML models. Our findings revealed that all ML methods correctly classified the electrical signal associated with each trial type with a high degree of accuracy, and accuracy remained high after parameterization was applied. We discuss the models and the usefulness of the parameterization.

Morphological Electrical and Hardness Characterization of Carbon Nanotube-Reinforced Thermoplastic Polyurethane (TPU) Nanocomposite Plates.

The impacts on the morphological, electrical and hardness properties of thermoplastic polyurethane (TPU) plates using multi-walled carbon nanotubes (MWCNTs) as reinforcing fillers have been investigated, using MWCNT loadings between 1 and 7 wt%. Plates of the TPU/MWCNT nanocomposites were fabricated by compression molding from extruded pellets. An X-ray diffraction analysis showed that the incorporation of MWCNTs into the TPU polymer matrix increases the ordered range of the soft and hard segments. SEM images revealed that the fabrication route used here helped to obtain TPU/MWCNT nanocomposites with a uniform dispersion of the nanotubes inside the TPU matrix and promoted the creation of a conductive network that favors the electronic conduction of the composite. The potential of the impedance spectroscopy technique has been used to determine that the TPU/MWCNT plates exhibited two conduction mechanisms, percolation and tunneling conduction of electrons, and their conductivity values increase as the MWCNT loading increases. Finally, although the fabrication route induced a hardness reduction with respect to the pure TPU, the addition of MWCNT increased the Shore A hardness behavior of the TPU plates.

Low expression of E-Cadherin and CDH1 variants associated with diffuse gastric cancer.

Background: Reduced or null expression of E-cadherin protein is a frequent cause of diffuse gastric cancer (DGC). More than 50% of patients with DGC present somatic variants in CDH1 gene. Objectives: The objectives of this study were to study E-cadherin expression and identify variants in the CDH1 gene in gastric tumors of patients with DGC. Methods: We studied 18 Mexican DGC patients who attended a hospital of the Mexican Social Security Institute; E-cadherin expression was determined by immunohistochemistry, and variants were identified by Sanger sequencing in promoter and coding regions. Predictive analysis was performed using PolyPhen-2 and HOPE software. Results: We found that 56% of DGC patients showed reduced expression of E-cadherin. All patients carried CDH1 variants; overall, 12 different CDH1 variants were identified. Predictive analysis revealed that the rs114265540 variant was probably damaging, with a value of 0.985, indicating a functional impact on the E-cadherin protein. Variants rs34939176 and rs33964119 were identified as risk factors for DGC (odds' ratios [OR] = 31.3, 95% CI 6.3-154.0, p < 0.001; OR = 6.1, 95% CI 2.0-19.0, p < 0.001, respectively) given their elevated frequency and by comparing it with those reported for MXL population in the 1000 Genomes Project database. Conclusions: In this Mexican population, the percentage of diffuse gastric tumors with reduced expression of E-cadherin was similar to that reported in other populations. All gastric tumors of DGC patients studied had somatic CDH1 gene variants; however, the rs114265540, rs34939176, and rs33964119 variants were importantly related to DGC.

Characterization of Nuclear Pleomorphism and Tubules in Histopathological Images of Breast Cancer.

Breast cancer (BC) diagnosis is made by a pathologist who analyzes a portion of the breast tissue under the microscope and performs a histological evaluation. This evaluation aims to determine the grade of cellular differentiation and the aggressiveness of the tumor by the Nottingham Grade Classification System (NGS). Nowadays, digital pathology is an innovative tool for pathologists in diagnosis and acquiring new learning. However, a recurring problem in health services is the excessive workload in all medical services. For this reason, it is required to develop computational tools that assist histological evaluation. This work proposes a methodology for the quantitative analysis of BC tissue that follows NGS. The proposed methodology is based on digital image processing techniques through which the BC tissue can be characterized automatically. Moreover, the proposed nuclei characterization was helpful for grade differentiation in carcinoma images of the BC tissue reaching an 0.84 accuracy. In addition, a metric was proposed to assess the likelihood of a structure in the tissue corresponding to a tubule by considering spatial and geometrical characteristics between lumina and its surrounding nuclei, reaching an accuracy of 0.83. Tests were performed from different databases and under various magnification and staining contrast conditions, showing that the methodology is reliable for histological breast tissue analysis.

Rectus abdominis muscle thickness as a predictor of peritoneal catheter dysfunction in emergency-start peritoneal dialysis patients.

BACKGROUND: Percutaneous insertion of a peritoneal dialysis catheter (PDc) is an alternative to open surgical techniques, and the anatomical characteristics of the abdominal wall may predict PDc dysfunction. We evaluated the role of rectus abdominis muscle (RAM) thickness as a predictor of PDc dysfunction. MATERIALS AND METHODS: A prospective cohort of emergency-start PD patients (EmPD) who had their first percutaneous PDc insertion were included. PDc failure was defined as the removal of a PDc due to mechanical failure within the first 30 PD fluid exchanges. Clinical variables were recorded. The skin to parietal peritoneum depth and RAM thickness were determined by abdominal ultrasound. Univariate and multivariate logistic regression models were developed to test associations between clinical parameters and PDc dysfunction. RESULTS: Over 6 months, 119 patients underwent PDc insertion; 73 (61.3%) were males, with a mean age of 46.0 ± 17.8 years. The mean skin-to-peritoneum depth was 2.5 ± 1.0 cm, the RAM thickness was 0.91 ± 0.3 cm, and catheter implantation was successful in 116 (97.4%) patients. Insertion failed in 3 (2.5%) cases, and 30 (25.8%) patients presented with catheter dysfunction. Univariate analysis indicated that RAM thickness ≥ 1.0 cm, skin-to-peritoneum depth > 2.88 cm, abdominal waist > 92.5 cm, and skin-to-RAM fascia distance > 2.3 cm were associated with PDc dysfunction; in multivariate logistic regression analysis, only greater RAM thickness remained a significant predictor (OR 1.6, 95% CI 1.38 - 1.88, p < 0.001). CONCLUSION: In EmPD patients, RAM thickness is associated with PDc dysfunction and could aid in identifying patients at risk for PDc dysfunction in emergency settings. Additional adequately powered studies are needed to confirm our findings.

Territorial aggression by dwarf hamster females (Phodopus campbelli): A hormonal approach.

Females of many vertebrate species are territorial. However, few studies have been performed on territorial aggression and its hormonal bases in females. The present study determined whether dwarf hamster females (Phodopus campbelli) display territorial aggression and the role that estradiol (E2 ) and progesterone (P4 ) play in this behavior. Two experiments were carried out. First, 28 virgin females were mated with sexually inexperienced males. The females were submitted to oviduct ligation 2 weeks before mating to prevent pregnancy. After 15 days of mating, 16 out of 28 females were submitted to resident-intruder tests, whereas the remaining 12 females were nonconfronted. Blood samples were collected 30 min after the aggression tests to determine E2 and P4 by ELISA. In the second experiment, 40 females were mated with vasectomized males. Thirty days after mating, 30 dwarf hamsters were subjected to ovariectomy; 10 were nontreated, 10 were treated with E2 , and 10 with P4 . The remaining 10 were sham-operated. All females were submitted to resident-intruder tests, and blood samples were taken to quantify E2 and P4 . In the first experiment, 87.5% of dwarf hamster females displayed territorial aggression, and in the second, 100% of females were aggressive. Ovariectomy and ovariectomy plus E2 or P4 replacement did not affect aggressive territorial behavior. These results showed that this species' females are territorial, and this behavior is not dependent on ovarian steroid hormones.

Intensification of the O3/TiO2/UV advanced oxidation process using a modified flotation cell.

The present work reports the use of a flotation cell as a prospective reactor for ozonation and the intensification of ozonation (catalytic ozonation and photocatalytic ozonation). The effect of the pH, ozone concentration and loading catalyst was investigated. The performance of the flotation cell was compared with that of conventional reactors used in ozonation through the ozone utilized index (OUI), which was proposed in this work and relates the amount of ozone supplied to the system per milligram of degraded pollutant. The flotation cell has the lowest OUI, which indicates that the ozone supplied is highly consumed. It was found that the modified flotation cell is an efficient reactor for ozonation, catalytic ozonation and photocatalytic ozonation processes because total diclofenac degradation was achieved in a short time, mass transfer limitations were not found (Ha = 7.26), and it presented a relatively low energy consumption (1.15 kW h m-3).

Changes in amino acid profiles and liver alterations in pregnant rats with a high carbohydrate/low protein diet.

INTRODUCTION AND AIM: Intake of a high-carbohydrate, low-protein diet (HCD/LPD) during pregnancy promotes metabolic disturbances. It has been suggested that liver function during pregnancy contributes to the synthesis of proteins necessary for fetal development during this stage. The liver is a site of response to the synthesis of macronutrients such as proteins. However, it is unknown how HCD/LPD is associated with modifications to the amino acid profiles and hepatic alterations in the maternal environment during pregnancy. MATERIALS AND METHODS: A transverse longitudinal study was done in primiparous mothers during gestation (G) (G1 day 1, G5 day 5, G15 day 15, and G20 day 20). Histological analysis was used to assess hepatic alterations, and amino acid profiles in the liver were analyzed with high performance liquid chromatography (HPLC). Food and water intake was quantified, and peripheral biochemical indicators in serum were measured. RESULTS: Mothers with HCD/LPD had increased micro and macro vesicles of fat, necrosis, and inflammation in the liver on G5. The total concentration of hepatic amino acids increased by 40% on G1, 17% on G5, and 25% on G15; and, there was a 12% decrease on G20. The following increases were observed in the liver on G1: arginine 68%, histidine 75%, alanine 18%, methionine 71%, and phenylalanine 51% (p>0.05); on G5: arginine 12%, methionine 34%, and phenylalanine 83% (p>0.05); on G15: arginine and phenylalanine 66%, tryptophan 81% and histidine 60.4% (p>0.05); and on G20: arginine 32% (p>0.05). No weight loss, changes in food consumption, or hepatomegaly occurred. CONCLUSIONS: HCD/LPD during pregnancy in primiparous mothers may promote development of fat vesicles. Possibly, this condition causes metabolic adaptations and nitrogen management reflected in decreased levels of serum urea and altered amino acid profiles in the liver.

Motion-based signaling in sympatric species of Australian agamid lizards.

Signaling species occurring in sympatry are often exposed to similar environmental constraints, so similar adaptations to enhance signal efficacy are expected. However, potentially opposing selective pressures might be present to ensure species recognition. Here, we analyzed the movement-based signals of two pairs of sympatric lizard species to consider how reliable communication is maintained while avoiding misidentification. Our novel approach allows us to quantify signal contrast with plant motion noise at any site we measure, including those utilized by other species. Ctenophorus caudicinctus and Gowidon longirostris differed in display complexity and motor pattern use. They also differed in overall morphology, but their signal contrast scores are strikingly similar. These results demonstrate similar adaptations to their shared environment while maintaining species recognition cues. In contrast, Ctenophorus fordi and Ctenophorus pictus are much closer in appearance, but C. pictus produces considerably higher signal contrast scores, which we suggest is attributable to the absence of territoriality in C. fordi. Taken together, our data provide evidence for adaptation to the local environment in movement-based signals, while also meeting species recognition requirements, but the selective pressure to deal with local conditions is mediated by signal function.

Endocannabinoids and Neurodegenerative Disorders: Parkinson's Disease, Huntington's Chorea, Alzheimer's Disease, and Others.

This review focuses on the role of the endocannabinoid signaling system in controlling neuronal survival, an extremely important issue to be considered when developing new therapies for neurodegenerative disorders. First, we will describe the cellular and molecular mechanisms, and the signaling pathways, underlying these neuroprotective properties, including the control of glutamate homeostasis, calcium influx, the toxicity of reactive oxygen species, glial activation and other inflammatory events; and the induction of autophagy. We will then concentrate on the preclinical studies and the few clinical trials that have been carried out targeting endocannabinoid signaling in three important chronic progressive neurodegenerative disorders (Parkinson's disease, Huntington's chorea, and Alzheimer's disease), as well as in other less well-studied disorders. We will end by offering some ideas and proposals for future research that should be carried out to optimize endocannabinoid-based treatments for these disorders. Such studies will strengthen the possibility that these therapies will be investigated in the clinical scenario and licensed for their use in specific disorders.

Improvement in Bilateral Carpal Valgus Deviation in 9 Foals After Unilateral Distolateral Radial Periosteal Transection and Elevation.

OBJECTIVES: To evaluate the effect of periosteal transection and elevation in foals with naturally occurring carpal valgus deviation. STUDY DESIGN: Prospective clinical study. ANIMALS: Foals (n = 9) with bilateral carpal valgus. METHODS: Foals with bilateral carpal valgus had distolateral radial periosteal transection and elevation (PE) including distal ulnar transection on 1 limb. Foals were stall confined until the skin incisions healed, and then allowed free exercise in a small paddock or round pen. Dorsopalmar carpal radiographs were obtained at 14 day intervals to determine the carpal valgus angle (CVA) until it was <5°. RESULTS: All limbs had a reduction in CVA and there was no significant difference in total carpal valgus angular correction or the rate at which the correction occurred between the surgical and control limb. CONCLUSIONS: Unilateral distolateral radial PE had no effect on carpal angulation in 9 foals with naturally occurring bilateral carpal valgus deviation when performed between 19 and 43 days.

Dietary fat and antioxidant vitamin intake in patients of neurodegenerative disease in a rural region of Jalisco, Mexico.

OBJECTIVE: To evaluate and compare the intake of lipids and (A, E, and C) vitamins in patients with and without possible neurodegenerative diseases. METHODS: Twenty adults with possible Alzheimer's disease or Parkinson's disease and 41 control subjects (50-89 years old) from a rural region were studied. Dietary intake was evaluated with the analysis of macronutrients and micronutrients conducted by a food frequency questionnaire and 24 hours dietary record. Analyses were adjusted for age, sex, body mass index, and energy intake. Through interrogation and use of medical record form of health secretary we obtained information about the sociodemographic characteristics. Multivariate analysis of variance to allow for covariated adjustment was used. RESULTS: Patients had a lower energy intake, vitamin C (P = 0.016), fruits (P < 0.001), vegetables (P = 0.037), and oils and fat (P = 0.002), than the controls. Interestingly, the C vitamin intake in patients was still higher than the recommended. Patients had a higher consumption of cereals (P = 0.017), high-animal fat diet (P = 0.024), and whole milk (P < 0.001); 2.4% of the controls smoke and 5% are alcohol consumers. Eighty-five percent of patients and 78% of the controls do not have physical activity. Family history of subjects in this study indicated chronic diseases. CONCLUSION: The subjects included in this study had a high intake of C vitamin, this is due to the consumption of fruits and vegetables. However, patients with possible Alzheimer's or Parkinson's disease had a lower intake of fruits and vegetables, which could be due to type of food to which they have access.

Simultaneous detection of mycotoxins and pesticides in human urine samples: A 24-h diet intervention study comparing conventional and organic diets in Spain.

Pesticides and mycotoxins, prominent chemical hazards in the food chain, are commonly found in plant-based foods, contributing to their pervasive presence in the human body, as evidenced by biomonitoring programs. Despite this, there is limited knowledge about their co-occurrence patterns. While intervention studies have demonstrated that organic diets can significantly reduce pesticide levels, their impact on mycotoxin exposure has been overlooked. To address this gap, this study pursued two objectives: first, to characterize the simultaneous presence of mycotoxins and pesticides in human urine samples by means of the control of the biomarkers of exposure, and second, to investigate the influence of consuming organic foods on these co-exposure patterns. A pilot study involving 20 healthy volunteers was conducted, with participants consuming either exclusively organic or conventional foods during a 24-h diet intervention in autumn 2021 and spring 2022 to account for seasonal variability. Participants provided detailed 24-h dietary records, and their first-morning urine samples were collected, minimally treated and analysed using LC-Q-ToF-MS by means of a multitargeted method in order to detect the presence of these residues. Results indicated that among the 52 screened compounds, four mycotoxins and seven pesticides were detected in over 25% of the samples. Deoxynivalenol (DON) and the non-specific pesticide metabolite diethylphosphate (DEP) exhibited the highest frequency rates (100%) and concentration levels. Correlations were observed between urine levels of mycotoxins (DON, ochratoxin alpha [OTα], and enniatin B [ENNB]) and organophosphate pesticide metabolites DEP and 2-diethylamino-6-methyl-4-pyrimidinol (DEAMPY). The pilot intervention study suggested a reduction in ENNB and OTα levels and an increase in ß-zearalenol levels in urine after a short-term replacement with organic food. However, caution is advised due to the study's small sample size and short duration, emphasizing the need for further research to enhance understanding of the human chemical exposome and refine chemical risk assessment.

Thermal, viscoelastic, and electrical properties of thermoplastic polyurethane films reinforced with multi-walled carbon nanotubes.

Thermoplastic polyurethane (TPU) doped with multi-walled carbon nanotubes (MWCNTs) at 1, 3, 5, and 7 wt% has been studied. The effect of MWCNTs on thermal, viscoelastic, and electric properties in the TPU matrix was characterized by differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and by impedance spectroscopy. The results show that the thermal, electrical, and viscoelastic properties, such as the glass transition temperature, shifted towards high temperatures. The melting temperature decreased, and the conductivity and the storage modulus increased by 61.5 % and 58.3 %. The previously observed behavior on the films is due to the increase in the mass percentage of carbon nanotubes (CNTs) in the TPU matrix. Also, it can be said that the CNTs were homogeneously dispersed in the TPU matrix, preventing the movement of the polymer chains, and generating channels or connections that increase the conductivity and improve the thermal properties of the material.

Identification of Green-Leaf Volatiles Released from Cabbage Palms (Sabal palmetto) Infected with the Lethal Bronzing Phytoplasma.

Lethal bronzing (LB) is a fatal infection that affects over 20 species of palms (Arecaceae) and is caused by the phytoplasma 'Candidatus Phytoplasma aculeata'. This pathogen causes significant economic losses to landscape and nursery companies in Florida, USA. Recently, the vector was determined to be the planthopper Haplaxius crudus, which was more abundant on LB-infected palms. Herein, the volatile chemicals emitted from LB-infected palms were characterized using headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME/GC-MS). Infected Sabal palmetto were identified and confirmed as positive for LB via quantitative PCR. Healthy controls of each species were selected for comparison. All infected palms exhibited elevated levels of hexanal and E-2-hexenal. Threatened palms showed high releasing concentrations of 3-hexenal and Z-3-hexen-1-ol. The volatiles characterized herein are common green-leaf volatiles (GLVs) emitted by plants under stress. This study considers the first documented case of GLVs in palms attributed to phytoplasma infection. Due to the apparent attraction of LB-infected palms to the vector, one or several of the GLVs identified in this study could serve as a lure for the vector and supplement management programs.

MINOCA: A Working Diagnosis.

Cases of patients presenting with myocardial infarction (MI) without angiographic obstructive CAD are not trivial and have significant prevalence. "The Fourth Universal Definition of MI" (4UDMI) published in 2018 introduced MI with non-obstructive coronary arteries (MINOCA). The new section was of great importance as it validated the diagnosis by defining its criteria and recognizing its presence in the community and the need for further investigation. Given the nature of the diagnosis of MINOCA, coronary angiography provides limited information about prognosis and risk stratification for future major adverse cardiovascular events (MACE). Thus, additional imaging to understand the underlying etiology of MINOCA in conjunction with a better understanding of prognostic factors is necessary to expand on the current guidelines and aid in screening for possible complications, risk of MACE, and all-cause mortality. Discerning the etiology of the presentation is crucial, and physiologic studies, as well as additional imaging, are an important part of this evaluation. These modalities include intravascular studies such as optical coherence tomography (OCT), intravascular ultrasound (IVUS), fractional flow reserve (FFR), and imaging in the form of cardiac CT (CCT) and cardiac MRI (CMR). This step is essential to target treatment regimens more efficiently. The purpose of promoting multiple imaging modalities beyond traditional angiography is to address the working MINOCA diagnosis, with the finality of identifying the specific ischemic pathophysiology. MINOCA has multiple causative mechanisms, making it a heterogeneous collection of etiologies, resulting in acute MI: atherosclerotic, and non-atherosclerotic. This literature revision demonstrates that MINOCA prevalence and mortality are not trivial, and the diagnosis affects quality of life. MINOCA presents a definitive risk of MACE without proper stratification and targeted medical therapy. Several prognostic factors of morbidity and mortality in MI-CAD patients have been identified to correlate with MINOCA patients, especially inflammatory markers. MINOCA is not an exclusion diagnosis but a working diagnosis for which further imaging studies should be performed.

Differential activities of three families of specific beta(1,3)glucan synthase inhibitors in wild-type and resistant strains of fission yeast.

Three specific ß(1,3)glucan synthase (GS) inhibitor families, papulacandins, acidic terpenoids, and echinocandins, have been analyzed in Schizosaccharomyces pombe wild-type and papulacandin-resistant cells and GS activities. Papulacandin and enfumafungin produced similar in vivo effects, different from that of echinocandins. Also, papulacandin was the strongest in vitro GS inhibitor (IC(50) 10(3)-10(4)-fold lower than with enfumafungin or pneumocandin), but caspofungin was by far the most efficient antifungal because of the following. 1) It was the only drug that affected resistant cells (minimal inhibitory concentration close to that of the wild type). 2) It was a strong inhibitor of wild-type GS (IC(50) close to that of papulacandin). 3) It was the best inhibitor of mutant GS. Moreover, caspofungin showed a special effect for two GS inhibition activities, of high and low affinity, separated by 2 log orders, with no increase in inhibition. pbr1-8 and pbr1-6 resistances are due to single substitutions in the essential Bgs4 GS, located close to the resistance hot spot 1 region described in Saccharomyces and Candida Fks mutants. Bgs4(pbr)(1-8) contains the E700V change, four residues N-terminal from hot spot 1 defining a larger resistance hot spot 1-1 of 13 amino acids. Bgs4(pbr)(1-6) contains the W760S substitution, defining a new resistance hot spot 1-2. We observed spontaneous revertants of the spherical pbr1-6 phenotype and found that an additional A914V change is involved in the recovery of the wild-type cell shape, but it maintains the resistance phenotype. A better understanding of the mechanism of action of the antifungals available should help to improve their activity and to identify new antifungal targets.

Lieber-DeCarli Diet Promotes Different Hepatic Histological Changes During Early and Late Pregnancy: An Example of Maternal Resilience.

BACKGROUND/AIM: During pregnancy, maternal liver can be affected by ethanol (ETOH) intake, whose effects depend on concentration levels ingested. This study aims to describe histological and serum marker characteristics of maternal liver during two metabolic conditions: gestation (G), and sustained ETOH intake, in early and late pregnancy. MATERIALS AND METHODS: Wistar rats were fed with Lieber-DeCarli diet during pregnancy, following an experimental protocol that allows a semi-chronic intake of ETOH (5%). Liver and serum samples were processed for histological characterization and biochemical profiling. Hematoxylin/eosin and Schiff's Periodic Acid staining were used. RESULTS: During pregnancy, a significant elevation in ballooned and edamatous hepatocytes, and a significant increase in micro and macrovesicular deposits were observed in rats fed with the ETOH diet at gestation days 3G, 8G and 15G. These changes were reverted by 20G. Liver glycogen content increased significantly at 15G. Serum metabolites in pregnant rats fed with the ETOH diet showed a significant reduction in urea (from 3G to 15G), an increase in albumin and uric acid at 20G, and a reduction in creatinine. Number of offsprings and weight of male newborns were reduced by 20% and 14%, respectively. Liver function markers in serum showed no significant changes. CONCLUSION: ETOH diet intake promotes hepatic histological changes and histological modifications during pregnancy. These results support the assumption that pregnancy is an adaptive procedure that is associated with nutritional conditions and has a strong influence on hepatic histology. They suggest that pregnancy promotes a state of resilience to the liver function during the sustained intake of 5% ETOH.

Clinical Characteristics and Transplant-Free Survival Across the Spectrum of Pulmonary Vascular Disease.

BACKGROUND: PVDOMICS (Pulmonary Vascular Disease Phenomics) is a precision medicine initiative to characterize pulmonary vascular disease (PVD) using deep phenotyping. PVDOMICS tests the hypothesis that integration of clinical metrics with omic measures will enhance understanding of PVD and facilitate an updated PVD classification. OBJECTIVES: The purpose of this study was to describe clinical characteristics and transplant-free survival in the PVDOMICS cohort. METHODS: Subjects with World Symposium Pulmonary Hypertension (WSPH) group 1-5 PH, disease comparators with similar underlying diseases and mild or no PH and healthy control subjects enrolled in a cross-sectional study. PH groups, comparators were compared using standard statistical tests including log-rank tests for comparing time to transplant or death. RESULTS: A total of 1,193 subjects were included. Multiple WSPH groups were identified in 38.9% of PH subjects. Nocturnal desaturation was more frequently observed in groups 1, 3, and 4 PH vs comparators. A total of 50.2% of group 1 PH subjects had ground glass opacities on chest computed tomography. Diffusing capacity for carbon monoxide was significantly lower in groups 1-3 PH than their respective comparators. Right atrial volume index was higher in WSPH groups 1-4 than comparators. A total of 110 participants had a mean pulmonary artery pressure of 21-24 mm Hg. Transplant-free survival was poorest in group 3 PH. CONCLUSIONS: PVDOMICS enrolled subjects across the spectrum of PVD, including mild and mixed etiology PH. Novel findings include low diffusing capacity for carbon monoxide and enlarged right atrial volume index as shared features of groups 1-3 and 1-4 PH, respectively; unexpected, frequent presence of ground glass opacities on computed tomography; and sleep alterations in group 1 PH, and poorest survival in group 3 PH. PVDOMICS will facilitate a new understanding of PVD and refine the current PVD classification. (Pulmonary Vascular Disease Phenomics Program PVDOMICS [PVDOMICS]; NCT02980887).